CPG FOR COPD by mikesanye

VIEWS: 147 PAGES: 173

									VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

                CHRONIC OBSTRUCTIVE PULMONARY DISEASE



                                   Veterans Health Administration
                                           Department of Defense
                                                                Prepared by:

                    The Chronic Obstructive Pulmonary Disease Workgroup

                                                           With support from :

The Office of Performance and Quality. VHA Headquarters, Washington, D.C.
                                                                        &
             Quality Management Directorate, United States Army MEDCOM
                                                                        &
                                         The External Peer Review Program




                     Contractor and Subcontractor:

                   West Virginia Medical Institute, Inc.
                     Birch & Davis Associates, Inc.




                 Contract number: V101(93)P-1633



                              August 1999
                              Version 1.1a
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE
                                                                                                                                           VHA/DoD Clinical Practice Guideline



                  VHA/DOD CLINICAL PRACTICE GUIDELIN E FOR THE MANAGEMENT OF
                             CHRONIC OBSTRUCTIVE PUL MONARY DIS EAS E

                                                                               Table of Contents


                                                                                                                                                                                      Page


PARTICIPANTS



INTRODUCTION ............................................................................................................................................................                    i



ALGORITHMS AND S UMMARY ANNOTATIONS



     OUTPATIENT MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DIS EAS E

          Core ...........................................................................................................................................................................   1

          Acute Exacerbation (A 1) .......................................................................................................................................                   8

          Pharmacotherapy (A2) .......................................................................................................................................... 12

          Long-Term Oxygen Therapy (A3)....................................................................................................................... 19

          Preoperative Evaluation And Management (A4) .............................................................................................. 22

          Management of Air Travel (A5) .......................................................................................................................... 25

          Insomnia (A 6) ........................................................................................................................................................ 28



     INPATIENT MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DIS EAS E

          Emergency Roo m and Hospital Ward (B1) ....................................................................................................... 30

          Pharmacotherapy (B2) ........................................................................................................................................... 36

          Oxygen Therapy (B3) ............................................................................................................................................ 40




                                                                                                                                      Management of COPD: Table of Contents
                                                                                                                                         VHA/DoD Clinical Practice Guideline



                  VHA/DOD CLINICAL PRACTICE GUIDELIN E FOR THE MANAGEMENT OF
                             CHRONIC OBSTRUCTIVE PUL MONARY DIS EAS E

                                                                  Table of Contents (Conti nued)



ALGORITHMS AND EXPANDED ANNOTATIONS



     OUTPATIENT MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DIS EAS E

          Core ........................................................................................................................................................................... 42

          Acute Exacerbation (A 1) ....................................................................................................................................... 51

          Pharmacotherapy (A2) .......................................................................................................................................... 59

          Long-Term Oxygen Therapy (A3)....................................................................................................................... 71

          Preoperative Evaluation And Management (A4) .............................................................................................. 75

          Management of Air Travel (A5) .......................................................................................................................... 79

          Insomnia (A 6) ........................................................................................................................................................ 83



     INPATIENT MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DIS EAS E

          Emergency Roo m and Hospital Ward (B1) ....................................................................................................... 87

          Pharmacotherapy (B2) ........................................................................................................................................... 94

          Oxygen Therapy (B3) ............................................................................................................................................ 99




BIB LIOGRAPHY ........................................................................................................................................................... 1




                                                                                                                                    Management of COPD: Table of Contents
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE



                                     PARTICIPANTS
                                                                            VHA/DoD Clinical Practice Guideline



                                        MANAGEMENT OF COPD

                                           Working Group


Peter Al menoff, MD *                                   Bary.cusack@med.va.gov
National Program Director                               Bcusack@boise.va.gov
Pulmonary/Crit ical Care (111)
VA Headquarters                                         Donald W. Deg roff, MAJ, MSC, USA
4801 Linwood Blvd.                                      Pharmacist
Kansas City, MO 64128                                   DoD Pharmacoeconomic Center
816-861-4700                                            1750 Greeley Road
peter.almenoff@med.va.gov                               Bldg 4011, Room 217
                                                        Fort Sam Houston, TX 78234-6190
Gregg Anders, LTC, MC, USA                              210-295-9635
Pulmonologist                                           Maj_donald+E18_degroff@smtplink.amedd.army.
Brooke Army Medical Center                              mil
Depart ment of Health Plan Management
Fort Sam Houston, TX 78224                              Thomas Dillard, COL, M C, USA
210-916-2727                                            Co mmander-MAM C
LTC_gregg_anders@smtplin k.bamc.                        Pulmonary/Crit ical Care and Respiratory
                                                        Therapy
Teresa Bisnett, Maj, MC, USAF                           Madigan Army Medical Center
Pulmonologist                                           MCHI-M PU
Malcolm Gro w Medical Center                            Tacoma, WA 98431
89 M G/SGHM R                                           Col_Tho mas_Dillard@smtplink.mamc .
1050 West Perimeter Road                                amedd.army .mil
Suite H1-38
Andrews Air Force Base, MD 20331-6600                   Alan Fein, MD
301-981-7428                                            American College of Chest Physicians Rep.
bisnett@bigfoot.com                                     Director
                                                        Center for Pu lmonary and Crit ical Care
John Brown, LCDR , M C, USN                             North Shore University Hospital
Internist                                               300 Co mmun ity Drive
Dept. of Internal Medicine                              Manhassett, NY 11030
National Naval Med ical Center                          516-562-4217
8901 Wisconsin Avenue                                   Afein@nshs.edu
Building 9, Roo m 1636
Bethesda, MD 20889-5600                                 Thomas Fraser, Capt, M C, USAF
301-295-4191                                            Staff Internist
john_e.brown@bethva.nav.mil                             Andrews AFB
                                                        1050 West Perimeter Road
John Christ man, MD                                     89 AMDS/SGPM I
Chief, Pulmonary & Critical Care                        Andrews AFB, M D 20762
Nashville VAMC (111)                                    301-981-0617
1310 24th                                               fraset@mg mc.af.mil
Nashville, TN 37212
615-327-4751, ext. 7928                                 Maqual Infranca Graham, PharmD
john.christman@mcmail.vanderbilt.edu                    VAM C Kansas City
                                                        4801 Linwood Blvd.
Barry Cusack, MD                                        Kansas City, MO 64108
Chief, Geriatric Medicine                               816-861-4700 ext . 7055
Boise VAM C (111)                                       Maqual.infranca@med.va.gov
500 West Fort Street
Boise, ID 83702
208-422-1325



* Indicates Super Champi on of Gui deline Development                     Management of COPD: Working Group
                                                                             VHA/DoD Clinical Practice Guideline



Nicholas Gross, MD, PhD                                 Jennifer Maher, Capt, MC, USAF
Hines VAMC (111)                                        Family Practit ioner
5th Avenue and Roosevelt Road                           Family Practice Clinic
Hines, IL 60141                                         Malcolm Gro w Medical Center
708-216-2738                                            89NOS/SGOEF
                                                        1075 West Perimeter Road
Michael Habib, M D                                      Andrews AFB, M D 20762
Director, ICU                                           301-981-3956
Tucson VAM C                                            jmaherva@aol.co m
3601 South 6th Avenue (111)
Tucson, AZ 85723                                        John P. Mitchell, Lt Col, MC, USAF*
520-629-4627                                            Consultant to AF Surgeon General
mhabib@resp-sci.arizona.edu                             David Grant Medical Center
                                                        60 MDOS/SGOM P
Wayne T. Honeycutt, LTC, M C, USA                       101 Bodin Circle, Suite 1C508
Chief Depart ment of Medicine                           Travis AFB, CA 94535-1800
7 Woodbridge Drive                                      707-423-5008
Evans, GA 30809                                         john.mitchell@60mdg.t ravis.af.mil
Ltc_wayne_honeycutt@ddeamc.smtplink.amedd.ar
my.mil                                                  Toni Mitchell, M D
                                                        Chief, Consultant, Acute Care
David Hudgel, MD                                        VHA, VA CO 111
American College of Chest Physicians Rep.               8110 Vermont Avenue, NW
Professor of Medicine                                   Washington, DC 20420
Case Western Reserve University                         Toni.mitchell@hq.med.va.gov
Metro Health Medical Center
2500 Metropolitan Health Drive                          Joe Parker, LTC, M C, USA
Cleveland, OH 44109-1998                                Chief, Pulmonary and Critical Care Medicine
216-778-8393                                            Trip ler Army Medical Center
Dhudgel@metrohealth.org                                 One Jarrett-White Road
                                                        Honolulu, HI 96859
Kenneth Hurwitz, MAJ, M C, USA                          808-433-5759
Pulmonary and Critical Care Medicine                    Josephmparker@yahoo.com
Walter Reed AMC
Washington, DC 20307                                    Lu is A. Ramos, LT, M SC, USN
202-782-6745                                            Physician Assistant
Maj_kenneth_hurwit z@wramc1.amedd.army.mil              Naval Medical Clinic, Annapolis
                                                        250 Wood Road
Michael Krafczy k, CPT, M C, USA                        Annapolis, MD 21402
9501 Farrell Road                                       410-293-1764
FBFAC                                                   Laramos@us.med.navy.mil
Ft. Belvoir, VA 22060
703-805-0045                                            Go rdon Snider, MD
cpt_michael_ krafczy k@smtplink.amedd.                  American Thoracic Society Rep.
army.mil                                                Chief, Medical Serv ice
                                                        Boston VAMC
Michael Littner, M D                                    Medical Service (111)
Chief, Pulmonary Medicine                               150 South Huntington Avenue
Sepulveda VAMC (111)                                    Boston, MA 02130
16111 Plu mmer Street                                   Snider.gordon_l.md@boston.va.gov
Sepulveda, CA 91343                                     Go rdon.snider@medn.va.gov
818-895-4388
mlittner@ucla.edu                                       Oded Susskind, MPH
                                                        Instructional Design Facilitator
                                                        oded@tiac.net




* Indicates Super Champi on of Gui deline Development                      Management of COPD: Working Group
                                                                            VHA/DoD Clinical Practice Guideline



Sean Tunis, MD                                          Joy Williams, RN, RRT, M HA
American College of Physicians Rep.                     Chief, Respiratory Care and Diagnostic Service
194 Oakdale Road                                        James A. Haley Veterans’ Hospital (111)
Baltimore, M D 21210                                    13000 Bruce B. Downs Blvd.
Stunis@earthlink.net                                    Tampa, FL 33612
                                                        Williams.joy@tampa.va.gov




* Indicates Super Champi on of Gui deline Development                     Management of COPD: Working Group
                                                                             VHA/DoD Clinical Practice Guideline



                                            Other Participants

J. B. Aguera-Arcas, MD                                   Sarah Ingersoll, RN
Senior Medical Consultant                                Network Coordinator
Birch & Dav is Associates, Inc.                          Birch & Dav is Associates, Inc.
104 South Rolling Road                                   1263 S. El Mo lino Avenue
Catonsville, M D 21228                                   Pasadena, CA 91106
410-747-3144                                             626-796-4745
aguera@home.co m                                         singerso@hsc.usc.edu

Sid Atkinson, COL, M C, USA                              Barbara Jones, RRA
Chief, Quality Management Division                       Program Develop ment Coord inator
Co mmander M CHO-CL-Q                                    Birch & Dav is Associates, Inc.
2050 Worth Road, Suite 10                                8905 Fairview Road
Ft. Sam Houston, TX 78234                                Silver Spring, M D 20910
210-221-6195
col_sid_atkinson@smtplink.medco m.amedd.army .           Authur Kaufman, M D
mil                                                      Medical Director
                                                         Birch & Dav is Associates, Inc.
Marsha Beaugrand, CDR, MSC, USN                          8905 Fairview Road
Health Care Operations, Clinical Plans (Med-32)          Silver Spring, M D 20910
Bureau of Medicine & Surgery                             akaufman@birchdavis.com
2300 E Street NW
Washington, DC 20372                                     Genny Krakau
202-762-3110                                             Health Systems Specialist
mjbeaugrand@us.med.navy.mil                              U.S. Army Medical Co mmand
                                                         2050 Worth Road, Suite 10
Gerald Co x, CDR, MC, USN                                Ft. Sam Houston, TX 78234
Director, Clin ical Management & Plans (M ED-32)         210-221-6195
Bureau of Medicine & Surgery                             genny_krakau@smtplin k.medco m.amedd.army .mil
2300 E Street NW
Washington, DC 20372                                     Louise H. Nelson, RN
202-767-3138                                             Education and CQI Coordinator
erco x@us.med.navy.mil                                   West Virginia Medical Institute, Inc.
                                                         3001 Chesterfield Place
Kathryn J. Dolter, RN, Ph D, LTC, AN                     Charleston, WV 25304
Chief, Outcomes Management                               304-346-9864
Quality Management                                       lnelson@wvmi.org
USA Medical Co mmand
2050 Worth Road, Suite 10                                George Pickett, M D, M PH
Ft. Sam Houston, TX 78234                                Clin ical Pro ject Director
ltc_kathryn_dolter@smtplin k.medco m.                    West Virginia Medical Institute, Inc.
amedd.army .mil                                          3001 Chesterfield Place
                                                         Charleston, WV 25304
Rosalie Fish man, RN, MSN, CPHQ                          304-346-4590, ext. 270
Clin ical Coord inator                                   gpickett@.wv mi.org
Birch & Dav is Associates, Inc.
8905 Fairview Road                                       Arnyce Pock, Lt Col, M C, USAF
Silver Spring, M D 20910                                 AF/SG Consultant for Internal Medicine
301-650-0218                                             Office o f the Air Force Surgeon General
rfishman@birchdavis.com                                  110 Lu ke Avenue, Rm. 405
                                                         Bolling AFB, DC 20332
                                                         202-767-40073
                                                         arnyce.pock@usafsg.bolling.af.mil




                                                                         Management of COPD: Other Participants
                                                      VHA/DoD Clinical Practice Guideline



Janet Spinks, RN, MS, CPHQ        Debby Walder, RN, MSN
Birch & Dav is Associates, Inc.   Performance Mgmt. Facilitator
8905 Fairview Road                Depart ment of Veterans Affairs
Silver Spring, M D 20910          810 Vermont Avenue, NW
301-650-0285                      Washington, DC 20420
jspinks@birchdavis.com            202-273-8336
                                  debby.walder@mail.va.gov




                                                  Management of COPD: Other Participants
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE




                                    INTRODUCTION
                                                                                      VHA/DoD Clinical Practice Guideline



              VHA/DOD CLINICAL PRACTICE GUIDELIN E FOR THE MANAGEMEN T OF
                       CHRONIC OBSTRUCTIVE PUL MONARY DIS EAS E

                                                       Introduction

This clinical practice guideline on the management of chronic obstructive pulmonary disease (COPD) is
intended to update the 1997 version on Management of Persons with COPD. Th is guideline can ass ist primary
care providers or specialists in the early detection of symptoms, assessment of the clinical situation,
determination of appropriate treat ment, and delivery of indiv idualized interventions. Although it is developed
for a broad range of clinical settings, it should be applied with enough flexibility to accommodate local practice
and individual situations.

The guideline was developed under the auspices of the Veterans Health Administration (VHA) and the
Depart ment of Defense (DoD) pursuant to directives from the Depart ment of Veterans Affairs Undersecretary
for Health and the DoD Assistant Secretary of Defense, Health Affairs and by consultants of the contractor
(West Virg inia Medical Institute, Inc.) and the subcontractor (Birch & Davis Associat es, Inc.). Topic selection
is based on informat ion about the prevalence of COPD and asthma in the VHA and DoD populations and the
risks that are associated with this condition. It is known that early diagnosis and preventive treatment decreases
progression to more severe COPD and reduces mo rtality.

The VHA and DoD define clin ical p ractice guidelines as:

         "Recommendations for the performance or exclusion of specific procedures or services derived
         through a rigorous methodological approach that includes the following:

         1.    Determination of appropriate criteria, such as effectiveness, efficacy, population benefit, or
               patient satisfaction; and
         2.    Literature rev iew to determine the strength of the evidence in relat ion to these criteria." (1)

The VHA/DoD Clinical Pract ice Guideline for COPD is displayed in algorithmic fo rmat. The algorithm and
annotations are based on an exhaustive review of the literature. The goal of the literature review is to provide a
systematic basis for the development of an evidence-based guideline. The criteria for the literature search is
related to the population being studied (adult) and the treatment setting (primary care).

This guideline is divided into three sections: algorithm, annotations, and bibliography. An algorithm is a set of
rules for solving a problem in a finite number of steps. A letter within the box of an algorithm refers the reader
to the corresponding annotation. A clinical algorith m allo ws the practitioner to follow a linear approach to the
recognition and treatment of COPD. Clin ical practice however, often requires a nonlinear approach. For
example, COPD may be the initial presenting complaint, but a coexisting condition such as congestive heart
failure may require attention first.

The annotations elaborate on the recommendations and statements that are noted in each box of the algorith m.
These annotations include a reference, when required, and evidence grading for each of these
recommendations—the strength of recommendation (SR) and level of evidence (LE). The bib liography
includes all the sources used directly or indirectly in the substantiation of this guideline.

The algorith m and annotations are in part based on the COPD guideline developed in 1997. Additional
literature related to the population being studied (adult) and the treatment setting (primary care) was provided
on an adhoc basis by Birch and Davis Associates, Inc., to supplement the orig inal search.

The Medical Subject Headings (MeSH) include: (Diseases; Respiratory Tract Diseases; Lung Diseases; Lung
Diseases - Obstructive, Atelectasis, Bronchopulmonary Dysplasia; Asthma, Bronchitis, Pu lmonary
Emphysema). Selection of art icles was then based on key therapies in COPD, study characteristics, and study
design. In this search, ―study characteristics‖ are those of analytic studies, case-control studies, retrospective
studies, cohort studies, longitudinal studies, follow-up studies, prospective studies, cross -sectional studies,
clin ical protocols, controlled clinical trials, randomized clinical trials (RCT)s, intervention studies, and



                                                                                 Management of COPD: Introduction Page i
                                                                                      VHA/DoD Clinical Practice Guideline



sampling studies. Study design includes crossover studies, double-blind studies, matched pair analysis, meta-
analysis, random allocation, reproducibility of results, and sample size.

The literature search is followed by critical analysis of the literature, primarily by the clinical experts. To
promote an evidence-type approach, the quality of evidence is rated using a hierarchical rat ing scheme. The
value of a hierarchical rat ing scheme is that it provides a systematic means for evaluating the scientific basis for
health care services (3). The rating scheme used for this guideline is based on a system used by the
Agency for Health Care Po licy and Research. Decision points in the algorithm are annotated, and th e primary
source documents for the annotation are graded.

This Gu ideline, expressed in 10 modules, is divided into two major sections: outpatient management (A1-6),
and inpatient intervention (B1-3)

1.    Core annotations for COPD
2.    Acute exacerbation of COPD (A 1)
3.    Pharmacotherapy for COPD (A2)
4.    Long-term o xygen therapy in COPD (A 3)
5.    Preoperative evaluation and management of COPD (A4)
6.    Management of air travel in COPD (A5)
7.    Insomnia in COPD (A6)
8.    Emergency room and hospital ward management of COPD (B1)
9.    Pharmacotherapy for COPD (B2)
10.   Oxygen therapy in COPD (B3)

The grading scheme used for this guideline is:

STRENGTH OF RECOMMENDATION GRADING (4)


      Grade                                        Strength of Recommendation

         I         Usually indicated, always acceptable, and considered useful and effective.

        IIa        Acceptable, of uncertain effectiveness, and may be controversial. Weight of evidence in
                   favor of usefulness/effectiveness.

        IIb        Acceptable, of uncertain effectiveness, and may be controversial. Not well established by
                   evidence, can be helpful and probably not harmful.

LEVEL OF EVID ENCE GRADING


                             Level of Evidence            Level of Evidence                 Level of Evidence
                               Grading = A                  Grading = B                       Grading = C

 Primary Evidence         Randomized clinical         Well-designed clin ical          Panel consensus
                          trials                      studies

 Secondary Evidence       Other clinical studies      Clin ical studies related to     Clin ical studies related to
                                                      topic but not in this            topic but not in this clin ical
                                                      clin ical population             population


The clinical experts subjected all decision points in the algorithm to simulat ion e xercises. A variety of
hypothetical "patients" were run through the algorithm to test whether it was likely to work in a real clin ical
situation. Whenever an irregularity was encountered, changes were made. The clinical experts are thus


                                                                                Management of COPD: Introduction Page ii
                                                                                     VHA/DoD Clinical Practice Guideline



reasonably confident that the algorith m will prove to be useful in real clinical encounters.

The ultimate goal of this guideline is to promote evidence-based management of persons with COPD and
thereby improve clinical outcomes. Ev idence based practice involves integrating clinical expertise with the best
available clin ical ev idence derived fro m systematic research . (5) The reader is reminded that this document is
intended as a guideline and accordingly, should not supersede the clinical judgment of the healthcare provider.
This init ial version will be updated, as further research results become available and based on end -user feedback
fro m field trials.

Clin ical guideline algorith ms provide a basis for local development of more specific clinical pathways, defined
as:

         Clin ical management tools that organize, sequence, and specify the timing for the major
         patient care activities and interventions of the entire interdiscip linary team for a part icular
         diagnosis or procedure. Clin ical pathways define key processes and ev ents in the day-to-day
         management of care and often serve as a component of the patient record. Variance fro m the
         pathway along with causes of divergence should be documented. Clinical pathways should be
         developed locally, as they are specific to the particular setting where utilized.

This guideline and algorithm is the product of many months of consensus building among knowledgeable
individuals, including private sector experts provided by the contractor, the Veterans Health Administration and
Depart ment of Defense professionals from across the health care continuum. Many of the experts involved in
developing this guideline have previously participated in the development of other VHA/DoD Clinical Practice
Gu idelines. The process included contributions from pulmonologists, internal medicine, emergency med icine,
primary care physicians, program specialists, external peer review physicians, nurses, administrators, and expert
consultants in the field o f guideline and algorithm development.




                                                                              Management of COPD: Introduction Page iii
                                                                                    VHA/DoD Clinical Practice Guideline




REFERENCES

(1) VHA Directive 96-053; VA HSR&D M DRC 1998
(2) Modified by Birch & Davis Associates, Inc. fro m: A CC/AHA Task Fo rce Report. Gu idelines for the early
    management of patients with acute myocardial infarction. Journal of the American College of Cardiology,
    August 1990;16:251
(3) Woolf et al., 1996
(4) Modified by Birch & Davis Associates, Inc. fro m: A HCPR Clinical Practice Gu ideline No. 10. Unstable
    angina: diagnosis and management. March 1994:12
(5) Sackett et al. 1996

BIB LIOGRAPHY

ACC/AHA Task Force Report. Gu idelines for the early management of patients with acute myocardial
   infarct ion. J Am College Cardiology, 1990;16:251

AHCPR Clin ical Pract ice Gu ideline No. 10. Unstable angina: diagnosis and management. March 1994:12

Kazis LE; M iller DR; Clark J; et al.. Health-related quality of life in patients served by the Department of
    Veterans Affairs: Results fro m the Veterans Health Study. Arch Intern Med 1998; 158:626-632

Sackett DL; Rosenberg WMC; Gray JAM, Richardson WS. Evidence based medicine: What it is and what it
    isn’t. Brit Med J 1996; 312:71-72

VA Health Serv ices Research and Development Service Management Decision and Research Center. Clinical
   Practice Gui delines: Gui delines Pri mer. Boston, MA. VA HSR&D 1998

VHA Directive 96-053. Roles and Definitions for Clinical Practice Gu idelines and Clinical Pathways. August
   29, 1996.

Woolf SH; DiGu iseppi CG; Atkins D; Kamerow DB. Develop ing evidence-based clinical pract ice guidelines:
   Lessons learned by the U.S. Preventive Serv ices Task Force. Ann Rev Pub Health 1996;17;511-38




                                                                              Management of COPD: Introduction Page iv
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

                         OUTPATIENT MANAGEMENT



            ALGORITHM AND SUMMARY ANNOTATIONS
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

                     OUTPATIENT MANAGEMENT: Core



            ALGORITHM AND SUMMARY ANNOTATIONS
                         VHA/DoD Clinical Practice Guideline




Management of COPD: Outpatient Management - Core Algorithm
                                                                                            VHA/DoD Clinical Practice Guideline



                    CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                      Outpatient Management of COPD: (Core)

A. Patient wi th Suspected or Confirmed Chronic Obstructi ve Pul monary Disease Presents to Pri mary Care


    Chronic obstructive pulmonary disease (COPD) is defined by the American Thoracic Society (ATS) in
    Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease (1995). Further
    detail on lung function testing is found in another ATS publication (1991). [The British Thoracic Society (BTS)
    and the European Respiratory Society (ERS) have definitions that differ slightly with the ATS definition.]

    DEFINITIONS

    1.   Chronic obstructive pulmonary disease is a disorder characterized by the presence of airflow obstruction
         due to chronic bronchitis or emphysema; the airflo w obstruction is generally slowly p rogressive, may be
         accompanied by airway hyperactivity, and may be partially reversible.
    2.   Chronic bronchitis is defined as the presence of chronic productive cough for 3 months of each of two
         successive years in a patient in who m other causes of chronic cough have been excluded (asthma, post
         nasal discharge, gastroesophageal reflu x disease (GERD), etc.).
    3.   Emphysema is defined as abnormal permanent enlargement of the air spaces distal to the terminal
         bronchioles, accompanied by destruction of their walls and without obvious fibrosis.
    4.   Asthma is by definition associated with reversible airflo w obstruction. Patients wit h asthma whose airflo w
         obstruction is completely reversible are not considered to have COPD. The obstruction in many patients
         with COPD may include a significant reversible co mponent. Some patients with asthma may develop
         irreversible airflo w obstruction indistinguishable fro m COPD.

B. Perform Clinical Assessment, History, Physical Examinati on, Laboratory Tests

    OBJECTIVE

    To collect informat ion needed to assess the patient.

    ANNOTATION

    1.   History.
         a.   Smoking—Age at init iation, quantity smoked per day, whether or not still smoker and if not, date of
              cessation.
         b.   Environmental (chronological), e.g., dust exposure—may disclose important risk factors.
         c.   Cough (chronic, productive)—Frequency and duration, whether or not productive (especially on
              awakening).
         d.   Wheezing.
         e.   Acute chest illnesses—Frequency, productive cough, wheezing, dyspnea, fever.
         f.   Dyspnea.
         g.   Evaluate current therapy.


    2.   Physical Examination of Chest.
         a. Airflow obstruction evidenced by:
             —Wheezing during auscultation on slow or forced breathing.
             —Forced exp iratory time of mo re than 6 seconds.


                                                            Outpatient Management of COPD: Core - Summary Annotations - Page 1
                                                                                        VHA/DoD Clinical Practice Guideline



         b. Severe emphysema indicated by:
            —Overdistention of lungs in stable state, low d iaphragmat ic position
              —Decreased intensity of breath and heart sounds.
         c. Severe d isease suggested by (characteristics not diagnostic):
            —Pursed-lip breathing
              —Use of accessory respiratory muscles
              —Indrawing of lower interspaces.
         d. Other—Unusual positions to relieve dyspnea at rest, digital clubbing (suggests possibility of lung
            cancer or bronchiectasis), and mild dependent edema that may be seen in absence of right heart failure.

    3.   Laboratory.
         a.   Spiro metry : FEV1 and VC (vital capacity).
         b.   Chest radiography—Diagnostic only of severe emphysema but essential to exclude other lung diseases.
         c.   Oximetry should be done to help determine if there is a need for o xygen therapy. It may be done at
              this time or at the time of apply ing the long-term o xygen therapy module (A3).
         d.   Alpha1-antitrypsin (AAT)—AAT deficiency accounts for less than one percent of COPD. If ATT
              deficiency is suspected, obtain a serum AAT level. Strongly consider referral to specialist in the
              following situations:
              —Premature onset of COPD with moderate or severe impairment before age 50
              —A predominance of basilar emphysema; development of unremitting asthma, especially in a patient
                under age 50
              —A family h istory of AAT deficiency or of COPD onset before age 50
              —Chronic bronchitis with airflow obstruction in a person who has never smoked
              —Bronchiectasis, especially in the absence of clear risk factors for the disease
              —Cirrhosis in a patient without apparent risk factors (ATS 1995). If diagnosis of COPD or asthma is
               made, refer to specialist for reco mmendations for therapy.

C. Is Patient in Acute Exacerbati on?


    OBJECTIVE

    To identify patients in an acute exacerbation.

    ANNOTATION

    An acute exacerbation of COPD is defined as an acute clinical deteriorat ion in a patient's respiratory status due
    to a worsening of the underlying COPD. Sy mpto ms and signs of acute exacerbation of COPD may include:

    1.   Increased dyspnea.
    2.   Tachycardia.
    3.   Increased cough.
    4.   Increased sputum production.
    5.   Change in sputum color or character.
    6.   Accessory muscle use.
    7.   Peripheral edema.
    8.   Develop ment of or increase in wheeze.
    9.   Loss of alertness.


                                                        Outpatient Management of COPD: Core - Summary Annotations - Page 2
                                                                                          VHA/DoD Clinical Practice Guideline



    10. Loss of energy.
    11. Fever.
    12. Increased respiratory rate.
    13. Decrease in FEV1 or peak exp iratory flow.
    14. Worsening of arterial b lood gases or pulse oximetry.
    15. Chest tightness.

D. Is there Evi dence of Severe Exacerbation?


    OBJECTIVE

    To identify patients with a severe exacerbation that requires emergency roo m care.

    ANNOTATION

    Loss of alertness or a combination of two or more of the fo llo wing parameters indicate a severe exacerbation
    and suggest a need for referral to an emergency department.

    1.   Dyspnea at rest.
    2.   Respiratory rate > 25 per minute.
    3.   Heart rate > 110 per minute.
    4.   Use of accessory muscles.

E. Order/Review S pirometry

    OBJECTIVE

    To objectively assess pulmonary function in patients with COPD.

    ANNOTATION

    On in itial visit :

         Spiro metry pre - and postbronchodilation are essential to confirm presence and reversibility of airflow
         obstruction and to quantify maximu m level of ventilatory function (ATS 1995), guide management, and
         estimate prognosis.

    On follow up visits:

         Repeat spirometry if major change in patient’s condition. On new patients previous spirometry may be used
         if availab le and no change in patient's condition.

         1.    Airflow limitation is diagnosed by a reduction in FEV1 / VC (v ital capacity).

         2.    Lung volu mes—Unnecessary except in special circu mstances (e.g., coexisting interstitial lung disease,
               presence of giant bullae, and decrease in vital capacity).

         3.    Carbon mono xide d iffusing capacity—Unnecessary except in special instances (e.g., dyspnea out of
               proportion to severity of airflow limitation).




                                                          Outpatient Management of COPD: Core - Summary Annotations - Page 3
                                                                                          VHA/DoD Clinical Practice Guideline



     DISCUSSION

     SEVERITY OF AIR FLOW OBSTRUCTION
     COPD severity can be graded on the basis of percentage of predicted FEV1 as Mild, Moderate, or Severe.
     Grading or staging, based on severity of airflo w obstruction, facilitates the application of clinical
     recommendations and attempts to offer a composite picture of d isease severity. Forced exp iratory spiro metry is
     used in the diagnosis of COPD as well as in the assessment of its severity, progression, and prognosis. The use
     of an FEV1 < 50 percent corresponds to a grade of moderate to severe as adopted in the 1995 ATS document.
                                         Table I. Severity of COPD Based on FEV1
                                        Severity                 FEV1 Percent Predicted (1)
                                          Mild                              50 to 79
                                        Moderate                            35 to 49
                                         Severe                               < 35
                           (1) In the presence of obstruction assessed as a low FEV1 / VC ratio.

F.   Initiate/Adjust Pharmacological Therapy
     OBJECTIVE
     To determine the appropriate therapy based on severity of symptoms.

     ANNOTATION
                                               Table II. Step Care In COPD
     Step    Symptoms and FEV1                             Therapy
     1       Asymptomat ic AND                            Smoking cessation, vaccination, employ education. No
             FEV1 > 50 percent of p redicted (1)          med ication indicated.
     2a      Sympto ms less than daily AND                Smoking cessation, vaccination, employ education.
             FEV1 > 50 percent of p redicted (2)          Inhaled short-acting beta2 -ag onist (2 puffs PRN up to 12
                                                          puffs/day)
     2b      Asymptomat ic AND                            Smoking cessation, vaccination, employ education.
             FEV1 < 50 percent of p redicted              Inhaled anticholinergic (2 puffs qid)
                                                          Consider use of inhaler containing a short acting beta 2 -
                                                          agonist and an anticholinergic.
     2c      Sympto ms less than daily AND                Smoking cessation, vaccination, employ education.
             FEV1 < 50 percent of p redicted              Inhaled anticholinergic (2 puffs qid)
                                                          Short-acting beta2 ag onist (2 puffs PRN up to 12
             OR
                                                          puffs/day)
             Daily sympto ms                              Consider use of inhaler containing a short acting beta 2 -
                                                          agonist and an anticholinergic.
     3       Sympto ms not controlled (2)                 Increase dose of both:
                                                          Inhaled anticholinergic (2 to 6 puffs qid) and
                                                           inhaled short-acting beta2 agonist (2 -4 puffs PRN up to
                                                          12 puffs/day)
     4       Sympto ms not controlled (2)                 Consider adding long-acting inhaled beta2 -agonist. (3)
     5       Sympto ms not controlled (2)                 Consider adding theophylline tri al (slow release
                                                          theophylline adjusted to level of 5 to 12 µg/ ml) (4)
     6       Sympto ms not controlled (2)                 Consider adding corticosteroi d tri al (prednisone 40 to 60
                                                          mg po qd or h igh dose inhaled steroids (5).
                                                          Consider specialist consultation.
     7       Sympto ms not controlled (2)                 Refer to specialist promptly.



                                                        Outpatient Management of COPD: Core - Summary Annotations - Page 4
                                                                                           VHA/DoD Clinical Practice Guideline




     1.   Spiro metry is essential to confirm the presence of airflo w obstruction (low FEV1 and FEV1 / VC rat io). Base
          therapy on symptoms, but consider alternate diagnoses (heart disease, pulmonary embo li, etc.) if out of
          proportion to spirometry.
     2.   Use the lowest level of therapy that satisfactorily relieves symptoms and maximizes activity level. Assure
          compliance and proper use of medications before escalating therapy.
     3.   Inhaled long acting beta 2 -agonists should not be used as rescue therapy. Short-acting inhaled beta 2 -agonist
          (less than12 puffs/day) may continue to be used PRN. Nighttime symptoms are frequently better controlled
          with long-acting inhaled beta 2 -agonist. Oral beta 2 -agonists are associated with a higher rate of side effects,
          and should be reserved for patients who cannot take inhaled beta 2 -agonist medications.
     4.   Theophylline should be used with caution because of potential for severe side effects. Nighttime respiratory
          symptoms are frequently controlled but theophylline may lead to insomnia. Theophylline should be
          discontinued if a sympto matic o r objective benefit is not evident within several weeks.
     5.   A corticosteroid trial o f prednisone (40 to 60mg/day) 10 to14 days, or high dose inhaled steroids
          (equivalent to 880 µg or more of fluticasone or 800 µg or more of budesonide) of 14 to 21 days can help
          identify patients who may benefit fro m long term steroid use. Responders to oral steroids should transition
          to the lowest effective dose of inhaled steroids, or to the lowest effective dose of a combination of inhaled
          and oral steroids, if possible, to avoid the long term co mplications of systemic co rticosteroids. If oral
          steroids are used other than for an acute exacerbation, obtain spiro metry prior to and after trial to confirm
          an objective response.


G. Appl y Long-Term Oxygen Therapy


     OBJECTIVE

     To maintain an acceptable level of O2 saturation and improve survival.

     ANNOTATION

     In COPD patients with hypoxemia and cor pulmonale, treat ment with long -term o xygen therapy (LTOT) may
     increase the life span by six to seven years. Mortality is reduced in patients with chronic hypoxemia when
     oxygen is ad ministered for more than 12 hours daily and greater survival benefits have been shown with
     continuous oxygen admin istration. See Module A3, Long-term Oxygen Therapy for details and references.

H. Is There Evi dence of Cardi ac Disease?


     OBJECTIVE

     To identify patients with sympto matic left ventricu lar heart d isease.

     ANNOTATION

     Card iac disease fro m systolic or d iastolic left ventricu lar dysfunction leading to pulmonary edema can produce
     symptoms similar to that of COPD, namely dyspnea, wheezing, tachycardia, chest discomfort, o rthopnea,
     paroxys mal nocturnal dyspnea. A history of coronary artery disease, hypertension, o r cardio myopathy should
     prompt further evaluation or treat ment modifications.

I.   Are There Symptoms of Sleep Apnea?

     OBJECTIVE

     To identify patients who may benefit fro m t reatment by a sleep disorder specialist.


                                                           Outpatient Management of COPD: Core - Summary Annotations - Page 5
                                                                                            VHA/DoD Clinical Practice Guideline




     ANNOTATION

     Some signs and symptoms of COPD, including hypercapnia, are precipitated by sleep apnea.
     Major sympto ms of sleep apnea include:

     1.   Excessive daytime sleepiness (EDS).
     2.   Heavy snoring.
     3.   Observed apnea during sleep.
     4.   Choking during sleep.

J.   Patient Complains of Insomni a?


     OBJECTIVE

     To identify patients who may benefit fro m treat ment of insomnia.

     ANNOTATION

     Insomnia is defined as an inability to in itiate or maintain sleep to the patient's satisfaction plus a deleterious
     subjective or objective effect on daytime activit ies. Medications, such as beta2 -agonists, theophylline and
     steroids, can produce insomnia. See Insomn ia Module A6.

K. Initiate/Continue Preventi ve Care and Patient Educati on


     OBJECTIVE

     To init iate and optimize preventive care and patient education for COPD.

     ANNOTATION

     The ma in items in COPD patient education are:

     1.   Smoking Cessation.
          All s mokers should be strongly advised to quit. Smo king cessation results in a small imp rovement in lung
          function and a slowing of the rate of decline to appro ximately that seen in never smokers of the same age.
          Patients not willing to quit should receive motivational intervention to promote subsequent quitting
          attempts. The smoker willing to make a quit attempt should be assisted by being asked to set a quit date,
          providing self-help materials, encouraging nicotine replacement therapy, and referring to intensive
          treatments when appropriate. All patients attempting to quit should have follo w-up contact scheduled.
          For additional details, see VHA/DoD CPG for Tobacco Use Cessation also see DHHS Gu idelines on
          Smoking Cessation (1996).
     2.   Medication and delivery system training.
     3.   Exercise and nutritional counseling.
          A well-rounded program should include good dietary habits and encourage adjustment of weight to
          approximate ideal body weight. If malnourished, attempts should be made to restore nutritional balance
          with several s mall meals a day to help maintain caloric needs but avoid undue dyspnea. Forced nutrition or
          special diets are not recommended.
     4.   Immunizations.
          The Advisory Committee on Immun ization Pract ices (CDC 1997) reco mmends pneumococcal vaccination
          for all patients with chronic obstructive pulmonary disease. They recommend that patients age 65 or o lder


                                                            Outpatient Management of COPD: Core - Summary Annotations - Page 6
                                                                                             VHA/DoD Clinical Practice Guideline



        that were vaccinated more than five years previously should be revaccinated. When the status of previous
        vaccination is unsure, vaccination is indicated. However, the evidence for the efficacy of pneumococcal
        vaccination in patients with COPD is inconclusive. One s mall, rando mized controlled trial failed to
        demonstrate vaccine efficacy for pneumococcal infection-related or other medical outcomes in the
        heterogeneous group of subjects labeled as high-risk. Case-controlled trials suggest an effectiveness of 65
        to 84 percent among high-risk patients including those with COPD.
        An annual influenza vaccination is recommended for individuals with chronic pulmonary d isease unless
        contraindicated due to severe anaphylactic hypersensitivity to egg protein. Influenza vaccination has been
        shown to be 30 to 80 percent effect ive in preventing illness, complicat ions, and death in high-risk
        populations. Pneumococcal and influenza vaccines can be admin istered concurrently at different sites
        without increasing side effects.
   5.   Management of environ ment.
   6.   Patients with COPD should avoid environmental exposures that exacerbate their sympto ms (e.g.,
        occupational exposures, second-hand smoke, and air and dust pollution) or results in respiratory infections.
   7.   Self-assessment and self-management.
        Pulmonary Rehabilitation—Referral is indicated in patients on optimal medical therapy and who:
        a. Continue to display moderate to severe respiratory symptoms, including dyspnea.
        b.   Have had several emergency room or hospital ad missions per year.
        c.   Exh ib it limited functional status, restricting activit ies of daily living.
        d.   Experience impairment in quality of life.
   8.   Occupational disabilities.
   9.   Sexual function.


L. Schedule Follow-Up

   OBJECTIVE

   To maintain long term appropriate level of care for patients with COPD.

   ANNOTATION

   For mild COPD, spiro metry is the test used for measuring disease progress ion. As the disease becomes mo re
   severe, oximetry and ABG assume greater importance. The frequency of obtaining these measures is based on
   clin ical symptoms and status. In general, patients with mild COPD should be seen annually; moderate COPD,
   six months to one year, depending upon status; and severe COPD, every six months at a minimu m. Spiro metry
   should be repeated at least every two to three years to follow the progression of disease and effects of therapy
   unless there is a clinically indicated reason not to do so.




                                                            Outpatient Management of COPD: Core - Summary Annotations - Page 7
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

       OUTPATIENT MANAGEMENT: Acute Exacerbation (A1)



             ALGORITHM AND SUMMARY ANNOTATIONS
                                           VHA/DoD Clinical Practice Guideline




Management of COPD: Outpatient Management - Acute Exacerbation (A1) Algorithm
                                                                                           VHA/DoD Clinical Practice Guideline



                  CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                              Outpatient Management of COPD: Acute Exacerbation (A1)

A. Patient wi th Acute Exacerbation of COPD Presenting to Pri mary Care


    DEFINITION

    Acute exacerbation is defined as a recent deterioration of a previously stable patient's clinical and functional
    state that is due to worsening of their COPD. Typical sy mptoms and signs of COPD exacerbation are g iven
    below (adapted fro m the European Respiratory Society Consensus Statement, Siafakas 1995).

    1.   Increased dyspnea.
    2.   Tachycardia.
    3.   Increased cough.
    4.   Increased sputum production.
    5.   Change in sputum color or character.
    6.   Accessory muscle use.
    7.   Peripheral edema.
    8.   Develop ment of or increase in wheeze.
    9. Loss of alertness.
    10. Loss of energy.
    11. Fever.
    12. Increased respiratory rate.
    13. Decrease in FEV1 or peak exp iratory flow.
    14. Worsening of arterial b lood gases or pulse oximetry.
    15. Chest tightness.

B. Administer Oxygen Therapy to Keep O 2 Saturation > 90 Percent


    OBJECTIVE

    Initiate o xygen therapy to maintain o xygen saturation > 90 percent.

    ANNOTATION

    There is not a good relationship between spiromet ry and blood gases in COPD exacerbation, at least in
    Emergency Depart ment patients; a PaO2 less than 60 mmHg may be found in patients with a FEV1 up to 54
    percent of normal. For that reason, O2 saturation should be obtained for patients with mild -to-moderate COPD
    exacerbations.

    If ambu latory facilities are available, o xygen should be given to keep O 2 saturation  90 percent wh ile the
    patient receives more aggressive bronchodilator therapy. In so me centers this may require ED management .
    Blood gases should be obtained to guide oxygen therapy in patients with known hypercapnea or where the
    status of CO2 retention is unknown.

    Patients who are stabilized after aggressive drug therapy but continue to have hypoxemia may require outpatient
    oxygen therapy at least on a temporary basis. Blood gases should be checked or oximetry performed in one
    month or soon thereafter when the patient is stable to determine the need for continued long -term o xygen
    therapy (LTOT).




                                         Outpatient Management of COPD: Acute Exacerbation (A1) - Summary Annotations - Page 8
                                                                                            VHA/DoD Clinical Practice Guideline




C. Is There Evi dence of Res piratory Infection?


    OBJECTIVE

    Identify the presence of a respiratory infection.

    ANNOTATION

    This often is due to viral illness. In cases of bacterial infection, S. pneumoniae, H. in fluenzae and M.
    catarrhalis are frequent pathogens. Other organisms include Mycoplasma and Chlamydia.

    Ev idence of infection include:

    1.   Increased cough.
    2.   Increase in volu me and changes in the color of sputum.
    3.   Increased shortness of breath.
    4.   Fever.

D. Consider Anti biotic Treatment


    OBJECTIVE

    Initiate appropriate therapy for a suspected bacterial respiratory infection.

    ANNOTATION

    In patients with evidence of respiratory infect ion, a white cell count and chest X-ray may be considered.
    Ev idence of respiratory infect ion with a clear chest X-ray suggests that the exacerbation of COPD is due to
    purulent bronchitis. Antibiotic therapy should be considered.

    Patients with a clin ical p resentation and chest radiograph consistent with pneumonia should be considered for
    admission. There are no published guidelines specifically regard ing admission of COPD patients. The severity
    of the underlying COPD, the presence of co-morbid conditions, the judgement and reliab ility of the patient and
    caregivers, and the distance to medical care should be considered in this decision. Drug interact ion should be
    considered if patient is under treatment with theophylline.


E. Consider and Treat Other Factors Contri buting to COPD Exacerbati on


    OBJECTIVE

    Identify and treat other factors contributing to or mimicking a COPD exacerbation.

    ANNOTATION

    1.   Congestive heart failu re.
    2.   Card iac ischemia or arrhythmia.
    3.   Drugs (hypnotics, tranquilizers, etc.).
    4.   Pulmonary embolism.
    5.   Spontaneous pneumothorax.
    6.   Inappropriate o xygen therapy.


                                          Outpatient Management of COPD: Acute Exacerbation (A1) - Summary Annotations - Page 9
                                                                                             VHA/DoD Clinical Practice Guideline



     7.     Metabolic diseases (diabetes mellitus, electro lyte disorders such as hypophosp hatemia, hypokalemia).
     8.     Myopathy (e.g., steroid myopathy).
     9. Other diseases (undernutrition, GI hemorrhage, stroke, thoracic vertebral co llapse).
     10. Air pollutants.

     These factors require treat ment in their own right and some may require ad mission to hospital. A h igh degree
     of suspicion is required to detect some relatively co mmon d isorders in the presence of COPD such as heart
     failure, pu lmonary embolism and pneumothorax.

F.   Initiate Pharmacotherapy for Acute Exacerbation


     OBJECTIVE

     To init iate medication to improve respiratory function.

     ANNOTATION

     Initiate or adjust short-acting inhaled beta 2 -agonists (SAIBA) and inhaled anticholinergic metered dose inhalers
     with spacer to maximu m levels as appropriate.

                                       Table 1. Medicati on for Acute Exacerbation
                Medication              MDI Dose            Nebulizer Dose         Special Instructions
           Short Acting Beta2
           Agonists
          Albuterol                 3-4 puffs q½-2 h        2.5 mg q½-2 h

          Metaproterenol            3-4 puffs q½-2 h        10 –15 mg q½-2 h            Deliver medication with
                                                                                        nebulizer if unable to use MDI
          Terbutaline               3-4 puffs q½-2 h        N/A                         with spacer (1)


      Anticholinergics
           Ipratropiu m Bro mide     3-6 puffs q2-4h        500 µg q2-4h
      Systemic Steroi ds             Oral
           Prednisone                40-60 mg q day                                     Taper off or change to qod
           Prednisilone              30-50 mg q day                                     within 1 to 2 weeks

          Theophylline                If on theophylline check level                    Aim fo r levels of 5 to 12 µg/ ml

     (1) Assess use of metered dose inhaler (MDI and spacer). Frequency and dose can be titrated as the patient’s
     condition allows. Patient can be discharged on minimu m dose or less.

G. Is Patient’s Condi tion Improved and Patient is Able to Go Home?
     OBJECTIVE

     To identify patients who can go home.

     ANNOTATION

     The following should be considered in evaluating the possibility of discharge:
     1. Patient clinical condition has improved.
     2.     Patient has adequate support system at ho me.


                                          Outpatient Management of COPD: Acute Exacerbation (A1) - Summary Annotations - Page 10
                                                                                            VHA/DoD Clinical Practice Guideline



     3.   Patient is able to continue necessary therapy at home (e.g., o xygen supply)


H. Has Patient's Condi tion Improved in 1 to 3 Days?

     OBJECTIVE

     Identify imp rovement in COPD exacerbation.

     ANNOTATION

     Ev idence of imp rovement of COPD exacerbation includes:

     1.   Decrease in cough, sputum production or dyspnea.
     2.   Decrease in respiratory rate.
     3.   Decrease in heart rate.
     4.   Increase in function and endurance.

I.   Slowl y Taper Intensity of Medicati on(s) to Baseline Maintenance Regimen

     OBJECTIVE

     Initiate appropriate reduction in medicat ions in order to return to maintenance levels.

     ANNOTATION

     1.   Once the patient is stabilized, with improvement in the level of function, reduce intensity of the
          bronchodilator reg imen down to the usual level of t reat ment over the course of a few days.
     2.   Tapering of corticosteroids depends on the prior history of use and tapering, but often is done over one to
          two weeks. This can be done in consultation with the primary care provider.
     3.   The provider should see the patient soon to ensure that the course of action is appropriate and for
          consideration of any further therapy such as smoking cessation, or changes in pharmacotherapy in view of
          the recent exacerbation.




                                         Outpatient Management of COPD: Acute Exacerbation (A1) - Summary Annotations - Page 11
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

         OUTPATIENT MANAGEMENT: Pharmacotherapy (A2)



            ALGORITHM AND SUMMARY ANNOTATIONS
                             VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Pharmacotherapy (A2) - Algorithm
                                                                                               VHA/DoD Clinical Practice Guideline



                     CLINICA L PRACTICE GUIDELINE FOR THE MANA GEM ENT OF COPD

                                 Outpatient Management of COPD: Pharmacotherapy (A2)

A. Patient wi th COPD Requiring Pharmacotherapy


   This algorith m outlines the criteria for the med ication treat ment of COPD. The aim of therapy is to use those
   med ications needed to maintain control and imp rove function and quality of life with the least risk for adverse
   effects. The medicat ion plan for COPD is summarized in Table I.

                                                  Table II. Step Care In COPD
   Step                Symptoms and FEV1                                                  Therapy
        1      Asymptomat ic AND                               Smoking cessation, vaccination, employ education. No
               FEV1 > 50 percent of p redicted (1)             med ication indicated.
     2a        Sympto ms less than daily AND                   Smoking cessation, vaccination, employ education.
               FEV1 > 50 percent of p redicted (2)             Inhaled short-acting beta2 -ag onist (2 puffs PRN up to 12
                                                               puffs/day)
    2b         Asymptomat ic AND                               Smoking cessation, vaccination, employ education.
               FEV1 < 50 percent of p redicted                 Inhaled anticholinergic (2 puffs qid)
                                                               Consider use of inhaler containing a short acting beta 2 -
                                                               agonist and an anticholinergic.
     2c        Sympto ms less than daily AND                   Smoking cessation, vaccination, employ education.
               FEV1 < 50 percent of p redicted                 Inhaled anticholinergic (2 puffs qid)
               OR                                              Short-acting beta2 ag onist (2 puffs PRN up to 12
                                                               puffs/day)
               Daily sympto ms
                                                               Consider use of inhaler containing a short acting beta 2 -
                                                               agonist and an anticholinergic.
        3      Sympto ms not controlled (2)                    Increase dose of both:
                                                               Inhaled anticholinergic (2 to 6 puffs qid) and
                                                                inhaled short-acting beta2 agonist (2 -4 puffs PRN up to
                                                               12 puffs/day)
        4      Sympto ms not controlled (2)                    Consider adding long-acting inhaled beta2 -agonist. (3)
        5      Sympto ms not controlled (2)                    Consider adding theophylline tri al (slow release
                                                               theophylline adjusted to level of 5 to 12 µg/ ml) (4)
        6      Sympto ms not controlled (2)                    Consider adding corticosteroi d tri al (prednisone 40 to 60
                                                               mg po qd or h igh dose inhaled steroids (5).
                                                               Consider specialist consultation.
        7      Sympto ms not controlled (2)                    Refer to specialist promptly.

   1.       Spiro metry is essential to confirm the presence of airflo w obstruction (low FEV1 and FEV1 / VC rat io). Base
            therapy on symptoms, but consider alternate diagnoses (heart disease, pulmonary emboli, etc.) if out of
            proportion to spirometry.
   2.       Use the lowest level of therapy that satisfactorily relieves symptoms and maximizes activity level. Assure
            compliance and proper use of medications before escalating therapy.
   3.       Inhaled long acting beta 2 -agonists should not be used as rescue therapy. Short-acting inhaled beta 2 -agonist
            (less than 12 puffs/day) may continue to be used PRN. Nighttime sympto ms are frequently better controlled
            with long-acting inhaled beta 2 -agonist. Oral beta 2 -agonists are associated with a higher rate of side effects,
            and should be reserved for patients who cannot take inhaled beta 2 -agonist medications.




                                             Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 12
                                                                                            VHA/DoD Clinical Practice Guideline



     4.   Theophylline should be used with caution because of potential for severe side effects. Nighttime respiratory
          symptoms are frequently controlled but theophylline may lead to insomnia. Theophylline should be
          discontinued if a sympto matic o r objective benefit is not evident within several weeks.
     5.   A corticosteroid trial o f prednisone (40 to 60mg/day) 10 to 14 days, or high dose inhaled steroids
          (equivalent to 880 µg or more of fluticasone or 800 µg or more of budesonide) of 14 to 21 days can help
          identify patients who may benefit fro m long term steroid use. Responders to oral steroids should transition
          to the lowest effective dose of inhaled steroids, or to the lowest effective dose of a combination of inhaled
          and oral steroids, if possible, to avoid the long term co mplications of systemic co rticosteroids. If oral
          steroids are used other than for an acute exacerbation, obtain spiro metry p rior to and after trial to confirm
          an objective response.


B. Are Symptoms Occurring Less frequentl y than Daily AND FEV 1 is > 50% of predicted?

     OBJECTIVE

     To identify patients with COPD who may benefit fro m therapy.

     ANNOTATION

     1.   Typical daily sympto ms of COPD include exert ional dyspnea, wheezing, or cough. Chest tightness is
          common, but should be further evaluated to exclude co -existing heart disease. These symptoms may occur
          daily or less than daily, thus resulting in different med ication reco mmendations.
     2.   Routine use of ipratropiu m does not slow the rate of decline in pulmonary function in patients with mild
          COPD. Patients with symptoms less often than daily may be med icated as needed.
     3.   A trial of inhaled anticholinergic therapy is reco mmended in apparently asympto matic patients with an
          FEV1 of less than 50 percent of predicted, since this degree of obstruction is usually associated with
          dyspnea. A lack of sy mptoms may result fro m the patient avoiding activities and adapting to his/her
          disability, or fro m the assumption that dyspnea is part of the natural aging process.
     4.   Asymptomat ic patients with an FEV1 less than 50 percent predicted may benefit fro m regular inhaled
          anticholinergic therapy without a short acting inhaled beta2 -agonist (SAIBA). Sy mpto matic patients in this
          category should be prescribed both a chronic anticholinergic inhaler or SAIBA as well as a beta 2 -agonist
          for prn use, especially prior to exertion.


C.   Short Acting Inhaled Beta2 -Agonists


     OBJECTIVE

     To init iate or adjust appropriate prn therapy with SAIBA.

     ANNOTATION

     1.   Short acting beta 2 -agonists are available in M DI, dry powder inhalers, nebulizer and oral forms. They can
          improve function and quality of life.
     2.   Short-acting selective inhaled beta 2 -agonists such as albuterol are preferred for prn use because of
          demonstrated efficacy, rap id action, and selective action on airways. The short -acting adrenergic agents
          have similar efficacy, though inhaled beta2 selective agents should be favored for lo wer side effect profiles.
     3.   SAIBA should be prescribed for prn use in most symptomatic patients with COPD. The usual maximu m
          dose in stable patients is 12 puffs per day for short-acting agents such as albuterol, metaproterenol or
          terbutaline. Patients who have not responded to greater than maximu m doses such as 12 to 20 puffs over
          three to four hours during an acute exacerbation of COPD should seek medical attention.




                                           Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 13
                                                                                           VHA/DoD Clinical Practice Guideline



    4.   Sympto ms may imp rove without substantial improvement in FEV1 , indicating that continuation of therapy
         does not depend on routine assessment with spiro metry. For example, SA IBA and ipratropiu m can
         improve exercise performance without necessarily improving FEV1 .
    5.   SAIBA, but not ipratropium, may increase the alveolar-arterial o xygen difference, and this may be a reason
         to decrease the dose of beta2 -agonist while titrat ing a patient’s medicat ion.


D. Inhaled Anticholinergics


    OBJECTIVE

    To init iate or adjust appropriate therapy with inhaled anticholinergics.

    ANNOTATION

    1.   Ipratropiu m bro mide, the prototype anticholinergic bronchodilator, is available as a metered dose inhaler
         (MDI) or as a nebulizer solution.
    2.   Ipratropiu m bro mide has similar, or according to some studies, greater efficacy than SAIBA. It has a slower
         onset of action, a longer duration of action, and minimal systemic absorption. It may cause fewer systemic
         side effects than beta 2 -agonists. For these reasons, it is preferred as a regularly scheduled inhaled
         bronchodilator.
    3.   In patients with COPD, ipratrop iu m bro mide at peak effect typically increases the FEV1 by 0.15 to 0.35 L.
         At high doses, ipratropiu m bro mide can improve exercise tolerance.
    4.   The starting dose of ipratropiu m should be at least two puffs tid. Use of typical reco mmended doses of
         ipratropiu m (two puffs qid) produces less than maximal bronchodilation. Improvement in pulmo nary
         function is maximal at 6 to 14 puffs as a single dose of ipratropiu m. If sy mptoms do not resolve with two
         to four puffs qid, up to six and possibly eight puffs qid may be needed. Imp rovement in level of function
         and in activities in daily living can be used to guide therapy. The risk of to xicity at h igher doses appears to
         be relatively lo w co mpared to inhaled beta 2 -agonists.
    5.   The sequence of admin istration of ipratrop iu m and SAIBA does not generally make any difference in the
         bronchodilator benefit.

E. Combination Therapy with Inhaled Anticholinergics and Short Acting Beta 2 -Ag onists


    OBJECTIVE

    To init iate or adjust appropriate therapy with a co mbination of inhaled SAIBA.

    ANNOTATION

    1.   Patients with COPD whose symptoms are inadequately controlled with th e reco mmended doses of either an
         inhaled short acting inhaled beta 2 -agonist or ipratropium should be treated with a co mbination of both
         inhaled agents. The combination at reco mmended doses provides added symptomatic benefit without
         incurring the risk of to xicity fro m using very high doses of single agents.
    2.   SAIBA may be added to ipratropium as regularly scheduled medications, typically two to four puffs qid, as
         well as additional p rn dosing, to a usual reco mmended maximu m of 12 puffs per day. Demonstratio n of an
         acute improvement in FEV1 is not necessary in order to obtain clin ical benefit. The lack of an immediate
         bronchodilator response should not preclude a clinical trial of these medications.
    3.   As the dose of ipratropiu m or inhaled SAIBA increases, the added benefit becomes less fro m the other
         agent, but some patients will have an added benefit even with high doses of each. There is no way to
         predict, other than in a trial of therapy, wh ich patients will have this combined effect.
    4.   A product that dispenses 90 µg albuterol and 18 µg ipratropiu m per puff fro m one metered dose inhaler is
         available co mmercially (Co mb ivent ™). This should not generally be used as a first line agent, but may


                                          Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 14
                                                                                             VHA/DoD Clinical Practice Guideline



          provide enhanced compliance and resultant benefit in patients who require co mbination therapy. Patients
          taking a regularly scheduled combination inhaler should continue to use a SAIBA for breakthrough
          symptoms.

F.   Consider Addi ng Long-Acting Inhaled Beta2 -Ag onist


     OBJECTIVE

     To init iate or adjust appropriate therapy with long acting inhaled beta 2 -agonists.

     ANNOTATION

     1.   The long acting inhaled beta2 -agonist, salmeterol (2 puffs or 50 µg bid), is an effective bronchodilator in
          COPD patients, and has been approved for use in COPD.
     2.   Salmetero l produces a similar peak bronchodilator response to SAIBA, but the onset is delayed. The
          bronchodilator effect is prolonged compared to short-acting agents. This has the potential to produce more
          consistent control of symptoms than SAIBA in some patients.
     3.   Chronic use is not associated with significant tachyphylaxis, and may decrease the need for rescue us e of
          SAIBA.
     4.   Strong evidence for symptomat ic benefit of salmeterol over other regularly inhaled short acting
          bronchodilators in patients with COPD is not currently available. Thus, its place in the scheme of therapy
          is not well defined at this time. It may be considered for patients whose need for SAIBA exceeds 8 to 12
          puffs daily.
     5.   The princip le advantage of salmeterol is its long duration of action, which may be of benefit in treating
          nocturnal dyspnea. Additionally, enhanced compliance with a t wice daily rather than qid regimen may
          provide smoother symptomatic control.
     6.   Because the onset and duration of action are both prolonged compared to SAIBA, salmetero l should not be
          used for prn, rescue use. Patients should be educated to continue to use SAIBA prn.
     7.   Oral fo rms of beta 2 -agonists may be useful in patients who cannot use any inhaled form, although such
          cases are rare. The risk of systemic adverse reactions is increased significantly with oral beta 2 -adrenergic
          bronchodilators.
     8.   Inhaled salmeterol should be continued only in those patients who experience symptomatic benefit fro m its
          addition to their regimen.

G. Consider Theophylline Tri al


     OBJECTIVE

     To init iate or adjust appropriate therapy with oral theophylline.

     ANNOTATION

     1.   Theophylline can be added to improve pulmonary function, sympto ms, or activ ities in patients with COPD
          who do not achieve adequate symptom control with inhaled bronchodilators.
     2.   Many theophylline preparations are availab le, but sustained release formulat ions may provide longer
          control and better benefit for nocturnal dyspnea.
     3.   Theophylline has a narrow therapeutic index, with the potential for dose related adverse reactions that
          include insomn ia, an xiety, nausea, vomit ing, tremor, arrhythmias, deliriu m, seizures, and death.
     4.   Typical starting doses are 400 to 600 mg daily, but blood levels should be measured carefully at the start of
          therapy. The therapeutic target for most patients should be a blood level of 10 µg/ ml (range 5 -12 µg/ ml).
          In some cases, if benefit has been demonstrated and with careful mon itoring, a blood level of 15 µg/ ml of



                                           Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 15
                                                                                            VHA/DoD Clinical Practice Guideline



         theophylline can be a therapeutic target. However, with an increase in concentrations over 12 µg/ ml, the
         risk to benefit ratio increases, especially in o lder patients. After initial stability, repeat levels should be
         obtained when symptoms change, acute illness develops, potentially interacting drugs are added, non -
         compliance is suspected, dose adjustments are made, or sympto ms suggestive of toxicity develop.
    5.   Drug interactions with theophylline are co mmon, and may either increase or decrease theophylline
         metabolism. All changes in medical reg imens should be evaluated for potential impact on theophylline
         levels.
    6.   Theophylline should be continued only in patients who demonstrate a symptomatic benefit, such as
         improved dyspnea or exercise tolerance. The improvement in function fro m theophylline may not be
         evident in pulmonary function testing. However, therapy should be discontinued in patients who
         demonstrate no subjective or objective improvement after several weeks of theophylline therapy.


H. Consider Corticosteroi d Trial


    OBJECTIVE

    To init iate or adjust appropriate therapy with corticosteroids in patients with COPD.

    ANNOTATION

    1.   Unlike the high response rate seen in asthma, in patients with COPD a respons e to chronic oral
         corticosteroid use is beneficial in less than about 20 to 25 percent. The benefit fro m inhaled steroids is not
         precisely defined.
    2.   Patients on maximal bronchodilator therapy who have not had a satisfactory response may be considered
         candidates for a corticosteroid trial. An objective measure of imp rovement should be sought in all patients
         undergoing a steroid trial. A response may be defined as an imp rovement in symptoms and an increase in
         FEV1 of > 20 percent fro m baseline. An objective measurement of the steroid effects can only be obtained
         in patients who are otherwise stable.
    3.   A typical trial o f oral prednisone is 40 to 60 mg/day for 10 to 14 days. There is less published experience
         with high-dose inhaled steroids, but in some patients this may be a reasonable alternative. The appropriate
         dose of inhaled steroids has not been determined, but a trial for 14 to 21 days of the equivalent of
         beclomethasone 1500 µg/day (30 puffs) or fluticasone 880 µg /day has been suggested.
    4.   Patients who show no objective response to a steroid trial should have their steroids promptly discontinued.
         Patients who have a response should be tapered to the lowest possible dose. Supplementation or
         substitution with a high-dose inhaled steroid may allow further reduction or d iscontinuation of the oral
         steroid.
    5.   Adverse effects of oral cort icosteroids are numerous and include: hypertension, hyperglycemia, weight
         gain, immunosupression, skin thinning, personality, purpura, mental status changes, depression, glaucoma,
         cataracts, and adrenal suppression. Patients requiring long-term steroids should be evaluated for risk of
         osteoporosis and preventive measures instituted, such as calciu m and vitamin D supplements, weight -
         bearing exercise and hormone replacement therapy if appropriate. The risks of long-term t reat ment should
         be discussed with the patient.
    6.   The role of chronic inhaled corticosteroids in COPD remains under investigation. Preliminary work
         suggests that chronic inhaled steroid use may slow the rap id decline in F EV1 typically seen in patients with
         COPD. Response to an oral steroid trial, as well as a brisk bronchodilator response may help identify
         patients who will respond better to inhaled steroids.
    7.   The use of MDI spacers and rinsing of the mouth after drug use is recommended to help improve drug
         delivery to the lung and avoid local co mp licat ions, such as hoarseness or oral candidiasis.




                                           Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 16
                                                                                            VHA/DoD Clinical Practice Guideline



I.   Review Precauti ons and Recommendations for Medications?


     OBJECTIVE

     To apply precautions and educate patients about the use of medicat ions.

     ANNOTATION

     Method of administering aerosols

     1.   Metered-Dose Inhalers (MDI).
          a.   Inhaled bronchodilators are preferred to oral med ications to reduce the risk of systemic adverse effects.
          b.   Ensure proper education and technique in the use of MDIs (see DISCUSSION).
          c.   Use spacers as required to enhance drug delivery.
          d.   Emphasize the maximu m doses of bronchodilators to avoid overuse.
          e.   Educate the patient to use bronchodilators before exercise.
          f.   Co mpliance declines when inhaler regimens become co mp licated.
          g.   Consider other drug delivery systems (such as dry powder inhalers) if patient cannot use MDI with
               spacer.

     2.   Small Volu me Nebulizer.
          a. There is little ev idence that nebulizer delivery offers improvement in control over adequate MDI
             delivery fo r management of the stable COPD patient.
          b.   Situations where a nebulizer is preferable include difficulty in managing a MDI (with spacer) due to
               impaired hand strength or dexterity, visual impairment, cognitive problems, or severe dyspnea.

     3.   Precautions when using beta 2 -agonists.
          a. Inhaled beta2 -agonists may cause tremor, increased heart rate, insomnia, restlessness, hypokalemia, or
              a paradoxical reduction in arterial o xygenation.
          a.   Avoid overuse. Check number of metered dose inhalers (M DIs) used per month against number of
               puffs per MDI (200 to 300+, depending on brand).
          b.   Instruct patients on maximu m nu mber of puffs per day (usually 8 to 12) and on number allowed during
               an exacerbation (e.g., 12 to 24 over 3 to 4 hours) before additional intervention is required.
          c.   If a long-acting agent is used for maintenance therapy, educate the patient that only SAIBA should be
               used for breakthrough symptoms.
          d.   Ho me nebulizers with inhalant solutions providing large dosages are rarely needed.

     4.   Precautions when using ipratropium
          a.   Inhaled ipratropiu m may cause dry mouth or increased heart rate, or exacerbate glauco ma, benign
               prostatic hypertrophy or other conditions potentially worsened by the drug’s anti-cholinergic act ivity.
          b.   Patients should generally use a spacer and should avoid spraying into eyes.
          c.   Caution patients that onset of effect is relatively slo w co mpared to SAIBA, and that additional doses
               should not be taken for acute symptom relief.
          d.   In general, dose related systemic side effects of inhaled anticholinerg ics are less severe when using
               ipratropiu m than those produced by inhaled beta 2 -agonists.

     5.   Precautions when using theophylline.
          a.   Theophylline has dose related side effects that include insomnia, an xiety, nausea, vomiting, tremo r,
               arrhythymias, deliriu m, seizures, and death.



                                           Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 17
                                                                                       VHA/DoD Clinical Practice Guideline



     b.   Drug interactions with theophylline are co mmon, and all changes in a patient’s medical regimen
          should be reviewed fo r their potential impact on seru m theophylline levels.
     c.   Initiate treat ment with a low dose (e.g., 400 mg/day) and adjust after a few days.
     d.   Aim fo r a seru m level o f 5 to 12 µg/ ml; ad just dosage and follow serum level when indicated.
     e.   Check the seru m level of theophylline when sympto ms change, acute illness develops, new drugs are
          added, or symptoms suggestive of toxicity develop.
     f.   Reduce dosage if drug clearance is likely to be impaired because of illness, liver malfunction, or
          concomitant drugs.
     g.   Instruct patients not to take additional theophylline preparat ions.
     h.   Theophylline should be taken at the same time each day with respect to meals.
     i.   Attempts to withdraw theophylline, even at lo wer p lasma levels, should be done cautiously, since
          deterioration in pulmonary function and exercise performance may occur.

6.   Precautions when using oral corticosteroids.
     a.   Adverse effects of oral cort icosteroids include hypertension, hyperg lycemia, weight gain, personality
          changes, depression, immunosuppression, glaucoma, cataracts, skin thinning, purpura, osteoporosis,
          osteonecrosis, and adrenal supression. In general, side effects are more co mmon with prolonged
          therapy.
     b.   Reduce dosage to lowest effective daily dose or to alternate-day dosing as quickly as symptoms allow.
     c.   Admin ister stress dose steroid therapy to patients with severe illness or injury who have received
          prolonged oral corticosteroid treatment. Adrenal insufficiency may extend fo r up to a year fo llo wing
          the discontinuation of steroids.
     d.   Prevent or treat osteoporosis with calciu m, vitamin D, hormone replacement therapy or other therapies
          as appropriate for patients on prolonged oral corticosteroid therapy.

7.   Precautions when using inhaled corticosteroids.
     a.   Adverse effects of inhaled corticosteroids include oral candid iasis, hoarseness, and possible adrenal
          suppression at high doses.
     b.   Instruct patients to use a spacer and rinse the mouth after use to decrease the likelihood of local
          complications.
     c.   Be aware that systemic effects of corticosteroids may occur in skin, bone, eyes, and other organs,
          especially with the use of high dose inhaled corticosteroids.
     d.   Stress dose oral or intravenous corticosteroids may be necessary in some patien ts with severe illness or
          injury who have been treated with high dose inhaled corticosteroids.
     e.   Seek object ive evidence of the value of this therapy, because its use may decrease compliance with
          other aerosol usage.
     f.   When introducing aerosol steroids in a patient taking an oral steroid, wean slowly off the oral drug.




                                      Outpatient Management of COPD: Pharmacotherapy (A2) - Summary Annotations - Page 18
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

 OUTPATIENT MANAGEMENT: Long-Term Oxygen Therapy (A3)



             ALGORITHM AND SUMMARY ANNOTATIONS
                                       VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: - Long-Term Oxygen Therapy (A3)- Algorithm
                                                                                         VHA/DoD Clinical Practice Guideline



                CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                      Outpatient Management of COPD: Long-term Oxygen Therapy (A3)

A. Patient wi th COPD on Maxi mal Medical Therapy and Stable for 30 Days


   OBJECTIVE

   In chronic obstructive pulmonary disease (COPD), patients with hypoxemia and cor pulmonale, long-term
   oxygen therapy (LTOT) may increase the life span by six to seven years. Mortality is reduced in patients with
   chronic hypoxemia when o xygen is administered for mo re than 12 hours daily and greater survival benefits
   have been shown with continuous oxygen admin istration.

   ANNOTATION

   Patient should be on maximal med ical therapy and stable for 30 days before decisions about LTOT are made.
   Short-term o xygen may be instituted in the interim. In addit ion to treating acu te exacerbations, therapy to
   correct anemia and congestive heart failure should be instituted. Intensify smoking cessation efforts, since
   smoking poses a safety hazard for patients on LTOT. The benefits of long -term o xygen therapy may not be
   realized in patients who continue to smoke and have high levels of carbo xyhemoglobin.

B. Are There Signs of Tissue Hypoxia?


   OBJECTIVE

   To identify patient with signs of tissue hypoxia who may benefit fro m LTOT.

   ANNOTATION

   Occasionally severe dyspnea with exercise is the result of arterial o xygen desaturation. Evaluation of saturation
   during exercise should be performed in COPD patients with such dyspnea.

   Signs of tissue hypoxia include:

   1. Hematocrit (Hct) greater or equal 55.
   2. "p" pulmonale on electrocardiogram (ECG) or other evidence of pulmonary hypertension.
   3. Impaired mental status.
   4. Cor pulmonale.

C. Is PaO2  55 mm Hg?


   OBJECTIVE

   To identify hypoxemia.

   ANNOTATION

   Based on a randomized controlled trial (NOTT 1980), long -term o xygen therapy of COPD patients with a PaO2
    55, or a PaO2  60 with signs of tissue hypoxia, is associated with improved survival. Although pulse
   oximetry can be used to exclude hypoxemia, measurement of resting PaO 2 after 30 minutes of breathing room
   air is the clinical standard for init iating LTOT. Oximetry may be used to adjust oxygen flow settings over time.




                                 Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Summary Annotations- Page 19
                                                                                         VHA/DoD Clinical Practice Guideline



D. Institute Long-Term, 24-Hour Oxygen Therapy


   OBJECTIVE

   To define the goals of o xygen therapy.

   ANNOTATION

    The precise PaO2 level to improve quality of life or increase survival has not been well defined. Arterial
   oxygen saturations of 90 to 92 percent or PaO2 of 60 to 65 mmHg are usual acceptable targets because of the
   shape of the oxygen hemoglobin saturation curve. A mbulatory patients should be provided ambulatory and
   stationary oxygen equip ment to reach the target of use 24 hours a day to correct PaO 2 greater or equal 60 or
   SaO2 greater or equal 90 percent. Immob ile patients may only require a stationary system with a portable
   system for use during transport. In most cases, changes in flow rate are not indicated for sleep and exercise.
   Some authorities reco mmend increasing flow rates by one liter per minute to treat possible desaturation during
   sleep, but evidence for this approach is not strong. If there are signs of cor pulmonale despite adequate daytime
   oxygenation, the patient may be mon itored with o ximetry during sleep to determine the best sleep setting.
   Some patients may be candidates for o xygen-conserving devices (e.g., reservoir cannulae, demand o xygen
   delivery device, transtracheal oxygen) to improve mobility and portability of o xygen therapy.

E. Order Overnight Oxi metry and/ or Exercise Oximetry

   OBJECTIVE

   To identify patients with PaO2 desaturation who may benefit fro m LTOT.

   ANNOTATION

   It is unusual that patients with COPD and a PaO2 of 70 at rest to desaturate low enough to require o xygen.
   During exercise, noninvasive pulse oximetry may be inaccurate, particu larly in patients with poor peripheral
   perfusion. Verification of o ximetry accuracy can be accomp lished by obtaining ABG before and after exercise.
   The level of exercise tested should be appropriate to the patient's normal or anticipated level o f activ ity.

   In COPD patients who have PaO2  60 mmHg during wakefu lness, signs of tissue hypoxia occur mo re often
   and survival is reduced when sleep desaturation is present (more than five minutes during the night). However,
   studies documenting imp roved outcome with o xygen supplementation during sleep have yet to be conducted.
   One night of overnight o ximetry is sufficient to determine the present of arterial o xygen desaturation during
   sleep. Such desaturation can occur as the patient's COPD evolves with t ime and the overnight oximetry may
   need to be repeated at regular intervals (such as six months to yearly) in patients who have or develop an
   indication.

F. Arrange for Long-Term Oxygen Therapy During Sleep and/ or Exercise

   OBJECTIVE

   To discuss the benefits of oxygen therapy.

   ANNOTATION

   Studies showing the long-term benefit of o xygen solely for exercise or sleep desaturation have yet to be
   conducted. Short-term studies have shown more immediate benefits in reduction in dyspnea, improvement in
   exercise performance, and prevention of transient increases in pulmonary artery pressure and pulmonary
   vascular resistance. Oxygen should be admin istered to increase SaO 2 to greater than 90 percent. To maximize
   mobility, liquid or light tanks such as those made fro m alu minum are preferable for use during exercise.


                                 Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Summary Annotations- Page 20
                                                                                         VHA/DoD Clinical Practice Guideline




G. Continue Medical Care and Follow-up


   OBJECTIVE

    To continue with appropriate fo llo w up of o xygen therapy.

   ANNOTATION

   Patients started on oxygen therapy at the time of an exacerbation require reevaluation within one to three
   months when stable. For patients started when stable on maximal med ical therapy, LTOT most likely
   represents a lifetime co mmit ment. Reevaluation every 12 months is appropriate to assess for continued need
   and adequacy of flow rate. Results of O2 saturation greater than 90 percent should not be used as a sole
   rationale fo r discontinuing therapy.

H. If AB Gs Are Available, Is PaCO2  45 mmHg?


   OBJECTIVE

    Identify COPD patients with hypercarbia and its relationship to hypoxia.

   ANNOTATION

   Hypercapnia during the day predicts a high prevalence of sleep desaturatio n even in patients who have PaO2 60
   mm Hg during wakefu lness. Noninvasive ventilation for treat ment of nocturnal hypoventilation for chronic
   home use has been investigated but unproven and is not endorsed for general use.




                                 Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Summary Annotations- Page 21
        CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

                  CHRONIC OBSTRUCTIVE PULMONARY DISEASE

OUTPATIENT MANAGEMENT: Preoperative Evaluation and Management (A4)



                       ALGORITHM AND SUMMARY ANNOTATIONS
                                                    VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Algorithm
                                                                                            VHA/DoD Clinical Practice Guideline



                  CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

               Outpatient Management of COPD: Preoperati ve Eval uation and Management (A4)

A. Does Condition Require Emergency Surgery?

    OBJECTIVE

    To refer patients who need emergency surgery.

    ANNOTATION

    In-hospital respiratory specialist or intensivist should be notified for perioperative care, but emergency
    surgeries, including repair of femoral neck and hip fractures, should not be held up pending consultation.

B. Inform Physician in Charge of Postoperati ve Care of COPD Conditi on. Stress Need for IV
   Corticosteroi ds if Patient is on Systemic Steroi ds

    OBJECTIVE

    To ensure proper care for the patient at risk.

    ANNOTATION

    Determine who m to call when emergency surgery is performed. An in -house respiratory specialist should be
    notified for perioperative care. If the patient is on systemic steroids, s witch to IV steroids using hydrocortisone
    300 mg/day or an equivalent.

C. Is This a Minor Surgery Requiring Local Anesthesia?

    OBJECTIVE

    To determine need for patients undergoing local anesthesia for minor surgery.

    ANNOTATION

    Admin istration of local anesthesia presents a very low risk, even in the presence of severe COPD. In clin ically
    stable patients with mild or moderate COPD, a phone inquiry about exacerbation might suffice. Pu lmonary
    function test (PFT) is not required.

D. Obtain Pul monary Function Tests, Arterial Blood Gases

    OBJECTIVE

    To obtain spirometry values to guide the decision about preoperative care.

    ANNOTATION

    There is no universal opinion on the value of pulmonary function testing preoperatively. A common opinion is
    that when a preoperative evaluation of a patient about to undergo elective CABG surgery suggests lung disease,
    simp le spiro metry can better characterize the nature of the patient’s pulmonary problems and aid in the decision
    about appropriate preoperative med ical therapy (Zibrak et al. 1993). One study (Wong 1995) showed that low
    FEV1 predicted postoperative complications such as prolonged ICU stay, prolonged hospital stay, prolonged
    mechanical ventilat ion, and pneumonias, but this study involved only patients with severe C OPD (FEV1 < 0.75



                     Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Summary Annotations - Page 22
                                                                                             VHA/DoD Clinical Practice Guideline



     L), with mixed surgical sites. On the other hand, other studies (Kroenke 1993) have shown that pulmonary
     function testing does not predict perioperative complications.

E. Obtain Chest X-Ray

     OBJECTIVE

     To identify patients at risk for developing co mplications.

     ANNOTATION

     Chest X-ray should be done preoperatively in patients with an established diagnosis of COPD who may require
     general anesthesia, since an abnormal chest x-ray is a pred ictor of perioperative co mplications in thoracic and
     major abdo minal surgery. A preoperative chest x-ray in patients for non-cardiothoracic surgery is sensible,
     because patients with COPD are at increased risk of pulmonary neoplasm (ATS Gu idelines 1995).

F. Is FEV1 < 35 Percent of Predicted?

     OBJECTIVE

     To identify patients who are likely candidates for surgery based on pulmonary function tests.

     ANNOTATION

     Severe chronic obstructive pulmonary disease (FEV1 < 0.75 L) is a predictor of prolonged ICU stay.
     FEV1 /FVC predicts postoperative complicat ions. See Evidence for Annotation D.

G. Refer to Pul monary S pecialist

     OBJECTIVE

     To determine when a pulmonary consult is indicated.

     ANNOTATION

     Patients should be referred to a respiratory or thoracic specialist prior to scheduling of a lung resection. In some
     cases, for examp le in patients with mild COPD and a solitary pulmonary nodule, the patients can be referred
     directly to a thoracic surgeon.

H. Is PaCO2 > 45?

     OBJECTIVE

     To determine risk factors for postoperative pulmonary co mplications.

     ANNOTATION

     Hypercapnia is an independent risk factor fo r patients with moderate to severe COPD who are having upper
     abdominal or thoracic surgery.

I.   Is Surgery on Upper Abdomen or Thorax?

     OBJECTIVE

     To determine wh ich patients are at high risk for postoperative pulmonary co mplications based on type of
     surgery.

                      Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Summary Annotations - Page 23
                                                                                             VHA/DoD Clinical Practice Guideline




     ANNOTATION

     The guidelines for the A merican Thoracic Society (1995) state that upper abdominal surgery poses a risk of
     postoperative pulmonary comp licat ions for all patients. Upper abdo minal surgery shifts the re spiratory pump
     fro m the diaphrag m to the accessory muscles, due to a non pain -related reflex. Non imperative upper
     abdominal surgery such as cholecystectomy should be avoided in patients with moderate to severe COPD. If
     surgery is necessary, provide careful anesthesia. Another potential way to decrease operative risk may be to
     perform the procedure laparoscopically.

J.   Preoperati ve Management

     OBJECTIVE

     To determine preventive measures for postoperative pulmonary co mplications.

     ANNOTATION

     COUNSEL TOBACCO USE CESSATION

     There is evidence that stopping cigarette smoking two months before surgery reduces perioperative
     complications. For smo kers quitting less than eight weeks preoperatively, no such evidence exists, but
     consensus exists that quitting even immed iately before surgery could be beneficial (Celli 1993).

     ADMINISTER POSTOPERATIVE SUBCUTA NEOUS HEPARIN

     Postoperative subcutaneous heparin is useful for prophylaxis for pulmonary embo li, and should be considered
     strongly in patients who start with limited pulmonary reserve.

     Arrange for postoperative incentive spirometry o r controlled deep breathing and cough.
     Deep breathing and controlled cough with or without incentive spirometry should be done postoperatively.




                      Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Summary Annotations - Page 24
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

  OUTPATIENT MANAGEMENT: Management of Air Travel (A5)



             ALGORITHM AND SUMMARY ANNOTATIONS
                       VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Air Travel (A5) - Algorithm
                                                                                           VHA/DoD Clinical Practice Guideline



               CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                        Outpatient Management of COPD: Management of Air Travel (A5)


A. Patient wi th Stable COPD Planning Air Travel

    OBJECTIVE

    The algorith m emp loys the most practical and least invasive methods to apply current recommendations
    regarding o xygen supplementation during flight.

    ANNOTATION

    Co mmercial airliners can cruise at altitudes over 40,000 feet with their cabins pressurized fro m 6,000 to 8,000
    feet. Th is is equivalent to an inspired O2 concentration at sea-level of about 15 percent. Pat ients with severe
    COPD experience falls in their PaO2 that average 25 mmHg but may be mo re than 30 mmHg at 8,000 feet than
    at sea level. Since their sea level PaO2 values are on the steep part of the oxygen-hemoglobin dissociation curve,
    the fall in SaO2 with falls in PaO2 may be quite sharp. Altitude PaO2 is a co mmonly used marker to assess risk
    of air travel adverse effects on patients with COPD.

B. Is Patient Hypercapnic or On Long-Term Oxygen Therapy?

    OBJECTIVE

    To identify patients at increased risk for adverse physiologic effects of alt itude exposure. Determine factors
    that may influence health risks of exposure to decreased PiO2 during air t ravel.

    ANNOTATION

    Identify patients who require specialist-level evaluation fo r advanced testing to determine whether supplemental
    oxygen is necessary and safe. Specialists will perform effect ive o xygen titration if required.

C. Obtain Calcul ated Predicted PaO2 During Flight

    OBJECTIVE

    To determine whether the patient is at increased risk for potentially physiologically significant hypoxemia in a
    pressurized co mmercial aircraft.

    ANNOTATION

    As noted in Annotation A, predicted altitude hypoxemia serves as a parameter for decision -making regarding
    oxygen supplementation during air travel for ambu latory patients with stable COPD. Predict ion of altitude -
    induced hypoxemia can be acco mplished by several methods. Regression equations have been validated for this
    purpose. Individual variability in the populations studied for development of predict ion equations limits the
    applicability of the results in clin ical decisionmaking for patients with borderline values of predicted PaO2 at
    altitude. Indiv idualized hypo xia inhalat ion testing is advised for these patients to determine whether
    supplemental o xygen therapy is advised during air travel. Hypobaric chamber testing, face mask hypoxic ga s
    inhalation, Venturi mask nitrogen enriched gas, and normobaric hypoxic gas chamber methods have all been
    utilized for this purpose. Hypoxic gas mixture testing by face mask delivery has been shown to yield similar
    PaO2 decrements similar to those in hypobaric chamber testing, as has normobaric hypoxic gas chamber
    exposure. These specialized hypoxia simu lation studies are available in appropriately equipped laboratories and
    are usually conducted under the direction of a pulmonary specialist.



                                                Outpatient Management of COPD: Air Travel (A5) - Summary Annotations - Page 25
                                                                                          VHA/DoD Clinical Practice Guideline



   Regression equation predictions are applicable to the majority of COPD patients. These equations apply only to
   non-hypercapnic patients. There is good agreement between the regression equations. The PaO 2 at sea level
   (PaO2 SL), FEV1 percent predicted, and FEV1 /FVC ratio are the best independent predictors of the PaO2 during
   hypobaric chamber or hypo xic gas inhalation testing (PaO 2 Alt), accord ing to the following equation:

                       PaO2 Alt mmHg = 0.453 [PaO2 SL mmHg ] + 0.386 [FEV1 % pred] + 2.44
                                             (r = 0.847, p < 0.0001)

   Since FEV1 percent predicted and FEV1/ FVC influence PaO2 Alt, it is important to optimize FEV1 by
   pharmacotherapy before and during air t ravel. Table I provides the calculated values of PaO 2 Alt for given
   values of PaO2 SL in the range of 60 to 80 mmHg. If the PaO2 is > 80, the patient probably does not need
   oxygen for t ravel


                  Table 1. Predicted in flight PaO2 based on PaO2 at Sea Level and FEV1
        FEV1 % Predicted    100        90         80       70        60        50       40                           30
     PaO2            80         56.2        54.9       52.7        50.9        49.2        47.4         45.7        44.9
     at sea level    70         51.6        49.9       48.1        46.4        44.6        42.9         41.1        39.4
                     60         47.1        45.4       43.6        41.9        40.1        38.4         36.6        34.9


D. Is predicted PaO2 < 55?

   OBJECTIVE

   To identify appropriate dosing, titration, and delivery of supplemental o xygen for patients to minimize alt itude
   hypoxemia -related health risks and avoid potential adverse effects of increased oxygen concentration for
   hypercapnic patients.

   ANNOTATION

   Supplementation of o xygen for COPD patients who are eucapnic and without cardiac or cerebrovascular disease
   has been studied in several hypoxic environ ments with mult iple delivery systems. Nasal cannula (NC) and
   Venturi masks in a hypobaric chamber, NC in hypoxic gas inhalation trials, and NC in a normobaric hypo xic
   chamber have all been investigated. The sum of these studies sugges ts that most patients with moderate to
   severe COPD will have PaO2 values above 60 mmHg or 90 percent saturation by pulse oximet ry with 1 to 3
   liters of NC o xygen supplementation during simulated aircraft cabin environ mental exposure. When practical, a
   supplementation trial by one of these methods can be used to individualize dosing of oxygen. Emp iric dosing
   of two liters by NC utilizes common ly available equip ment and will allow an adequate supply for all but long -
   haul flights, with maintenance of PaO2 > 60 mmHg for most patients.

   A patient’s PaO2 during commercial air travel p redicted by regression equations to be borderline (51 to 54)
   should be individually evaluated. Indiv idual variability in the populations studied for development of
   prediction limits the applicability of the results for clin ical decision making in patient with "borderline" values
   of predicted PaO2 at altitude. Ind ividualized hypo xia inhalat ion testing is advised for these patients, to
   determine if supplemental o xygen therapy is advisable during air travel. Hypobaric chamber testing, face mask
   hypoxic gas inhalation, Venturi mask nit rogen enriched gas, and normobaric hypoxic gas chamber methods
   have all been utilized fo r this purpose. Hypoxic gas mixture testing by face mask delive ry has been show to be
   cause similar PaO2 decrements as hypobaric chamber testing, similar to those in normobaric hypoxic gas
   chamber exposure.

   Patients with hypercapnia have not been included in the patient populations from wh ich prediction equations
   were developed. Therefore, these patients require indiv idualized hypo xia testing to determine whether
   supplemental o xygen is advised. If so, carefu l t itration of the additional flow rate should be accomplished prior


                                               Outpatient Management of COPD: Air Travel (A5) - Summary Annotations - Page 26
                                                                                           VHA/DoD Clinical Practice Guideline



   to flight, with attention to the effect on ventilation. Specialized testing and titration of o xygen should be
   accomplished in an appropriately equipped laboratory with specialist supervision.

E. Oxygen Supplementation Recommendations for Patients wi thout Hypercapnia, Cerebrovascular Disease,
   or Cardi ovascular Disease

   OBJECTIVE

   To identify patients at low risk and those at increased risk for adverse physiological effects of altitude exposure.

   ANNOTATION

   Some authors have chosen a predicted altitude PaO2 of 50 mmHg as the threshold below which supplementary
   oxygen should be prescribed. However, this value is arbit rary, with no outcome studies to support it. Many
   eucapnic COPD patients are well acclimated to hypoxemia and in altitude simulation tests, many stable
   eucapnic patients with COPD and no known heart disease are relatively asymptomat ic at rest. They do not
   experience card iac arrhythmias and have good short-term tolerance to PaO2 values of 35 to 40 mmHg (Gong
   1992). Exercise in this environ ment however, causes a further decline in PaO2 . Thus, the advising physician
   must still rely largely on clinical evaluation, judg ment, and a history of successful flights in advising each
   patient who wishes to fly. Several published recommendations suggest that stable COPD patients without
   cardiac or cerebrovascular disease who are predicted to have a PaO2  50mmHg during flight require
   supplemental o xygen. These recommendations seem practical, and prudent.

   There is no reco mmendation or evidence suggests that stable COPD patients without cardiac o r cerebrovascular
   disease who are predicted to have a PaO2 > 50mmHg during flight require supplemental o xygen. Because of
   considerable indiv idual variability in the prediction equation, a threshold of 55 mmHg for this method is
   advised as a lower-limit threshold for this reco mmendation. Patients with a pred icted PaO 2 of 51 to 54 by
   regression equation should therefore undergo individualized testing to determine their predicted alt itude PaO 2.




                                                Outpatient Management of COPD: Air Travel (A5) - Summary Annotations - Page 27
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

              OUTPATIENT MANAGEMENT: Insomnia (A6)



            ALGORITHM AND SUMMARY ANNOTATIONS
                      VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Insomnia (A6) - Algorithm
                                                                                         VHA/DoD Clinical Practice Guideline



                 CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                    Outpatient Management of COPD: Insomnia (A6)


A. Institute Sleep Hygiene Measures


   OBJECTIVE

    To educate the patient regarding proper sleep hygiene.

   ANNOTATION

   Institute sleep hygiene measures (Zarcone 1994).

   1.   Ho meostatic drive for sleep :
        a. Avoid naps.
        b. Too much time in bed can decrease sleep quality on the subsequent night.
        c.   Exercise each day. It is best to finish exercise at least six hours before bedtime.
        d.   Take a hot bath for 30 minutes within two hours before bedtime. A hot drin k may help you relax as
             well as warm you.

   2.   Circadian factors:
        a. Keep a regular rising time seven days a week.
        b.   Do not expose yourself to bright light if you have to get up at night.
        c.   Get at least one-half hour of sunlight within 30 minutes after arising.

   3.   Drug effects:
        a. Evaluate patient medicat ion profile for drug likely to cause insomnia (beta 2 -agonists, theophylline, oral
            steroids).
        b.   Stop tobacco use.
        c.   Avoid caffeine entirely fo r a 4-week trial period; limit caffeine use to no more than three cups before
             10 a.m. if caffeine cannot be stopped.
        d.   Avoid alcoholic beverages before bedtime.

   4.   Arousal in sleep setting:
        a.   Keep clock face turned away, and do not find out what time it is when you wake up at night.
        b.   Avoid strenuous exercise after six p.m.
        c.   Avoid eating or drinking heavily for three hours before bedtime. A light bedtime snack may help.
        d.   If you have trouble with regurgitation, be especially careful to avoid heavy meals and spices in the
             evening. Do not retire too hungry or too full. Head of bed may need to be raised.
        e.   Keep your room dark, quiet, well ventilated, and at a co mfortable temperature throughout the night.
             Ear plugs and eyeshades are OK.
        f.   Have a non stressful bedtime ritual.
        g.   Set aside a worry time other than bedtime.
        h.   Do not try too hard to sleep; instead, concentrate on the pleasant feeling of relaxation.
        i.   Use stress management in the daytime.
        j.   Avoid unfamiliar sleep environments.
        k.   Be sure the mattress is not too soft or too firm, and the pillow is of the right height and firmness.



                                                Outpatient Management of COPD: Insomnia (A6) - Summary Annotations - Page 28
                                                                                          VHA/DoD Clinical Practice Guideline



         l. An occasional sleeping pill probably is acceptable.
         m. Use the bedroom only for sleep or sex; avoid other activ ities that lead to prolonged arousal.

B. Initiate a Trial of Zol pi dem (5 mg/ qhs)


     OBJECTIVE

    To determine the effects of a therapeutic trial with zo lpidem.

    ANNOTATION:

    Hypnotics should be used only after other measures have been tried (see Annotation A) and should be used
    sparingly with close attention to the possibility of abuse and untoward side effects. If the decision is made to
    use a hypnotic, zolpidem is the first choice in patients with moderate/severe COPD (FEV1 < 50 percent
    predicted; SaO2  90 percent; and CO2 retention) since it has generally been shown to be safe when given
    repeatedly in these patients. If the patient snores habitually, all hypnotics must be used with great caution, as
    they may induce or exaggerate sleep apnea and hypopnoia, even in asymptomatic patients. If zolp idem
    5mg/qhs is not effective, the dose may be increased to 10mg/qhs.

C. Initiate a Trial of Tri azol am (0.125 mg/ qhs)


    OBJECTIVE

     To determine the therapeutic effects of a trial with triazolam.

    ANNOTATION

    Hypnotics may have adverse effects for patients with moderate to severe COPD. Triazolam has no obvious
    effect on respiration when used in single doses for patients with an awake supine SaO 2 > 90 percent and no
    carbon dioxide retention (PaCO2 < 45), and may be considered in addition to zo lpidem in such patients. If the
    patient has supine SaO2 < 90 percent, zolp idem is clearly the first choice; triazolam and other benzodiazep ines
    must be used with extreme caution. Other short-acting benzodiazep ines (e.g., temazepam) may substitute for
    triazolam based on availability, cost, and experience of the practitioner.

D. Follow-Up with Routine Care


    1.   Refer to respiratory specialist if sympto ms do not resolve as expected, if there are co mplications limiting
         therapy or if these recommendations do not readily apply to the p atient.
    2.   If general measures and occasional hypnotics are unsuccessful, referral to a psychiatrist or sleep specialist.




                                                 Outpatient Management of COPD: Insomnia (A6) - Summary Annotations - Page 29
   CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

            CHRONIC OBSTRUCTIVE PULMONARY DISEASE

INPATIENT MANAGEMENT: Emergency Room and Hospital Ward (B1)



                 ALGORITHM AND SUMMARY ANNOTATIONS
                                            VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Emergency Room and Hospital Ward (B1) - Algorithm
                                            VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Emergency Room and Hospital Ward (B1) - Algorithm
                                                                                           VHA/DoD Clinical Practice Guideline



                   CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

              Inpatient Management of COPD: Emergency Room and Hos pital Ward Management (B1)

A. Patient Presents With Acute Exacerbation of COPD

    DEFINITION

    An acute exacerbation of COPD is defined as an acute clinical deteriorat ion in a patient's respiratory status due
    to a worsening of the underlying COPD. Sy mptoms and signs of acute exacerbation of COPD include:

    1.   Increased dyspnea.
    2.   Tachycardia.
    3.   Increased cough.
    4.   Increased sputum production.
    5.   Change in sputum color or character.
    6.   Accessory muscle use.
    7.   Peripheral edema.
    8.   Develop ment of or increase in wheeze.
    9.   Loss of alertness.
    10. Loss of energy.
    11. Fever.
    12. Increased respiratory rate.
    13. Decrease in FEV1 or peak exp iratory flow.
    14. Worsening of arterial b lood gases or pulse oximetry.
    15. Chest tightness.

B. Does Patient Need Mechanical Ventilati on?

    OBJECTIVE

    To init iate immediate action for a patient with life-threatening acute respiratory failure due to acute
    exacerbation of COPD.

    ANNOTATION

    Decision to in itiate mechanical ventilat ion and tracheal intubation can be made prior to obtaining arterial blood
    gases. Advance directives should be considered prior to in itiating these supportive measures.

    1.   Indications for mechanical ventilation (invasive or noninvasive/BiPAP) include:

         a.    Severe respiratory or co mb ined respiratory and metabolic acidosis.
         b.    Sustained respiratory rate > 40 per minute.
         c.    Abnormal b reathing pattern suggestive of increased respiratory workload and/or respiratory muscle
               fatigue.
         d.    Depressed mental status.
         e.    Severe hypoxemia.




                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Summary Annotations - Page 30
                                                                                            VHA/DoD Clinical Practice Guideline



   2.   Indications for tracheal intubation include:

        a.   Suspected airway obstruction.
        b.   Depressed mental status.
        c.   High risk of gastropulmonary reflu x and aspiration.
        d.   Difficulty managing secretions.

C. Ventilate and Perform CPR as Indicated

   OBJECTIVE

   To init iate immediate action for a patient who presents with life threatening acute respiratory failure due to
   acute exacerbation of COPD.

   ANNOTATION

   CPR should be performed according to Advanced Cardiac Life Support (ACLS) protocol. A physician with
   special expertise in crit ical care med icine should be consulted at this point. Care should be used to avoid
   complications of auto PEEP and acute respiratory alkalosis.

D. Perform Clinical and Laboratory Eval uation

   The crit ical elements of the clinical evaluation, adapted fro m both the ATS and ERS guidelines, include:

   1.   History:
        a. Baseline respiratory status.
        b.   Sputum volu me and characteristics.
        c.   Cough.
        d.   Duration and progression of symptoms
        e.   Dyspnea severity.
        f.   Exercise limitations.
        g.   Sleep and eating difficu lties.
        h.   Ho me care resources.
        i.   Ho me therapeutic regimen.
        j.   Sympto ms of co morbid acute and chronic conditions .

   2.   Clinical assessment:
        a. Temperature.
        b.   Respiratory rate.
        c.   Heart rate.
        d.   Cyanosis.
        e.   Accessory muscle use.
        f.   Edema.
        g.   Cor pulmonale.
        h.   Bronchospasm.
        i.   Hemodynamic instability.
        j.   Altered mentation.
        k.   Parado xical abdo minal retract ions.
        l.   Use of accessory respiratory muscles.


                                 Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Summary Annotations - Page 31
                                                                                           VHA/DoD Clinical Practice Guideline




    3.   Spiro metry (optional):
         a.   Peak expiratory flow rate.
         b.   FEV1 .

    4.   Laboratory:
         a. ABG.
         b. Chest radiograph.
         c.   EKG.
         d.   Theophylline level (if applicab le).
         e.   WBC count.
         f.   Blood cultures if pneumonia.
         g.   Electrolytes.
         h.   BUN.
         i.   Glucose.

E. Complete Eval uation and Treatment of Comorbi d Conditi ons and Other Factors Contri buting to
   Exacerbation

    OBJECTIVE

    To identify co morbid conditions that are likely in patients with COPD, and might contribute to acute
    exacerbation and for which specific interventions should be considered.

    ANNOTATION

    Co morbid conditions that may impact upon the treatment of exacerbation of COPD inclu de the following wh ich
    were adapted and modified fro m ERS table:


    1.   Congestive heart failure o r disturbances in cardiac rhythm.
    2.   Pneumonia.
    3.   Pulmonary embolism.
    4.   Spontaneous pneumothorax.
    5.   Inappropriate o xygen therapy.
    6.   Psychotropic drugs (hypnotics, tranquilizers, narcotics, etc.).
    7.   Drug allergy (penicillin, cephalosporin, etc.).
    8.   Metabolic disease (diabetes mellitus, electrolyte disorders such as hypophosphatemia, hypokalemia).
    9.   Poor nutritional status.
    10. Myopathy.
    11. Other acute illness (acute abdomen, GI hemo rrhage, CVA, etc.).
    12. Systemic use of corticosteroids.


    Some of these comorbid ities will require hospitalization.




                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Summary Annotations - Page 32
                                                                                           VHA/DoD Clinical Practice Guideline



F. Admit to ICU

     OBJECTIVE

     To provide direct observation and 24-hour monitoring for patient with severe exacerbation.

     ANNOTATION

     ICU patients are treated the same as ward patients except for card iopulmonary monitoring and direct
     observation. A specialist in critical care medicine should be consulted for these patients.

G. Does Patient Meet ICU Admission Criteria?

     OBJECTIVE

     To identify patients who will benefit fro m special care.

     ANNOTATION

     Any of the following would pro mpt ad mission to the ICU for closer observation and monitoring (adapted and
     modified fro m A merican Thoracic Society guidelines).

     1.   Severe dyspnea that responds inadequately to initial emergency roo m therapy.
     2.   Confusion, lethargy, or respiratory muscle fatigue.
     3.   Persistent or worsening hypoxemia despite supplemental O 2 or severe or worsening of respiratory acidosis
          (pH < 7.30).
     4.   Required assisted mechanical ventilation, whether through means of tracheal intubation or noninvasive
          techniques.

H.   Does Patient Meet Discharge Criteri a?

     OBJECTIVE

     To establish criteria for d ischarge fro m the emergency roo m.

     ANNOTATION

     Discharge criteria for patients with acute exacerbation of COPD (adapted and modified fro m A merican
     Thoracic Society guidelines):

     1.   Features of the severe exacerbation are resolved (see Annotation D in the Core Module).
     2.   Anticipated need for inhaled bronchodilators is not more frequent than every 4 hou rs and the patient is on
          oral med ication.
     3.   Reversible co mponent of airway obstruction, if present, is under stable control.
     4.   Patient or caregiver understands appropriate use of medications.
     5.   Follow-up and home care arrangements have been completed (e.g., v isiting nurse, o xygen delivery, meal
          provisions).
     6.   Patient, family, and physicians are confident that the patient can manage successfully.




                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Summary Annotations - Page 33
                                                                                           VHA/DoD Clinical Practice Guideline



I.   Admi t to Ward

     OBJECTIVE

     To establish criteria for ad mission to a general medical ward for acute exacerbation of COPD.

     ANNOTATION

     Indications for hospitalizat ion of patients with COPD (adapted and modified fro m A merican Thoracic Society
     guidelines):

     1.   Patient has acute exacerbation plus one or more of the following:
          a. Inadequate response of symptoms to outpatient management.
          b. Inability to walk between rooms (patient previously mobile).
          c.   Inability to eat or sleep due to dyspnea.
          d.   Conclusion by family and/or physician that patient cannot manage at home and supplementary ho me
               care resources are not immediately available.
          e.   A high-risk co mo rbid condition, pulmonary (e.g., pneu monia) or non pulmonary.
          f.   Prolonged, progressive symptoms before emergency department visit.
          g.   Altered mentation.
          h.   Worsening hypoxemia.
          i.   New or worsening hypercarbia.
     2.   Patient has new or worsening cor pulmonale unresponsive to outpatient management.
     3.   A planned invasive surgical or d iagnostic procedure requires analgesics or sedatives that may worsen
          pulmonary function.
     4.   Co morbid conditions (e.g., steroid myopathy or vertebral compression fractures) have wo rsened pulmonary
          function.

     Other indicat ions for hospitalizat ion may apply to patients undergoing pulmonary rehabilitation.

J. Is Patient Improving?

     OBJECTIVE

     To establish criteria for measuring a favorable response to treatment.

     ANNOTATION

     Improvement is indicated by:

     1.   Reduced dyspnea.
     2.   Decreased respiratory rate.
     3.   Improved air movement.
     4.   Decreased use of accessory muscles.
     5.   Improved peak exp iratory flow.
     6.   Improved FEV1 and/or ABGs.




                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Summary Annotations - Page 34
                                                                                           VHA/DoD Clinical Practice Guideline



K. Continue Treatment.

    OBJECTIVE

    To establish guidelines for tapering treatment fo r patients who are imp roving.

    ANNOTATION

    1.   Decrease frequency of inhaled beta 2 -agonists to every 4 to 6 hours (see Module B3).
    2.   Switch to MDI with spacers.
    3.   Switch fro m parenteral to oral med ication.
    4.   Titrate o xygen as per o xygen protocol (see Module B3).

L. Intensify Treatment

    OBJECTIVE

    To establish guidelines for treating patients who fail to respond to the initial therapy (e.g., intensification of the
    management regimen)

    ANNOTATION

    1.   Consider using aerosol beta-agonists if MDI cannot be used effectively. (see Module B3).
    2.   Consider using IV steroids and/or antibiotics (see Module B3).
    3.   Titrate o xygen, using oxygen therapy (see Module B4).
    4.   Consider como rbidit ies or other contributory causes of COPD and treat.


M. Reassess in 30 Minutes. Consider S pecialist Consultati on

    OBJECTIVE

    To establish criteria for consultation by a specialist in chest med icine.

    ANNOTATION

    1.   Patients who require more intensive treatment but do not require ICU ad mission should be considered for
         consultation with a pulmonary specialist.
    2.   Repeated intensification of treat ment without improvement would warrant consultation with a pulmonary
         specialist.




                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Summary Annotations - Page 35
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

           INPATIENT MANAGEMENT: Pharmacotherapy (B2)



            ALGORITHM AND SUMMARY ANNOTATIONS
                           VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Pharmacotherapy (B2) - Algorithm
                                                                                            VHA/DoD Clinical Practice Guideline




                  CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                               Inpatient Management of COPD: Pharmacotherapy (B2)

A. Can Patient Effecti vel y Use Metered Dose Inhaler (MDI) with S pacer?


    OBJECTIVE

    To establish guidelines for the appropriate use and dosing of inhaled bronchodilators in the in -patient setting
    and to establish criteria for the use of a small-volu me nebulizers (SVN) versus metered dose inhaler (MDI) with
    spacer in the hospital setting.

    ANNOTATION

    Selective beta 2 -adrenergic agonists are first-line agents:

    1.   Aerosolization using a low-volu me nebulizer is generally the first mode used when the patient is severely
         dyspneic.
    2.   After the patient has stabilized and can use the MDI, there is no difference between using an MDI with a
         spacer and nebulized aerosolizat ion.
    3.   An optimal dosing schedule of beta 2 -agonists cannot be suggested.
    4.   Beta2 -agonists should be titrated to maximal effect.
    5.   Monitor closely for adverse effects of the larger-than-usual doses that are sometimes necessary to relieve
         airway obstruction.

    Selective beta 2 -agonists are less likely to cause tachycardia.

    Nebulizer aerosolization is used when the patient is severely dyspneic and can neither effectively breathe nor
    coordinate for effect ive MDI use. After the patient has stabilized and can use the MDI, there is no difference
    between using an MDI with a spacer compared with nebulized aerosolizat ion. The patient’s skill with MDI
    should be evaluated by demonstration.

    No large, well-done, rando mized, placebo-controlled clin ical trials have been conducted. Therefore, an optimal
    dosing schedule of beta 2 -agonists cannot be suggested. Beta 2 -agonists should be titrated to maximu m effect
    when possible, monitoring closely for adverse effects of the larger-than-usual doses that are sometimes
    necessary to relieve airway obstruction. Beta 2 -agonists have a reduced functional half-life in exacerbation of
    COPD and therefore, if tolerated, may be g iven every 30 to 60 minutes under close supervision (including EKG
    monitoring). High-dose beta2 -agonist treatment regimens have not been investigated widely in this patient
    population and should be used cautiously until results of more controlled clinical trials are availab le.




                                                     Inpatient Management of COPD: Pharmacotherapy (B2) - Annotations - Page 36
                                                                                             VHA/DoD Clinical Practice Guideline




                                 Table 1. Medication for Acute Exacerbation of COPD

            Medication                  MDI Dose               Nebulizer Dose                 Special Instructions
       Short Acting Beta2
       Agonists
      Albuterol                    3-4 puffs q½-2 h         2.5 mg q½-2 h

      Metaproterenol               3-4 puffs q½-2 h         10 –15 mg q½ -2 h           Deliver medication with
                                                                                        nebulizer if unable to use MDI
      Terbutaline                  3-4 puffs q½-2 h         N/A                         with spacer (1)


     Anticholinergics
       Ipratropiu m Bro mide        3-6 puffs q2-4h         500 µg q2-4h
     Systemic Steroi ds             Intravenous
       So lu medrol                 125 mg q6h x 72                                     Taper schuedule
                                    hours                                                 Days 4-7: 60 mg oral
                                                                                        prednisone qd
                                                                                          Days 8-11: 40mg oral
                                                                                        prednisone qd
                                                                                          Days 12-15: 20 mg oral
                                                                                        prednisone qd
                                    Oral

       Prednisone                   40-60 mg q day
                                                                                        Taper off or change to qod
       Prednisilone                 30-50 mg q day                                      within 1 to 2 weeks
      Theophylline                  If on theophylline check level                      Aim fo r levels of 5 to 12 µg/ ml

B. Admi nister Corticosteroi ds

    OBJECTIVE

    To establish criteria for the use of corticosteroids.

    ANNOTATION

    Steroids should be given early in patients with acute exacerbation (A E) o f COPD. Studies demonstrating t he
    benefits of corticosteroids in AE involved a s mall nu mber of patients and show small improvement in lung
    function. A VA cooperative trial (the SCCOPE trial) addressed the role of corticosteroids in AE, presented at
    an American Thoracic Society meet ing in 1998 indicating a benefit fro m the use of steroids in this clin ical
    situation. We believe corticosteroids are of benefit in AE and should be given early, particularly in patients
    with severe underlying lung function and in those with severe exacerbatio n. The reco mmend dose equivalents
    of at least 0.5 mg/ kg of methylprednisolone every 6 hours for at least 3 days.

C. Consider Other Drug Therapies or Treatments as Indicated


    OBJECTIVE

    To identify the role of anticholinergic agents, theophylline, other pharmaco logic agents, and miscellaneous
    adjunctive agents/therapies.




                                                      Inpatient Management of COPD: Pharmacotherapy (B2) - Annotations - Page 37
                                                                                           VHA/DoD Clinical Practice Guideline




     ANNOTATION

     1.   Anticholinergic agents may be valuable as additive or single agents particularly if the patient is intolerant
          of beta2 -agonist or has side effects, have significant coronary artery disease or severe left ventricular
          dysfunction.
          High-dose ipratropriu m bro mide, although possibly effective, has not been studied in acute exacerbation of
          COPD. If the decision to use ipratropium is made, the fo llo wing dose is suggested: 500 µg every six hours
          by nebulizer, or six to eight puffs every four hours by MDI with spacer.
     2.   Theophylline Use—There is inadequate evidence in the literature to reco mmend the routine use of
          theophylline or amce to exclude a benefit for selected patients. Toxicity occurs frequently in hospitalized
          patients and is associated with a pro longed stay. Clin icians who choose to use this agent must be
          thoroughly familiar with its metabolis m, drug interactions, and toxicity.
     3.   Other Parenteral Agents—Parenteral ad min istration of terbutaline or ep inephrine has a prompt effect but is
          accompanied by an increased risk for tachycardia and may be more arrhyth mogenic when co mpared with
          the inhaled route in theophylline in t reatment of acute exacerbation of COPD. However, there is also
          inadequate evidence. Since an increased potential for myocardial ischemia is an unintended consequence
          of parenteral adrenergic use, it cannot be recommended in adult patients with COPD. This is a particular
          concern in patients in whom cigarette use is a potent risk factor for both COPD and coronary artery disease.
          Terbutaline and epinephrine are not reco mmended.
     4.   Additional Therapies Treat ment Considerations —The follo wing measures lack adequate evidence to
          support their routine use in the manage ment of acute exacerbation of COPD: directed coughing, chest
          physiotherapy, positive end-expiratory pressure, nasotracheal suctioning, systemic hydration beyond
          replacement to euvolumia, intermittent positive pressure breathing, bland aerosol therapy and mucolytic
          therapy. Further research is indicated in these areas.

          The nutritional status of the patient is another important consideration. Care must be exercised so that
          patients receive adequate and appropriate nutrition during their stay. Also, patie nts should be encouraged
          to mobilize as soon as is practical. When confined to bed, range-of-motion exercises should be performed.
          Consider deep-vein thrombosis prophylaxis.

D. Consider Anti biotics


     OBJECTIVE

     To identify criteria for using antibiotics in the treat ment of acute exacerbation of COPD.

     ANNOTATIONS

     Many patients with AE do well without antibiotic treatment. Ho wever, for patients whose exacerbation is
     associated with changes in sputum (quality, volu me, color) or fever, antib iotics are a reasonable treatment
     option. Patients who are older than 60 years or have severe underlying lung function are more likely to benefit
     fro m the use of antibiotics. In most studies, the choice of antibiotic was not important. Usually, the older, less
     expensive antibiotics, such as amo xicillin, trimethoprim-sulfamethoxazo le, and do xycycline, will suffice.
     However, the choice may be affected by the history of exacerbation in the individual patient and by the pattern
     of microbial resistance found in the community. It is important to keep the possibility of drug interactions in
     mind when selecting antibiotics. Th is should be a consideration for any patient on theophylline.

E.   Has the Patient’s Respiratory Status Improved?


     OBJECTIVE

     To establish criteria for measuring a favorable response to treatment.



                                                    Inpatient Management of COPD: Pharmacotherapy (B2) - Annotations - Page 38
                                                                                             VHA/DoD Clinical Practice Guideline




     ANNOTATION

     Improvement is indicated by:

     1.   Reduced dyspnea.
     2.   Decreased respiratory rate.
     3.   Improved air movement.
     4.   Decreased use of accessory muscles.
     5.   Improved peak exp iratory flow, improved FEV1 and/or ABGs.


     Improvement is indicated by reduced dyspnea, decreased respiratory rate, improved air movement, and
     decreased use of accessory muscles. Ob jective measures such as peak exp iratory flow, FEV1 , and/or ABGs
     should demonstrate improvement. An elevated heart rate may indicate beta 2 -agonist toxicity.

F.   Modi fy Treatment. Consider Tapering Medicati on


     OBJECTIVE

     To establish guidelines for tapering treatment fo r patients who are imp roving.

     ANNOTATION

     1.   Decrease frequency of inhaled beta 2 -agonists to every four to six hours.
     2.   Switch to MDI with spacers.
     3.   Switch fro m parenteral to oral med ication.
     4.   Titrate o xygen per o xygen protocol (see Module B3).

G. Intensify Treatment


     OBJECTIVE

     To establish guidelines for the treatment of patients who fail to respo nd to the initial therapy (e.g.,
     intensification of the management regimen).

     ANNOTATION

     1.   Consider using aerosol beta2 -agonists if M DI cannot be used effectively.
     2.   Consider using IV steroids and/or antibiotics.
     3.   Titrate o xygen, using oxygen therapy (see Module B3).
     4.   Consider como rbidit ies or other contributory causes of COPD and treat.


     Optimal dosing schedules for beta 2 -agonists cannot be recommended due to the lack of acceptable placebo -
     controlled clinical trials. Ho wever, beta 2 -agonists should be titrated to maximal effect when possible,
     monitoring closely for adverse effects of the larger-than-usual doses that are sometimes necessary to relieve
     airway obstruction. Beta 2 -agonists have a reduced functional half-life in exacerbation of COPD and therefore,
     if to lerated, may be given every 30 to 60 minutes under close supervision (including EKG monitoring). High -
     dose beta2 -agonist treatment regimens have not been investigated widely in this patient population and should
     be used cautiously until results of better controlled clinical trials are available.




                                                      Inpatient Management of COPD: Pharmacotherapy (B2) - Annotations - Page 39
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

           INPATIENT MANAGEMENT: Oxygen Therapy (B3)



            ALGORITHM AND SUMMARY ANNOTATIONS
                            VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Oxygen Therapy (B3) - Algorithm
                                                                                           VHA/DoD Clinical Practice Guideline



                   CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                Inpatient Management of COPD: Oxygen Therapy (B3)

              The American Thoracic Society and European Respiratory Society guidelines were relied
              upon in devising this algorithm. A paucity of well-designed trials in this area mandated the
              use of consensus.

A. Using Oxi metry, Titrate O2 by Venturi Mask or Nasal Cannula (24 to 35 Percent) to 35 to an SaO 2 of 90
   Percent

    OBJECTIVE

    To delineate general princip les of o xygen administration in patients with acute exacerbation of COPD.

    ANNOTATION

    The goal of o xygen therapy is to optimize o xygenation and min imize respiratory acidosis, if present. Thus, all
    patients presenting with acute exacerbation of chronic obstructive pulmonary disease should receive oxygen by
    Venturi mask (24 to 35 percent), which delivers a precise oxygen concentration, until the PaCO 2 is determined.
    The lowest fraction of inspired oxygen (FiO2 ) resulting in an SaO2 of 90 percent is optimal. The nasal cannula
    is to be avoided initially because of its inability to deliver a precise FiO2 . ABGs should be obtained initially
    and SaO2 should be monitored continuously. If a ventilator is used in the ER, the init ial FiO 2 setting should be
    1.0.

B. Obtain AB Gs

    OBJECTIVE

    To emphasize the role o f ABG determination in the init ial man agement of patients with acute exacerbation of
    COPD and to define the role and limits of pulse oximetry in this setting.

    ANNOTATION

    Analysis of ABGs is to be used initially in all cases when it is unknown whether the patient is a chronic CO 2
    retainer and to determine acid-base status. Pulse o ximetry, which should be continuously monitoring SaO 2 , is
    not sufficient until it is clear that the CO2 level is not elevated or is stable and the acid-base status is known and
    is stable.

C. Does Patient Need Mechanical Ventilati on?

    OBJECTIVE

    To define the guidelines for life saving mechanical ventilat ion and endotracheal intubation.

    ANNOTATION

    A decision to initiate mechanical ventilat ion and endotracheal intubation can be made prior to measuring
    arterial blood gases. Advance directives should be considered prior to in itiating these supportive measures.

    1.   Indications for mechanical ventilation (invasive or non invasive) include:
         Severe respiratory or co mb ined respiratory and metabolic acidosis.
         a. Sustained respiratory rate greater than 40 per minute.
         b.   Abnormal b reathing pattern suggestive of increased respiratory workload and/or respiratory muscle
              fatigue.



                                           Outpatient Management of COPD: Oxygen Therapy (B3) - Summary Annotations - Page 40
                                                                                           VHA/DoD Clinical Practice Guideline



         c.   Depressed mental status.
         d.   Severe hypoxemia.

     2. Indications for tracheal intubation include:
         a. Suspected airway obstruction.
         b.   Depressed mental status.
         c.   High-risk o f gastro-pulmonary reflu x and aspiration.
         d.   Difficulty managing secretions.

D. Stepwise Increase in FiO2

     OBJECTIVE

     To encourage the use of a high flow controlled o xygen source in an acute exacerbation o f COPD when PaCO2
     is suspected to be elevated.

     ANNOTATION

     An SaO2 of 90 percent is optimal. Th is usually corresponds to a PaO2 of 55 to 60 mmHg. Pulse o ximetry alone
     may be used in this situation once it is clear that PaCO2 is not elevated and acid-base status is known and stable.
     Use of a Venturi mask, with analysis of arterial blood gases after 20 minutes (earlier if indicated clin ically), is
     the most judicious approach to the management of acute exacerbation of COPD with o xygen in a patient having
     an elevated PaCO2 . If chronic elevation of PaCO2 is not demonstrated and repeated measurement of acid base
     status is not a clinical concern, pulse o ximetry alone to assess adequacy of oxygenation is acceptable, as is the
     use of nasal prongs or a cannula to deliver o xygen. However, when CO2 retention exists, or when the acid-base
     status is unclear, assessment of PaCO2 and pH are required. Use of pulse o ximetry alone in this situation is to be
     avoided.

E. Are AB Gs Acceptable?

     OBJECTIVE
     To establish goals for PaO2 and pH in patients with acute exacerbation of COPD.
     ANNOTATION

     Acceptable blood gases would include a PaO2 close to 60 mmHg, a stable PaCO2 , and a pH > 7.25.

F.   Decrease FiO2 Progressively, Keeping PaO2 or SaO2 at 90 Percent AND Monitor Oxi metry and AB Gs

     OBJECTIVE

     To delineate the salient points of oxygen administration in patients with elevated PaCO 2 .

     ANNOTATION

     Monitor with o ximet ry or A BGs. If CO2 retention has been worsened by the use of a high concentration of
     oxygen, it may be difficult to reverse the rise in PaCO2 and reduce acidosis without resorting to mechanical
     ventilation. A stepwise reduction in FiO2 may be useful in this setting if clin ical circu mstances permit. An
     abrupt reduction in FiO2 is unwise, since it may result in severe hypoxemia.




                                           Outpatient Management of COPD: Oxygen Therapy (B3) - Summary Annotations - Page 41
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

                         OUTPATIENT MANAGEMENT



           ALGORITHMS AND EXPANDED ANNOTATIONS
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

                     OUTPATIENT MANAGEMENT: Core



           ALGORITHMS AND EXPANDED ANNOTATIONS
             VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Core - Algorithm
                                                                                         VHA/DoD Clinical Practice Guideline



                    CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                      Outpatient Management of COPD: (Core)

A. Patient wi th Suspected or Confirmed Chronic Obstructi ve Pul monary Disease Presents to Pr i mary Care


    Chronic obstructive pulmonary disease (COPD) is defined by the American Thoracic Society (ATS) in
    Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease (1995). Further
    detail on lung function testing is found in another ATS publication (1991). [The British Thoracic Society (BTS)
    and the European Respiratory Society (ERS) have definitions that differ slightly with the ATS definition.]

    DEFINITIONS

    1.   Chronic obstructive pulmonary disease is a disorder characterized by the presence of airflow obstruction
         due to chronic bronchitis or emphysema; the airflo w obstruction is generally slowly p rogressive, may be
         accompanied by airway hyperactivity, and may be partially reversible.
    2.   Chronic bronchitis is defined as the presence of chronic productive cough for 3 months of each of two
         successive years in a patient in who m other causes of chronic cough have been excluded (asthma, post
         nasal discharge, gastroesophageal reflu x disease (GERD), etc.).
    3.   Emphysema is defined as abnormal permanent enlargement of the air spaces distal to the terminal
         bronchioles, accompanied by destruction of their walls and without obvious fibrosis.
    4.   Asthma is by definition associated with reversible airflo w obstruction. Patients with asthma whose airflo w
         obstruction is completely reversible are not considered to have COPD. The obstruction in many patients
         with COPD may include a significant reversible co mponent. Some patients with asthma may develop
         irreversible airflo w obstruction indistinguishable fro m COPD.

    EVIDENCE

    Definition of COPD: A merican Thoracic Society 1991, 1995; European Respiratory Society 1991; Siafakas
        1995; British Thoracic Society 1997. LE=C, SR=IIa

B. Perform Clinical Assessment, History, Physical Examinati on, Laboratory Tests


    OBJECTIVE

    To collect informat ion needed to assess the patient.

    ANNOTATION

    4.   History.

         a.   Smoking—Age at init iation, quantity smoked per day, whether or not still smoker and if not, date of
              cessation.
         b.   Environmental (chronological), e.g., dust exposure—may disclose important risk factors.
         c.   Cough (chronic, productive)—Frequency and duration, whether or not productive (especially on
              awakening).
         d.   Wheezing.
         e.   Acute chest illnesses—Frequency, productive cough, wheezing, dyspnea, fever.
         f.   Dyspnea.
         g.   Evaluate current therapy.



                                                        Outpatient Management of COPD: Core - Expanded Annotations - Page 42
                                                                                     VHA/DoD Clinical Practice Guideline




2.   Physical examination of chest.

     a.   Airflow obstruction evidenced by:
          —Wheezing during auscultation on slow or forced breathing.
          —Forced exp iratory time of mo re than 6 seconds.
     b.   Severe emphysema indicated by:
          —Overdistention of lungs in stable state, low d iaphragmat ic position
          —Decreased intensity of breath and heart sounds.
     c.   Severe disease suggested by (characteristics not diagnostic):
          —Pursed-lip breathing
          —Use of accessory respiratory muscles
          —Indrawing of lower interspaces.
     d.   Other—Unusual positions to relieve dyspnea at rest, digital clubbing (suggests possibility of lung
          cancer or bronchiectasis), and mild dependent edema that may be seen in absence of right heart failure.

3.   Laboratory.

     a.   Spiro metry : FEV1 and VC (vital capacity).
     b.   Chest radiography—Diagnostic only of severe emphysema but essential to exclude other lung diseases.
     c.   Oximetry should be done to help determine if there is a need for o xygen therapy. It may be done at
          this time or at the time of apply ing the long-term o xygen therapy module (A3).
     d.   Alpha1-antitrypsin (AAT)—AAT deficiency accounts for less than one percent of COPD. If ATT
          deficiency is suspected, obtain a serum AAT level. Strongly consider referral to specialist in the
          following situations:
          —Premature onset of COPD with moderate or severe impairment before age 50
          —A predominance of basilar emphysema; development of unremitting asthma, especially in a patient
           under age 50
          —A family h istory of AAT deficiency or of COPD onset before age 50
          —Chronic bronchitis with airflow obstruction in a person who has never smoked
          —Bronchiectasis, especially in the absence of clear risk factors for the disease
          —Cirrhosis in a patient without apparent risk factors (ATS 1995). If diagnosis of COPD or asthma is
           made, refer to specialist for reco mmendations for therapy.

DISCUSSION

The crit ical elements of the clinical evaluation adapted from the ATS, ERS, and BTS guidelines, include but are
not limited to:

1.   History.

     a.   Baseline respiratory status.
     b.   Sputum volu me and characteristics.
     c.   Cough.
     d.   Duration and progression of symptoms.
     e.   Dyspnea severity.
     f.   Exercise limitations.
     g.   Sleep and eating difficu lties.


                                                    Outpatient Management of COPD: Core - Expanded Annotations - Page 43
                                                                                         VHA/DoD Clinical Practice Guideline



         h.   Ho me care resources.
         i.   Ho me therapeutic regimen.
         j.   Sympto ms of co-morb id acute and chronic conditions.

    2.   Clin ical assessment.

         a.   Temperature.
         b.   Respiratory rate.
         c.   Heart rate.
         d.   Cyanosis.
         e.   Accessory muscle use.
         f.   Edema.
         g.   Cor pulmonale.
         h.   Bronchospasm.
         i.   Hemodynamic instability.
         j.   Parado xical abdo minal retract ions.
         k.   Pneumonia.
         l.   Altered mentation.

    3.   Laboratory (as appropriate).


         a.   Arterial Blood Gas (A BG).
         b.   Chest radiograph.
         c.   ElectrocardiogramEKG.
         d.   Theophylline level (if applicab le).
         e.   WBC count.
         f.   Blood cultures if pneumonia.
         g.   Electrolytes.
         h.   Blood urea nitrogen (BUN).
         i.   Glucose.

    EVIDENCE

    Clinical and laboratory evaluation: ATS 1995; ERS, Siafakas 1995; BTS 1997. LE=C, SR=IIa

C. Is Patient in Acute Exacerbati on?

    OBJECTIVE

    To identify patients in an acute exacerbation.

    ANNOTATION

    An acute exacerbation of COPD is defined as an acute clinical deteriorat ion in a patient's respiratory status due
    to a worsening of the underlying COPD. Sy mpto ms and signs of acute exacerbation of COPD may include:

    1.   Increased dyspnea.
    2.   Tachycardia.


                                                        Outpatient Management of COPD: Core - Expanded Annotations - Page 44
                                                                                        VHA/DoD Clinical Practice Guideline



    3.   Increased cough.
    4.   Increased sputum production.
    5.   Change in sputum color or character.
    6.   Accessory muscle use.
    7.   Peripheral edema.
    8. Develop ment of or increase in whee ze.
    9. Loss of alertness.
    10. Loss of energy.
    11. Fever.
    12. Increased respiratory rate.
    13. Decrease in FEV1 or peak exp iratory flow.
    14. Worsening of arterial b lood gases or pulse oximetry.
    15. Chest tightness.

    EVIDENCE

    Definition of acute exacerbation: ERS, Siafakas 1995; BTS 1997. LE=C, SR=IIa

D. Is there Evi dence of Severe Exacerbation?


    OBJECTIVE

    To identify patients with a severe exacerbation that requires emergency roo m care.

    ANNOTATION

    Loss of alertness or a combination of two or more of the fo llo wing parameters indicate a severe exacerbation
    and suggest a need for referral to an emergency department.

    1.   Dyspnea at rest.
    2.   Respiratory rate > 25 per minute.
    3.   Heart rate > 110 per minute.
    4.   Use of accessory muscles.

    EVIDENCE

    Severity of exacerbation: ERS, Siafakas 1995. LE=C, SR=IIa

E. Order/Review S pirometry

    OBJECTIVE

    To objectively assess pulmonary function in patients with COPD.




                                                       Outpatient Management of COPD: Core - Expanded Annotations - Page 45
                                                                                            VHA/DoD Clinical Practice Guideline



     ANNOTATION

     On in itial visit :

          Spiro metry pre - and postbronchodilation are essential to confirm presence and reversibility of airflow
          obstruction and to quantify maximu m level of ventilatory function (ATS 1995), guide management, and
          estimate prognosis.

     On follow up visits:

          Repeat spirometry if major change in patient’s condition. On new patients previous spirometry may be used
          if availab le and no change in patient's condition.

          1.    Airflow limitation is diagnosed by a reduction in FEV1 / VC (v ital capacity).

          2.    Lung volu mes—Unnecessary except in special circu mstances (e.g., coexisting interstitial lung disease,
                presence of giant bullae, and decrease in vital capacity).

          3.    Carbon mono xide d iffusing capacity—Unnecessary except in special instances (e.g., dyspnea out of
                proportion to severity of airflow limitation).

     DISCUSSION

     SEVERITY OF AIR FLOW OBSTRUCTION

     COPD severity can be graded on the basis of percentage of predicted FEV1 as Mild, Moderate, or Severe.
     Grading or staging, based on severity of airflo w obstruction, facilitates the application of clinical
     recommendations and attempts to offer a composite picture of d isease severity. Forced exp iratory spiro metry is
     used in the diagnosis of COPD as well as in the assessment of its severity, progression, and prognosis. The use
     of an FEV1 < 50 percent corresponds to a grade of moderate to severe as adopted in the 1995 ATS document.

                                           Table I. Severity of COPD Based on FEV1
                                           Severity                  FEV1 Percent Predicted (1)
                                            Mild                              50 to 79
                                          Moderate                            35 to 49
                                           Severe                               < 35
                             (2) In the presence of obstruction assessed as a low FEV1 :VC ratio.

     EVIDENCE

     Interpretation of pulmonary function: ATS 1995 ERS; Siafakas 1995; BTS 1997. LE=C, SR=IIa


F.   Initiate/Adjust Pharmacological Therapy


     OBJECTIVE

     To determine the appropriate therapy based on severity of symptoms.




                                                           Outpatient Management of COPD: Core - Expanded Annotations - Page 46
                                                                                        VHA/DoD Clinical Practice Guideline



ANNOTATION

                                           Table II. Step Care In COPD
Step    Symptoms and FEV1                              Therapy
1       Asymptomat ic AND                               Smoking cessation, vaccination, employ education. No
        FEV1 > 50 percent of p redicted (1)             med ication indicated.
2a      Sympto ms less than daily AND                   Smoking cessation, vaccination, employ education.
        FEV1 > 50 percent of p redicted (2)             Inhaled short-acting beta2 -ag onist (2 puffs PRN up to 12
                                                        puffs/day)
2b      Asymptomat ic AND                               Smoking cessation, vaccination, employ education.
        FEV1 < 50 percent of p redicted                 Inhaled anticholinergic (2 puffs qid)
                                                        Consider use of inhaler containing a short acting beta 2 -
                                                        agonist and an anticholinergic.
2c      Sympto ms less than daily AND                   Smoking cessation, vaccination, employ education.
        FEV1 < 50 percent of p redicted                 Inhaled anticholinergic (2 puffs qid)
        OR                                              Short-acting beta2 ag onist (2 puffs PRN up to 12
                                                        puffs/day)
        Daily sympto ms
                                                        Consider use of inhaler containing a short acting beta 2 -
                                                        agonist and an anticholinergic.
3       Sympto ms not controlled (2)                    Increase dose of both:
                                                        Inhaled anticholinergic (2 to 6 puffs qid) and
                                                         inhaled short-acting beta2 agonist (2 to 4 puffs PRN up
                                                        to 12 puffs/day)
4       Sympto ms not controlled (2)                    Consider adding long-acting inhaled beta2 -agonist. (3)
5       Sympto ms not controlled (2)                    Consider adding theophylline tri al (slow release
                                                        theophylline adjusted to level of 5 to 12 µg/ ml) (4)
6       Sympto ms not controlled (2)                    Consider adding corticosteroi d tri al (prednisone 40 to 60
                                                        mg po qd or h igh dose inhaled steroids (5).
                                                        Consider specialist consultation.
7       Sympto ms not controlled (2)                    Refer to specialist promptly.

1.   Spiro metry is essential to confirm the presence of airflo w obstruction (low FEV1 and FEV1 / VC rat io). Base
     therapy on symptoms, but consider alternate diagnoses (heart disease, pulmonary emboli, etc.) if out of
     proportion to spirometry.
2.   Use the lowest level of therapy that satisfactorily relieves symptoms and maximizes activit y level. Assure
     compliance and proper use of medications before escalating therapy.
3.   Inhaled long acting beta 2 -agonists should not be used as rescue therapy. Short-acting inhaled beta 2 -agonist
     (less than12 puffs/day) may continue to be used PRN. Nighttime s ymptoms are frequently better controlled
     with long-acting inhaled beta 2 -agonist. Oral beta 2 -agonists are associated with a higher rate of side effects,
     and should be reserved for patients who cannot take inhaled beta 2 -agonist medications.
4.   Theophylline should be used with caution because of potential for severe side effects. Nighttime respiratory
     symptoms are frequently controlled but theophylline may lead to insomnia. Theophylline should be
     discontinued if a sympto matic o r objective benefit is not evident within several weeks.
5.   A corticosteroid trial o f prednisone (40 to 60mg/day) 10 to14 days, or high dose inhaled steroids
     (equivalent to 880 µg or more of fluticasone or 800 µg or more of budesonide) of 14 to 21 days can help
     identify patients who may benefit fro m long term steroid use. Responders to oral steroids should transition
     to the lowest effective dose of inhaled steroids, or to the lowest effective dose of a combination of inhaled
     and oral steroids, if possible, to avoid the long term co mplications o f systemic co rticosteroids. If oral



                                                      Outpatient Management of COPD: Core - Expanded Annotations - Page 47
                                                                                            VHA/DoD Clinical Practice Guideline



          steroids are used other than for an acute exacerbation, obtain spiro metry prior to and after trial to confirm
          an objective response.

G. Appl y Long-Term Oxygen Therapy


     OBJECTIVE

     To maintain an acceptable level of O2 saturation and improve survival.

     ANNOTATION

     In COPD patients with hypoxemia and cor pulmonale, treat ment with long -term o xygen therapy (LTOT) may
     increase the life span by six to seven years. Mortality is reduced in patients with chronic hypoxemia when
     oxygen is ad ministered for more than 12 hours daily and greater survival benefits have been shown with
     continuous oxygen admin istration. See Module A3, Long Term Oxygen Therapy for details and references.

H. Is There Evi dence of Cardi ac Disease?


     OBJECTIVE

     To identify patients with sympto matic left ventricu lar heart d isease.

     ANNOTATION

     Card iac disease fro m systolic or d iastolic left ventricu lar dysfunction leading to pulmonary edema can produce
     symptoms similar to that of COPD, namely dyspnea, wheezing, tachycardia, chest discomfort, o rthopnea,
     paroxys mal nocturnal dyspnea. A history of coronary artery disease, hypertension, or cardio myopathy should
     prompt further evaluation or treat ment modifications.

I.   Are There Symptoms of Sleep Apnea?

     OBJECTIVE

     To identify patients who may benefit fro m t reatment by a sleep disorder specialist.

     ANNOTATION

     Some signs and symptoms of COPD, including hypercapnia, are precipitated by sleep apnea.
     Major sympto ms of sleep apnea include:

     1.   Excessive daytime sleepiness (EDS).
     2.   Heavy snoring.
     3.   Observed apnea during sleep.
     4.   Choking during sleep.

     EVIDENCE

     COPD patients do not normally have EDS, even with nocturnal desaturation: Orr 1990. LE=C, SR=IIa
     COPD patients with obstructive sleep apnea are likely to have day time hypercapnia : Brad ley 1990. LE=C,
        SR=IIA




                                                           Outpatient Management of COPD: Core - Expanded Annotations - Page 48
                                                                                            VHA/DoD Clinical Practice Guideline



J.   Patient Complains of Insomni a?


     OBJECTIVE

     To identify patients who may benefit fro m treat ment of insomnia.

     ANNOTATION

     Insomnia is defined as an inability to in itiate or maintain sleep to the patient's satisfaction plus a de leterious
     subjective or objective effect on daytime activit ies. Medications, such as beta2 -agonists, theophylline and
     steroids, can produce insomnia. See Insomn ia Module A6.

K. Initiate/Continue Preventi ve Care and Patient Educati on


     OBJECTIVE

     To init iate and optimize preventive care and patient education for COPD.

     ANNOTATION

     The main items in COPD patient education are:

     1.   Smoking Cessation.
          All s mokers should be strongly advised to quit. Smo king cessation results in a small imp rovement in lung
          function and a slowing of the rate of decline to appro ximately that seen in never smokers of the same age.
          Patients not willing to quit should receive motivational intervention to promote subsequent quitting
          attempts. The smoker willing to make a quit attempt should be assisted by being asked to set a quit date,
          providing self-help materials, encouraging nicotine replacement therapy, and referring to intensive
          treatments when appropriate. All patients attempting to quit should have follo w-up contact scheduled.
          For additional details, see VHA/DoD CPG for Tobacco Use Cessation also see DHHS Gu idelines on
          Smoking Cessation (1996).
     2.   Medication and delivery system training.
     3.   Exercise and nutritional counseling.
          A well-rounded program should include good dietary habits and encourage adjustment of weight to
          approximate ideal body weight. If malnourished, attempts should be made to restore nutritional balance
          with several s mall meals a day to help maintain caloric needs but avoid undue dyspnea. Forced nutrition or
          special diets are not recommended.
     4.   Immunizations.
          The Advisory Committee on Immun ization Pract ices (CDC 1997) reco mmends pneumococcal vaccination
          for all patients with chronic obstructive pulmonary disease. They recommend that patients age 65 or o lder
          that were vaccinated more than five years previously should be revaccinated. When the status of previous
          vaccination is unsure, vaccination is indicated. However, the evidence for the efficacy of pneumococcal
          vaccination in patients with COPD is inconclusive. One s mall, rando mized controlled trial failed to
          demonstrate vaccine efficacy for pneumococcal infection-related or other medical outcomes in the
          heterogeneous group of subjects labeled as high-risk. Case-controlled trials suggest an effectiveness of 65
          to 84 percent among high-risk patients including those with COPD.
          An annual influenza vaccination is recommended for individuals with chronic pulmonary d isease unless
          contraindicated due to severe anaphylactic hypersensitivity to egg protein. Influenza vaccina tion has been
          shown to be 30 to 80 percent effect ive in preventing illness, complicat ions, and death in high -risk
          populations. Pneumococcal and influenza vaccines can be admin istered concurrently at different sites
          without increasing side effects.




                                                           Outpatient Management of COPD: Core - Expanded Annotations - Page 49
                                                                                        VHA/DoD Clinical Practice Guideline



   5.   Management of environ ment.
   6.   Patients with COPD should avoid environmental exposures that exacerbate their sympto ms (e.g.,
        occupational exposures, second-hand smoke, and air and dust pollution) or results in respiratory infections.
   7.   Self-assessment and self-management.
        Pulmonary Rehabilitation—Referral is indicated in patients on optimal medical therapy and who:
        e.   Continue to display moderate to severe respiratory symptoms, including dyspnea.
        f.   Have had several emergency room or hospital ad missions per year.
        g.   Exh ib it limited functional status, restricting activit ies of daily living.
        h. Experience impairment in quality of life.
   8.   Occupational disabilities.
   9.   Sexual function.


   EVIDENCE

   Pneumococcal vaccination: Most studies show an advantage, but one small randomized, placebo -controlled
       trial did not. BTS 1997; CDC A CIP 1997, Fine 1994; Shapiro 1984; 1991; Farr 1995; Sims 1988;
       Forrester 1987; Simberko ff 1986. LE=C, SR=I
   Annual influenza vaccination: CDC ACIP 1997; BTS 1997; Govaert 1994; Nichol 1994; Gross 1988; Fedson
       1993; Foster 1992. LE=C, SR=I
   Smoking cessation slows lung function decline: Anthonison 1994; BTS 1997; Xu 1992; Camilli 1987; Fletcher
       1977. LE=A, SR=I
   Nutritional counseling: ATS 1995; BTS 1997; Wilson 1986. LE=C, SR=IIb
   Pulmonary rehabilitation: ATS 1995; Go ldstein 1994; BTS 1997. LE=C, SR=IIa
   Occupational Disability: BTS 1997. LE=C, SR=IIb

L. Schedule Follow-Up

   OBJECTIVE

   To maintain long term appropriate level of care for patients with COPD.

   ANNOTATION

   For mild COPD, spiro metry is the test used for measuring disease progression. As the disease becomes mo re
   severe, oximetry and ABG assume greater importance. The frequency of obtaining these measures is based on
   clin ical symptoms and status. In general, patients with mild COPD should be seen annually; moderate COPD,
   six months to one year, depending upon status; and severe COPD, every six months at a minimu m. Spiro metry
   should be repeated at least every two to three years to follow the progression of disease and effects of therapy
   unless there is a clinically indicated reason not to do so.




                                                       Outpatient Management of COPD: Core - Expanded Annotations - Page 50
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

       OUTPATIENT MANAGEMENT: Acute Exacerbation (A1)



            ALGORITHM AND EXPANDED ANNOTATIONS
                                VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: - Acute Exacerbation (A1) - Algorithm
                                                                                            VHA/DoD Clinical Practice Guideline



                  CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                              Outpatient Management of COPD: Acute Exacerbation (A1)

A. Patient wi th Acute Exacerbation of COPD Presenting to Pri mary Care


    DEFINITION

    Acute exacerbation is defined as a recent deterioration of a previously stable patient's clinic al and functional
    state that is due to worsening of their COPD. Typical sy mptoms and signs of COPD exacerbation are g iven
    below (adapted fro m the European Respiratory Society Consensus Statement, Siafakas 1995).

    1.   Increased dyspnea.
    2.   Tachycardia.
    3.   Increased cough.
    4.   Increased sputum production.
    5.   Change in sputum color or character.
    6.   Accessory muscle use.
    7.   Peripheral edema.
    8.   Develop ment of or increase in wheeze.
    9. Loss of alertness.
    10. Loss of energy.
    11. Fever.
    12. Increased respiratory rate.
    13. Decrease in FEV1 or peak exp iratory flow.
    14. Worsening of arterial b lood gases or pulse oximetry.
    15. Chest tightness.

B. Administer Oxygen Therapy to Keep O 2 Saturation > 90 Percent


    OBJECTIVE

    Initiate o xygen therapy to maintain o xygen saturation > 90 percent.

    ANNOTATION

    There is not a good relationship between spiromet ry and blood gases in COPD exacerbation, at least in ED
    patients; a PaO2 less than 60 mmHg may be found in patients with a FEV1 up to 54 percent of normal. For that
    reason, O2 saturation should be obtained for patients with mild -to-moderate COPD exacerbations.

    If ambu latory facilities are available, o xygen should be given to keep O 2 saturation  90 percent wh ile the
    patient receives more aggressive bronchodilator therapy. In so me centers this may require ED man agement.
    Blood gases should be obtained to guide oxygen therapy in patients with known hypercapnea or where the
    status of CO2 retention is unknown.

    Patients who are stabilized after aggressive drug therapy but continue to have hypoxemia may require outpa tient
    oxygen therapy at least on a temporary basis. Blood gases should be checked or oximetry performed in one
    month or soon thereafter when the patient is stable to determine the need for continued long -term o xygen
    therapy (LTOT).




                                        Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 51
                                                                                              VHA/DoD Clinical Practice Guideline



    EVIDENCE

    Benefit from oxygen therapy in COPD exacerbation: ERS, Siafakas 1995. LE=C, SR=IIa
    Oxygen should be given when PaO2  60 mmHg, particularly in COPD with cardiac disease: ATS Consensus
        Statement 1995. LE=C, SR=I
    Benefit from maintaining O2 saturation  90 percent: Schmidt & Hall 1989. LE=B, SR=I


C. Is There Evi dence of Res piratory Infection?


    OBJECTIVE

    Identify the presence of a respiratory infection.

    ANNOTATION

    This often is due to viral illness. In cases of bacterial infection, S. pneumoniae, H. in fluenzae and M.
    catarrhalis are frequent pathogens. Other common organisms include Mycoplasma and Chlamydia.

    Ev idence of infection include:

    1.   Increased cough.
    2.   Increase in volu me and changes in the color of sputum.
    3.   Increased shortness of breath.
    4.   Fever.

D. Consider Anti biotic Treatment

    OBJECTIVE

    Initiate appropriate therapy for a suspected bacterial respiratory infection.

    ANNOTATION

    In patients with evidence of respiratory infect ion, a white cell count and chest X-ray may be considered.
    Ev idence of respiratory infect ion with a clear chest X-ray suggests that the exacerbation of COPD is due to
    purulent bronchitis. Antibiotic therapy should be considered.

    Patients with a clin ical p resentation and chest radiograph consistent with pneumonia should be cons idered for
    admission. There are no published guidelines specifically regard ing admission of COPD patients. The severity
    of the underlying COPD, the presence of co-morbid conditions, the judgement and reliab ility of the patient and
    caregivers, and the distance to medical care should be considered in this decision. Drug interaction should be
    considered if patient is under treatment with theophylline.

    DISCUSSION

    A recent meta-analysis of nine randomized, placebo-controlled studies suggested a small benefit fro m antibiotic
    treatment. Antibiot ic therapy may be of greater importance in preventing deterioration rather than expedit ing
    improvement in outpatients with COPD exacerbation. A mild COPD exacerbation may not benefit fro m
    antibiotics. Older patients, those with a more severe COPD and exacerbations featured by increased purulent
    sputum production are more likely to benefit.




                                          Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 52
                                                                                              VHA/DoD Clinical Practice Guideline



     A conventional antibiotic usually is sufficient, such as sulfamethoxazole -trimethroprim (SMZ-TM P) or
     doxycycline. The choice may be influenced by community antibiot ic resistance patterns. Broader spectrum
     antibiotics may be required if the patient had a recent hospitalizat ion or course(s) of antibiotics, or if the patient
     does not respond to conventional antibiotics.

     EVIDENCE

     Benefit from antibiotic therapy: Saint et al. 1995. LE=B, SR=I
     Benefit from antibiotic therapy prevention of further deterioration: Anthonisen et al. 1987. LE=B, SR=I
     Clinical benefit from antibiotic therapy: Sachs et al. 1995. LE=B, SR=I
     Admission should be considered for pneumonia in COPD: ATS Consensus Statement, Community -acquired
         Pneumonia 1993. LE=C, SR=IIa

E. Consider and Treat Other Factors Contri buting to COPD Exacerbati on


     OBJECTIVE

     Identify and treat other factors contributing to or mimic king a COPD exacerbation.

     ANNOTATION

     1.   Congestive heart failure.
     2.   Card iac ischemia or arrhythmia.
     3.   Drugs (hypnotics, tranquilizers, etc.).
     4.   Pulmonary embolism.
     5.   Spontaneous pneumothorax
     6.   Inappropriate o xygen therapy.
     7.   Metabolic diseases (diabetes mellitus, electro lyte disorders such as hypophosphatemia, hypokalemia).
     8.   Myopathy (e.g., steroid myopathy).
     9. Other diseases (undernutrition, GI hemorrhage, stroke, thoracic vertebral co llapse).
     10. Air pollutants.


     These factors require treat ment in their own right and some may require ad mission to hospital. A h igh degree
     of suspicion is required to detect some relatively co mmon d isorders in the presence of COPD such as heart
     failure, pu lmonary embolism and pneumothorax.

F.   Initiate Pharmacotherapy for Acute Exacerbation


     OBJECTIVE

     To init iate medication to improve respiratory function.

     ANNOTATION

     Initiate or adjust short-acting inhaled beta 2 -agonists (SAIBA) and inhaled anticholinergic metered dose inhalers
     with spacer to maximu m levels as appropriate.




                                          Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 53
                                                                                          VHA/DoD Clinical Practice Guideline



                                   Table 1. Medicati on for Acute Exacerbation

           Medication                MDI Dose               Nebulizer Dose                Special Instructions
      Short Acting Beta2
      Agonists
     Albuterol                  3-4 puffs q½-2 h        2.5 mg q½-2 h

     Metaproterenol             3-4 puffs q½-2 h        10 –15 mg q½ -2 h           Deliver medication with
                                                                                    nebulizer if unable to use MDI
     Terbutaline                3-4 puffs q½-2 h        N/A                         with spacer (1)


 Anticholinergics
      Ipratropiu m Bro mide      3-6 puffs q2-4h        500 µg q2-4h
 Systemic Steroi ds              Oral
      Prednisone                 40-60 mg q day                                     Taper off or change to qod
      Prednisilone               30-50 mg q day                                     within 1 to 2 weeks

 Theophylline                     If on theophylline check level                    Aim fo r levels of 5 to 12 µg/ ml

(1) Assess use of metered dose inhaler (MDI and spacer). Frequency and dose can be titrated as the patient’s
condition allows. Patient can be discharged on minimu m dose or less.

DISCUSSION

In the acute setting, the following medicat ions may react differently than in chronic conditions of COPD.

Short-Acting Inhaled Beta2 Agonists

1.     Albuterol, metaproterenol, and terbutaline are the bronchodilators of ch oice in COPD exacerbations.
2.     They incur less risk of causing tachycardia, card iac arrhyth mias and tremor than nonselective
       bronchodilators. These agents are comparable in efficacy, durat ion of effect, and adverse effects when
       given as aerosols. A small nu mber of studies suggest that SAIBAs, as a class, are of benefit in
       exacerbations of COPD, showing improvements in FEV1 and in dyspnea scores.
3.     The maximal effective dose of SAIBA in COPD exacerbation is not known. Ho wever, limited data fro m
       studies of COPD e xacerbations indicate that three to four puffs of beta2 -agonists produce significant (18 to
       22 percent) levels of bronchodilation. The functional duration of effect of SAIBA is decreased in COPD
       exacerbations. Thus, if three to four puffs every four hours have not been effective, SA IBA should be
       administered three to four puffs every one to two hours, if tolerated, until clinical imp rovement occurs. The
       ATS reco mmendation for severe COPD exacerbation is six to eight puffs every 30 minutes to two hours
       (ATS Consensus Statement 1995).
4.     The frequency and dose of admin istration then can be reduced as the progress of improvement of the
       exacerbation allows.
5.     It should be noted that spacers were used in most studies of MDI beta 2 -agonists in COPD exacerbations.
       Use of spacers in COPD exacerbation is strongly encouraged.
6.     The risk o f adverse reactions, such as tremor and cardiac arrhythmia, also is increased with use of maximal
       doses of these agents. Caution should be used in patients with known coronary artery disease, left
       ventricular dysfunction, or history of arrhythmia if using maximal doses (three to four puffs every one to
       two hours) of inhaled beta 2 -agonists. In this group, a wise alternative is to emp loy additional inhaled
       ipratropiu m at h igher doses in association with moderate doses of beta2 -agonists.




                                      Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 54
                                                                                        VHA/DoD Clinical Practice Guideline




EVIDENCE

Metaproterenol 1.95 mg (3 puffs) produced 18 percent increase in FEV 1 : Karpel et al. 1990. LE=B, SR=I
Albuterol 400 µg (4 puffs) over 60 min produced 22 percent increase in FEV 1 : Lloberes et al. 1988. LE=B,
    SR=I

ANTICHOLINERGICS

Ipratropi um Bromi de

1.   This is the only antimuscarin ic (anticholinergic) agent available at present. It is of benefit in COPD
     exacerbations; doses of 54 to 72 µg (three to four puffs) p roduce increases of 25 percent in FEV1 ,
     comparable with the effect of short-acting inhaled beta 2 -agonists.
2.   Ipratropiu m is less well documented than SAIBA in COPD exacerbations, and as yet should be used as
     monotherapy only in cases with a history of poor response to SAIBA or for those who cannot tolerate
     SAIBA.
3.   The onset of bronchodilation is slower with ipratropiu m than short -acting beta2 -agonists, but the duration of
     action is longer.
4.   A reasonable maximu m dose is three to six puffs every two to four hours. Since systemic to xicity is lo w
     (Gross 1988), higher doses may be given, although the dose-response relationship of ipratropiu m in COPD
     exacerbation at higher doses has not been established. The ATS reco mmendation for severe exacerbation is
     six to eight puffs every two to four hours.
5.   Ipratropiu m can be given by nebulizer, 0.5 mg every two to eight hours to patients who cannot use an MDI
     properly.
6.   Use of a spacer with MDI delivery of ipratropiu m is reco mmended.


EVIDENCE

Similar increase in FEV 1 following ipratropium or metaproterenol by MDI in ED and clinic patients: Karpel et
    al. 1990. LE=B, SR=I
Similar increase in FEV 1 following ipratropium or metaproterenol by NEB in ED patients: Rebuck et al. 1987.
    LE=B, SR=I

Combination Therapy

While the effect of ip ratropiu m or a beta 2 -agonist are comparable in COPD exacerbation, the evidence that
addition of ipratropiu m to a beta 2 -agonist regimen imp roves outcomes in moderate COPD exacerbation is not
proven. However, since some patients may benefit fro m the comb ination, and the toxicity of ipra tropiu m is
low, it is reasonable to add ipratropium to a beta 2 -agonist regimen. Th is is especially the case in unmon itored
patients in who m there may be concern about toxicity fro m h igh -dose SAIBA.

EVIDENCE

Combined agents produced similar increase in FEV1 compared to fenoterol or ipratropium alone by NEB in
    ED patients: Rebuck et al. 1987. LE=B, SR=IIb
Addition of ipratropium MDI to standard multidrug therapy did not increase improvement in FEV 1 over 24
    hours in hospitalized patients: Patrick et al. 1990. LE=B, SR=I
Ipratropium MDI shortened ED stay but did not alter FEV 1 in patients who received isoetharine NEB: Shestra
    et al. 1991. LE=B, SR=I
Addition of ipratropium by NEB did not improve PFR compared with albuterol NEB alone in ED patients:
    O'Driscoll et al. 1989. LE=B, SR=I



                                    Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 55
                                                                                        VHA/DoD Clinical Practice Guideline




Deli very Method

A limited nu mber of studies in ED or hospitalized settings indicate that administration of inhaled beta 2 -agonists
by MDI offers as much benefit as by nebulizer. Metaproterenol (three puffs) or albuterol (four puffs) M DI were
deemed equivalent in effect to nebulized delivery of metaproterenol (15 mg) or albuterol (2.5 mg ). It is likely,
but not certain, that results can be extrapolated to non-ED outpatients. MDIs were delivered v ia spacer
technique.

EVIDENCE

Similar benefit from MDI or NEB metaproterenol on dyspnea or FEV 1 in ED patients: Turner et al. 1988.
    LE=B, SR=IIa
Similar effect of albuterol MDI or NEB on FEV 1 and dyspnea in hospitalized patients: Berry et al. 1989.
    LE=B, SR=IIa
Benefit from NEB > MDI metaproterenol on FVC in hospitalized patients: Maguire et al. 1991. LE=B, SR=IIa
Benefit from low- or high-dose albuterol NEB on FEV 1 in ED patients: Emerman et al. 1997. LE=B, SR=IIa

Patient on maximu m dose steroids (40 to 60 mg per day) o f prednisone or equivalent. Patients already on
higher doses of oral corticosteroids in the range used for treatment of COPD exacerbation (typically 40 to 60
mg daily), and who have not responded to the more intensive bronchodilator therapy as outlined ab ove, are
unlikely to benefit fro m further outpatient management. They should be referred on an emergent basis for
specialist consultation or for ad mission to the hospital.

Indications for S ystemic Corticosteroi d Therapy


Certain patients should be considered for systemic cort icosteroid treatment. Indications for steroids in COPD
exacerbation represent consensus based on expert opin ion.

These include patients:

1.   On oral steroids or on inhaled steroids.
2.   Who recently stopped oral steroids.
3.   Who previously responded to oral steroids.
4.   With O2 saturation less than 90 percent.
5.   With PEF less than 100 L/ min.
6.   Not responding to initial bronchodilator therapy.

EVIDENCE

More serious illness. Inadequate response to bronchodilators. Previous response to steroids: ATS Consensus
    Statement 1995. LE=C, SR=IIa
Systemic corticosteroids are used empirically in COPD exacerbation: ERS, Siafakas 1995. LE=C, SR=IIa
Suggest use in mild/moderate COPD exacerbation: Hudson & Monti1990. LE=C, SR=IIa


Prednisone

1.    Although corticosteroids are widely used in patients with COPD exacerbations, this practice is based on a
     small nu mber of studies. These studies do not uniformly support the use of corticosteroids.
2.    A typical oral dose is 0.6 to 0.8 mg/ kg prednisone per day. Once the patient is stabilized, the dose should
     be tapered carefully, monitoring for relapse of the exacerbation. The goal should be to wean the patient off




                                    Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 56
                                                                                             VHA/DoD Clinical Practice Guideline



          steroids. This may not be possible in some patients who should then be treated with the smallest effective
          dose ideally qod. (See also COPD Pharmacotherapy Module A2).


     EVIDENCE

     Methylprednisolone added to standard multidrug therapy: Albert et al. 1980. LE=B, SR=IIa
     Early administration of methylprednisolone did not improve FEV1 or reduce hospitalization in ED patients:
         Emerman et al. 1989. LE=B, SR=IIa
     IV and oral steroids reduced relapse rate in ED patients with COPD exacerbation and a history of relapses:
         Murata et al. 1990. LE=B, SR=IIa
     Oral prednisone improved FEV 1 , and reduced treatment failure in veteran outpatients: Tho mpson et al. 1996.
         LE=B, SR=IIa

     Theophylline

     1.   Theophylline used chronically may benefit COPD patients by means of bronchodilation and other effects
          including imp rovement of respiratory muscle strength.
     2.   Limited evaluation of COPD exacerbation has not demonstrated a definitive ro le for introduction of
          theophylline in acute COPD exacerbations. Theophylline is unlikely to be indicated in moderate COPD
          exacerbation.
     3.   If the patient is already taking theophylline, it would be prudent to measure a plasma theophylline
          concentration and if low (less than five µg/ ml) addit ional dosing can be given to achieve therapeutic levels
          (5 to 12 µg/ml). Assuming 100 percent bioavailability, the oral loading dose (mg) of short -acting
          theophylline required to reach a concentration of 10 µg/ml equals (10 - plas ma concentration in g/ml) x 0.5
          body weight in kg (vo lu me of d istribution is 0.5 L/ kg).

     EVIDENCE

     Aminophylline did not add any observable benefit when added to standard multidrug therapy in hospi talized
        patients: Rice 1987. LE=B, SR=IIa
     Aminophylline did not add any measurable or symptomatic benefit with a trend to decreasing admission rate in
        ED patients: Wrenn 1991. LE=B, SR=IIa

J.   Is Patient’s Condi tion Improved and Patient is Able to Go Home?
     OBJECIVE

     To identify patients who can go home

     ANNOTATION

     The following should be considered in evaluating the possibility of discharge:
     1. Patient clinical condition has improved.
     2. Patient has adequate support system at ho me.
     3.   Patient is able to continue necessary therapy at home (e.g., o xygen supply)

K. Has Patient Condition Improved in 1 to 3 Days?

     OBJECTIVE

     Identify imp rovement in COPD exacerbation.




                                         Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 57
                                                                                            VHA/DoD Clinical Practice Guideline



    ANNOTATION

    Ev idence of imp rovement of COPD exacerbation includes:

    1.   Decrease in cough, sputum production or dyspnea.
    2.   Decrease in respiratory rate.
    3.   Decrease in heart rate.
    4.   Increase in function and endurance.

L. Slowl y Taper Intensity of Medicati on(s) to Baseline Maintenance Regimen

    OBJECTIVE

    Initiate appropriate reduction in medicat ions in order to return to maintenance levels.

    ANNOTATION

    1.   Once the patient is stabilized, with improvement in the level of function, reduce intensity of the
         bronchodilator reg imen down to the usual level of t reat ment over the course of a few days.
    2.   Tapering of corticosteroids depends on the prior history of use and tapering, but often is done over one to
         two weeks. This can be done in consultation with the primary care provider.
    3.   The provider should see the patient soon to ensure that the course of action is appropriat e and for
         consideration of any further therapy such as smoking cessation, or changes in pharmacotherapy in view of
         the recent exacerbation.




                                        Outpatient Management of COPD: Acute Exacerbation (A1) - Expanded Annotations - Page 58
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

         OUTPATIENT MANAGEMENT: Pharmacotherapy (A2)



            ALGORITHM AND EXPANDED ANNOTATIONS
                            VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Pharmacotherapy (A2) - Algorithm
                                                                                               VHA/DoD Clinical Practice Guideline



                     CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                 Outpatient Management of COPD: Pharmacotherapy (A2)

A. Patient wi th COPD Requiring Pharmacotherapy


   This algorith m outlines the criteria for the med ication treat ment of COPD. The aim of therapy is to use those
   med ications needed to maintain control and imp rove function and quality of life with the least risk for adverse
   effects. The medicat ion plan for COPD is summarized in Table I.

                                                  Table II. Step Care In COPD
   Step                Symptoms and FEV1                                                  Therapy
        1      Asymptomat ic AND                               Smoking cessation, vaccination, employ education. No
               FEV1 > 50 percent of p redicted (1)             med ication indicated.
     2a        Sympto ms less than daily AND                   Smoking cessation, vaccination, employ education.
               FEV1 > 50 percent of p redicted (2)             Inhaled short-acting beta2 -ag onist (2 puffs PRN up to 12
                                                               puffs/day)
     2b        Asymptomat ic AND                               Smoking cessation, vaccination, employ education.
               FEV1 < 50 percent of p redicted                 Inhaled anticholinergic (2 puffs qid)
                                                               Consider use of inhaler containing a short acting beta 2 -
                                                               agonist and an anticholinergic.
     2c        Sympto ms less than daily AND                   Smoking cessation, vaccination, employ education.
               FEV1 < 50 percent of p redicted                 Inhaled anticholinergic (2 puffs qid)
               OR                                              Short-acting beta2 ag onist (2 puffs PRN up to 12
                                                               puffs/day)
               Daily sympto ms
                                                               Consider use of inhaler containing a short acting beta 2 -
                                                               agonist and an anticholinergic.
        3      Sympto ms not controlled (2)                    Increase dose of both:
                                                               Inhaled anticholinergic (2 to 6 puffs qid) and
                                                                inhaled short-acting beta2 agonist (2 to 4 puffs PRN up
                                                               to 12 puffs/day)
        4      Sympto ms not controlled (2)                    Consider adding long-acting inhaled beta2 -agonist. (3)
        5      Sympto ms not controlled (2)                    Consider adding theophylline tri al (slow release
                                                               theophylline adjusted to level of 5 to 12 µg/ ml) (4)
        6      Sympto ms not controlled (2)                    Consider adding corticosteroi d tri al (prednisone 40 to 60
                                                               mg po qd or h igh dose inhaled steroids (5).
                                                               Consider specialist consultation.
        7      Sympto ms not controlled (2)                    Refer to specialist promptly.

   1.       Spiro metry is essential to confirm the presence of airflo w obstruction (low FEV1 and FEV1 / VC rat io). Base
            therapy on symptoms, but consider alternate diagnoses (heart disease, pulmonary emboli, etc.) if out of
            proportion to spirometry.
   2.       Use the lowest level of therapy that satisfactorily relieves symptoms and maximizes activity level. Assure
            compliance and proper use of medications before escalating therapy.
   3.       Inhaled long acting beta 2 -agonists should not be used as rescue therapy. Short-acting inhaled beta 2 -agonist
            (less than 12 puffs/day) may continue to be used PRN. Nighttime sympto ms are frequently better controlled
            with long-acting inhaled beta 2 -agonist. Oral beta 2 -agonists are associated with a higher rate of side effects,
            and should be reserved for patients who cannot take inhaled beta 2 -agonist medications.




                                             Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 59
                                                                                           VHA/DoD Clinical Practice Guideline



     4.   Theophylline should be used with caution because of potential for severe side effects. Nighttime respiratory
          symptoms are frequently controlled but theophylline may lead to insomnia. Theophylline should be
          discontinued if a sympto matic o r objective benefit is not evident within several weeks.
     5.   A corticosteroid trial o f prednisone (40 to 60mg/day) 10 to14 days, or high dose inhaled steroids
          (equivalent to 880 µg or more of fluticasone or 800 µg or more of budesonide) of 14 to 21 days can help
          identify patients who may benefit fro m long term steroid use. Responders to oral steroids should transition
          to the lowest effective dose of inhaled steroids, or to the lowest effective dose of a combination of inhaled
          and oral steroids, if possible, to avoid the long term co mplications of systemic co rticosteroids. If oral
          steroids are used other than for an acute exacerbation, obtain spiro metry prior to and after trial to confirm
          an objective response.


B. Are Symptoms occurring less frequentl y than daily and FEV1 is > 50% of predicted?

     OBJECTIVE

     To identify patients with COPD who may benefit fro m therapy.

     ANNOTATION

     1.   Typical daily sympto ms of COPD include exert ional dyspnea, wheezing, or cough. Chest tightness is
          common, but should be further evaluated to exclude co -existing heart disease. These symptoms may occur
          daily or less than daily, thus resulting in different med ication reco mmendations.
     2.   Routine use of ipratropiu m does not slow the rate of decline in pulmonary function in patients with mild
          COPD. Patients with symptoms less often than daily may be med icated as needed.
     3.   A trial of inhaled anticholinergic therapy is reco mmended in apparently asympto matic patients with an
          FEV1 of less than 50 percent of predicted, since this degree of obstruction is usually associated with
          dyspnea. A lack of sy mptoms may result fro m the patient avoiding activities and adapting to his/her
          disability, or fro m the assumption that dyspnea is part of the natural aging p rocess.
     4.   Asymptomat ic patients with an FEV1 less than 50 percent predicted may benefit fro m regular inhaled
          anticholinergic therapy without a short acting inhaled beta2 -agonist (SAIBA). Sy mpto matic patients in this
          category should be prescribed both a chronic anticholinergic inhaler or SAIBA as well as a beta 2 -agonist
          for prn use, especially prior to exertion.


     EVIDENCE

     Consensus recommendations on initiation of pharmacotherapy: American Thoracic Society 1995; European
        Respiratory Society, Siafakas 1995; British Thoracic Society 1997. LE=C, SR=IIa
     Ipratropium 36 µg tid for 5 years did not affect the rate of decline in FEV 1 : The Lung Health Study,
         Anthonisen 1994. LE=A, SR=I

C.   Short Acting Inhaled Beta2 -Agonists


     OBJECTIVE

     To init iate or adjust appropriate prn therapy with SAIBA.

     ANNOTATION

     1.   Short acting beta 2 -agonists are available in M DI, dry powder inhalers, nebulizer and oral forms. They can
          improve function and quality of life.




                                          Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 60
                                                                                          VHA/DoD Clinical Practice Guideline



   2.   Short-acting selective inhaled beta 2 -agonists such as albuterol are preferred for prn use because of
        demonstrated efficacy, rap id action, and selective action on airways. The short -acting adrenergic agents
        have similar efficacy, though inhaled beta2 selective agents should be favored for lo wer side effect profiles.
   3.   SAIBA should be prescribed for prn use in most symptomatic patients with COPD. The usual maximu m
        dose in stable patients is 12 puffs per day for short-acting agents such as albuterol, metaproterenol or
        terbutaline. Patients who have not responded to greater than maximu m doses such as 12 to 20 puffs over
        three to four hours during an acute exacerbation of COPD should seek medical attention.
   4.   Sympto ms may imp rove without substantial improvement in FEV1 , indicating that continuation of therapy
        does not depend on routine assessment with spiro metry. For example, SA IBA and ipratropiu m can
        improve exercise performance without necessarily improving FEV1 .
   5.   SAIBA, but not ipratropium, may increase the alveolar-arterial o xygen difference, and this may be a reason
        to decrease the dose of beta2 -agonist while titrat ing a patient’s medicat ion.

   EVIDENCE

   Metaproterenol inhalation (5 puffs) led to an improvement in the 12 -minute walk that was not present with
      placebo. Spirometry was not improved: Berger 1988. LE=C, SR=I
   Terbutaline (2 puffs = 500 µg) decreased breathlessness: Pino-Garcia 1996. LE=B, SR=IIa
   Albuterol (270 µg) decreased breathlessness with exercise: Belman 1996. LE=B, SR=I
   Pirbuterol and ipratropium produced similar increases in FEV 1 . Pirbuterol increased the [A-a] O2 difference:
       Ashutosh 1995. LE=B, SR=I
   Significant dose-related improvement in spirometry with inhaled albuterol. One mg as a single dose offered
       most benefit versus side effects: Vathenen 1988. LE=B, SR=I
   Average dose of albuterol inhalation for optimal improvement was 430 µg (range up to 800 µg) and for
       terbutaline was 1,160 µg (range up to 2.5 mg): Jaeschke 1993. LE=B, SR=I

D. Inhaled Anticholinergics

   OBJECTIVE

   To init iate or adjust appropriate therapy with inhaled anticholinergics.

   ANNOTATION

   1.   Ipratropiu m bro mide, the prototype anticholinergic bronchodilator, is available as a metered dose inhaler
        (MDI) or as a nebulizer solution.
   2.   Ipratropiu m bro mide has similar, or according to some studies, greater efficacy than SAIBA. It has a slower
        onset of action, a longer duration of action, and minimal systemic absorption. It may cause fewer systemic
        side effects than beta 2 -agonists. For these reasons, it is preferred as a regularly scheduled inhaled
        bronchodilator.
   3.   In patients with COPD, ipratrop iu m bro mide at peak effect typically increases the FEV1 by 0.15 to 0.35 L.
        At high doses, ipratropiu m bro mide can improve exercise tolerance.
   4.   The starting dose of ipratropiu m should be at least two puffs tid. Use of typical reco mmended doses of
        ipratropiu m (two puffs qid) produces less than maximal bronchodilation. Improvement in pulmonary
        function is maximal at 6 to 14 puffs as a single dose of ipratropiu m. If sy mptoms do not resolve with two
        to four puffs qid, up to six and possibly eight puffs qid may be needed. Imp rovement in level of function
        and in activities in daily living can be used to guide therapy. The risk of to xicity at h igher doses appears to
        be relatively lo w co mpared to inhaled beta 2 -agonists.
   5.   The sequence of admin istration of ipratrop iu m and SAIBA does not generally make any difference in the
        bronchodilator benefit.



                                         Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 61
                                                                                          VHA/DoD Clinical Practice Guideline




    EVIDENCE

    Baseline FEV1 and FVC increased within 90 days after ipratropium initiation : Rennard 1996. LE=B, SR=IIa
    Ipratropium 40 µg qid (2 puffs) or metaproterenol 1.5mg qid by inhalation were equally efficacious and safe
        over a 90-day period: Tashkin 1986. LE=A, SR=I
    No difference between 200 µg albuterol (2 puffs) and 40 µg ipratropium in magnitude, but duration was 1 hour
        longer with ipratropium on day 85: Co mbivent 1994. LE=A, SR=I
    Ipratropium produced more and longer bronchodilation than did albuterol : Braun 1989. LE=B, SR=IIa
    The distance walked was greater with 7 days of albuterol (180 µg, 2 puffs) or ipratropium (36 µg) qid (2 puffs);
        also dyspnea was less with albuterol: Blosser 1995. LE=B, SR=IIa
    Of 80 responsive patients in a group of 100, 16 responded only to albuterol; 17 responded only to ipratropium;
        and 47 responded to both: Nisar 1992. LE=C, SR=IIa
    Between 6 and 14 puffs of ipratropium (240 µg) produced maximum increase in pulmonary function: Ikeda
        1995. LE=B, SR=I
    160 µg of ipratropium(8-9 puffs) is needed to give maximum benefit in pulmonary function and to give any
        benefit at all with exercise: Ikeda 1996. LE=B, SR=I
    0.4 mg of nebulized ipratropium provided a maximum response in pulmonary function. Suggested this was
         equivalent to 160 µg (8-9 puffs) from MDI: Gross 1989. LE=B, SR=IIa

E. Combination Therapy with Inhaled Anticholinergics and Short Acting Beta 2 -Ag onists


    OBJECTIVE

    To init iate or adjust appropriate therapy with a co mbination of inhaled SAIBA.

    ANNOTATION

    1.   Patients with COPD whose symptoms are inadequately controlled with the reco mmended doses of either an
         inhaled short acting inhaled beta 2 -agonist or ipratropium should be treated with a co mbination of both
         inhaled agents. The combination at reco mmended doses provides added symptomatic benefit without
         incurring the risk of to xicity fro m using very high doses of single agents.
    2.   SAIBA may be added to ipratropium as regularly s cheduled medications, typically two to four puffs qid, as
         well as additional p rn dosing, to a usual reco mmended maximu m of 12 puffs per day. Demonstration of an
         acute improvement in FEV1 is not necessary in order to obtain clin ical benefit. The lack of an immediate
         bronchodilator response should not preclude a clinical trial of these medications.
    3.   As the dose of ipratropiu m or inhaled SAIBA increases, the added benefit becomes less fro m the other
         agent, but some patients will have an added benefit even with high doses of each. There is no way to
         predict, other than in a trial of therapy, wh ich patients will have this combined effect.
    4.   A product that dispenses 90 µg albuterol and 18 µg ipratropiu m per puff fro m one metered dose inhaler is
         available co mmercially (Co mb ivent ™). This should not generally be used as a first line agent, but may
         provide enhanced compliance and resultant benefit in patients who require co mbination therapy. Patients
         taking a regularly scheduled combination inhaler should continue to use a SAIBA for breakthrough
         symptoms.




                                         Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 62
                                                                                             VHA/DoD Clinical Practice Guideline



     EVIDENCE

     80 µg ipratropium (4 puffs) plus 400 µg (4 puffs) albuterol was better than 40 µg or 80 µg ipratropium plus
         200 µg albuterol in improving FEV 1 : Ikeda 1995. LE=C, SR=I
     There was no added benefit of doubling the ipratropium dose or adding 1,300 µg of inhaled metaproterenol.
         Two of 12 patients benefited from this combination: LeDou x 1989. LE=B, SR=I
     40 µg ipratropium plus 200 µg inhaled albuterol yielded a greater increase in pulmonary function than did
         either 40 µg ipratropium or 200 µg albuterol: Co mbivent 1994. LE=A, SR=I
     120 µg of ipratropium or 800 µg of albuterol gives maximal bronchodilation in a single dose. Some patients
         may benefit from combination: Easton 1986. LE=B, SR=IIa
     200 µg ipratropium added to 5 mg terbutaline or 500 µg terbutaline added to 200 µg ipratropium improved
         pulmonary function: Newnham 1993. LE=C, SR=IIa

F.   Consider Addi ng Long-Acting Inhaled Beta2 -Ag onist


     OBJECTIVE

     To init iate or adjust appropriate therapy with long acting in haled beta2 -agonists.

     ANNOTATION

     1.   The long acting inhaled beta 2 -agonist, salmeterol (2 puffs or 50 µg bid), is an effective bronchodilator in
          COPD patients, and has been approved for use in COPD.
     2.   Salmetero l produces a similar peak bronchodilator response to SAIBA, but the onset is delayed. The
          bronchodilator effect is prolonged compared to short-acting agents. This has the potential to produce more
          consistent control of symptoms than SAIBA in some patients.
     3.   Chronic use is not associated with significant tachyphylaxis, and may decrease the need for rescue use of
          SAIBA.
     4.   Strong evidence for symptomat ic benefit of salmeterol over other regularly inhaled short acting
          bronchodilators in patients with COPD is not currently available. Thus, its place in the sche me of therapy
          is not well defined at this time. It may be considered for patients whose need for SAIBA exceeds 8 to 12
          puffs daily.
     5.   The princip le advantage of salmeterol is its long duration of action, which may be of benefit in treating
          nocturnal dyspnea. Additionally, enhanced compliance with a t wice daily rather than qid regimen may
          provide smoother symptomatic control.
     6.   Because the onset and duration of action are both prolonged compared to SAIBA, salmetero l should not be
          used for prn, rescue use. Patients should be educated to continue to use SAIBA prn.
     7.   Oral fo rms of beta 2 -agonists may be useful in patients who cannot use any inhaled form, although such
          cases are rare. The risk of systemic adverse reactions is increased significantly with oral beta 2 -adrenergic
          bronchodilators.
     8.   Inhaled salmeterol should be continued only in those patients who experience symptomatic benefit fro m its
          addition to their regimen.

     EVIDENCE

     Four weeks of 50 µg bid (or 2 puffs) salmeterol led to an increase in FEV 1 : Grove 1996. LE=B, SR=I
     16 weeks of treatment with 50 µg bid salmeterol added to existing regimen improved FEV 1 and symptoms:
         Boyd 1997. LE=A, SR=I




                                           Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 63
                                                                                           VHA/DoD Clinical Practice Guideline



    16 weeks of 50 µg bid (but not 100 µg bid) salmeterol improved health related quality of life: Jones 1997.
        LE=A, SR=I
    Salmeterol acute dose response curve plateaus at 50 µg: Cazzola 1995. LE=B, SR=I
    4 weeks of 50 µg bid salmeterol improved peak flow and symptoms: Ulrik 1995. LE=A, SR=I
    Combination of salmeterol (50 µg) and ipratropium was no different than either alone for peak effect; duration
       was similar to that for salmeterol: Matera 1996. LE=B, SR=IIb
    Single-dose 50 µg salmeterol caused more prolonged acute bronchodilation than 200 but not 400 µg
        oxitropium inhaler: Cazzo la 1998. LE=B, SR=IIa

G. Consider Theophylline Tri al


    OBJECTIVE

    To init iate or adjust appropriate therapy with oral theophylline.

    ANNOTATION

    1.   Theophylline can be added to improve pulmonary function, sympto ms, or activ ities in patients with COPD
         who do not achieve adequate symptom control with inhaled bronchodilators.
    2.   Many theophylline preparations are availab le, but sustained release formulat ions may provide longer
         control and better benefit for nocturnal dyspnea.
    3.   Theophylline has a narrow therapeutic index, with the potential for dose related adverse reactions that
         include insomn ia, an xiety, nausea, vomit ing, tremor, arrhythmias, deliriu m, seizures, and death.
    4.   Typical starting doses are 400-600 mg daily, but blood levels should be measured carefully at the start of
         therapy. The therapeutic target for most patients should be a blood level of 10 µg/ ml (range 5 -12 µg/ ml).
         In some cases, if benefit has been demonstrated and with careful mon itoring, a blood level of 15 µg/ ml of
         theophylline can be a therapeutic target. However, with an increase in concentrations over 12 µg/ ml, the
         risk to benefit ratio increases, especially in o lder patients. After initial stability, repeat levels should be
         obtained when symptoms change, acute illness develops, potentially interacting drugs are added, non -
         compliance is suspected, dose adjustments are made, or sympto ms suggestive of toxicity develop.
    5.   Drug interactions with theophylline are co mmon, and may either increase or decrease theophylline
         metabolism. All changes in medical reg imens should be evaluated for p otential impact on theophylline
         levels.
    6.   Theophylline should be continued only in patients who demonstrate a symptomatic benefit, such as
         improved dyspnea or exercise tolerance. The improvement in function fro m theophylline may not be
         evident in pulmonary function testing. However, therapy should be discontinued in patients who
         demonstrate no subjective or objective improvement after several weeks of theophylline therapy.


    DISCUSSION

    Mechanisms of Benefit

    EVIDENCE
    Theophylline is usually a bronchodilator: Fragoso 1993. LE=A, SR=I
    Mucociliary clearance improved in some patients: Fragoso 1993. LE=C, SR=IIa
    Some patients have an improvement in respiratory muscle performance: Fragoso 1993. LE=B, SR=IIa
    Generally consistent improvement in function of the right heart: Fragoso 1993. LE=C, SR=IIa
    Theophylline may increase respiratory drive: Ashutosh 1998. LE=B, SR=IIa



                                          Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 64
                                                                                           VHA/DoD Clinical Practice Guideline




    Theophylline Therapy

    EVIDENCE

    Two months of theophylline at 14.8 µg/ml led to less dyspnea, an increase in PaO 2 , a decrease in PaCO2 , and
       an increase in vital capacity and FEV 1 : Murciano 1989. LE=A, SR=IIa
    Pulmonary function and exercise performance were improved on 9.5 mg/L of theophylline: Newman 1994.
        LE=B, SR=IIa
    17 mg/L improved pulmonary function and symptoms: McKay 1993. LE=B, SR=IIa
    Withdrawal of theophylline (11 mg/L) led to a decline in pulmonary function, an increase in symptoms, and less
        distance in the 6-minute walk test: Kristen 1993. LE=A, SR=IIa
    Theophylline at 12.2 mg/L improved FVC 1 , MVV, and exercise: Fin k 1994. LE=B, SR=IIa
    Higher awake PaO2 , lower awake PaCO2 , higher sleep SaO2 ,, improved FEV1 , and lower trapped gas
        volume were seen with a theophylline level of 11.8 mg/L: Mulloy 1993. LE=B, SR=IIa
    Theophylline (14.2 mg/L) improved FEV 1 ; SaO2 increased during non-rapid eye movement (NREM) sleep.
        There were fewer arousals; sleep architecture was unaffected: Berry 1991. LE=B, SR=IIa
    Twice-a-day theophylline (15 µg/ml) improved FEV 1 more than once a day (11 µg/ml). No effect on arterial
        saturation or sleep architecture: Martin 1992. LE=B, SR=IIa
    Theophylline (9.2 µg/ml) improved pulmonary function, reduced nocturnal wheezing, and improved nocturnal
        saturation. Sleep quality unaffected: Man 1996. LE=B, SR=IIa

    Theophylline Combinati on Therapy

    EVIDENCE

    Theophylline (12.5 mg/L) significantly improved FEV 1 and PEF (daily) to a small degree, even after the
        inhalation of salbutamol and ipratropium: Nishimura 1993. LE=B, SR=IIa
    In combination with 400 µg salbutamol qid and 80 µg (or 4 puffs) ipratropium qid, theophylline (15 mg/L) had
         a small additive effect on FEV 1 and PEF: Thomas 1992. LE=B, SR=IIa
    Theophylline (12.9 mg/L) and salbutamol improved pulmonary function; the combination was better than either
        alone: Thomas 1992. LE=B, SR=IIa
    Combination theophylline (12 to 18mg/L), albuterol, and ipratropium improved pulmonary function more than
       did theophylline and albuterol or ipratropium alone: Karpel 1994. LE=A, SR=IIa

H. Consider Corticosteroi d Trial

    OBJECTIVE

    To init iate or adjust appropriate therapy with corticosteroids in patients with COPD.

    ANNOTATION

    1.   Unlike the high response rate seen in asthma, in patients with COPD a response to chronic oral
         corticosteroid use is beneficial in less than about 20 to 25 percent. The benefit fro m inhaled ste roids is not
         precisely defined.
    2.   Patients on maximal bronchodilator therapy who have not had a satisfactory response may be considered
         candidates for a corticosteroid trial. An objective measure of imp rovement should be sought in all patients



                                          Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 65
                                                                                             VHA/DoD Clinical Practice Guideline



      undergoing a steroid trial. A response may be defined as an imp rovement in symptoms and an increase in
      FEV1 of > 20 percent fro m baseline. An objective measurement of the steroid effects can only be obtained
      in patients who are otherwise stable.
3.    A typical trial o f ora l prednisone is 40 to 60 mg/day for 10 to 14 days. There is less published experience
      with high-dose inhaled steroids, but in some patients this may be a reasonable alternative. The appropriate
      dose of inhaled steroids has not been determined, but a trial for 14 to 21 days of the equivalent of
      beclomethasone 1500 µg/day (30 puffs) or fluticasone 880 µg /day has been suggested.
4.    Patients who show no objective response to a steroid trial should have their steroids promptly discontinued.
      Patients who have a response should be tapered to the lowest possible dose. Supplementation or
      substitution with a high-dose inhaled steroid may allow further reduction or d iscontinuation of the oral
      steroid.
5.    Adverse effects of oral cort icosteroids are numerous and include: hyp ertension, hyperglycemia, weight
      gain, immunosupression, skin thinning, personality, purpura, mental status changes, depression, glaucoma,
      cataracts, and adrenal suppression. Patients requiring long-term steroids should be evaluated for risk of
      osteoporosis and preventive measures instituted, such as calciu m and vitamin D supplements, weight -
      bearing exercise and hormone replacement therapy if appropriate. The risks of long -term t reat ment should
      be discussed with the patient.
6.    The role of chronic inhaled corticosteroids in COPD remains under investigation. Preliminary work
      suggests that chronic inhaled steroid use may slow the rap id decline in FEV1 typically seen in patients with
      COPD. Response to an oral steroid trial, as well as a brisk bronchodilator response may help identify
      patients who will respond better to inhaled steroids.
7.    The use of MDI spacers and rinsing of the mouth after drug use is recommended to help improve drug
      delivery to the lung and avoid local co mp licat ions, such as hoarseness or oral can didiasis.


DISCUSSION

                            Table II. Comparati ve Dosing Of Inhaled Corticosteroi ds
     Inhale d Steroid   Dose per puff    Dose per puff     Maximum        High Dose (1)         Comments            # Puffs/
                         (µg) (PDR)       (µg) (PDR)       Dose (PDR)      (puffs/day)                              canister
                        (Released from    (Available to    (puffs/day)
                            valve)          patient)
 Triamcinolone               200              100              16             > 20        Built-in spacer            240
 Flunisolide                N/A               250               8             >8          Spacer can be used         100
 Beclomethasone              50                42              20             >20         Spacer can be used         200
 Beclomethasone              100               84              10             >10         Spacer can be used         120
 Fluticasone                 50                44              40             >12         Spacer can be used        60-120
 Fluticasone                 125              110              16             > 6         Spacer can be used         120
 Fluticasone                 250              220               8             >3          Spacer can be used         120
 Budesonide                  200              160               8             > 3         Dry powder inhaler         200
                                                                                          No spacer necessary
(1) NAEPP, Expert Panel Report 2 for asthma

EVIDENCE

Oral steroid meta-analysis: 10 percent of patients with COPD using oral steroids (30 to 80 mg/day or
    equivalent prednisone) had a 20 percent improvement in FEV 1 : Callahan 1991. LE=A, SR=I
Alternate-day oral steroids (64 mg) as effective as daily oral steroids (8 mg qid): Blair 1984. LE=A, SR=I
Equal or more than 7.5 mg/day oral prednisolone slows decline of FEV 1 and improves survival in severe
   COPD: Postma 1985. LE=C, SR=IIa




                                         Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 66
                                                                                           VHA/DoD Clinical Practice Guideline



     7.5 mg/day oral prednisolone or more decreases decline in FEV 1 in moderately severe COPD: Postma 1988.
         LE=C, SR=IIa
     40 mg/day of prednisolone added to inhaled beclomethasone of 1,500 and 3,000 µg/day did not further improve
         pulmonary function: Weir 1993. LE=A, SR=IIa
     It can take more than 2 weeks to reach maximum benefit from oral (40 mg prednisolone) or inhaled (1,500 µg
          beclomethasone) steroids: Weir 1990. LE=A, SR=I
     Emphysema and nonemphysema COPD respond similarly to oral prednisolone (40 mg/day) and inhaled
        beclomethasone (1,500 µg/day): Weir 1991. LE=B, SR=I
     20 of 100 subjects responded to 30 mg prednisolone for 2 weeks, 17 of whom responded to ipratropium or
         albuterol and 3 of whom were nonresponders: Nisar 1992. LE=C, SR=IIa
     Inhaled beclomethasone (1,500 µg/day) produced 2/3 the response of oral prednisolone. Response to oral
         correlated with response to inhaled steroid: Weir 1990. LE=A, SR=I
     Response to high-doses inhaled beclomethasone (1,500 g/day) predicts which patients will respond to oral
         prednisolone (30 mg/day): Wardman 1988. LE=C, SR=IIa
     Addition of oral prednisolone (30 mg/day) produces further improvement in responders to inhaled
         beclomethasone (1,500 g/day): Wardman 1988. LE=C, SR=IIa
     Meta-analysis: More than 800 µg of inhaled beclomethasone or budesonide was required for improvement in
        pulmonary function or symptoms: Van Schayck. LE=B, SR=IIa
     Two years of 800 µg/day of budesonide plus either albuterol or ipratropium reduced the decline in FEV 1 and
        improved symptoms: Do mpeling 1993. LE=C, SR=IIa
     800 µg/day of budesonide for 12 weeks decreased cough but did not improve any other measure or symptom:
         Engel 1989. LE=B, SR=IIa
     Two years of budesonide at 1,600 µg/day improved symptoms, and there were fewer dropouts for pulmonary
        reasons compared to placebo: Ren kema 1996. LE=A, SR=IIa
     Six weeks of 800 µg/day of budesonide improved 5 of 8 beta2-agonist acute responders and 1 of 22
         nonresponders to beta2-agonist: Weiner 1995. LE=B, SR=IIa
     Inhaled fluticasone (500 µg bid) for 6 months improved FEV 1 , peak flow, 6 minute walk, symptoms and severity
         of exacerbations: Paggiaro 1998. LE=A, SR=IIa

I.   Review Precauti ons and Recommendations for Medicati ons?

     OBJECTIVE

     To apply precautions and educate patients about the use of medicat ions.

     ANNOTATION

     Method of administering aerosols

     1.   Metered-Dose Inhalers (MDI).
          a. Inhaled bronchodilators are preferred to oral med ications to reduce the risk of systemic adverse effects.
          b.   Ensure proper education and technique in the use of MDIs (see DISCUSSION).
          c.   Use spacers as required to enhance drug delivery.
          d.   Emphasize the maximu m dos es of bronchodilators to avoid overuse.
          e.   Educate the patient to use bronchodilators before exercise.
          f.   Co mpliance declines when inhaler regimens become co mp licated.




                                          Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 67
                                                                                       VHA/DoD Clinical Practice Guideline



     g.   Consider other drug delivery systems (such as dry powder inhalers) if patient cannot use MDI w ith
          spacer.

2.   Small Volu me Nebulizer.
     a. There is little ev idence that nebulizer delivery offers improvement in control over adequate MDI
        delivery fo r management of the stable COPD patient.
     b. Situations where a nebulizer is preferable include difficulty in manag ing a MDI (with spacer) due to
        impaired hand strength or dexterity, visual impairment, cognitive problems, or severe dyspnea.

3.   Precautions when using beta 2 -agonists.
     a. Inhaled beta 2 -agonists may cause tremor, increased heart rate, insomnia, restlessness, hypokalemia, or
         a paradoxical reduction in arterial o xygenation.
     b. Avoid overuse. Check number of metered dose inhalers (M DIs) used per month against number of
         puffs per MDI (200 to 300+, depending on brand).
     c.   Instruct patients on maximu m nu mber of puffs per day (usually 8 to 12) and on number allowed during
          an exacerbation (e.g., 12 to 24 over 3 to 4 hours) before additional intervention is required.
     d.   If a long-acting agent is used for maintenance therapy, educate the patient that only SAIBA should be
          used for breakthrough symptoms.
     e.   Ho me nebulizers with inhalant solutions providing large dosages are rarely needed.

4.   Precautions when using ipratropium
     a. Inhaled ipratropiu m may cause dry mouth or increased heart rate, or exacerbate glauco ma, benign
         prostatic hypertrophy or other conditions potentially worsened by the drug’s anti-cholinergic act ivity.
     b.   Patients should generally use a spacer and should avoid spraying into eyes.
     c.   Caution patients that onset of effect is relatively slo w co mpared to SAIBA, and that addition al doses
          should not be taken for acute symptom relief.
     d.   In general, dose related systemic side effects of inhaled anticholinerg ics are less severe when using
          ipratropiu m than those produced by inhaled beta 2 -agonists.

5.   Precautions when using theophylline.
     a. Theophylline has dose related side effects that include insomnia, an xiety, nausea, vomiting, tremo r,
         arrhythymias, deliriu m, seizures, and death.
     b.   Drug interactions with theophylline are co mmon, and all changes in a patient’s medical regimen
          should be reviewed fo r their potential impact on seru m theophylline levels.
     c.   Initiate treat ment with a low dose (e.g., 400 mg/day) and adjust after a few days.
     d.   Aim fo r a seru m level o f 5 to 12 µg/ ml; ad just dosage and follow serum level when indicated.
     e.   Check the seru m level of theophylline when sympto ms change, acute illness develops, new drugs are
          added, or symptoms suggestive of toxicity develop.
     f.   Reduce dosage if drug clearance is likely to be impaired because of illness, liver malfunction, or
          concomitant drugs.
     g.   Instruct patients not to take additional theophylline preparat ions.
     h.   Theophylline should be taken at the same time each day with respect to meals.
     i.   Attempts to withdraw theophylline, even at lo wer p lasma levels, should be done cautiously, since
          deterioration in pulmonary function and exercise performance may occur.

6.   Precautions when using oral corticosteroids.
     a. Adverse effects of oral cort icosteroids include hypertension, hyperglycemia, weight gain, personality
         changes, depression, immunosuppression, glaucoma, cataracts, skin thinning, purpura, osteoporosis,




                                      Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 68
                                                                                        VHA/DoD Clinical Practice Guideline



          osteonecrosis, and adrenal supression. In general, side effects are more co mmon with prolonged
          therapy.
     b.   Reduce dosage to lowest effective daily dose or to alternate-day dosing as quickly as symptoms allow.
     c.   Admin ister stress dose steroid therapy to patients with severe illness or injury who have received
          prolonged oral corticosteroid treatment. Adrenal insufficiency may extend fo r up to a year fo llo wing
          the discontinuation of steroids.
     d.   Prevent or treat osteoporosis with calciu m, vitamin D, hormone replacement therapy or other therapies
          as appropriate for patients on prolonged oral corticosteroid therapy.

7.   Precautions when using inhaled corticosteroids.
     a. Adverse effects of inhaled corticosteroids include oral candid iasis, hoarseness, and possible adrenal
         suppression at high doses.
     b. Instruct patients to use a spacer and rinse the mouth after use to decrease the likelihood of local
         complications.
     c.   Be aware that systemic effects of corticosteroids may occur in skin, bon e, eyes, and other organs,
          especially with the use of high dose inhaled corticosteroids.
     d.   Stress dose oral or intravenous corticosteroids may be necessary in some patients with severe illness or
          injury who have been treated with high dose inhaled corticosteroids.
     e.   Seek object ive evidence of the value of this therapy, because its use may decrease compliance with
          other aerosol usage.
     f.   When introducing aerosol steroids in a patient taking an oral steroid, wean slowly off the oral drug.

DISCUSSION

Metered dose inhaler technique (Newman 1984).
1. Remove the cap and shake the inhaler thoroughly.
2.   Breathe out slowly.
3.   Hold the inhaler upright.
4.   Place the mouthpiece two cm (appro ximately t wo fingers) in front of the lips. (Placing the mouthpiece
     between the lips with the teeth and tongue out of the way is also acceptable.) The use of a spacer instead is
     highly reco mmended.
5.   Press down on the inhaler while inhaling slowly and deeply.
6.   Hold the breath for 10 seconds, if possible.
7.   Breathe out slowly through nose or pursed lips.
8.   Take one puff at a t ime. Pause at least 20 seconds before the next inhalat ion.

EVIDENCE
Precautions when using pharmacotherapy: ATS 1995. LE=C, SR=IIa
MDI technique: Newman 1984. LE=C, SR=IIa
52 percent used an MDI once or less daily rather than the required three times daily: Rand 1995. LE=C, SR=I
Adherence with intermittent positive pressure breathing (IPPB) or nebulizers was 50.6 percent: Turner 1995.
    LE=C, SR=I
Maximum bronchodilation was similar between nebulizer and MDI beta2 -agonist. Nebulizer dose of twice MDI
    dose to produce same effect: Mestitz 1989. LE=B, SR=I
Dose of nebulized albuterol producing the same bronchodilation was about 10 times higher than with MDI:
    Jenkins 1987. LE=B, SR=I
No difference in outcome between nebulizer and MDI. Nebulized metaproterenol dose was about seven times
    higher than with the MDI: Turner 1988. LE=B, SR=I




                                      Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 69
                                                                                          VHA/DoD Clinical Practice Guideline



    It takes about 12.5 times as much nebulized albuterol to achieve the same increase in FEV 1 as with an MDI:
         Harrison 1983. LE=B, SR=I

                                             ADDITIONA L REFERENCES

Ashutosh K; et al. Effects of theophylline on respiratory drive in patients with chronic obstructive pulmonary
    disease. J Clin Pharmacol 1997 Dec; 37(12):1100-7
Boyd G; et al. An evaluation of salmetero l in the treatment of chronic obstructive pulmonary disease (COPD). Eur
    Respir J 1997 Apr; 10(4):815-21
Cazzola M; et al. Effects of fo rmoterol, salmeterol or o xitropiu m bro mide on airway responses to salbutamol in
    COPD. Eur Respir J 1998 Jun;11(6):1337-41
Newman SP; Clarke SW. The proper use of metered-dose inhalers. Chest 1984; 86:342-3
Paggiaro PL; et al. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with
    chronic obstructive pulmonary disease. International COPD Study Group . Lancet 1998 Mar 14;351(9105):773-
    80
Veterans Health Administration. The pharmacologic management of chronic obstructive pulmonary disease.
    Depart ment of Veterans Affairs Veterans Health Administration Publication No. 980012, Nov 1998.




                                         Outpatient Management of COPD: Pharmacotherapy (A2) - Expanded Annotations - Page 70
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

 OUTPATIENT MANAGEMENT: Long-Term Oxygen Therapy (A3)



             ALGORITHM AND EXPANDED ANNOTATIONS
                                        VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: - Long-Term Oxygen Therapy (A3) - Algorithm
                                                                                          VHA/DoD Clinical Practice Guideline



                CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                      Outpatient Management of COPD: Long-term Oxygen Therapy (A3)

A. Patient wi th COPD on Maxi mal Medical Therapy and Stable for 30 Days


   OBJECTIVE

   In chronic obstructive pulmonary disease (COPD), patients with hypoxemia and cor pulmonale, long -term
   oxygen therapy (LTOT) may increase the life span by six to seven years. Mortality is reduced in patients with
   chronic hypoxemia when o xygen is administered for mo re than 12 hours daily and greater survival benefits
   have been shown with continuous oxygen admin istration.

   ANNOTATION

   Patient should be on maximal med ical therapy and stable for 30 days before decisions about LTOT are made.
   Short-term o xygen may be instituted in the interim. In addit ion to treating acute exacerbations, therapy to
   correct anemia and congestive heart failure should be instituted. In tensify smoking cessation efforts, since
   smoking poses a safety hazard for patients on LTOT. The benefits of long -term o xygen therapy may not be
   realized in patients who continue to smoke and have high levels of carbo xyhemoglobin.

   EVIDENCE

   LTOT prolongs life in hypoxemic patients, with greater benefit with 24-hr/day than 12-hr/day therapy: Medical
      Research Council, 1981; Nocturnal Oxygen Therapy Trials 1980. LE=A, SR=I. Timms 1981; Levi-
      Valensi 1986. LE=C, SR=I


B. Are There Signs of Tissue Hypoxia?


   OBJECTIVE

   To identify patient with signs of tissue hypoxia who may benefit fro m LTOT.

   ANNOTATION

   Occasionally severe dyspnea with exercise is the result of arterial o xygen desaturation. Evaluation of saturation
   during exercise should be performed in COPD patients with such dyspnea.

   Signs of tissue hypoxia include:

   1.   Hct greater or equal 55.
   2.   "p" pulmonale on electrocardiogram (ECG) or other evidence of pulmonary hypertension.
   3.   Impaired mental status.
   4.   Cor pulmonale.

C. Is PaO2  55 mm Hg?


   OBJECTIVE

   To identify hypoxemia.




                                Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Expanded Annotations - Page 71
                                                                                          VHA/DoD Clinical Practice Guideline



   ANNOTATION

   Based on a randomized controlled trial (NOTT 1980), long -term o xygen therapy of COPD patients with a PaO2
    55, or a PaO2  60 with signs of tissue hypoxia, is associated with improved survival. Although pulse
   oximetry can be used to exclude hypoxemia, measurement of resting PaO 2 after 30 minutes of breathing room
   air is the clinical standard for init iating LTOT. Oximetry may be used to adjust oxygen flow settings over time.

   EVIDENCE

   Pulse oximetry is less accurate than arterial blood gases to determine oxygenation, especially during exercise:
       Carone 1997; Carlin 1994; McGovern 1996; ATS 1995; Pierson 1990. LE=C, SR=I


D. Institute Long -Term, 24-Hour Oxygen Therapy


   OBJECTIVE

   To define the goals of o xygen therapy.

   ANNOTATION

    The precise PaO2 level to improve quality of life or increase survival has not been well defined. Arterial
   oxygen saturations of 90 to 92 percent or PaO2 of 60 to 65 mmHg are usual acceptable targets because of the
   shape of the oxygen hemoglobin saturation curve. A mbulatory patients should be provided ambulatory and
   stationary oxygen equip ment to reach the target of use 24 hours a day to correct PaO 2 greater or equal 60 or
   SaO2 greater or equal 90 percent. Immob ile patients may only require a stationary system with a portable
   system for use during transport. In most cases, changes in flo w rate are not indicated for sleep and exercise.
   Some authorities reco mmend increasing flow rates by one liter per minute to treat possible desaturation during
   sleep, but evidence for this approach is not strong. If there are signs of cor pulmonale despite adequate daytime
   oxygenation, the patient may be mon itored with o ximetry during sleep to determine the best sleep setting.
   Some patients may be candidates for o xygen-conserving devices (e.g., reservoir cannulae, demand o xygen
   delivery device, transtracheal oxygen) to improve mobility and portability of o xygen therapy.

   EVIDENCE

   Oxygen-conserving devices may reduce costs and increase patient mobility: ATS 1995; Petty 1994. LE=C,
      SR=IIa.

E. Order Overnight Oxi metry and/ or Exercise Oximetry

   OBJECTIVE

   To identify patients with PaO2 desaturation who may benefit fro m LTOT.

   ANNOTATION

   It is unusual that patients with COPD and a PaO2 of 70 at rest to desaturate low enough to require o xygen.
   During exercise, noninvasive pulse oximetry may be inaccurate, particu larly in patients with poor peripheral
   perfusion. Verification of o ximetry accuracy can be accomp lished by obtaining ABG before and after exercise.
   The level of exercise tested should be appropriate to the patient's normal or anticipated level o f activ ity.

   In COPD patients who have PaO2  60 mmHg during wakefu lness, signs of tissue hypoxia occur mo re often
   and survival is reduced when sleep desaturation is present (more than five minutes during the night). However,
   studies documenting imp roved outcome with o xygen supplementation during sleep have yet to be conducted.


                                Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Expanded Annotations - Page 72
                                                                                            VHA/DoD Clinical Practice Guideline



     One night of overnight o ximetry is sufficient to determine the present of arterial o xygen desaturation during
     sleep. Such desaturation can occur as the patient's COPD evolves with t ime and the overnight oximetry may
     need to be repeated at regular intervals (such as six months to yearly) in patients who have or develop an
     indication.

     EVIDENCE

     Nocturnal oxygen therapy in patients who have daytime PaO2 60 mmHg with nocturnal desaturation of less
          than 90%: Fletcher 1989, 1992a, 1992b. LE=C, SR=IIa
     Exercise desaturation does not predict nocturnal desaturation: Baldwin 1995. LE=C, SR=IIa
     A diffusing capacity greater than 55% of predicted was 100% specific in excluding exercise desaturation
          compared with 82% specificity for FEV 1 > 55% of predicted: Owens 1984. LE=C, SR=IIa
     One overnight oximetry is sufficient to diagnose nocturnal desaturation in stable COPD patients: Vos 1995.
          LE=C, SR=IIa


F.   Arrange for Long-Term Oxygen Therapy During Sleep and/ or Exercise


     OBJECTIVE

     To discuss the benefits of oxygen therapy.

     ANNOTATION

     Studies showing the long-term benefit of o xygen solely for exerc ise or sleep desaturation have yet to be
     conducted. Short-term studies have shown more immediate benefits in reduction in dyspnea, improvement in
     exercise performance, and prevention of transient increases in pulmonary artery pressure and pulmonary
     vascular resistance. Oxygen should be admin istered to increase SaO 2 to greater than 90 percent. To maximize
     mobility, liquid or light tanks such as those made fro m alu minum are preferable for use during exercise.

     EVIDENCE

     Oxygen during exercise provides short-term physiologic benefits, reduces dyspnea, and improves exercise
         tolerance at submaximal workloads: McDonald 1995; ATS 1995; Light 1989; Zack 1985. LE=C, SR=IIa
     Lightweight portable ambulatory equipment should be used for patients who are able and will ing to be active:
         Petty 1994. LE=C, SR=IIa

G. Continue Medical Care and Follow-up


     OBJECTIVE

     To continue with appropriate fo llo w up of o xygen therapy.

     ANNOTATION

     Patients started on oxygen therapy at the time of an exacerbation require reevaluation within one to three
     months when stable. For patients started when stable on maximal med ical therapy, LTOT most likely
     represents a lifetime co mmit ment. Reevaluation every 12 months is appropriate to assess for continued need
     and adequacy of flow rate. Res ults of O2 saturation greater than 90 percent should not be used as a sole
     rationale fo r discontinuing therapy.




                                  Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Expanded Annotations - Page 73
                                                                                         VHA/DoD Clinical Practice Guideline



   EVIDENCE

   Increased PaO2 after 6 months LTOT may be due to reparative effect of LTOT : Su mmary conference report
       1990; O'Donohue 1991. LE=C, SR=IIa

H. If AB Gs are Available, Is PaCO2  45 mmHg?

   OBJECTIVE

    Identify COPD patients with hypercarbia and its relationship to hypoxia.

   ANNOTATION

   Hypercapnia during the day predicts a high prevalence of sleep desaturation even in patients who have PaO 2 60
   mm Hg during wakefu lness. Noninvasive ventilation for treat ment of nocturnal hypoventilation for chronic
   home use has been investigated but unproven and is not endorsed for general use.

   EVIDENCE

   Hypercapnia (PaCO2 greater than 45) during the day predicts a high prevalence of nocturnal arterial oxygen
      desaturation: Littner 1980; Fletcher 1991; Douglas 1990; Mulloy 1995; Vos 1995. LE=C, SR=I
   NPPV+ nocturnal O2 improved ABGs, sleep efficiency, quality of life, respiratory muscle function : Meecham
      Jones 1995; Gigliotti 1994; Elliott 1994; A mbrosimo 1992. LE=B, SR=IIa
   NPPV + nocturnal O2 did not improve ABGs, sleep efficiency, quality of life, respiratory muscle function: Lin
      1996; Stru mpf 1991; Shapiro 1992; Gay 1994: LE=B, SR=IIa




                               Outpatient Management of COPD: Long-term Oxygen Therapy (A3) - Expanded Annotations - Page 74
        CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

                  CHRONIC OBSTRUCTIVE PULMONARY DISEASE

OUTPATIENT MANAGEMENT: Preoperative Evaluation and Management (A4)



                       ALGORITHM AND EXPANDED ANNOTATIONS
                                                   VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Algorithm
                                                                                             VHA/DoD Clinical Practice Guideline



                  CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

               Outpatient Management of COPD: Preoperati ve Eval uation and Management (A4)

A. Does Condition Require Emergency Surgery?

    OBJECTIVE

    To refer patients who need emergency surgery.

    ANNOTATION

    In-hospital respiratory specialist or intensivist should be notified for perioperative care, but emergency
    surgeries, including repair of femoral neck and hip fractures, should not be held up pending consultation.

B. Inform Physician in Charge of Postoperati ve Care of COPD Conditi on. Stress Need for IV
   Corticosteroi ds if Patient is on Systemic Steroi ds

    OBJECTIVE

    To ensure proper care for the patient at risk.

    ANNOTATION

    Determine who m to call when emergency surgery is performed. An in -house respiratory specialist should be
    notified for perioperative care. If the patient is on systemic steroids, switch to IV steroids using hydrocortisone
    300 mg/day or an equivalent.

C. Is This a Minor Surgery Requiring Local Anesthesia?

    OBJECTIVE

    To determine need for patients undergoing local anesthesia for minor surgery.

    ANNOTATION

    Admin istration of local anesthesia presents a very low risk, even in the presence of severe COPD. In clin ically
    stable patients with mild or moderate COPD, a phone inquiry about exacerbation might suffice. Pu lmonary
    function test (PFT) is not required.

    EVIDENCE

    Cataract surgery is very low risk even with COPD: Go zu m 1992. LE=C, SR=IIa
    Ophthalmic procedures carry a low (< 1 percent) mortality rate: ATS 1995. LE= C, SR=IIa

D. Obtain Pul monary Function Tests, Arterial Bl ood Gases

    OBJECTIVE

    To obtain spirometry values to guide the decision about preoperative care.

    ANNOTATION

    There is no universal opinion on the value of pulmonary function testing preoperatively. A common opinion is
    that when a preoperative evaluation of a patient about to undergo elective CABG surg ery suggests lung disease,

                              Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Annotations - Page 75
                                                                                              VHA/DoD Clinical Practice Guideline



     simp le spiro metry can better characterize the nature of the patient’s pulmonary problems and aid in the decision
     about appropriate preoperative med ical therapy (Zibrak et al. 1993). One study (Wong 1995) showed that low
     FEV1 predicted postoperative complications such as prolonged ICU stay, prolonged hospital stay, prolonged
     mechanical ventilat ion, and pneumonias, but this study involved only patients with severe COPD (FEV1 < 1.2
     L), with mixed surgical sites. On the other hand, other studies (Kroenke 1993) have shown that pulmonary
     function testing does not predict perioperative complications.

     EVIDENCE

     Spirometry does not predict postoperative complications: Kroenke 1993. LE=B, SR=IIb
     Spirometry cannot be performed reliably in the presence of abdominal pain: Hall 1991b LE=C, SR=IIb
     FEV1 < 0.75 L raises the risk of prolonged ICU stay and FEV 1 /FVC < 0.5 raises the risk of all postoperative
         pulmonary complications, such as pneumonia and prolonged hospital stay: Wong 1995. LE=B, SR=IIb
     Spirometry can aid in the decision about appropriate perioperative care: Zibrak 1990. LE=C, SR=IIb

E. Obtain Chest X-Ray

     OBJECTIVE

     To identify patients at risk for developing co mplications.

     ANNOTATION

     Chest X-ray should be done preoperatively in patients with an established diagnosis of COPD who may require
     general anesthesia, since an abnormal chest X-ray is a predictor of perioperative comp licat ions in thoracic and
     major abdo minal surgery. A preoperative chest X-ray in patients for non-cardiothoracic surgery is sensible,
     because patients with COPD are at increased risk of pulmonary neoplasm (ATS Gu idelines 1995).

     EVIDENCE

     Abnormal chest x-ray is predictive of perioperative pulmonary complications (defined as CXR showing
        hyperinflation, nodules or masses, hilar fullness, or interstitial changes): Kroenke 1993. LE=A, SR=I
     COPD clients have an increased risk of pulmonary neoplasm: ATS 1995. LE=C, SR=IIb

F.   Is FEV1 < 35 Percent of Predicted?

     OBJECTIVE

     To identify patients who are likely candidates for surgery based on pulmonary function tests.

     ANNOTATION

     Severe chronic obstructive pulmonary disease (FEV1 < 0.75 L) is a predictor of prolonged ICU stay.
     FEV1 /FVC predicts postoperative complicat ions. See Evidence for Annotation D.

G. Refer to Pul monary S pecialist

     OBJECTIVE

     To determine when a pulmonary consult is indicated.




                               Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Annotations - Page 76
                                                                                              VHA/DoD Clinical Practice Guideline



     ANNOTATION

     Patients should be referred to a respiratory or thoracic specialist prior to scheduling of a lung resection. In some
     cases, for examp le in patients with mild COPD and a solitary pulmonary nodule, the patients can be referred
     directly to a thoracic surgeon.

H.   Is PaCO2 > 45?

     OBJECTIVE

     To determine risk factors for postoperative pulmonary co mplications.

     ANNOTATION

     Hypercapnia is an independent ris k factor fo r patients with moderate to severe COPD who are having upper
     abdominal or thoracic surgery.

     EVIDENCE

     PaCO2 > 45 mmHg poses higher surgical risk: ATS 1995. LE= C, SR=IIb
     A high PaCO2 indicates a need for intense and careful preoperative support: Celli 1993. LE=C, SR=IIb

I.   Is Surgery on Upper Abdomen or Thorax?

     OBJECTIVE

     To determine wh ich patients are at high risk for postoperative pulmonary co mplications based on type of
     surgery.

     ANNOTATION

     The guidelines for the A merican Thoracic Society (1995) state that upper abdominal surgery poses a risk of
     postoperative pulmonary comp licat ions for all patients. Upper abdo minal surgery shifts the respiratory pump
     fro m the diaphrag m to the accessory muscles, due to a non pain -related reflex. Non imperative upper
     abdominal surgery such as cholecystectomy should be avoided in patients with moderate to severe COPD. If
     surgery is necessary, provide careful anesthesia. Another potential way to decrease operative risk may be to
     perform the procedure laparoscopically.

     EVIDENCE

     Thoracic or upper abdominal surgery is high-risk in patients with moderate to severe COPD: ATS 1995.
          LE=C, SR=I
     Shift in respiratory pump activity from the diaphragm to other muscles: Fo rd 1993. LE=C, SR=I
     Upper abdominal incision is a risk factor for postoperative pulmonary complications: Hall 1991. LE=A SR=I


J.   Preoperati ve Management

     OBJECTIVE

     To determine preventive measures for postoperative pulmonary co mplications.




                               Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Annotations - Page 77
                                                                                        VHA/DoD Clinical Practice Guideline



ANNOTATION

COUNSEL TOBACCO USE CESSATION

There is evidence that stopping cigarette smoking two months before surgery reduces perioperative
complications. For smo kers quitting less than eight weeks preoperatively, no such evidence exists, but
consensus exists that quitting even immed iately before surgery could be beneficial (Celli 1993).

EVIDENCE

Stopping cigarette smoking 8 weeks preoperatively reduces pulmonary complications: Warner 1989, 1984.
    LE=C, SR=IIb
Every effort should be made to have the patient stop smoking : Celli 1993. LE=C, SR=IIb

ADMINISTER POSTOPERATIVE SUBCUTA NEOUS HEPARIN

Postoperative subcutaneous heparin is useful for prophylaxis for pulmonary embo li, and should be considered
strongly in patients who start with limited pulmonary reserve.

EVIDENCE

Subcutaneous heparin reduces fatal pulmonary emboli: Collins 1988. LE=B, SR=I

INCENTIVE SPIROM ETRY RESPIRATORY CARE

Arrange for postoperative incentive spirometry o r controlled deep breathing and cough.
Deep breathing and controlled cough with or without incentive spirometry should be done postoperatively.

EVIDENCE

Incentive spirometry can reduce hospital stay: ATS 1995. LE=C, SR=I




                         Outpatient Management of COPD: Preoperative Evaluation and Management (A4) - Annotations - Page 78
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

  OUTPATIENT MANAGEMENT: Management of Air Travel (A5)



            ALGORITHM AND EXPANDED ANNOTATIONS
                      VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: Air Travel (A5) - Algorithm
                                                                                          VHA/DoD Clinical Practice Guideline



              CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                       Outpatient Management of COPD: Management of Air Travel (A5)


A. Patient wi th Stable COPD Planning Air Travel

   OBJECTIVE

   The algorith m emp loys the most practical and least invasive methods to apply current recommendations
   regarding o xygen supplementation during flight.

   ANNOTATION

   Co mmercial airliners can cruise at altitudes over 40,000 feet with their cabins pressurized fro m 6,000 to 8,000
   feet. Th is is equivalent to an inspired O2 concentration at sea-level of about 15 percent. Pat ients with severe
   COPD experience falls in their PaO2 that average 25 mmHg but may be mo re than 30 mmHg at 8,000 feet than
   at sea level. Since their sea level PaO2 values are on the steep part of the oxygen-hemoglobin dissociation curve,
   the fall in SaO2 with falls in PaO2 may be quite sharp. Altitude PaO2 is a co mmonly used marker to assess risk
   of air travel adverse effects on patients with COPD.

B. Is Patient Hypercapnic or On Long-Term Oxygen Therapy?

   OBJECTIVE

   To identify patients at increased risk for adverse physiologic effects of alt itude exposure. Determine factors
   that may influence health risks of exposure to decreased PiO 2 during air t ravel.

   ANNOTATION

   Identify patients who require specialist-level evaluation fo r advanced testing to determine whether supplemental
   oxygen is necessary and safe. Specialists will perform effect ive o xygen titration if required.

   DISCUSSION

   The mo rbidity and mortality due to in-flight hypoxemia in COPD patients are unknown. Cardiovascular and
   neurological events are mo re frequent than respiratory events. It seems reasonable to take the position that the
   effects of hypoxemia in COPD patients at altitude are most likely to be man ifest in the cardiovascular or central
   nervous system. Hence, greater caution should be exercised in correcting in -flight hypoxemia in COPD patients
   who have known cardiovascular disease or ischemic cerebrovascular disease. COPD patients vary in their
   ability to hyperventilate and decrease their PaCO2 in response to worsening hypoxemia. Hypercapnic persons
   have the least ability to hyperventilate in response to hypoxemia, and will may have more severe hypoxemia at
   altitude than eucapnic persons. In the presence of cerebrovascular or cardiovascular disease, it is prudent to
   recommend o xygen therapy for patients with predicted PaO 2 less than 60 mmHg during flight. This threshold is
   higher than that advised for COPD patients without these complications.

   Ventilatory response to enriched oxygen exposure varies in hypercapnic patients, some of who m may have
   decreased ventilation and increased hypercapnia upon exposure to increased oxygen concentrations. Predict ion
   equations do not apply to hypercapnic patients. For thes e reasons, individualized titrat ion of augmented flow
   rates in hypercapnic patients is advised. Supplementation is required during flight for all persons who are on
   long-term o xygen therapy. (See Module A5, Long-Term Oxygen Therapy). There are no studies of the range of
   augmentation required in th is population. Individual responses to the hypoxic environment and to o xygen
   supplementation are likely to be highly variable, due to variable ventilation perfusion parameters and other
   physiological factors in this group. Individualized t itration of supplemental o xygen dosing for LTOT is advised.
   Several methods may be used for this purpose.


                                               Outpatient Management of COPD: Air Travel (A5) - Expanded Annotations - Page 79
                                                                                         VHA/DoD Clinical Practice Guideline




   EVIDENCE

   Safety of air travel for cardiopulmonary patients with severe lung disease: Medical Gu idelines for Air Travel
       1996 (A SEM); Lien 1998. LE=B, SR=IIb
   Prediction of Altitude hypoxemia in COPD: Dillard 1989, 1993, 1995; Gong 1984; Naughton 1995. LE=B,
       SR=IIb
   Morbidity and mortality during air travel: Cu mmins 1988, 1989; Speizer 1989. LE=B, SR=IIb

C. Obtain Calculated Predicted PaO2 During Flight

   OBJECTIVE

   To determine whether the patient is at increased risk for potentially physiologically significant hypoxemia in a
   pressurized co mmercial aircraft.

   ANNOTATION

   As noted in Annotation A, predicted altitude hypoxemia serves as a parameter for decision-making regarding
   oxygen supplementation during air travel for ambu latory patients with stable COPD. Predict ion of altitude -
   induced hypoxemia can be acco mplished by several methods. Regression equations have been v alidated for this
   purpose. Individual variability in the populations studied for development of predict ion equations limits the
   applicability of the results in clin ical decisionmaking for patients with borderline values of predicted PaO 2 at
   altitude. Indiv idualized hypo xia inhalat ion testing is advised for these patients to determine whether
   supplemental o xygen therapy is advised during air travel. Hypobaric chamber testing, face mask hypoxic gas
   inhalation, Venturi mask nitrogen enriched gas, and normob aric hypoxic gas chamber methods have all been
   utilized for this purpose. Hypoxic gas mixture testing by face mask delivery has been shown to yield similar
   PaO2 decrements similar to those in hypobaric chamber testing, as has normobaric hypoxic gas chambe r
   exposure. These specialized hypoxia simu lation studies are available in appropriately equipped laboratories and
   are usually conducted under the direction of a pulmonary specialist.

   Regression equation predictions are applicable to the majority of COPD patients. These equations apply only to
   non-hypercapnic patients. There is good agreement between the regression equations. The PaO 2 at sea level
   (PaO2 SL), FEV1 percent predicted, and FEV1 /FVC ratio are the best independent predictors of the PaO2 during
   hypobaric chamber or hypo xic gas inhalation testing (PaO 2 Alt), accord ing to the following equation:

                      PaO2 Alt mmHg = 0.453 [PaO2 SL mmHg ] + 0.386 [FEV1 % pred] + 2.44
                                            (r = 0.847, p < 0.0001)

   Since FEV1 percent predicted and FEV1 /FVC influence PaO2 Alt, it is important to optimize FEV1 by
   pharmacotherapy before and during air t ravel. Table I provides the calculated values of PaO 2 Alt for given
   values of PaO2 SL in the range of 60 - 80 mmHg. If the PaO2 is > 80, the patient probably does not need oxygen
   for travel

                  Table 1. Predicted in flight PaO2 based on PaO2 at Sea Level and FEV1
        FEV1 % Predicted    100        90         80       70        60        50       40                           30
     PaO2            80         56.2       54.9       52.7        50.9         49.2        47.4        45.7         44.9
     at sea level    70         51.6       49.9       48.1        46.4         44.6        42.9        41.1         39.4
                     60         47.1       45.4       43.6        41.9         40.1        38.4        36.6         34.9




                                              Outpatient Management of COPD: Air Travel (A5) - Expanded Annotations - Page 80
                                                                                           VHA/DoD Clinical Practice Guideline



   EVIDENCE

   Predicting PaO2 at altitude from Pa O2 at ground level. Methods: Breathing Hypoxic gas mixtures at SL;
   exposure to simulated altitude in hypobaric chamber: Dillard 1989, 1993, 1995; Gong 1984; Naughton 1995.
   LE=B, SR=IIb

D. Is predicted PaO2 < 55?

   OBJECTIVE

   To identify appropriate dosing, titration, and delivery of supplemental o xygen for patients to minimize alt itude
   hypoxemia -related health risks and avoid potential adverse effects of increased oxygen concentration for
   hypercapnic patients.

   ANNOTATION

   Supplementation of o xygen for COPD patients who are eucapnic and without cardiac or cerebrovascular disease
   has been studied in several hypoxic environ ments with mult iple delivery systems. Nasal cannula (NC) and
   Venturi masks in a hypobaric chamber, NC in hypoxic gas inhalation trials, and NC in a normobaric hypo xic
   chamber have all been investigated. The sum of these studies suggests that most patients with moderate to
   severe COPD will have PaO2 values above 60 mmHg or 90 percent saturation by pulse oximet ry with 1 to 3
   liters of NC o xygen supplementation during simulated aircraft cabin environ mental exposure. When practical, a
   supplementation trial by one of these methods can be used to individualize dosing of oxygen. Emp iric dosing
   of two liters by NC utilizes common ly available equip ment and will allow an adequate supply for all but long -
   haul flights, with maintenance of PaO2 > 60 mmHg for most patients.

   A patient’s PaO2 during commercial air travel p redicted by regression equations to be borderline (51 to 54)
   should be individually evaluated. Indiv idual variability in the populations studied for development of
   prediction limits the applicability of the results for clin ical decision making in patient with "bo rderline" values
   of predicted PaO2 at altitude. Ind ividualized hypo xia inhalat ion testing is advised for these patients, to
   determine if supplemental o xygen therapy is advisable during air travel. Hypobaric chamber testing, face mask
   hypoxic gas inhalation, Venturi mask nit rogen enriched gas, and normobaric hypoxic gas chamber methods
   have all been utilized fo r this purpose. Hypoxic gas mixture testing by face mask delivery has been show to be
   cause similar PaO2 decrements as hypobaric chamber testing, s imilar to those in normobaric hypoxic gas
   chamber exposure.

   Patients with hypercapnia have not been included in the patient populations from wh ich prediction equations
   were developed. Therefore, these patients require indiv idualized hypo xia testing to determine whether
   supplemental o xygen is advised. If so, carefu l t itration of the additional flow rate should be accomplished prior
   to flight, with attention to the effect on ventilation. Specialized testing and titration of o xygen should be
   accomplished in an appropriately equipped laboratory with specialist supervision.

   EVIDENCE

   Published evidence regarding oxygen supplementation during flight: Berg 1992; Vohra 1993; Cramer 1996.
       LE=B, SR=IIb

E. Oxygen Supplementation Recommendations for Patients wi thout Hypercapnia, Cerebrovascular Disease,
   or Cardi ovascular Disease

   OBJECTIVE

   To identify patients at low risk and those at increased risk for adverse physiological effects of altitude exposure.




                                                Outpatient Management of COPD: Air Travel (A5) - Expanded Annotations - Page 81
                                                                                      VHA/DoD Clinical Practice Guideline



ANNOTATION

Some authors have chosen a predicted altitude PaO2 of 50 mmHg as the threshold below which supplementary
oxygen should be prescribed. However, this value is arbit rary, with no outcome studies to support it. Many
eucapnic COPD patients are well acclimated to hypoxemia and in altitude simulation te sts, many stable
eucapnic patients with COPD and no known heart disease are relatively asymptomat ic at rest. They do not
experience card iac arrhythmias and have good short-term tolerance to PaO2 values of 35 to 40 mmHg (Gong
1992). Exercise in this environ ment however, causes a further decline in PaO2 . Thus, the advising physician
must still rely largely on clinical evaluation, judg ment, and a history of successful flights in advising each
patient who wishes to fly. Several published recommendations sugg est that stable COPD patients without
cardiac or cerebrovascular disease who are predicted to have a PaO 2  50mmHg during flight require
supplemental o xygen. These recommendations seem practical, and prudent.

There is no reco mmendation or evidence sugges ts that stable COPD patients without cardiac or cerebrovascular
disease who are predicted to have a PaO2 > 50mmHg during flight require supplemental o xygen. Because of
considerable indiv idual variability in the prediction equation, a threshold of 55 mmHg for this method is
advised as a lower-limit threshold for this reco mmendation. Patients with a pred icted PaO 2 of 51 to 54 by
regression equation should therefore undergo individualized testing to determine their predicted alt itude PaO 2.

EVIDENCE

Published recommendations regarding oxygen supplementation thresholds: Gong 1992; Lien 1998; AMA
    Co mmission 1982; Medical Gu idelines for Air Travel – 1996 (ASEM ). LE=B, SR=IIb




                                           Outpatient Management of COPD: Air Travel (A5) - Expanded Annotations - Page 82
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

              OUTPATIENT MANAGEMENT: Insomnia (A6)



            ALGORITHM AND EXPANDED ANNOTATIONS
                       VHA/DoD Clinical Practice Guideline




Outpatient Management of COPD: - Insomnia (A6) - Algorithm
                                                                                             VHA/DoD Clinical Practice Guideline



                   CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                     Outpatient Management of COPD: Insomnia (A6)


A. Institute Sleep Hygiene Measures


   OBJECTIVE

    To educate the patient regarding proper sleep hygiene.

   ANNOTATION

   Institute sleep hygiene measures.

   1.    Ho meostatic drive for sleep :
         a. Avoid naps.
         b. Too much time in bed can decrease sleep quality on the subsequent night.
         c.   Exercise each day. It is best to finish exercise at least six hours before bedtime.
         d.   Take a hot bath for 30 minutes within two hours before bedtime. A hot drin k may help you relax as
              well as warm you.

   2.    Circadian factors:
         a. Keep a regular rising time seven days a week.
         b.   Do not expose yourself to bright light if you have to get up at night.
         c.   Get at least one-half hour of sunlight within 30 minutes after arising.

   3.    Drug effects:
        a.   Evaluate patient medicat ion profile for drug likely to cause insomnia (beta2-agonists, theophylline,
             oral steroids).
        b.    Stop tobacco use.
        c.    Avoid caffeine entirely fo r a 4-week trial period; limit caffeine use to no more than three cups before
              10 a.m. if caffeine cannot be stopped.
        d.    Avoid alcoholic beverages before bedtime.

   5.    Arousal in sleep setting:
        a.    Keep clock face turned away, and do not find out what time it is when you wake up at night.
        b.    Avoid strenuous exercise after six p.m.
        c.    Avoid eating or drinking heavily for three hours before bedtime. A light bedtime snack may help.
        d. If you have trouble with regurgitation, be especially careful to avoid heavy meals and spices in the
           evening. Do not retire too hungry or too full. Head of bed may need to be raised.
        e. Keep your room dark, quiet, well ventilated, and at a co mfortable temperature throughout the night. Ear
            plugs and eyeshades are OK.
        f. Have a non stressful bedtime ritual.
        g. Set aside a worry time other than bedtime.
        h.    Do not try too hard to sleep; instead, concentrate on the pleasant feeling of relaxation.
        i.    Use stress management in the daytime.
        j.    Avoid unfamiliar sleep environments.
        k.    Be sure the mattress is not too soft or too firm, and the pillow is of the right height and firmness.



                                                   Outpatient Management of COPD: Insomnia (A6) - Expanded Annotations - Page 83
                                                                                           VHA/DoD Clinical Practice Guideline



        l. An occasional sleeping pill probably is acceptable.
        m. Use the bedroom only for sleep or sex; avoid other activ ities that lead to prolonged arousal.

    EVIDENCE


    ASDA Practice Parameters for Indications for Polysomnography: ASDA 1997. LE=B, SR=I
    ASDA nosology of sleep disorders: ASDA 1990. LE=B, SR=I
    Sleep hygiene: Zarcone 1994. LE=C, SR=I

B. Initiate a Trial of Zol pi dem (5 mg/ qhs)


     OBJECTIVE

    To determine the effects of a therapeutic trial with zo lpidem.

    ANNOTATION:

    Hypnotics should be used only after other measures have been tried (see Annotation A) and should be used
    sparingly with close attention to the possibility of abuse and untoward side effects. If the decision is made to
    use a hypnotic, zolpidem is the first choice in patients with severe COPD (FEV1 < 50 percent predicted; SaO2 
    90 percent; and CO2 retention) since it has generally been shown to be safe when given repeatedly in these
    patients. If the patient snores habitually, all hypnotics must be used with great caution, as they may induce or
    exaggerate sleep apnea and hypopnea, even in asymptomat ic patients. If zo lpidem 5mg/qhs is not effective, the
    dose may be increased to 10mg/qhs.

C. Initiate a Trial of Tri azol am (0.125 mg/ qhs)


    OBJECTIVE

     To determine the therapeutic effects of a trial with triazolam.

    ANNOTATION

    Hypnotics may have adverse effects for patients with moderate to severe COPD. Triazolam has no obvious
    effect on respiration when used in single doses for patients with an awake supine SaO2 >90 percent and no
    carbon dioxide retention (PaCO2 < 45), and may be considered in addition to zo lpidem in such patients. If the
    patient has supine SaO2 < 90 percent, zolp idem is clearly the first choice; triazolam and other benzodiazep ines
    must be used with extreme caution. Other short-acting benzodiazep ines (e.g., temazepam) may substitute for
    triazolam based on availability, cost, and experience of the practitioner.

    EVIDENCE:

    Hypnotic use of single and multiple doses of 10 mg zolpidem is safe and efficacious in stable patients with
        severe COPD (mean FEV1 0.84L): Girault 1996. LE=B, SR=I
    Hypnotic use of single doses of 0.125 and 0.25 mg of triazolam is safe and efficacious in stable COPD patients
        without significant hypoxemia or CO2 retention: Timms 1988. LE=B, SR=I
    Triazolam and zolpidem are safe in patients with mild COPD (mean FEV 1 62% predicted): Steens 1993.
        LE=B, SR=I
    Flunitrazepam produced a reduction in PaO2 and an increase in PaCO2 ; Triazolam decreased minute
        ventilation; Zolpidem produced no significant changes in awake patients with very severe COPD (mean
        FEV1 32% predicted): Murciano 1993. LE=B, SR=I



                                                 Outpatient Management of COPD: Insomnia (A6) - Expanded Annotations - Page 84
                                                                                          VHA/DoD Clinical Practice Guideline




D. Follow-Up with Routine Care


   1.   Refer to respiratory specialist if sympto ms do not resolve as expected, if there are co mplications limiting
        therapy or if these recommendations do not readily apply to the patient.
   2.   If general measures and occasional hypnotics are unsuccessful, referral to a psychiatrist or sleep specialist.




                                                Outpatient Management of COPD: Insomnia (A6) - Expanded Annotations - Page 85
   CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

            CHRONIC OBSTRUCTIVE PULMONARY DISEASE

INPATIENT MANAGEMENT: Emergency Room and Hospital Ward (B1)



                 ALGORITHM AND EXPANDED ANNOTATIONS
                                            VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Emergency Room and Hospital Ward (B1) - Algorithm
                                            VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Emergency Room and Hospital Ward (B1) - Algorithm
                                                                                             VHA/DoD Clinical Practice Guideline



                    CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

               Inpatient Management of COPD: Emergency Room and Hos pital Ward Management (B1)

A.   Patient Presents with Acute Exacerbation of COPD

     DEFINITION

     An acute exacerbation of COPD is defined as an acute clinical deteriorat ion in a patient's respiratory status due
     to a worsening of the underlying COPD. Sy mptoms and signs of acute exacerbation of COPD include:

     1.   Increased dyspnea.
     2.   Tachycardia.
     3.   Increased cough.
     4.   Increased sputum production.
     5.   Change in sputum color or character.
     6.   Accessory muscle use.
     7.   Peripheral edema.
     8.   Develop ment of or increase in wheeze.
     9.   Loss of alertness.
     10. Loss of energy.
     11. Fever.
     12. Increased respiratory rate.
     13. Decrease in FEV1 or peak exp iratory flow.
     14. Worsening of arterial b lood gases or pulse oximetry.
     15. Chest tightness.

     EVIDENCE

     Definition of acute exacerbation: ERS, Siafakas 1995, BTS 1997. LE=C, SR=IIa

B. Does Patient Need Mechanical Ventilati on?

     OBJECTIVE

     To init iate immediate action for a patient with life-threatening acute respiratory failure due to acute
     exacerbation of COPD.

     ANNOTATION

     Decision to in itiate mechanical ventilat ion and tracheal intubation can be made prior to obtaining arterial blood
     gases. Advance directives should be considered prior to in itiating these supportive measures.

     1.   Indications for mechanical ventilation (invasive or noninvasive/BiPAP) include:

          a.    Severe respiratory or co mb ined respiratory and metabolic acidosis.
          b.    Sustained respiratory rate > 40 per minute.
          c.    Abnormal b reathing pattern suggestive of increased respiratory workload and/or respiratory muscle
                fatigue.
          d.    Depressed mental status.



                                 Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 87
                                                                                               VHA/DoD Clinical Practice Guideline



          e.   Severe hypoxemia.

     2.   Indications for tracheal intubation include:

          a.   Suspected airway obstruction.
          b.   Depressed mental status.
          c.   High risk of gastropulmonary reflu x and aspiration.
          d.   Difficulty managing secretions.

     EVIDENCE

     Mechanical ventilation and endotracheal intubation: ATS 1995. LE=C, SR=I

C. Ventilate and Perform CPR as Indicated

     OBJECTIVE

     To init iate immediate action for a patient who presents with life threatening acute respiratory failure due to
     acute exacerbation of COPD.

     ANNOTATION

     CPR should be performed according to Advanced Cardiac Life Support (ACLS) protocol. A physician with
     special expertise in crit ical care med icine should be consulted at this point. Care should be used to avoid
     complications of auto PEEP and acute respiratory alkalosis.

D.   Perform Clinical and Laboratory Evaluati on

     The crit ical elements of the clinical evaluation, adapted fro m both the ATS and ERS guidelines, include:

     1.   History:
          a. Baseline respiratory status.
          b.   Sputum volu me and characteristics.
          c.   Cough.
          d.   Duration and progression of symptoms
          e.   Dyspnea severity.
          f.   Exercise limitations.
          g.   Sleep and eating difficu lties.
          h.   Ho me care resources.
          i.   Ho me therapeutic regimen.
          j.   Sympto ms of co morbid acute and chronic conditions .

     2.   Clinical assessment:
          a. Temperature.
          b.   Respiratory rate.
          c.   Heart rate.
          d.   Cyanosis.
          e.   Accessory muscle use.
          f.   Edema.
          g.   Cor pulmonale.


                                   Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 88
                                                                                            VHA/DoD Clinical Practice Guideline



         h.   Bronchospasm.
         i.   Hemodynamic instability.
         j.   Altered mentation.
         k.   Parado xical abdo minal retract ions.
         l.   Use of accessory respiratory muscles.

    3.   Spiro metry (optional):
         a. Peak expiratory flow rate.
         b.   FEV1 .

    4.   Laboratory:
         a.   ABG.
         b.   Chest radiograph.
         c.   EKG.
         d.   Theophylline level (if applicab le).
         e.   WBC count.
         f.   Blood cultures if pneumonia.
         g.   Electrolytes.
         h.   BUN.
         i.   Glucose.

    EVIDENCE

    Comorbid conditions: ERS, Siafakas 1995. LE=C, SR=I
    Clinical and laboratory evaluation: ATS 1995 and ERS, Siafakas 1995. LE=C, SR=I

E. Complete Eval uation and Treatment of Comorbi d Conditi ons and Other Factors Contri buting to
   Exacerbation

    OBJECTIVE

    To identify co morbid conditions that are likely in patients with COPD, and might contribute to acute
    exacerbation and for which specific interventions should be considered.

    ANNOTATION

    Co morbid conditions that may impact upon the treatment of exacerbation of COPD include the following wh ich
    were adapted and modified fro m ERS table:


    1.   Congestive heart failure o r disturbances in cardiac rhythm.
    2.   Pneumonia.
    3.   Pulmonary embolism.
    4.   Spontaneous pneumothorax.
    5.   Inappropriate o xygen therapy.
    6.   Psychotropic drugs (hypnotics, tranquilizers, narcotics, etc.).
    7.   Drug allergy (penicillin, cephalosporin, etc.).



                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 89
                                                                                             VHA/DoD Clinical Practice Guideline



     8.   Metabolic disease (diabetes mellitus, electrolyte disorders such as hypophosphatemia, hypokalemia).
     9.   Poor nutritional status.
     10. Myopathy.
     11. Other acute illness (acute abdomen, GI hemo rrhage, CVA, etc.).
     12. Systemic use of corticosteroids.


     Some of these comorbid ities will require hospitalization.

     EVIDENCE

     Comorbid conditions: ERS, Siafakas 1995. LE=C, SR=I

F.   Admit to ICU

     OBJECTIVE

     To provide direct observation and 24-hour monitoring for patient with severe exacerbation.

     ANNOTATION

     ICU patients are treated the same as ward patients except for card iopulmonary monitoring and direct
     observation. A specialist in critical care medicine should be consulted for these patients.

G. Does Patient Meet ICU Admission Criteria?

     OBJECTIVE

     To identify patients who will benefit fro m special care.

     ANNOTATION

     Any of the following would pro mpt ad mission to the ICU for closer observation and monitoring (adapted and
     modified fro m A merican Thoracic Society guidelines).

     1.   Severe dyspnea that responds inadequately to initial emergency room therapy.
     2.   Confusion, lethargy, or respiratory muscle fatigue.
     3.   Persistent or worsening hypoxemia despite supplemental O 2 or severe or worsening of respiratory acidosis
          (pH < 7.30).
     4.   Required assisted mechanical ventilation, whether through means of tracheal intubation or noninvasive
          techniques.

     EVIDENCE

     ICU admission criteria: ATS 1995. LE=C, SR=IIa

H. Does Patient Meet Discharge Criteria?

     OBJECTIVE

     To establish criteria for d ischarge fro m the emergency roo m.



                                 Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 90
                                                                                            VHA/DoD Clinical Practice Guideline



     ANNOTATION

     Discharge criteria for patients with acute exacerbation of COPD (adapted and modified fro m A merican
     Thoracic Society guidelines):

     1.   Features of the severe exacerbation are resolved (see Annotation D).
     2.   Anticipated need for inhaled bronchodilators is not more frequent than every 4 hours and the patient is on
          oral med ication.
     3.   Reversible co mponent of airway obstruction, if present, is under stable control.
     4.   Patient or caregiver understands appropriate use of medications.
     5.   Follow-up and home care arrangements have been completed (e.g., vis iting nurse, o xygen delivery, meal
          provisions).
     6.   Patient, family, and physicians are confident that the patient can manage successfully.

     EVIDENCE

     Discharge criteria: ATS 1995. LE=C, SR=I

I.   Admit to Ward

     OBJECTIVE

     To establish criteria for ad mission to a general medical ward for acute exacerbation of COPD.

     ANNOTATION

     Indications for hospitalizat ion of patients with COPD (adapted and modified fro m A merican Thoracic Society
     guidelines):

     1.   Patient has acute exacerbation plus one or mo re of the fo llo wing:
          a. Inadequate response of symptoms to outpatient management.
          b. Inability to walk between rooms (patient previously mobile).
          c.   Inability to eat or sleep due to dyspnea.
          d.   Conclusion by family and/or physician that patient cannot manage at home and supplementary h o me
               care resources are not immediately available.
          e.   A high-risk co mo rbid condition, pulmonary (e.g., pneu monia) or non pulmonary.
          f.   Prolonged, progressive symptoms before emergency department visit.
          g.   Altered mentation.
          h. Worsening hypoxemia.
          i. New or worsening hypercarbia.
     2.   Patient has new or worsening cor pulmonale unresponsive to outpatient management.
     3.   A planned invasive surgical or d iagnostic procedure requires analgesics or sedatives that may worsen
          pulmonary function.
     4.   Co morbid conditions (e.g., steroid myopathy or vertebral compression fractures) have worsened pulmonary
          function.

     Other indicat ions for hospitalizat ion may apply to patients undergoing pulmonary rehabilitation.

     EVIDENCE

     Ward admission criteria: ATS 1995. LE=C, SR=IIa

                                Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 91
                                                                                             VHA/DoD Clinical Practice Guideline




J.   Is Patient Improving?

     OBJECTIVE

     To establish criteria for measuring a favorable response to treatment.

     ANNOTATION

     Improvement is indicated by:

     1.   Reduced dyspnea.
     2.   Decreased respiratory rate.
     3.   Improved air movement.
     4.   Decreased use of accessory muscles.
     5.   Improved peak exp iratory flow.
     6.   Improved FEV1 and/or ABGs.

K. Continue Treatment. Address Patient Needs

     OBJECTIVE

     To establish guidelines for tapering treatment fo r patients who are imp roving.

     ANNOTATION

     1.   Decrease frequency of inhaled beta 2 -agonists to every 4 to 6 hours (see Module B3).
     2.   Switch to MDI with spacers.
     3.   Switch fro m parenteral to oral med ication.
     4.   Titrate o xygen as per o xygen protocol (see Module B3).

L. Intensify Treatment

     OBJECTIVE

     To establish guidelines for treating patients who fail to respond to the initial t herapy (e.g., intensification of the
     management regimen)

     ANNOTATION

     1.   Consider using aerosol beta-agonists if MDI cannot be used effectively. (see Module B2).
     2.   Consider using IV steroids and/or antibiotics (see Module B2).
     3.   Titrate o xygen, using oxygen therapy (see Module B3).
     4.   Consider como rbidit ies or other contributory causes of COPD and treat.


M. Reassess in 30 Minutes. Consider S pecialist Consultati on

     OBJECTIVE

     To establish criteria for consultation by a specialist in chest med icine.




                                 Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 92
                                                                                      VHA/DoD Clinical Practice Guideline



ANNOTATION

1.   Patients who require more intensive treatment but do not require ICU ad mission should be considered for
     consultation with a pulmonary specialist.
2.   Repeated intensification of treat ment without improvement would warrant consultation with a pulmonary
     specialist.




                          Inpatient Management of COPD: Emergency and Hospital Ward (B1) - Expanded Annotations - Page 93
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE

           INPATIENT MANAGEMENT: Pharmacotherapy (B2)



            ALGORITHM AND EXPANDED ANNOTATIONS
                           VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Pharmacotherapy (B2) - Algorithm
                                                                                           VHA/DoD Clinical Practice Guideline



                  CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                               Inpatient Management of COPD: Pharmacotherapy (B2)

A. Can Patients Effecti vely Use Metered Dose Inhalers (MDI) wi th Spacers?


    OBJECTIVE

    To establish guidelines for the appropriate use and dosing of inhaled bronchodilators in the in -patient setting
    and to establish criteria for the use of a small-volu me nebulizers (SVN) versus metered dose inhaler (MDI) with
    spacer in the hospital setting.

    ANNOTATION

    Selective beta 2 -adrenergic agonists are first-line agents:

    1.   Aerosolization using a low-volu me nebulizer is generally the first mode used when the patient is severely
         dyspneic.
    2.   After the patient has stabilized and can use the MDI, there is no difference between using an MDI with a
         spacer and nebulized aerosolizat ion.
    3.   An optimal dosing schedule of beta 2 -agonists cannot be suggested.
    4.   Beta2 -agonists should be titrated to maximal effect.
    5.   Monitor closely for adverse effects of the larger-than-usual doses that are sometimes necessary to relieve
         airway obstruction.

    Selective beta 2 -agonists are less likely to cause tachycardia.

    Nebulizer aerosolization is used when the patient is severely dyspneic and can neither effectively breathe nor
    coordinate for effect ive MDI use. After the patient has stabilized and can use the MDI, there is no difference
    between using an MDI with a spacer compared with nebulized aerosolizat ion. The patient’s skill with MDI
    should be evaluated by demonstration.

    No large, well-done, rando mized, placebo-controlled clin ical trials have been conducted. Therefore, an optimal
    dosing schedule of beta 2 -agonists cannot be suggested. Beta 2 -agonists should be titrated to maximu m effect
    when possible, monitoring closely for adverse effects of the larger -than-usual doses that are sometimes
    necessary to relieve airway obstruction. Beta 2 -agonists have a reduced functional half-life in exacerbation of
    COPD and therefore, if tolerated, may be g iven every 30 to 60 minutes under close supervision (including EKG
    monitoring). High-dose beta2 -agonist treatment regimens have not been investigated widely in this patient
    population and should be used cautiously until results of more controlled clinical trials are availab le.




                                           Inpatient Management of COPD: Pharmacotherapy (B2) - Expanded Annotations - Page 94
                                                                                           VHA/DoD Clinical Practice Guideline




                                 Table 1. Medication for Acute Exacerbation of COPD

            Medication                  MDI Dose              Nebulizer Dose                Special Instructions
       Short Acting Beta2
       Agonists
      Albuterol                    3-4 puffs q½-2 h         2.5 mg q½-2 h

      Metaproterenol               3-4 puffs q½-2 h         10 –15 mg q½ -2 h         Deliver medication with
                                                                                      nebulizer if unable to use MDI
      Terbutaline                  3-4 puffs q½-2 h         N/A                       with spacer (1)


     Anticholinergics
       Ipratropiu m Bro mide        3-6 puffs q2-4h         500 µg q2-4h
     Systemic Steroi ds             Intravenous
       So lu medrol                 125 mg q6h x 72                                   Taper schuedule
                                    hours                                               Days 4-7: 60 mg oral
                                                                                      prednisone qd
                                                                                        Days 8-11: 40mg oral
                                                                                      prednisone qd
                                                                                        Days 12-15: 20 mg oral
                                                                                      prednisone qd
                                    Oral

       Prednisone                   40-60 mg q day
                                                                                      Taper off or change to qod
       Prednisilone                 30-50 mg q day                                    within 1 to 2 weeks
      Theophylline                  If on theophylline check level                    Aim fo r levels of 5 to 12 µg/ ml

    EVIDENCE

    Beta 2 -agonists use in AECOPD: Rebuck et al. 1987; Carpel et al. 1990. LE=A, SR=I
    Use nebulizer or MDI with spacer in AECOPD: Turner 1988; Berry et al. 1989; Maguire et al. 1991; Jasper
       1987. LE=A, SR=IIa
    Give beta 2 -agonists every 30 to 60 minutes if tolerated in AECOPD: A merican Thoracic Society 1995. LE=C,
       SR=I

B. Admi nister Corticosteroi ds


    OBJECTIVE

    To establish criteria for the use of corticosteroids.

    ANNOTATION

    Steroids should be given early in patients with acute exacerbation (A E) o f COPD. Studies demonstrating the
    benefits of corticosteroids in AE involved a s mall nu mber of patients and show small improvement in lung
    function. A VA cooperative trial (the SCCOPE trial) addressed the role of corticosteroids in AE, at the
    American Thoracic Society meet ing in 1998 indicating a benefit fro m the use of steroids in this clin ical
    situation. We believe corticosteroids are of benefit in AE and should be given early, particularly in patients
    with severe underlying lung function and in those with severe exacerbation. The reco mmend dose equivalents



                                           Inpatient Management of COPD: Pharmacotherapy (B2) - Expanded Annotations - Page 95
                                                                                         VHA/DoD Clinical Practice Guideline



   of at least 0.5 mg/ kg of methylprednisolone every 6 hours for at least 3 days.

   EVIDENCE

   Budesonide with oral prednisone: Morice et al. 1996. LE=A, SR=I
   Corticosteroids: Niewoehner et al. 1999. LE=A, SR=1
   Methylprednisolone: Emerson et al. 1989. LE=B, SR=I
   Methylprednisolone: Albert et al. 1980. LE=A, SR=I
   Oral prednisone: Thompson et al. 1996. LE=A, SR=I
   Oral Prednisone: Neiwohner et al. 1998. LE=A, SR=I

C. Consider Other Drug Therapies or Treatments as Indicated

   OBJECTIVE

   To identify the role of anticholinergic agents, theophylline, other pharmaco logic agents, and miscellaneous
   adjunctive agents/therapies.

   ANNOTATION

   1.   Anticholinergic agents may be valuable as additive or single agents particularly if the patient is intolerant
        of beta2 -agonist or has side effects, have s ignificant coronary artery disease or severe left ventricular
        dysfunction.
        High-dose ipratropriu m bro mide, although possibly effective, has not been studied in acute exacerbation of
        COPD. If the decision to use ipratropium is made, the fo llo wing dose is s uggested: 500 µg every six hours
        by nebulizer, or six to eight puffs every four hours by MDI with spacer.
   2.   Theophylline Use—There is inadequate evidence in the literature to reco mmend the routine use of
        theophylline or amce to exclude a benefit for selected patients. Toxicity occurs frequently in hospitalized
        patients and is associated with a pro longed stay. Clin icians who choose to use this agent must be
        thoroughly familiar with its metabolis m, drug interactions, and toxicity.
   3.   Other Parenteral Agents—Parenteral ad min istration of terbutaline or ep inephrine has a prompt effect but is
        accompanied by an increased risk for tachycardia and may be more arrhyth mogenic when co mpared with
        the inhaled route in theophylline in t reatment of acute exacerbation of COPD. However, there is also
        inadequate evidence. Since an increased potential for myocardial ischemia is an unintended consequence
        of parenteral adrenergic use, it cannot be recommended in adult patients with COPD. This is a particular
        concern in patients in whom cigarette use is a potent risk factor for both COPD and coronary artery disease.
        Terbutaline and epinephrine are not reco mmended.
   4.   Additional Therapies Treat ment Considerations —The follo wing measures lack adequate evidence to
        support their routine use in the management of acute exacerbation of COPD: directed coughing, chest
        physiotherapy, positive end-expiratory pressure, nasotracheal suctioning, systemic hydration beyond
        replacement to euvolumia, intermittent positive pressure breathing, bland aeros ol therapy and mucolytic
        therapy. Further research is indicated in these areas.

        The nutritional status of the patient is another important consideration. Care must be exercised so that
        patients receive adequate and appropriate nutrition during their stay. Also, patients should be encouraged
        to mobilize as soon as is practical. When confined to bed, range-of-motion exercises should be performed.
        Consider deep-vein thrombosis prophylaxis.

   EVIDENCE

   Additive effect of B2 -agonists and ipratroprium bromide in AECOPD: Chap man et al. 1985; Shrestha et al.
      1991; Rebuck et al. 1987; O'Driscol et al. 1989; Karpel et al. 1990. LE=A, SR=IIa



                                         Inpatient Management of COPD: Pharmacotherapy (B2) - Expanded Annotations - Page 96
                                                                                          VHA/DoD Clinical Practice Guideline



    Ipratroprium bromide alone is effective in acute exacerbation of COPD : Rebuck et al. 1987; Karpel et al. 1990;
       Lloberes et al. 1988. LE=A, SR=I
    Aminophylline: Rice et al. 1987; Wrenn et al. 1991. LE=B, SR=IIb
    Other parenteral agents: ATS 1995. LE=C, SR=II
    Directed coughing: ATS 1990, 1991, 1995. LE=C, SR=IIa
    Chest physiotherapy, percussion & vibration, postural drainage: ATS 1990, 1991, 1995. LE=C, SR=IIb
    Positive end-expiratory pressure: ATS 1995. LE=C, SR=IIb
    Nasotracheal suctioning (non-intubated): ATS 1990, 1991, 1995. LE=C, SR=IIb
    Mini-tracheotomy: ATS 1995. LE=C, SR=IIb
    Systemic hydration to euvolemia: ATS 1990, 1991, 1995. LE=C, SR=I
    Intermittent positive pressure breathing: ATS 1995. LE=C, SR=II
    Bland aerosol therapy: ATS, 1995. LE=C, SR=IIb
    Mucolytics: ATS 1995. LE=C, SR=IIb
    Relaxation techniques: ERS, Siafakas 1995; ATS 1990, 1991. LE=C, SR=IIb
    Control of breathing, pursed lip breathing, diaphragmatic breathing : ERS, Siafakas 1995; ATS 1990, 1991.
       LE=C, SR=IIb
    Nutritional intervention to achieve ideal body weight: ATS 1995; ERS, Siafakas 1995. LE=C, SR=IIa

D. Consider Anti biotics


    OBJECTIVE

    To identify criteria for using antibiotics in the treat ment of acute exacerbation of COPD.

    ANNOTATIONS

    Many patients with AE do well without antibiotic treatment. Ho wever, for patients whose exacerbation is
    associated with changes in sputum (quality, volu me, color) or fever, antib iotics are a reasonable treatment
    option. Patients who are older than 60 years or have severe underlying lung function are more likely to benefit
    fro m the use of antibiotics. In most studies, the choice of antibiotic was not important. Usually, the older, less
    expensive antibiotics, such as amo xicillin, trimethoprim-sulfamethoxazo le, and do xycycline, will suffice.
    However, the choice may be affected by the history of exacerbation in the individual patient and by the p attern
    of microbial resistance found in the community. It is important to keep the possibility of drug interactions in
    mind when selecting antibiotics. Th is should be a consideration for any patient on theophylline.

    EVIDENCE

    Antibiotics should be used in acute exacerbation of COPD with change in phlegm: Anthonisen et al. 1987;
       Pines 1968; Saint et al. 1995; ERS Consensus statement. LE=A, SR=IIa
    Use antibiotics for severe exacerbation only: Anthonisen et al. 1987; Balter et al. 1994; ATS 1995. LE=A,
       SR=IIa

    DISCUSSION

    Although there have been no reported studies comparing trials using IV antibiotics in COPD exacerbation,
    extrapolation fro m the outpatient studies cited makes it reasonable to expect a similar effect. In fact, for
    patients admitted to hospital for acute exacerbations of COPD, the justification for antib iotics theoretically
    increases with the severity of the acute exacerbation.




                                          Inpatient Management of COPD: Pharmacotherapy (B2) - Expanded Annotations - Page 97
                                                                                            VHA/DoD Clinical Practice Guideline




E.   Has the Patient’s Respiratory Status Improved?


     OBJECTIVE

     To establish criteria for measuring a favorable response to treatment.

     ANNOTATION

     Improvement is indicated by:

     1.   Reduced dyspnea.
     2.   Decreased respiratory rate.
     3.   Improved air movement.
     4.   Decreased use of accessory muscles.
     5.   Improved peak exp iratory flow, improved FEV1 and/or ABGs.


     Improvement is indicated by reduced dyspnea, decreased respiratory rate, improved air movement, and
     decreased use of accessory muscles. Ob jective measures such as peak exp iratory flow, FEV1 , and/or ABGs
     should demonstrate improvement. An elevated heart rate may indicate bet a2 -agonist toxicity.

F. Modify Treatment. Consider Tapering Medication.


     OBJECTIVE

     To establish guidelines for tapering treatment fo r patients who are imp roving.

     ANNOTATION

     1.   Decrease frequency of inhaled beta2-agonists to every four to six hours.
     2.   Switch to MDI with spacers.
     3.   Switch fro m parenteral to oral med ication.
     4.   Titrate o xygen per o xygen protocol (see Module B3).

G. Intensify Treatment.


     OBJECTIVE

     To establish guidelines for the treatment of patients who fail to respond to the initial thera py (e.g.,
     intensification of the management regimen).

     ANNOTATION

     1.   Consider using aerosol beta2 -agonists if M DI cannot be used effectively.
     2.   Consider using IV steroids and/or antibiotics.
     3.   Titrate o xygen, using oxygen therapy (see Module B3).
     4.   Consider como rbidit ies or other contributory causes of COPD and treat.


     Optimal dosing schedules for beta 2 -agonists cannot be recommended due to the lack of acceptable placebo -
     controlled clinical trials. Ho wever, beta 2 -agonists should be titrated to maximal effect when possible,



                                            Inpatient Management of COPD: Pharmacotherapy (B2) - Expanded Annotations - Page 98
                                                                                     VHA/DoD Clinical Practice Guideline



monitoring closely for adverse effects of the larger-than-usual doses that are sometimes necessary to relieve
airway obstruction. Beta 2 -agonists have a reduced functional half-life in exacerbation of COPD and therefore,
if to lerated, may be given every 30 to 60 minutes under close supervision (including EKG monitoring). High -
dose beta2 -agonist treatment regimens have not been investigated widely in this patient population and should
be used cautiously until results of better controlled clinical trials are available.




                                     Inpatient Management of COPD: Pharmacotherapy (B2) - Expanded Annotations - Page 99
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE



           INPATIENT MANAGEMENT: Oxygen Therapy (B3)

            ALGORITHM AND EXPANDED ANNOTATIONS
                           VHA/DoD Clinical Practice Guideline




Inpatient Management of COPD: Oxygen Therapy (B3) - Algorithm
                                                                                           VHA/DoD Clinical Practice Guideline



                   CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF COPD

                                Inpatient Management of COPD: Oxygen Therapy (B3)

              American Thoracic Society and European Respiratory Society guidelines were relied upon in
              devising this algorithm. A paucity of well-designed trials in this area mandated the use of
              consensus.

A. Using Oxi metry, Titrate O2 by Venturi Mask or Nasal Cannula (24 to 35 Percent) to 35 to an SaO 2 of 90
   Percent

    OBJECTIVE

    To delineate general princip les of o xygen administration in patients with acute exacerbation of COPD.

    ANNOTATION

    The goal of o xygen therapy is to optimize o xygenation and min imize respiratory acidosis, if present. Thus, all
    patients presenting with acute exacerbation of chronic obstructive pulmonary disease should receive oxygen by
    Venturi mask (24 to 35 percent), which delivers a precise oxygen concentration, until the PaCO2 is determined.
    The lowest fraction of inspired oxygen (FiO2 ) resulting in an SaO2 of 90 percent is optimal. The nasal cannula
    is to be avoided initially because of its inability to deliver a precise FiO 2 . ABGs should be obtained initially
    and SaO2 should be monitored continuously. If a ventilator is used in the ER, the init ial FiO 2 setting should be
    1.0.

B. Obtain AB Gs

    OBJECTIVE

    To emphasize the role o f ABG determination in the init ial management of patients with acute exacerbation of
    COPD and to define the role and limits of pulse oximetry in this setting.

    ANNOTATION

    Analysis of ABGs is to be used initially in all cases when it is unknown whether the patient is a chronic CO 2
    retainer and to determine acid-base status. Pulse o ximetry, which should be continuously monitoring SaO 2 , is
    not sufficient until it is clear that the CO2 level is not elevated or is stable and the acid-base status is known and
    is stable.

C. Does Patient Need Mechanical Ventilati on?

    OBJECTIVE

    To define the guidelines for life saving mechanical ventilat ion and endotracheal intubation.

    ANNOTATION

    A decision to initiate mechanical ventilat ion and endotracheal intubation can be made prior to measuring
    arterial blood gases. Advance directives should be considered prior to in itiating these supportive measures.

    1.   Indications for mechanical ventilation (invasive or non invasive) include:
         Severe respiratory or co mb ined respiratory and metabolic acidosis.
         a. Sustained respiratory rate greater than 40 per minute.
         b.   Abnormal b reathing pattern suggestive of increased respiratory workload and/or respiratory muscle
              fatigue.



                                            Inpatient Management of COPD: Oxygen Therapy (B3) - Expanded Annotations - Page 99
                                                                                            VHA/DoD Clinical Practice Guideline



          c.   Depressed mental status.
          d.   Severe hypoxemia.

     2.    Indications for tracheal intubation include:
          a. Suspected airway obstruction.
          b.   Depressed mental status.
          c.   High-risk o f gastro-pulmonary reflu x and aspiration.
          d.   Difficulty managing secretions.

     EVIDENCE

     Mechanical ventilation and endotracheal intubation: American Thoracic Society 1995. LE=C, SR=I

D. Stepwise Increase in FiO2

     OBJECTIVE

     To encourage the use of a high flow controlled o xygen source in an acute exacerbation of COPD when PaCO 2
     is suspected to be elevated.

     ANNOTATION

     An SaO2 of 90 percent is optimal. Th is usually corresponds to a PaO2 of 55 to 60 mmHg. Pulse o ximetry alone
     may be used in this situation once it is clear that PaCO2 is not elevated and acid-base status is known and stable.
     Use of a Venturi mask, with analysis of arterial blood gases after 20 minutes (earlier if indicated clin ically), is
     the most judicious approach to the management of acute exacerbation of COPD with o xygen in a patient having
     an elevated PaCO2 . If chronic elevation of PaCO2 is not demonstrated and repeated measurement of acid base
     status is not a clinical concern, pulse o ximetry alone to assess adequacy of oxygenation is acceptable, as is the
     use of nasal prongs or a cannula to deliver o xygen. However, when CO 2 retention exists, or when the acid-base
     status is unclear, assessment of PaCO2 and pH are required. Use of pulse o ximetry alone in this situation is to be
     avoided.

E. Are AB Gs Acceptable?

     OBJECTIVE
     To establish goals for PaO2 and pH in patients with acute exacerbation of COPD.
     ANNOTATION

     Acceptable blood gases would include a PaO2 close to 60 mmHg, a stable PaCO2 , and a pH > 7.25.

F.   Decrease FiO2 Progressively, Keeping PaO2 or SaO2 at 90 Percent AND Monitor Oxi metry and AB Gs

     OBJECTIVE

     To delineate the salient points of oxygen administration in patients with elevated PaCO 2 .

     ANNOTATION

     Monitor with o ximet ry or A BGs. If CO2 retention has been worsened by the use of a high concentration of
     oxygen, it may be difficult to reverse the rise in PaCO2 and reduce acidosis without resorting to mechanical
     ventilation. A stepwise reduction in FiO2 may be useful in this setting if clin ical circu mstances permit. An
     abrupt reduction in FiO2 is unwise, since it may result in severe hypoxemia.




                                            Inpatient Management of COPD: Oxygen Therapy (B3) - Expanded Annotations - Page 100
CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF

        CHRONIC OBSTRUCTIVE PULMONARY DISEASE


                                    BIBLIOGRAPHY
                                                                                     VHA/DoD Clinical Practice Guideline



              CLINICAL PRACTICE GUID ELINE FOR THE MANAGEMENT OF C OPD

                                                   Bibliography


Albert RK; Mart in TR; Lewis S. Controlled clin ical trial of methylprednisolone in patients with chronic
    bronchitis and acute respiratory insufficiency. Ann Intern Med 1980;92:753-58

Allegra L; Grassi C; Grossi E; Pozzi E.. Ro le of antib iotics in the treat ment of chronic bronchitis exacerbation:
    follow up of a mu lticenter trial. Italian J of Chest Diseases 1991; 45:138-48

Ambrosino N; Nava S; Bertone P; et al. Physiologic evaluation of pressure support ventilation by nasal mask in
   patients with stable COPD. Chest 1992 Feb;101(2):385-91

American Sleep Disorders Association. Practice Parameters for indicat ions for polysomnography. Sleep
   1997;20:406-87

American Thoracic Society. Standards for the diagnosis and care of patients with ch ronic obstructive
   pulmonary d isease. Am J Respir Crit Care Med 1995;152:S77-121

American Thoracic Society. Standards for nursing care for adult patients with pulmonary dysfunction. Am Rev
   Respir Dis 1991;144:231-36

American Thoracic Society: Lung testing: selection of reference values and interpretative strategies. Am Rev
   Respir Dis 1991; 144:1202-18

American Thoracic Society. Research priorities in respiratory nursing. Am Rev Respir Dis 1990; 142:1459-64

Anthonisen NR; Connett JE; Kiley JP; et al. Effects of smoking intervention and the use of an inhaled
    anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA 1994 Nov
    16; 272 (19):1497-505

Anthonisen NR; Manfreda J; Warren CP; et al. Antibiotic therapy in exacerbations of chronic obstructive
    pulmonary d isease. Ann Intern Med 1987 Feb;106(2):196-204

Ashtutosh; Sedat M; Fragale-Jackson J. Effects of theophylline on respiratory drive in patients with chronic
    obstructive respiratory disease. J Clin Pharmacol 1997;37(12):1100-07

Ashutosh K; Dev G; Steele D. Nonbronchodilator effects of pirbuterol and ipratropiu m in chronic obstructive
   pulmonary d isease. Chest 1995 Jan;107(1):173-78

American Thoracic Society Statement. Standards for the diagnosis and care of patients with chronic obstructive
   pulmonary d isease. Resp Crit Care Med 1995; 152: S97-S106

Baldwin DR; Bates AJ; Evans AH; et al. Nocturnal o xygen desaturation and exercise -induced desaturation in
    subjects with chronic obstructive pulmonary disease. Respir Med 1995 Oct;89(9):599-601

Balter MS; Hyland RH; Lo w DE; et al. Recommendations on the management of ch ronic bronchitis. A
    practical guide for Canadian physicians. Can Med Assoc J 1994; 151(Suppl):5-23

Belman MJ; Botnick W C; Sh in JW. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in
    patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996 Mar;153(3):967-75

Berg BW; Dillard TA; Rajagopal KIZ; et al. Oxygen supplementation during air travel in patients with chronic
    obstructive lung disease. Chest 1992 Mar; 101(3):638-41




                                                                              Management of COPD: Bibliography Page 1
                                                                                   VHA/DoD Clinical Practice Guideline



Berger I; Argaman Z; Schwart z SB; et al. Efficacy of cort icosteroids in acute bronchiolitis: short -term and
    long-term fo llo w-up. Pediatr Pulmonol 1998 Sep;26(3):162-66

Berger R; Smith D. Effect of metaproterenol and exercise performance in patients with stable "fixed" airway
    obstruction. Am Rev Respir Dis 1988; 13 8:624-29

Berry RB; Desa MM; Branum JP; et al. Effect of theophylline on sleep and sleep -disordered breathing in
    patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1991 Feb;143(2):245-50

Berry RB; Shinto RA; Wong FH; et al. Nebulizer vs spacer for bronchodilator delivery in patients hospitalized
    for acute exacerbations of COPD. Chest 1989 Dec; 96(6):1241-46

Berry RB. Effect of theophylline on sleep and sleep-"fixed" airway obstruction. Am Rev Respir Dis 1988;13
    8:624-29

Blair GP; Light RW. Treat ment of chron ic obstructive pulmonary disease with corticosteroids. Co mparison of
    daily vs alternate-day therapy. Chest 1984 Oct;86(4):524-28

Blosser SA; Maxwell SL; Reeves -Hoche MK; et al. Is an anticholinerg ic agent superior to a B2-agonist in
    improving dyspnea and exercise limitation in COPD? Chest 1995;108:730-35

Boyd G; Morice AH; Pounsford JC; et al. An evaluation of salmetero l in the treatment of chronic obstructive
   pulmonary d isease (COPD). Eur Respir J 1997;10(4):815-21

Brad ley TD; Mateika J; Li D; Avendano M; et al. Daytime hypercapnia in the develop ment of nocturnal
    hypoxemia in COPD. Chest 1990;97:108-12

Braun SR; Wayland NM; Copeland C; et al. A co mparison of the effect of ip ratropiu m and albuterol in the
    treatment of chronic obstructive airway disease, Arch Intern Med 1989;149:544-47

British Thoracic Society. Nebulizer therapy. Gu idelines. British Thoracic Society Nebulizer Project Group.
     Thorax 1997 Apr;52 Suppl 2:S4-24

Callahan CM; Dittus RS; Kat z BP. Oral cort icosteroid for patients with stable chronic obstructive pulmonary
     disease. Ann Int Med 1991;114:216-223

Camilli A B; Burro ws B; Knudson RJ; et al. Longitudinal changes in forced exp iratory volu me in one second in
   adults: effects of smoking and smoking cessation. Am Rev Respir Dis 1987;135:794-99

Carlin BW; Clausen JL; Ries AL. The effects of exercise testing on the prescription of o xygen therapy. Chest
    1994 Aug;106(2):361-65

Carone M; Patessio A; Appendini L; et al. Co mparison of invasive and noninvasive saturation monitoring in
    prescribing o xygen during exercise in COPI) patients. Eur Respir J 1997;10:446-51

Cazzola M; Vinciguerra A; Beghi GF; et al. Co mparative evaluation of the clin ical and microbiological
    efficacy of co-amo xiclav vs cefixime or ciproflo xacin in bacterial exacerbation of chronic bronchitis. J
    Chemother 1995 Oct;7(5):432-41

Cazzola M; Di Perna F; Noschese P; et al. Effects of formoterol o r o xitropiu m on airway responses to
    salbutamol in COPD. Eur Respir J 1998;11(6):1337-41

Cazzola M; Matera M G; Santangelo G; et al. Salmetero l and formoterol in partially reversible severe chronic
    obstructive pulmonary diseas e: a dose-response study. Respir Med 1995 May;89(5):357-62




                                                                             Management of COPD: Bibliography Page 2
                                                                                   VHA/DoD Clinical Practice Guideline



Celli BR. Perioperative respiratory care of the patient undergoing upper abdominal surgery. Clin Chest Med
     1993 Jun;14(2):253-61

Centers for Disease Control and Prevention. Prevention and Con trol of influenza: reco mmendations of the
    Advisory Committee on Immun izat ion Pract ices. MMWR 1997;46(RR-9):1-24

Chap man KR; Rebuck AS. Bronchodilators, hypokalemia, and fatal asthma. Lancet 1985 Ju l 20; 2(8447):162

Collins R; Scrimgeour A; Yusuf S; et al. Reduction in fatal pulmonary embolism and venous thrombosis by
    perioperative ad min istration of subcutaneous heparin. Overview of results of randomized trials in general,
    orthopedic, and urologic surgery. N Engl J Med 1988:318:1162-73

COMBIVENT Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of
   ipratropiu m and albuterol is more effect ive than either agent alone. An 85 -day mult icenter trial. Chest 1994
   May;105(5):1411-19

Co mbivent Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of
    ipratropiu m and albuterol is more effect ive than either agent alone. Chest 1994;105:1411-1419

Cramer D; Ward S; Geddes D. Assessment of o xygen supplementation during air travel. Thorax 1996
    Feb;51(2):202-03

Crapo RO; Morris AH; Gardner RM . Reference spirometric values using techniques and equipment that meet
    ATS reco mmendations. Am Rev Respir Dis 1981; 123:659-65

Cu mmins RO; Shuback JA. Frequency and types of medical emergencies among commercial air travelers.
    JAAM 1989; 261:1295-99

Depart ment of Health and Hu man Services. Clinical Practice Gu ideline Nu mber 18. Smo king cessation. April
   1996, Agency for Health Care Policy and Research, Centers for Disease Control and Prevention. (A HCPR
   Pub No 96-0692)

Depart ment of Health and Hu man Services. Qu ick Reference Gu ide fo r Smo king Cessation Specialists Number
   18. Smoking cessation: information for specialists. Agency for Health Care Policy and Research, Centers
   for Disease Control and Prevention. (A HCPR Pub No 96-0694)

Diagnostic Classification Steering Co mmittee. Thorpy MJ, chairman. The international cl assification of sleep
    disorders: di agnostic and coding manual. Rochester, MN: A merican Sleep Disorders Association, 1990

Dillard TA; Berg BW; Rajagopal KR; et al. Hypoxemia during air travel in patients with chronic obstructive
     pulmonary d isease. Ann Int Med 1989;111:362-7

Dillard TA; Rosenberg AP; Berg BW. Hypoxemia during altitude exposure. A meta -analysis of chronic
     obstructive pulmonary disease. Chest 1993 Feb;103(2):422-25

Dillard TA; Moores LK; Bilello KL; et al. The preflight evaluation. A comparison of the hypoxia inhalation test
     with hypobaric exposure. Chest 1995;107:152-57

Do mpeling E; van Schayck CP; van Grunsven PM; et al. Slowing the deterioration of asthma and chronic
    obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A
    4-year p rospective study. Ann Intern Med 1993 May 15;118(10):770-78

Easton R; Jadue C; Dhingra S; et al. A co mparison of the bronchodilating effects of a beta-2 adrenergic agent
    (albuterol) and an anticholinergic agent (ipratropiu m b ro mide), given by aerosol Orin sequence. N Eng1J
    Med 1986;315(12):735-39




                                                                             Management of COPD: Bibliography Page 3
                                                                                  VHA/DoD Clinical Practice Guideline



Emennan CL; Cydulka RK. Effect of different albuterol dosing regimens in the treatment of acute exacerbations
   of chronic obstructive pulmonary disease. Ann Emerg Med 1997; 29:474-478

Emerman CL; Cydulka RK. A randomized controlled trial of methylprednisolone in the emergency treatment
   of acute exacerbations of COPD. Chest 1989 Mar;95(3):563-67

Emerman CL; Connors AF; Lukens TW; et al. Relationship between arterial gases and spirometry in acute
   exacerbations of chronic obstructive pulmonary d isease. Ann Emerg Med 1989;18:523-27

Engel T; Heinig JH; Madsen O; et al. A trial of inhaled budesonide on airway responsiveness in smokers with
    chronic bronchitis. Eur Respir J 1989 Nov;2(10):935-39

Erbland M L; Deupree RH; Niewoehner DE. Systemic Cort icosteroids in Chronic Obstructive Pulmonary
    Disease Exacerbations (SCCOPE): rat ionale and design of an equivalence trial. Veterans Administration
    Cooperative Trials SCCOPE Study Group. Control Clin Trials 1998 Aug;19(4):404-17

Farr BM; Johnston BL; Cobb DK; et al. Preventing pneumococcal bacteremia in patients at risk: results of a
     matched case-control study. Arch Intern Med 1995;155:2336-40

Fedson DS; Wajda A; Nicol JP; et al. Clinical effectiveness of influenza vaccination in Manitoba. JAAM
    1993;270:1956-61

Fine MJ; Smith MA; Carson CA; et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis of
    randomized controlled trials. Arch Intern Med 1994; 154:2666-77

Fink G; Kaye C; Su lkes J; et al. Effect of theophylline on exercise performance in patients with severe chronic
    obstructive pulmonary disease. Thorax 1994; 49:332-34

Fink JN; Forman S; Silvers WS; et al. A double-blind study of the efficacy of nedocromil sodium in the
    management of asthma in patients using high doses of bronchodilators. J Allergy Clin Immunol 1994
    Sep;94(3 Pt 1):473-81

Fletcher EC; Donner CF; Midgren B; et al. Survival in COPD patients with a daytime PaO, > 60 mmHg with
     and without nocturnal oxyhemoglobin desaturation. Chest l992a:101:649-55

Fletcher EC; Luckett RA; Goodnight-White S; et al. A double-blind trial of nocturnal supplemental o xygen for
     sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO above 60
     mmHg. A m Rev Respir Dis 1992b;145:1070-76

Fletcher EC; Scott D; Qian W; et al. Evolution of nocturnal o xyhemoglobin desaturation in patie nts with
     chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg. Am Rev Respir Dis 1991
     Aug;144(2):401-05

Fletcher EC; Luckett RA; Miller T; et al. Exercise hemodynamics and gas exchange in patients with chronic
     obstruction pulmonary disease, sleep desaturation, and a daytime PaO2 above 60 mm Hg. Am Rev Respir
     Dis 1989 Nov;140(5):1237-45

Fletcher EC; Luckett RA; Miller T; et al. Pu lmonary vascular hemodynamics in chronic lung disease patients
     with and without oxyhemoglobin desaturation during sleep. Chest 1989;95:157-66

Fletcher CM; Peto R. The natural history of chronic airflo w obstruction. BMJ 1977;1:16451648

Ford GT; Rosenal TW; Clergue F; et al. Respiratory physiology in upper abdominal surgery. Clinics in Chest
    Medicine 1993;14:237-52




                                                                            Management of COPD: Bibliography Page 4
                                                                                     VHA/DoD Clinical Practice Guideline



Forrester HL; Jahnigen DW; LaForce FM. Inefficacy of pneumococcal vaccine in a h igh -risk population. Am
    JMed 1987;83:425-30

Foster DA; Talsma A; Furu moto-Dawson A; et al. Influenza vaccine effectiveness in preventing hospitalizat ion
    for pneumonia in the elderly. Am JEpidemiol 1992; 136:296-30-37

Fragoso CAV; Miller MA. Rev iew o f the clinical efficacy of theophylline in the treatment of chronic
    obstructive pulmonary disease. Am Rev Respir Dis 1993;147:540-47

Gay PC; Hubmayr RD; Stroetz RW. Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive
    pulmonary d isease during a 3-month controlled trial. Mayo Clin Proc 1996 Jun;71(6):533-42

Gig liotti F; Sp inelli A; Duranti R; et al Four-week negative pressure ventilation imp roves respiratory function
     in severe hypercapnic COPD patients Chest 1994 Jan;105(1):87-94

Girault C; Muir JF; Mihaltan F; et al Effects of repeated administration of zolp idem on sleep, diurnal and
    nocturnal respiratory function, vigilance, and physical perfo rmance in patients with COPD. Chest 1996
    Nov;110(5):1203-11

Go ldstein MF; Pacana SM; Dvorin DJ. Retrospective analyses of methacholine inhalat ion challenges. Chest
     1994 Apr;105(4):1082-88

Go ldstein RS; Gort EH; Stubbing D; et al. Randomised controlled trial of respiratory rehabilitation. Lancet
     1994 Nov 19;344(8934):1394-97

Gong H Jr. A ir t ravel and patients with chronic obstructive pulmonary disease. Ann Intern Med 1984
   Apr;100(4):595-97

Gong HJ Jr. A ir travel and o xygen therapy in cardiopulmonary patients. Chest 1992;1101-04

Govaert T; Thijs CT; Masurel N; et al. The efficacy of vaccination in elderly individuals: a randomized double -
   blind placebo-controlled trial. AAM 1994;272:1661-65

Go zurn JE. Perioperative management of the ophthalmology p atient. In: Medical Management of the Surgical
    Patient. GJ Merli & HH Weit z (Eds.). Philadelphia, PA: W.B. Saunders 1992

Gross NJ; Petty TL; Fried man M; et al. Dose response to ipratropium as a nebulized solution in patients with
    chronic obstructive pulmonary disease. A three-center study. Am Rev Respir Dis 1989 May;139(5):1188-
    91

Gross NJ. Ipratropiu m bro mide. N Engl J Med 1988 Aug 25; 319(8):486-94

Gross NJ. The use of anticholinergic agents in the treatment of airways disease. Clin Chest Med 1988
    Dec;9(4):591-98

Grove A; Lip worth BJ; Reid P; et al. Effects of regular salmeterol on lung function and exercise capacity in
    patients with chronic obstructive airways disease. Thorax 1996 Ju l;51(7):689-93

Hall JC; Tarala R; Harris J; et al. Incentive spiro metry versus routine chest physiotherapy for prevention of
     pulmonary co mplications after abdominal surgery. Lancet 1991a;37:953 -56

Hall JC; Tarala RA; Hall JL; et al. A mu ltivariate analysis of the risk of pulmonary co mp licat ions after
     laparotorny. Chest 1991b;99:923-27

Harrison BA; Pierce RJ. Co mparison of wet and dry aerosol salbutamol. Aust N Z J Med 1983 Feb;13(1):29-33




                                                                               Management of COPD: Bibliography Page 5
                                                                                  VHA/DoD Clinical Practice Guideline



Hudson LD; Monti CM. Rat ionale and use of corticosteroids in chronic obstructive pulmonary disease. Med
   Clin North Am 1990 May;74(3):661-90

Ikeda A; Nishimura K; Koyama H; et al. Dose response study of ipratropiu m bro mide aerosol on maximu m
    exercise performance in stable patients with chronic obstructive pulmonary disease. Thorax 1996
    Jan;51(1):48-53

Ikeda A; Nishimura K; Izu mi T. Bronchodilating effects of co mbined therapy with clinical dosages of
    ipratropiu m bro mide and salbutamol for stable COPD: co mparison with ipratropiu m b ro mide alone. Chest
    1995 Feb;107(2):401-5

Ikeda A; Nishimura K; Koyama H; et al. Co mparative dose-response study of three anticholinergic agents and
    fenoterol using a metered dose inhaler in patients with chronic obstructive pulmonary disease. Thorax
    1995 Jan;50(1):62-66

Jaeschke R; Guyatt GH; Cook D; et al. The effect of increasing doses of bet a-agonists on airflow in patients
    with chronic airflow limitation. Respir Med 1993 Aug;87(6):433-8

Jasper AC; Mohsenifar Z; Kahan S; et al. Cost-benefit co mparison of aerosol bronchodilator delivery methods
    in hospitalized patients. Chest 1987 Apr;91(4):614-8

Jenkins CJ; Breslin A B. Long term study of the effect of sodium cro moglycate on non -specific bronchial
    hyperresponsiveness. Thorax 1987 Sep;42(9):664-69

Jones PW; Bosh TK. Quality of life changes in COPD patients treated with salmeterol. Am J Respir Crit Care
    Med 1997 Apr;155(4):1283-89

Karpel JP; Kotch A; Zinny M; et al. A co mparison of inhaled ipratropiu m, oral theophylline plus inhaled beta -
    agonist, and the combination of all three in patients with COPD. Chest 1994 Apr; 105(4):1089-94

Karpel JP; Pesin J; Greenberg D; et al. A co mparison of the effects of ipratrop iu m bro mide and metaproterenol
    sulfate in acute exacerbations of COPD. Chest 1990 Oct;98(4):835-39

Kroenke K; Lawrence VA; Therou x JF; et al. Postoperative complications after thoracic and major abdominal
    surgery in patients with and without obstructive lung disease. Chest 1993 Nov;104(5):1445-51

LeDou x EJ; Morris JF; Temp le WP; et al. Standard and double dose ipratropium bro mide and co mbined
   ipratropiu m bro mide and inhaled metaproterenol in COPD. Chest 1989 May;95(5):1013-16

Lien D; Turner M. Reco mmendations for patients with chronic respiratory disease considering air travel: a
    statement fro m the Canadian Thoracic Society. Can Respir J 1998 Mar-Apr; 5(2):95-100

Levi-Valensi P; Weitzenblu m E; Ped inielli JL; et al. Three-month follo w-up of arterial b lood gas
    determinations in candidates for long-term o xygen therapy: a mult icentric study. Am Rev Respir Dis
    1986;1:547-51

Light RW; Mahutte CK; Stansbury DW; et al. Relat ionship between improvement in exercise performance
    with supplemental o xygen and hypoxic ventilatory drive in patients with chronic airflo w obstruction.
    Chest 1989 Apr;95(4):751-56

Lin CC. Co mparison between nocturnal nasal positive pressure ventilation comb ined with o xygen therapy and
    oxygen monotherapy in patients with severe COPD. Am J Respir Crit Care Med 1996 Aug;154(2 Pt 1):
    353-8

Littner MR; McGinty DJ; Arand DL. Determinants of oxygen desaturation in the course of ventilation during
     sleep in chronic obstructive pulmonary disease. Am Rev Respir Dis 1980 Dec;122(6):849-57



                                                                            Management of COPD: Bibliography Page 6
                                                                                   VHA/DoD Clinical Practice Guideline




Lloberes P; Ramis L; Montserrat JM; et al. Effect of three different bronchodilators during an exacerbation of
    chronic obstructive pulmonary disease. Eur Respir J 1988 Jun;1(6):536-39

Maguire GP; Newman T; DeLoren zo LJ; et al. Co mparison of a hand -held nebulizer with a metered dose
   inhaler-spacer co mbination in acute obstructive pulmonary disease. Chest 1991 Nov;100(5):1300-05

Man GC; Champ man KR; Ali SH; et al. Sleep quality and nocturnal respiratory function with once-daily
   theophylline (Uniphyl) and inhaled salbutamo l in patients with COPD. Chest 1996 Sep;110(3):648-53

Martin RJ; Pak J. Overnight theophylline concentrations and effects on sleep and lung function in chronic
    obstructive pulmonary disease. Am Rev Respir Dis 1992 Mar;145(3):540-04

Matera M G; Caputi M; Cazzola M. A co mbination with clinical reco mmended dosages of salmetero l and
   ipratropiu m is not more effect ive than salmetero l alone in patients with chronic o bstructive pulmonary
   disease. Respir Med 1996 Sep;90(8):497-99

McDonald CF; Blyth CM; Lazarus MD; et al. Exert ional o xygen of limited benefit in patients with chronic
   obstructive pulmonary disease and mild hypoxemia. Am J Respir Crit Care Med 1995 Nov;152(5 Pt
   1):1616-19

McGovern JP; Sasse SA; Stansbury DW; et al. Co mparison of o xygen saturation by pulse oximet ry and co -
   oximetry during exercise testing in patients with COPD. Chest 1996 May;109(5):1151-55

McKay SE; Howie CA; Thomson AH; et al. Value of theophylline treat ment in patients handicapped by
   chronic obstructive lung disease. Thorax 1993 Mar;48(3):227-32

Medical guidelines for air travel. Aerospace Medical Association, Air Transport Medicine Co mmittee,
   Alexandria, Va. Aviat Space Environ Med 1996 Oct;67(10 Suppl):B1-16

Meecham Jones DJ; Paul EA; Jones PW; et al. Nasal pressure support ventilation plus oxygen co mpared with
   oxygen therapy alone in hypercapnic COPD. Am J Respir Crit Care Med 1995 Aug;152(2):538-44

Morice AH; Morris D; Lawson-Matthew P. A co mparison of nebulized budesonide with oral prednisolone in
   the treatment of exacerbations of obstructive pulmonary disease. Clin Pharmacol Ther 1996
   Dec;60(6):675-78

Mulloy E; Fit zpatrick M; Bourke S; et al. Oxygen desaturation d uring sleep and exercise in patients with severe
    chronic obstructive pulmonary disease. Respir Med 1995 Mar;89(3):193-98

Mulloy E; McNicholas WT. Theophylline imp roves gas exchange during rest, exercise, and sleep in severe
    chronic obstructive pulmonary disease. Am Rev Respir Dis 1993 Oct;148(4 Pt 1):1030-36

Murata GH; Gorby MS; Ch ick TW; et al. A minophylline in the outpatient management of decompensated
   chronic obstructive pulmonary disease. Chest 1990 Dec;98(6):1346-50

Murata GH; Gorby MS; Ch ick TW; et al. Intravenous and oral corticosteroids for the prevention of relapse
   after treat ment of decompensated COPD. Effect on patients with a history of multip le relapses. Chest 1990
   Oct;98(4):845-49

Murciano D; Armengaud MH; Cramer PH; et al. Acute effects of zo lpidem, triazo lam and flunitrazepam on
   arterial blood gases and control of breathing in severe COPD. Eur Respir J 1993 May;6(5):625-29

Murciano D; Auclair M H; Pariente R; et al. A randomized, controlled trial of theophylline in patients with
   severe chronic obstructive pulmonary disease. N Engl J Med 1989 Jun 8;320(23):1521-25




                                                                            Management of COPD: Bibliography Page 7
                                                                                   VHA/DoD Clinical Practice Guideline



National Institutes of Health. Expert Panel Report 2. Guidelines for the diagnosis and management of asthma.
    NIH publicat ion No. 97-4051 . April 1997

Naughton MT; Rochford PD; Pretto JJ; et al. Is normobaric simu lation of hypobaric hypoxia accurate in
   chronic airflow limitation? Am J Respir Crit Care Med 1995 Dec; 152(6 Pt 1):1956-60

Neiwohner DE; Erbland M L; Deupree RH; et al. Effect of systemic cort icosteroids on th e exacerbations of
    chronic obstructive pulmonary disease. N Engl J Med 1999;340:1941-7

Newman SP; Clarke SW. The proper use of metered-dose inhalers. Chest 1984;86:342-43

Newnham DM; Dh illon DP; Winter JH; et al. Bronchodilator reversibility to low an d high doses of terbutaline
   and ipratropiu m bro mide in patients with chronic obstructive pulmonary disease. Thorax 1993
   Nov;48(11):1151-55

Niederman MS; Bass JB Jr; Campbell GD; et al. Gu idelines for the init ial management of adults with
    community-acquired pneumonia: diagnosis, assessment of severity, and init ial antimicrobial therapy.
    American Thoracic Society. Med ical Section of the A merican Lung Association. Am Rev Respir Dis 1993
    Nov;148(5):1418-26

Nisar M; Earis JE; Pearson MG; et al. Acute bronchodilator trials in chronic obstructive pulmonary disease. Am
    Rev Respir Dis 1992 Sep;146(3):555-9

Nichol KL; Margolis KL; Wuorenma J; et al. The efficacy and cost effectiveness of vaccination against
    influenza among elderly persons living in the co mmunity. N Engl J Med 1994;1:778-84

Nishimura K; Koyama H; Ikeda A; Izu mi T. Is oral theophylline effective in comb ination with both inhaled
    anticholinergic agent and inhaled beta 2-agonist in the treat ment of stable COPD? Chest 1993
    Jul;104(1):179-84

O'Donohue WJ Jr. Effect of o xygen therapy on increasing arterial o xygen tension in hypoxemic patients with
   stable chronic obstructive pulmonary disease while breathing amb ient air. Chest 1991 Oct;100(4):968-72

O'Driscoll BR; Tay lor RJ; Horsley M G; et al. Nebulized salbutamo l with and without ipratropiu m bro mide in
    acute airflow obstruction. Lancet 1989 Jun 24; 1(8652):1418-20

Orr WC; Shamma -Oth man Z; Levin D; et al. Persistent hypoxemia and excessive daytime sleepiness in chronic
    obstructive pulmonary disease (COPD). Chest 1990 Mar;97(3):583-85

Owens GR; Rogers RM; Pennock BE; et al. The diffusing capacity as a predictor of arterial o xygen
   desaturation during exercise in patients with chronic obstructive pulmonary disease. N Engl J Med 1984
   May 10; 310(19):1218-21

Paggiaro PL; Dahle R; Bakran I; et al. Mu lticentre rando mised placebo -controlled trial of inhaled fluticasone
    propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.
    Lancet 1998 Mar 14;3519105):773-80

Patrick DM; Dales RE; Stark RM; et al. Severe exacerbations of COPD and asthma. Incremental benefit o f
     adding ipratropiu m to usual therapy. Chest 1990 Aug;98(2):295-97

Petty TL. Pu lmonary rehabilitation of early COPD. COPD as a systemic disease. Chest 1994 Jun;105(6):1636-
    37

Pierson WE; LaForce CF; Bell TD; et al. Long-term, double-blind comparison of controlled-release albuterol
     versus sustained-release theophylline in adolescents and adults with asthma. J Allergy Clin Immunol 1990
     Mar;85(3):618-26



                                                                            Management of COPD: Bibliography Page 8
                                                                                   VHA/DoD Clinical Practice Guideline




Pines A. Antibiotic regimens in severe and acute purulent exacerbations of chronic bronchitis. Br Med J 1968
    Jun 22; 2(607):735-38

Pino-Garcia JM; Garcia-Rio F; Go mez L; et al. Short-term effects of inhaled beta-adrenergic agonist on
    breathlessness and central inspiratory drive in patients with nonreversible COPD. Chest 1996
    Sep;110(3):637-41

Postma DS; de Graaf-Breederveld N; Koeter GH; et al. The relat ionship between reversibility and
    hyperreactivity. Eur Respir J 1988 May;1(5):483-5

Postma DS; Peters I; Steenhuis EJ; et al. Moderately severe chronic airflow obstruction. Can corticosteroids
    slow down obstruction? Eur Respir J 1988 Jan;1(1):22-6

Postma DS; Slu iter HJ. Reversibility of airflow obstruction. Lancet 1988 Mar 12;1(8585):586-7

Postma DS; Steenhuis EJ; van der Weele LT; et al. Severe chronic airflow obstruction: can corticosteroids
   slow down progression? Eur J Respir Dis 1985 Jul; 67(1):56-64

Rand CS; Nides M; Cowles MK; et al. Long-term metered-dose inhaler adherence in a clin ical trial. The Lung
   Health Study Research Group. Am J Respir Crit Care Med 1995 Aug;152(2):580-88

Rebuck AS; Chap man KR; Abboud R; et al. Nebulized anticholinergic and sympathomimet ic treat ment of
   asthma and chronic obstructive airways disease in the emergen cy roo m. Am J Med 1987 Jan;82(1):59-64

Renkema TE; Schouten JP; Koeter GH; et al. Effects of long-term treat ment with corticosteroids in COPD.
    Chest 1996 May;109(5):1156-62

Rennard SI; Serby CW; Ghafouri M; et al. Extended therapy with ipratropiu m is associated with improved lung
   function in patients with COPD. A retrospective analysis of data from seven clin ical trials. Chest 1996
   Jul;110(1):62-70

Report of the Medical Research Council Working Party. Long term domiciliary o xygen therapy in chronic
   hypoxic cor pulmonale co mp licat ing chronic bronchitis and emphysema. Lancet 1981 Mar
   28; 1(8222):681-86

Rice KL; Leatherman JW; Duane PG; et al. A minophylline for acute exacerbations of chronic obstructive
    pulmonary d isease. A controlled trial. Ann Intern Med 1987 Sep;107(3):305-09

Sachs AP; Koeter GH; Groen ier KH; et al. Changes in symptoms, peak exp iratory flo w, and sputum flora
    during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in
    general practice. Thorax 1995 Jul; 50(7):758-63

Saint S; Bent S; Vitt inghoff E; et al. Antibiot ics in chronic obstructive pulmonary disease exacerbations. A
    meta-analysis. JAMA 1995 Mar 22-29;273(12):957-60

Schmidt EW; Zimmermann I; Ritzerfeld W; et al. Controlled prospective study of oral amo xycillin/ clavulanate
   vs ciproflo xacin in acute exacerbations of chronic bronchitis. J Antimicrob Chemother 1989 Nov 24; Suppl
   B:185-93

Shapiro SH; Ernst P; Gray-Donald K; et al. Effect of negative pressure ventilation in severe chronic obstructive
    pulmonary d isease. Lancet 1992 Dec 12; 340(8833):1425-29

Shapiro ED; Clemens JE. A controlled evaluation of the protective efficacy of pneu mococcal vaccine for
    patients at high risk of serious pneumococcal infections. Ann Intern Med 1984;101:325-30




                                                                             Management of COPD: Bibliography Page 9
                                                                                  VHA/DoD Clinical Practice Guideline



Shapiro ED; Berg AT; Austrian R; et al. The protective efficacy of polyvalent pneumococcal polysaccharide
        vaccine. N Engl J Med 1991; 1325:14;433-460

Shrestha M; O'Brien T; Haddo x R; et al. Decreased duration of emergency department treat ment of chronic
    obstructive pulmonary disease exacerbations with the addition of ipratropiu m bro mide to beta -agonist
    therapy. Ann Emerg Med 1991 Nov;20(11):1206-09

Siafakas NM; Vermeire P; Pride NB; et al. Optimal assessment and management of chronic obstructive
     pulmonary d isease (COPD). The European Respiratory Society Task Force. Eur Respir J 1995
     Aug;8(8):1398-420

Simberkoff MS; Cross AP; Al-Ibrahim M; et al. Efficacy of pneumococcal vaccine in h igh -risk patients.
    Results of a Veterans Admin istration Cooperative Study. N Engl J Med 1986 Nov 20;315(21):1318-27

Sims RV; Stein mann WC; McConville JH; et al. The clinical effectiveness of pneumococcal vaccine in the
    elderly. Ann Intern Med 1988; 108:655-57

Speizer FE; Fay M E; Dockery DW; et al. Chron ic obstructive pulmonary disease mortality in six U.S. cities.
    Am Rev Respir Dis 1989 Sep;140(3 Pt 2):S49-55

Steens RD; Pouliot Z; Millar TW; et al. Effects of zo lpidem and triazolam on sleep and respiration in mild to
    moderate chronic obstructive pulmonary disease. Sleep 1993 Jun;16(4):318-26

Stru mpf DA; Millman RP; Carlisle CC; et al. Nocturnal positive-pressure ventilation via nasal mask in patients
     with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1991 Dec;144(6):1234-9

Summary of the 3rd Consensus Conference held in Washington, DC, March 15 -16, 1990. New problems in
   supply, reimbursement, and of med ical necessity for long-term o xygen therapy. Am Rev Respir Dis 1990;
   142:721-24

Tashkin DP; Ashutosh K; Bleecker ER; et al. Co mparison of the anticholinergic bronchodilator ipratropiu m
    bromide with metaproterenol in chronic obstructive pulmonary disease. A 90 -day multi-center study. Am J
    Med 1986 Nov 14;81(5A):81-90

Thomas P; Pugsley JA; Stewart JH. Theophylline and salbutamol improve pulmonary function in patients with
   irreversible chronic obstructive pulmonary d isease. Chest 1992 Jan;101(1):160-65

Thompson WH; et al. Controlled trial o f oral prednisone in outpatients with acute COPD exacerbation. Am J
   Respir Crit Care Med 1996 Aug;154(2 Pt 1):407-12

Timms RM. Effect of triazolam on sleep and arterial o xygen saturation in patients with chronic obstructive
   pulmonary d isease. Arch Intern Med 1988 Oct;148(10):2159-63

Timms RM. Selection of patients with chronic obstructive pulmonary disease for long-term o xygen therapy.
   JAMA 1981 Jun 26;245(24):2514-15

Turner J; Wright E; Mendella L; et al. and the IPPG Study Group. Predictors of patient adherence to long -term
    home nebulizer therapy for COPD. Chest 1995;105:394-400

Turner JR; Corkery KJ; Eckman D; et al. Equivalence of continuous flow nebulizer and metered -dose inhaler
    with reservoir bag for treat ment of acute airflow obstruction. Chest 1988 Mar;93(3):476-81

Turner MO; Johnston PR; Pizzichin i E; et al. Anti-inflammatory effects of salmetero l co mpared with
    beclomethasone in eosinophilic mild exacerbations of asthma: a randomized, p lacebo controlled trial. Can
    Respir J 1998 Jul-Aug;5(4):261-8




                                                                          Management of COPD: Bibliography Page 10
                                                                                  VHA/DoD Clinical Practice Guideline



Ulrik CS. Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary
    disease: a single centre randomised, double blind, placebo controlled, crossover study. Thorax 1995
    Jul;50(7):750-54

van Schayck CP. Continuous and on demand use of bronchodilators in patients with non -steroid dependent
    asthma and chronic bronchitis: four-year follow-up randomized controlled study. Br J Gen Pract 1995
    May;45(394):239-44

Vathenen AS; Britton JR; Ebden P; et al. High-dose inhaled albuterol in severe chronic airflow limitation. Am
    Rev Respir Dis 1988 Oct;138(4):850-55

Veterans Health Administration. The pharmacologic management of chronic obstructive pulmonary disease.
    Depart ment of Veterans Affairs. Veterans Health Ad min istration publication No. 980012, Nov 1998

Vohra KP; Klocke RA. Detection and correction of hypoxemia associated with air travel. Am Rev Respir Dis
    1993 Nov;148(5):1215-19

Vos PJ; Folgering HT; van Herwaarden CL. Visual attention in patients with chronic obstructive pulmonary
    disease. Biol Psychol 1995 Nov 16; 41(3):295-305

Wardman A G; Simpson FG; Kno x AJ; et al. The use of high dose inhaled beclomethasone dipropionate as a
   means of assessing steroid responsiveness in obstructive airways disease. Br J Dis Chest 1988
   Apr;82(2):168-71

Warner JO; Got z M; Landau LI; et al. Management of asthma: a consensus statement. Arch Dis Child 1989
   Jul;64(7):1065-79

Warner MA; Offord KP; Warner M E; et al. Role of preoperative cessation of smoking and other factors in
   postoperative pulmonary comp licat ions: a blinded prospective study of coronary art ery bypass patients.
   Mayo Clin Proc 1989; 64:609-16

Weiner P; Weiner M; Azgad Y. Long term clinical co mparison of single versus twice daily ad ministration of
   inhaled budesonide in moderate asthma. Thorax 1995 Dec;50(12):1270-73

Weir DC. Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms
   twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial
   hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction. Thorax 1993
   Apr;48(4):309-16

Weir DC. Response to corticosteroids in chronic airflow obstruction: relationship to emphysema and airways
   collapse. Eur Respir J 1991 Nov;4(10):1185-90

Weir DC. Co rticosteroid trials in non-asthmatic chronic airflo w obstruction: a comparison of oral p rednisolone
   and inhaled beclomethasone dipropionate. Thorax 1990 Feb;45(2):112-7

Wilson DO; Rogers RM; Openbrier D. Nutrit ional aspects of chronic obstructive pulmonary disease. Clin
    Chest Med 1986 Dec; 7(4):643-56

Wong DA, Weber EC, Schell MJ; et.al. Factors associated with postoperative pulmonary co mplications in
   patients with severe COPD. Anesth Analg 1995; 80:276-8

Wrenn K. A minophylline therapy for acute bronchospastic disease in the emergency roo m. Ann Intern Med
   1991 Aug 15;115(4):241-47

Xu X; Christiani DC; Dockery DW; et al. Exposure-response relationships between occupational exposures
    and chronic respiratory illness: a commun ity-based study. Am Rev Respir Dis 1992 Aug;146(2):413-18



                                                                           Management of COPD: Bibliography Page 11
                                                                                 VHA/DoD Clinical Practice Guideline




Zack M B; Palange A V. Oxygen supplemented exercise of ventilatory and nonventilatory muscles in pulmonary
    rehabilitation. Chest 1985 Nov;88(5):669-75

Zarcone VP Jr. Sleep hygiene. In : Principals and Pract ice of Sleep Medicine (Eds.). Second edition. 1994


Zibrak JD; O'Donnell CR; Marton K. Indications for pulmonary function testing. Ann Intern Med 1990 May
    15; 112(10) :763-71.




                                                                          Management of COPD: Bibliography Page 12

								
To top