Noncardiac Chest Pain

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					  RECERTIFICATION
    R EFRESHER




                 Noncardiac chest pain
                               A rational approach to
                                a common complaint
                        Identifying noncardiac chest pain early and treating it effectively
                        can relieve some of the enormous burden this complaint places
                                 on the health care system and the patient alike.
                                                            Gregory S. Watson, PA-C




                                                                             than $8 billion in health care costs annually,2 with car-

C
      hest pain is significant not only because of the
      health problem it might indicate but also because                      diac causes found in only 20% of admissions.3 Even after
      of how much it costs the health care system and                        removing patients with known cardiac disease, a popu-
how greatly it affects the lives of patients. Most persons                   lation-based study in Australia revealed that 33% of the
who are evaluated in a primary care setting will have a                      polled population had had noncardiac chest pain
noncardiac cause of their symptoms.1 Even so, the im-                        (NCCP) at some time.2 Conservatively extrapolated to
portance of ruling out possible cardiac pathology usual-                     the US population, this could mean up to 80 million pa-
ly leads to expensive and complicated workups.                               tients presenting to clinics with NCCP.2
                                                                                Accurately diagnosing and treating patients with
Incidence and prevalence                                                     musculoskeletal, GI, psychological, and other causes for
In the United States, the complaint of chest pain leads                      NCCP can be challenging. Nevertheless, all possible
to more than 6 million hospital admissions and more                          causes should be explored because patients with NCCP
                                                                             can have significant long-term morbidity due to their

      CME                       Earn Category I CME credit by reading this
                             article and the article beginning on page 26
                                                                             pain.2 All practitioners should assess for cardiac disease
                                                                             and be aware of the variety of noncardiac causes of
                                                                             chest pain in order to begin appropriate therapy.
                           and successfully completing the post-test on
                         page 33. Successful completion is defined as a
                      cumulative score of at least 70% correct.              Diagnosing nonspecific chest pain
                   This material has been reviewed and is approved for       Evaluate all patients presenting with chest pain initial-
     1 hour of clinical Category I (Preapproved) CME credit by the AAPA.
     The term of approval is for 1 year from the publication date of
                                                                             ly for possible cardiac causes. A careful, thorough
     January 2006.                                                           history looking for cardiac risk factors, followed by a
                                                                             12-lead ECG, chest radiograph, and serial measure-
  Learning objectives                                                        ments of cardiac enzymes, should help determine
  • Review the initial evaluation of chest pain                              whether the patient’s pain is cardiac in nature.4 If the
  • Discuss the anatomic dysfunction and other                               patient is stable and the etiology is still unclear, refer-
    causes responsible for musculoskeletal, GI,                              ral for a cardiology consult, echocardiography, or stress
    and psychological chest pain                                             ECG is warranted.4
  • List the key components of the history and physi-                           Once a cardiac cause has been ruled out, consider the
    cal examination that will help distinguish cardiac                       differential diagnosis for chest pain. A survey of pri-
    from noncardiac chest pain
  • Describe the most effective way to diagnose and
    treat each type of chest pain                                            The author works in a pulmonary medicine and critical care pri-
                                                                             vate practice in Iowa City, Iowa. He has indicated no relation-
                                                                             ships to disclose relating to the content of this article.

20    JAAPA VOL.19, NO. 1 JANUARY 2006                   www.jaapa.com
     Studies have shown
     that noncardiac chest
     pain most frequently
     has a musculoskeletal,
     gastrointestinal,
     pulmonary, or
     psychiatric cause.




                                                                                                                            Jim Dowdalls
mary care centers in Michigan revealed that musculo-         History and physical examination
skeletal conditions were responsible for 36% of cases of     Any history of new or excessive physical activity is
chest pain, followed by GI (19%), nonspecific (16%), psy-    important, as are trauma to the thorax, shoulder, or
chiatric (7.5%), and pulmonary (5%) conditions.1 The         back or a history of rheumatic diseases, such as rheuma-
three most common misunderstood causes of NCCP are           toid arthritis, ankylosing spondylitis, psoriatic arthritis,
musculoskeletal, GI, and psychosocial.                       fibromyalgia, or sternocostoclavicular hyperostosis. A
                                                             history of a cough or dyspnea can indicate musculo-
MUSCULOSKELETAL CAUSES                                       skeletal chest pain from intercostal muscle strain.
Fractures of any of the bones of the thoracic wall can       Musculoskeletal pain tends to have a deep, aching qual-
cause chest pain, as can localized inflammation or dislo-    ity that is hard to localize. Questions about systemic
cation of the costosternal, sternoclavicular, or costo-      signs such as weight loss and night sweats are impor-
chondral joints due to traumatic, rheumatic, or idiopath-    tant to rule out serious illnesses.6
ic conditions. Strains of the pectoralis or intercostal         The physical evaluation should begin with observa-
muscles may cause pain, while muscle or joint pain from      tion of the chest wall for obvious deformities or inflam-
the shoulders or spine can also be referred to the chest.5   mation. The hallmark of musculoskeletal chest pain is
In particular, low cervical spine and T1 nerve roots sup-    pain that is reproducible with palpation or with active/
ply the pectoralis muscles, and while they more com-         passive range of motion (ROM) movements of the joints
monly refer pain to the scapulae, they can cause chest       and musculature of the affected area. Palpate and use
pain.6 Herpes zoster infection may also have a prodrome      such ROM exercises to test areas with potential for
of severe unilateral chest pain that radiates along a        referred pain, such as the cervical and thoracic spine.
dermatome.                                                   Consider the diagnosis of fibromyalgia, particularly

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Noncardiac chest pain



                                                                                ful. If a joint infection is suspected, a CBC, Gram’s stain,
  IN THIS ARTICLE                                                               and culture of joint aspirate should be ordered.7
  Key Points
                                                                                Treatment
  ® The most common causes of noncardiac chest                                  For most patients with musculoskeletal chest pain, edu-
    pain are musculoskeletal, GI, and psychological.
                                                                                cation to relieve anxiety is part of the first-line treatment.
  ® A careful history and physical examination, along                           The patient should suspend or limit any activities that
    with selected ancillary tests, can determine the
    source of the patient’s pain and point the way to a                         exacerbate the pain and expect a gradual resolution of
    specific, effective treatment regimen.                                      symptoms over time. NSAIDs are useful to manage pain
  ® Support and reassurance are important corner-                               and reduce mild inflammation.8 Most severe, acute caus-
    stones in the management of noncardiac chest                                es of musculoskeletal chest pain, such as rib fracture, can
    pain.                                                                       be managed with short-term use of opioids such as hy-
                                                                                drocodone or oxycodone. Inflammatory diseases like cos-
  Competencies                                                                  tochondritis can be safely and successfully treated with
      Medical knowledge                                              NNNNN      joint injections of triamcinolone plus 1% lidocaine.9 Tri-
                                                                                cyclic antidepressants (TCAs) are useful in treating gen-
      Interpersonal & communication skills                           NNNN       eralized pain and are particularly effective for neurogenic
      Patient care                                                   NNNN       pain, such as that from herpes zoster.10 Herpes zoster
                                                                                infections should be treated with an antiviral agent such
      Professionalism                                                NNNN
                                                                                as acyclovir, valacyclovir, or famciclovir within 48 to 72
      Practice-based learning and improvement                        N          hours of the eruption to limit the outbreak’s duration.11
      Systems-based practice                                         N
                                                                                GI CAUSES
     For an explanation of competencies ratings, see the table of contents.     Gastroesophageal reflux disease (GERD) can cause
                                                                                substernal chest pain and is the most common cause of
                                                                                GI-associated chest pain.12 Abnormalities in esophageal
with the discovery of trigger points, in female patients                        function can produce chest pain and exacerbate GERD.
younger than 60 years who present with concomitant                              Studies using esophageal manometry to evaluate pa-
psychiatric issues, sleep problems, or chronic muscle                           tients with NCCP have found hypotensive tone of the
pain. Specific pain syndromes such as costochondritis                           lower esophageal sphincter (LES) to be the most com-
usually have multiple tender costosternal joints with                           mon abnormality. A decrease in sphincter tone allows
minimal swelling, while Tietze’s syndrome usually man-                          gastric contents and acid to reflux back into the esoph-
ifests with one particularly painful joint and significant                      agus, causing irritation to the esophageal lining, which
local swelling.6 A thorough clinical examination of the                         may be perceived as chest pain.13 Recent research sug-
heart, lungs, and abdomen is also necessary. Pay partic-                        gests that patients with GERD can have a CNS-medi-
ular attention to the skin since herpes zoster and psori-                       ated hypersensitivity to the acid irritation that results
atic arthritis can have associated rashes and can cause                         in a longer and more severe sensation of chest pain.14
musculoskeletal chest pain.7                                                       Abnormal contractions of portions of the esophagus
                                                                                can also cause chest pain. Nutcracker esophagus is one
Diagnosis                                                                       of the most common and is due to high-amplitude con-
If palpation or active/passive ROM movements of the                             tractions of the distal esophagus. The etiology of these
area of discomfort reproduce the pain, the pain is likely to                    contractions is unknown, but acid irritation of the
be musculoskeletal. No other tests may be necessary in                          esophageal mucosa has been implicated. Another con-
patients without risk factors or a history that suggests                        traction abnormality is hypertensive LES pressure,
systemic illnesses or fractures. Posteroanterior and lat-                       which has been found in 10% of patients with NCCP and
eral chest radiographs are cost-effective ways to identify                      abnormal manometry results.13 Another 10% of this
dislocations or solid tumors, and CT can be particularly                        group have nonspecific esophageal motor disorders that
useful in elucidating sternal or sternoclavicular structure                     can be caused by peristaltic abnormalities such as non-
as well as soft tissue swelling. An elevated ESR may                            transmitted or retrograde contractions and incomplete
indicate a rheumatic process in a patient with other clin-                      LES relaxation. Other causes are achalasia (absence of
ical signs, such as myalgias and joint tenderness. Should                       LES relaxation with swallowing) and diffuse esoph-
the patient’s clinical picture and history warrant it, fur-                     ageal spasms of 20% to 100% of the esophageal muscu-
ther workup with more specific tests, such as those for                         lature.15 Less common esophageal abnormalities are
antinuclear antibodies or rheumatoid factor, may be help-                       Mallory-Weiss tears and Zenker’s diverticulum of the

22      JAAPA VOL.19, NO. 1 JANUARY 2006                        www.jaapa.com
esophagus. Cholecystitis and pancreatitis can also cause       tests can be useful in more atypical cases. While they
chest pain and left shoulder discomfort because of             have limited sensitivity, tests for amylase and lipase
diaphragmatic or phrenic nerve irritation.                     levels can be useful in diagnosing pancreatitis, and
                                                               serum Helicobacter pylori testing can be helpful if the
History and physical examination                               pain is thought to be due to peptic ulcer. CT can aid in
Since GERD is the most common cause of GI-associated           the diagnosis of pancreatitis when amylase and lipase
chest pain, questions that tease out this possible diagno-     levels are indeterminate or do not match the clinical
sis are important. A history of heartburn is a significant     picture. Ultrasonography is the diagnostic test of
risk factor, independent of other GI complaints, age, and      choice for biliary pathology, followed by CT in uncer-
gender. Dysphagia and acid regurgitation are also signif-      tain cases.20
icant risk factors, although not independently predictive.2
Ask whether the pain is associated with supine or prone        Treatment
positions and if it occurs postprandially or after eating      Respond to patients who have GI-associated NCCP
spicy or fatty foods, all of which can suggest GERD.           with reassurance that the pain is probably not cardiac.
   A history of dysphagia can indicate possible esoph-         Encourage the patient to reduce fat intake, avoid foods
ageal motility dysfunction or, in association with late        that cause reflux, and stop smoking.17 While omeprazole
regurgitation, Zenker’s diverticulum.12,13 Mallory-Weiss       has been the only PPI tested, any PPI should be effec-
tears are the most common lacerations of the esophagus         tive as a first-line treatment for GERD-related NCCP.17
and are associated with chronic alcohol abuse and with         Studies show that omeprazole significantly decreases
severe vomiting or coughing. An abrupt onset of chest          the number and severity of chest pain episodes.17 Start
pain while vomiting or coughing and subsequent                 with double the usual dosage, titrating down to the low-
hematemesis are characteristic.16                              est effective dosage for long-term administration.17
   The physical examination, although important, is            Laparoscopic fundoplication is 85% to 90% effective in
somewhat limited in chest pain with a GI source. It            reducing chest pain, but it carries with it the complica-
should include a thorough abdominal examination not-           tions and cost of surgery and should not be a first-line
ing particular tender points, especially those along the       treatment.17
epigastrium, that could indicate peptic ulcer disease,
pancreatitis, or Murphy’s sign. A digital rectal examina-
tion and stool guaiac test can help determine whether                A relationship between certain
GI bleeding is present.
                                                                      psychological disorders and
Diagnosis
Ambulatory 24-hour esophageal pH monitoring can iden-                noncardiac chest pain has long
tify GERD-associated chest pain with 60% to 90% sensi-
tivity and 85% to 100% specificity.17 However, this test is                 been recognized.
expensive, invasive, and not always available. A 2-week
course of moderate to high doses of a proton pump
inhibitor (PPI) is an effective and cost-saving test, with        Pain from suspected esophageal dysmotility disor-
71% to 90% sensitivity and 67% to 88% specificity.17,18 If a   ders tends to respond well to low dosages of imipramine
PPI reduces or resolves the pain, GERD is likely the           and trazodone.19 A small study showing significant im-
cause. If a PPI does not reduce the pain or does so only       provement in chest pain symptoms with the use of ser-
minimally, a referral for ambulatory esophageal pH mon-        traline opens the possibility of using selective serotonin
itoring is advised.19 Ambulatory monitoring is advanta-        receptor inhibitors (SSRIs) to control NCCP.21 Several
geous because spikes in esophageal pH can be correlated        studies have tested whether calcium channel blockers
with the patient’s symptoms. Barium swallows and               are effective against confirmed dysmotility disorders.
upper endoscopy are poor diagnostic tests for GERD-            While they have shown some promise, their use has
related chest pain and should be used only when other          been controversial.19 Endoscopic band ligation and
tests are nondiagnostic or when Mallory-Weiss tears or         injections of epinephrine are effective treatments for
Zenker’s diverticulum is suspected. Esophageal manom-          Mallory-Weiss tears, and endoscopy or open surgery
etry may be useful in patients with suspected esophageal       can be used to treat Zenker’s diverticulum.22,23
dysmotility or dysphagia, although correlation between
dysmotility and chest pain events is only 20% to 30%.17        PSYCHIATRIC DISORDERS
   Laboratory tests do not generally help to diagnose          A relationship between certain psychological disorders
the more common GI causes of NCCP, but certain blood           and NCCP has long been recognized. Among patients

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Noncardiac chest pain



presenting to both inpatient and outpatient cardiology        marked by long-term worry or anxiety, may include
services for chest pain, 25% to 56% have panic disorder,      restlessness, easy tiring, muscle tension, sleep distur-
the most common psychological malady associated with          bances, and irritability.27 OCD and major depressive
NCCP.24 Of patients with NCCP, 15% to 60% have asso-          disorder are less common causes of NCCP. Ask ques-
ciated panic disorder.24                                      tions about irritable bowel syndrome, other psychiatric
   While the mechanisms behind the physiology of psy-         illnesses, and the family history of psychiatric illness-
chiatric NCCP are not clear, several studies have             es.19 Panic disorder that manifests as chest pain tends to
shown a relationship between hyperventilation, which          affect women younger than 30 years with no family his-
is known to induce panic attacks, and esophageal              tory of cardiac disease, but anyone can be affected.25
spasms.25 The theory is that these spasms are the             Pay special attention to signs of self-abuse or illicit drug
chest pains experienced by the patient. However, car-         use that could also indicate mental illness or depression.
bon dioxide is known to induce panic and cause chest          A complete physical examination, while necessary, is
pain, but it does so without effect on the esophagus          generally not helpful in diagnosing psychiatric causes of
and its physiology remains unclear. Since panic causes        chest pain.
an imbalance in several areas of the CNS, including
the serotonin and noradrenergic systems, centrally            Diagnosis
mediated visceral hypersensitivity may also play a            Several questionnaires are available to help with screen-
role.19 A hypersensitivity to visceral pain, particularly     ing. The Hospital Anxiety and Depression Scale (HADS),
esophageal, could trigger the classic panic cycle of anx-     the Patient Health Questionnaire (PHQ), and a screening
iety: catastrophic misunderstanding of symptoms,              question that simply asks if the patient has ever had a
leading to more anxiety, leading to more misunder-            sudden feeling of anxiety or panic all have good sensitivi-
standing, leading to further anxiety, and so forth.24         ty and specificity in identifying panic disorder. Although
   Generalized anxiety disorder, obsessive-compul-            the single question had only 78% specificity, at 93% sensi-
sive disorder (OCD), and major depressive disorder            tivity it is probably the most efficient screening tool avail-
have also been implicated as contributors to NCCP,            able.28 If a patient is exhibiting severe symptoms of one or
but to a much lesser degree.26 Little is known about          more of these disorders, or if the provider is uncomfort-
the physiology of the chest pain associated with these        able managing these issues, then the patient should be re-
disorders.                                                    ferred to a mental health specialist.

                                                              Treatment
   Benzodiazepines work quickly and                           When a patient’s chest pain has a psychiatric cause, reas-
                                                              surance and encouragement are vital. The patient may re-
     effectively in patients with panic                       quire regular clinic follow-up. In addition to reassurance,
                                                              both antidepressants and cognitive behavior therapy
  disorder and concomitant NCCP, but                          (CBT) are effective and can be used simultaneously.24
                                                                 Pharmacotherapeutic possibilities include trazo-
   use should generally be short term.                        done, imipramine, benzodiazepines, and SSRIs, al-
                                                              though trazodone or imipramine in low dosages are
                                                              preferred.29 Trazodone, 25 to 50 mg at bedtime, re-
History and physical examination                              duces symptoms of NCCP and insomnia.29 Imipramine
When assessing a patient with possible psychogenic            (25 mg) significantly decreases NCCP regardless of
chest pain, rule out potential cardiac causes first. After    coexisting esophageal or psychiatric illnesses, but
reasonable assurance that the cardiovascular system is        it has significant anticholinergic side effects.24 Benzo-
not causing the pain, questions concerning the patient’s      diazepines work quickly and effectively in patients
mental health are appropriate.                                with panic disorder and concomitant NCCP, but use
   Ask direct, specific questions about the symptoms of       should generally be short term to avoid physical
panic disorder: brief, intense feelings of doom, profuse      dependence. One approach to managing patients with
sweating, dizziness, palpitations, shortness of breath,       severe panic disorder and NCCP is to prescribe a
paresthesias, or a sensation of choking. Patients with        short course of a low-dose benzodiazepine until the
panic disorder may have agoraphobia or other phobias          patient can be seen by a mental health professional
regarding certain places or situations. Questions about       for further care.19 SSRIs have a more encouraging
recent stressors such as job loss, divorce, or the death of   side-effect profile than benzodiazepines, although
a loved one can be helpful in assessing a patient’s cur-      only one small study found them effective in patients
rent psychological state.24 Generalized anxiety disorder,     with NCCP.21

24   JAAPA VOL.19, NO. 1 JANUARY 2006     www.jaapa.com
   CBT is also useful for treating NCCP. Studies show        NCCP are five times more likely to present to a
that treated patients have a 48% to 80% improvement          provider than are patients with severe NCCP.2,3,30 Not
in symptoms over control populations and that these          only do these patients present more often, but the
improvements persist for at least 2 years after cessa-       majority will continue to have pain 5 years after being
tion of therapy.19,24                                        seen and have a significantly worse quality of life based
                                                             on the severity of their pain.2
Conclusion                                                      The burden on both the medical system and the
Patients with NCCP rarely fit neatly into one of the         patient with NCCP is significant. The clinician should
previously discussed categories. Indeed, NCCP often          take care to rule out potential cardiac causes of chest
has multiple causes, and the clinician should bear this      pain, particularly in patients with known risk factors.
in mind. For patients with atypical chest pain and few       Just as important, however, is being prepared to identi-
cardiac risk factors, questions designed to elicit a psy-    fy and treat the more common causes of NCCP.           I
chiatric cause for the pain might be asked early in the
evaluation, to avoid making a psychiatric diagnosis a        REFERENCES
diagnosis of exclusion.19 Although studies looking for a      1. Klinkman MS, Stevens D, Gorenflo DW. Episodes of care for chest pain: a preliminary
                                                                 report from MIRNET. J Fam Pract. 1994;38(4):345-352.
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                                                                 impact and consulting—a population-based study. Aliment Pharmacol Ther. 2003;
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                                                                 diac chest pain. Aliment Pharmacol Ther. 2002;16(7):1217-1223.
about 30% of patients with GERD.25 Furthermore, a pa-         4. Panju AA, Hemmelgarn BR, Guyatt GH, Simel DL. The rational clinical examination.
                                                                 Is this patient having a myocardial infarction? JAMA. 1998;280(14):1256-1263.
tient suffering from panic or generalized anxiety who is      5. Wise CM. Major causes of musculoskeletal chest pain. UpToDate. Available at:
                                                                 http://www.uptodate.com. Accessed November 4, 2005.
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                                                              7. Wise CM. Clinical evaluation of musculoskeletal chest pain. UpToDate. Available at:
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                                                              8. Chambers J, Bass C, Mayou R. Non-cardiac chest pain: assessment and manage-
                                                                 ment. Heart. 1999;82(6):656-657.
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                                                                 syndrome. Br J Rheumatol. 1997;36(5):547-550.
                                                             10. O’Malley PG, Jackson JL, Santoro J, et al. Antidepressant therapy for unexplained
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                                                             11. Chen TM, George S, Woodruff CA, Hsu S. Clinical manifestations of varicella-zoster
                                                                 virus infection. Dermatol Clin. 2002;20(2):267-282.
                                                             12. Lind CD. Dysphagia: evaluation and treatment. Gastroenterol Clin North Am. 2003;
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                                                             13. Dekel R, Pearson T, Wendel C, et al. Assessment of oesophageal motor function in
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                                                             14. Sarkar S, Aziz Q, Woolf CJ, et al. Contribution of central sensitisation to the develop-
                                                                 ment of non-cardiac chest pain. Lancet. 2000;356:1154-1159.
                                                             15. Lemme EM, Mores-Filho JP, Domingues G, et al. Manometric findings of esophageal
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a mystery, a vital part of managing affected patients—           esophagus: clinical presentation and endoscopic findings. Gastrointest Endosc.
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particularly those inclined toward anxiety and panic—is      17. Faybush EM, Fass R. Gastroesophageal reflux disease in noncardiac chest pain.
                                                                 Gastroenterol Clin North Am. 2004;33(1):41-54.
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                                                                 pathology. Radiol Clin North Am. 2003;41(6):1203-1216.
continuing drugs that patients had been taking when          21. Varia I, Logue E, O’Connor C, et al. Randomized trial of sertraline in patients with
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their chest pain was thought to be cardiac in origin, even   22. Park CH, Min SW, Sohn YH, et al. A prospective, randomized trial of endoscopic
after the pain was determined to have a noncardiac               band ligation vs. epinephrine injection for actively bleeding Mallory-Weiss syndrome.
                                                                 Gastrointest Endosc. 2004;60(1):22-27.
cause.30 Taking such a step would do more than prevent       23. Zaninotto G, Narne S, Costantini M, et al. Tailored approach to Zenker's diverticula.
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possible iatrogenic complications. It also would send a      24. Fleet RP, Beitman BD. Unexplained chest pain: when is it panic disorder? Clin
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                                                             25. Olden KW. The psychological aspects of noncardiac chest pain. Gastroenterol Clin
   The long-term outlook for patients with NCCP is               North Am. 2004;33(1):61-67.
                                                             26. Ho KY, Kang JY, Yeo B, Ng WL. Non-cardiac, non-oesophageal chest pain: the rel-
good, with a 10-year mortality rate of less than 1%.19           evance of psychological factors. Gut. 1998;43:105-110.
However, many patients suffer significant morbidity          27. American Psychiatric Association. Diagnostic and Statistical Manual of Mental
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from their pain and are more likely to be seen by a pri-         sociation; 2000.
                                                             28. Lowe B, Grafe K, Zipfel S, et al. Detecting panic disorder in medical and psycho-
mary health care provider than are members of the gen-           somatic outpatients: comparative validation of the Hospital Anxiety and Depression
                                                                 Scale, the Patient Health Questionnaire, a screening question, and physicians' diag-
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slightly more likely to use the health care system than      29. Botoman VA. Noncardiac chest pain. J Clin Gastroenterol. 2002;34(1):6-14.
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