Postoperative Nausea and Vomiting Prevention and Treatment by ooh30381

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									Postoperative Nausea and Vomiting:
Prevention and Treatment
    Phillip E. Scuderi, M.D.
    Department of Anesthesiology
    Wake Forest University School of Medicine
    Winston-Salem, NC 27157-1009
Topics
   Risk factors
   Pharmacologic approaches to management
   Adjuvants (nonpharmacologic)
   Efficacy versus outcome
   Prevention versus treatment
   Postdischarge nausea and vomiting
   Multimodal management
Risk Factors

      Non-anesthetic  factors
      Anesthetic related factors
      Postoperative factors
Risk Factors
    Non-anesthetic Factors
              Age
              Gender
              Body habitus
              Hx motion sickness
              Hx PONV
              Anxiety
              Concomitant disease
              Operative procedure
              Duration of surgery
Risk Factors

    Anesthetic Related Factors

               Preanesthetic medication
               Gastric distension
               Gastric suctioning
               Anesthetic technique
               Anesthetic agents
Risk Factors
    Postoperative Factors
               Pain
               Dizziness
               Ambulation
               Oral intake
               Opioids
Postoperative Nausea and Vomiting:
Anesthetic Related Factors


           Nitrous    oxide

           Volatile   anesthetics

           NMB   reversal

           Propofol
Risk Factors
Nitrous Oxide and PONV

  Omission of Nitrous Oxide during Anesthesia Reduces
  the Incidence of Postoperative Nausea and Vomiting. A
  Meta-Analysis
      Divatia et al. Anesthesiology 1996;85:1055-1062
  Twenty-Four of Twenty-Seven Studies Show a Greater
  Incidence of Emesis Associated with Nitrous Oxide than
  with Alternative Anesthetics
      Hartung. Anesth Analg 1996;83:114-116
  Omitting Nitrous Oxide in General Anaesthesia:
  Meta-Analysis of Intraoperative Awareness and
  Postoperative Emesis in Randomized Controlled Trials
      Tramer et al. BJA 1996;76:186-193
Risk Factors
Nitrous Oxide and PONV

Omitting nitrous oxide from general anesthesia:

    Decreases  POV significantly only if the
     baseline risk is high
    Does not affect nausea or complete control of
     emesis
    Increases the incidence of intraoperative
     awareness

                            Tramer et al. BJA 1996;76:186-193
Risk Factors
Volatile anesthetics

   Risk Factors           OR*                CI
   Volatile anesthetics
     isoflurane           3.41        2.18; 5.37
     sevoflurane          2.78        1.79; 4.31
     enflurane            3.11        1.98; 4.88

 * Compared to propofol
                           Apfel et al. BJA 2002;88:659-668
Risk Factors
Reversal of Neuromuscular Block

   Omitting  neostigmine may have a clinically
    relevant antiemetic effect when high doses
    are used
   Omitting NMB antagonism introduces a
    non-negligent risk of residual paralysis
    even when short acting NMB agents are
    used

                  Tramer MR, Fuchs-Buder T. BJA 1999;82:379-386
Risk Factors
Propofol and PONV
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Risk Factors
Antiemetic Effects               of Propofol
  Investigations    Randomized   Double-Blind   Placebo-Controlled   Effective
  Chemotherapy Induced Emesis
  Scher 1992             no          no                no              yes
  Borgeat 1993           no          no                no              yes
  Borgeat 1994           no          no                no              yes
  PONV
  Campbell 1991         yes          yes               yes              no
  Borgeat 1992          yes          yes               yes             yes
  Ewalenko 1996         yes          yes               yes             yes
  Montgomery 1996       yes          yes               yes              no
  Scuderi 1996          yes          yes               yes              no
  Gan 1997               no          no                no              yes
  Gan 1999              yes          yes               yes             yes
Risk Factors
Logistic Regression

  Palazzo M, Evans R. Logistic regression analysis of fixed patient
  factors for postoperative sickness: a model for risk assessment. Br J
  Anaesth 1993;70:135-40.

  Koivuranta M, Läärä E, Snåre L, Alahuhta S. A survey of postoperative
  nausea and vomiting. Anaesthesia 1997;52:443-49.

  Apfel CC, Greim CA, Haubitz I, et al. A risk score to predict the
  probability of postoperative vomiting in adults. Acta Anaesthesiol Scand
  1998;42:495-501.
Risk Factors
  Logistic Regression
      Younger  age
      Nonsmoking history
      Female
      Hx of motion sickness
      Hx of PONV
      Increased duration of operation
Risk Factors
  Simplified Scoring System
        Female
        Nonsmoking history
        Hx of motion sickness or PONV
        Use of postoperative opioids
    Incidence of PONV
     Risk Factors   Incidence
          0           10%
          1           21%
          2           39%
          3           61%
          4           79%       Apfel CC et al. Anesthesiology 1999;91:693-700.
Management of PONV:
Pharmacological Approaches

      Medications
      Dose response
      Comparative efficacy
      Combination therapy
      Timing of administration
Currently Available Medications

  5HT3 (serotonin) antagonists - ondansetron
  Butyrophenones - droperidol
  Benzamides - metoclopramide
  Antihistamines - promethazine, dimenhydrinate
  Steroids - dexamethasone
  Phenothiazines- promethazine, prochlorperazine
  Anticholinergics – scopolamine
5HT3 Antagonists and PONV
      5HT3 Antagonist    Clinical Trials

      Ondansetron *         275

      Dolasetron*            20

      Granisetron*           66

      Tropisetron            27

      Ramosetron             29

      Palenosetron            5

                        * Approved for PONV indication
Prevention of PONV:
Ondansetron Versus Placebo
All patients, 0 - 24 hrs

                                     100
      % of Patients with No Emesis




                                                                    †              †
                                                                   76             77
                                     80              *
                                                     62
                                     60
                                             46
                                     40

                                     20

                                      0
                                           Placebo   1 mg         4 mg           8 mg
   * p = 0.010                                              Ondansetron Dose
   † p < 0.001
                                                             McKenzie et al. Anesthesiology 1993;78:21-28
Ondansetron Dose Response:
Prevention
  Numbers Needed to be Treated

               Dose of           Early Efficacy        Late Efficacy
             Ondansetron           (0 - 6 hrs)          (0 - 48 hrs)
                 1 mg                   9.0                  15

                 4 mg                   5.5                  6.5

                 8 mg                   6.5                  5.0

 Only 4 mg and 8 mg were significantly different than placebo
 No further improvement with doses >8 mg


                                     Tramer et al. Anesthesiology 1997;87:1277-1289
Treatment of PONV:
Ondansetron Versus Placebo

                              100
   % with Complete Response




                              80
                                          *    *
                                               60   *
                                         57         57
                              60                                                    *      *
                                                                             *
                                                                             40
                                                                                    45     44
                              40    32
                                                                      20
                              20

                               0
                                         0 - 2 hr                            2 - 24 hr
                                              Placebo    1 mg      4 mg      8 mg
 * p < 0.001
                                                                Scuderi et al. Anesthesiology 1993;78:2-5
                                                                Hantler et al. Anesthesiology 1992;77:A16
Ondansetron Dose Response:
Treatment
 Numbers Needed to be Treated


               Dose of            Early Efficacy         Late Efficacy
             Ondansetron            (0 - 6 hrs)           (0 - 24 hrs)
                 1 mg                   3.8                  4.8

                 4 mg                   3.2                  3.9

                 8 mg                   3.1                  4.1


 All three doses significantly different than placebo
 No significant difference in antiemetic efficacy
   between the three doses of ondansetron
                                                Tramer et al. BMJ 1997;314:1088-1092
Breakthrough PONV:
Repeat Dosing With Ondansetron
                               100
                                                   * p = 0.074
   Percent Complete Response




                                80                 † p = 0.342

                                60
                                     43
                                             *
                                             34                               †
                                40                                  32
                                                                              28

                                20

                                 0
                                     0 - 2 hours                   0 - 24 hours

                                          Placebo       Ondansetron 4 mg

                                                      Kovac et al. J. Clin Anesth 1999;11:453-459
 Prevention of PONV:
 Dolasetron Versus Placebo

                           100
     Complete Response %




                           80
                                      * 52 **
                                       * ** 56                                        * *
                                                                                   * * *
                                                                                   * 55 57
                           60         50                   * * **
                                                           *                       52
                                                           46 * 43
                                                             39
                           40    31                   28                      33

                           20
                            0
                                 All Patients        Previous PONV              No PONV


                                           Placebo   12.5 mg      25 mg    50 mg

*p < 0.0003 compared to placebo
                                                            Graczyk et al. Anesth Analg 1997;84:325-330
Treatment of PONV:
Dolasetron Versus Placebo
                                    Placebo   12.5 mg   25 mg   50 mg     100 mg
                         100
   Complete Response %




                         80
                                     *
                                     * *
                                     55 *      *
                         60                  * *
                                            * 51
                                         50 48
                                                                     *
                                                                     *        * **
                         40                                          35   *
                                                                          *  *
                               27                                         28 29 29
                         20                                     11

                          0
                                      0 - 2 hrs                      0 - 24 hrs

*p < 0.001 compared to placebo
                                                           Kovac et al. Anesth Analg 1997;85:546-552
Prevention of PONV:
Ondansetron Versus Dolasetron
                            Placebo    Dolasetron 25 mg    Dolasetron 50 mg    Ondansetron 4 mg

                          100

                          80
                                                  *
                                                  *
                                                  71      *
                                                          *                            *
          % of Patients




                                                          64                           *
                                                                                       60      †
                          60               51                                                  54
                                      49
                                                                                43
                          40                                             36

                          20

                           0
                                      Complete Response                       Total Response

* p < 0.05 versus placebo and dolasetron 25 mg
† p < 0.05 versus placebo only

                                                 Korttila K et al. Acta Anaesthesiol Scand 1997;41:914-922
Prevention of PONV:
Ondansetron Versus Dolasetron
Postoperative Vomiting
        Dolasetron 12.5 mg              Dolasetron 25 mg     Ondansetron 4 mg        Ondansetron 8 mg
                                                      100
                             100                                                              98
        % without Symptoms




                                         96    96                               96      96
                                                                        94
                                   92




                             80
                                        In-hospital                          Postdischarge
 No statistically significant
 differences among the groups                              Zarate E, et al. Anesth Analg 2000;90:1352-1358
Prevention of PONV:
Ondansetron Versus Dolasetron
  Postoperative Nausea
          Dolasetron 12.5 mg              Dolasetron 25 mg   Ondansetron 4 mg        Ondansetron 8 mg

                               100                                                      87
          % without Symptoms




                                                                       82                     86
                                     73    76    77                             76
                               80                       70
                               60
                               40

                               20
                                0
                                          In-hospital                       Postdischarge
No statistically significant
                                                         Zarate E, et al. Anesth Analg 2000;90:1352-1358
differences among the groups
Prevention of PONV:
Ondansetron Versus Droperidol
Complete Response
                             Placebo   Droperidol 0.625 mg   Droperidol 1.25 mg    Ondansetron 4 mg

                             100

                              80                     *†
                                               *     69
                                                                                         *‡ *
             % of Patients




                                               63            *
                                                             62
                              60                                                   *     56    53
                                         46                                        48
                              40                                            36

                              20

                                0
                                                0 - 2 hr                           0 - 24 hr
* p < 0 .05 compared to placebo
† p < 0.05 compared to ondansetron 4 mg
‡ p ,<0.05 compared to droperidol 0.625 mg                        Fortney et al. Anesth Analg 1998;86:731-738
Prevention of PONV:
Ondansetron Versus Droperidol
No Nausea
                                        * p < 0 .05 compared to placebo
                                        † p < 0.05 compared to droperidol 0.625 mg
                     100                            and ondansetron 4 mg

                     80
     % of Patients




                     60                                                 †
                                                                       43        
                     40                                29                         29
                                        23
                     20
                      0
                                                            0 - 24 hr
                       Placebo   Droperidol 0.625 mg    Droperidol 1.25 mg    Ondansetron 4 mg


                                                              Fortney et al. Anesth Analg 1998;86:731-738
Droperidol Adverse Events Reports

   273 “reports” from 1997-2001
   127 serious adverse events
   89 total deaths
   Droperidol 2.5 mg or less
     – 6 deaths
     – 5 Torsades or VT (1 fatality)


                   Norton et al. Anesthesiology 2002:A-1196
Droperidol
FDA Box Warning
   No case details provided
   Droperidol has been used for over 40 years
   Why a problem now?
   No evidence of adverse events in published trials
   No published case reports
   An association does not prove cause and effect
   If prolonged QTc is an issue then 5HT3 antagonists should also
    carry the same warning
   At least 3 cases of VT associated with 5HT3 administration
   No “denominator” provided (or available)
Putting It in Perspective
      Circumstance             Annual Fatalities
      Transportation
        motor vehicle                      37,409
        pedestrian                          4,739
        cyclists                              690
        rail                                  518
        bus                                   299
        airline                                92
      Animal Related
        dog bite                              20
        auto-deer collisions                 130
      Other
        lightning                             90
        boating                              734
Prevention of PONV:
Metoclopramide

     “In summary, metoclopramide, although used as an
      antiemetic for almost 40 years in the prevention of PONV,
      has no clinically relevant antiemetic effect . . . it is very
      likely that the doses used in daily clinical practice are too
      low.”


 Henzi I, Walder B, and Tramer, MR. Metoclopramide in the prevention of
 postoperative nausea and vomiting: a quantitative systematic review of
 randomized, placebo-controlled studies. BJA 1999;83:761-771
Prevention of PONV:
Dexamethasone


     “In conclusion, in the surgical setting, a single prophylactic
      dose of dexamethasone is antiemetic compared with
      placebo without evidence of clinically relevant toxicity in
      otherwise healthy patients. Late efficacy (i.e., up to 24
      hours) seems to be most pronounced.”
 Henzi I, Walder B, and Tramer, MR. Dexamethasone for the prevention of
 postoperative nausea and vomiting: a quantitative systematic review. Anesth
 Analg 2000;90:186-194

 Eberhart LH. Morin AM. Georgieff M. Dexamethasone for prophylaxis of
 postoperative nausea and vomiting. A meta-analysis of randomized
 controlled studies. Anaesthesist. 2000 ;49:713-20
Prevention of PONV:
Dexamethasone

    Dose ranging
    Major gynecological surgery

                                  Placebo 1.25 mg 2.5 mg         5.0 mg     10.0 mg

          Patients                  30         30        30         30         30

          Vomiting                  19         15        8*         6*         6*

          Rescue required            5          0         0         0          0

         * P <0.05 compared with placebo and 1.25 mg

                                      Liu K, et al. Anesth Analg 1999;89:1316-1318
Prevention of PONV:
Scopolamine

 Undefined control event rate

                           Small Studies        Large Studies

        Outcome           Trials     NNT       Trials     NNT

          Vomiting          7         3.6         8        8.3

          Nausea            7         3.4         6        5.9

          PONV             11         2.5         9        7.1

          Rescue            4         3.8         6       20.0

                                Kranke, et al. Anesth Analg 2002;95:133-143
Prevention of PONV:
Scopolamine

 Defined control event rate

                              Small Studies       Large Studies

        Outcome           Trials       NNT       Trials     NNT

          Vomiting            6         3.3         5        5.9

          Nausea              2         5.3         5        5.0

          PONV                8         2.9         8        6.7

          Rescue              4         3.8         3        7.0

                                  Kranke, et al. Anesth Analg 2002;95:133-143
Prevention of PONV:
Scopolamine

 Adverse Events

              Event                         NNH

                  Visual disturbances         5.6

                  Dry mouth                  12.5

                  Dizziness                  50.0

                  Agitation                 100.1


                                  Kranke, et al. Anesth Analg 2002;95:133-143
Prevention of PONV:
Dimenhydrinate



                    Early (0-6 h)       Overall (0-48 h)

      Outcome      Trials     NNT       Trials    NNT

        PONV         8         8.3        16       5.0

        Vomiting     6         7.7        14       4.8

        Nausea       2         8.3        7        5.9




                         Kranke, et al. Acta Anaesth Scand 2002;46:238-244
Prevention of PONV:
Combination Therapy

Ondansetron/Dexamethasone
        McKenzie R, et al. Comparison of ondansetron with ondansetron plus
         dexamethasone in the prevention of postoperative nausea and
         vomiting. Anesth Analg 1994;79:961-964

        Lopez-Olaondo L, et al. Combination of ondansetron and
         dexamethasone in the prophylaxis of postoperative nausea and
         vomiting. BJA 1996;76:835-840

        Eberhart LH. Morin AM. Georgieff M. Dexamethasone for
         prophylaxis of postoperative nausea and vomiting. A meta-analysis of
         randomized controlled studies. Anaesthesist. 2000 ;49:713-20
Prevention of PONV:
Combination Therapy
Ondansetron/Droperidol
    Pueyo FJ, et al. Combination of ondansetron and droperidol in the
     prophylaxis of postoperative nausea and vomiting. Anesth Analg
     1996;83:117-122
    McKenzie R, et al. Droperidol/ondansetron combination controls nausea
     and vomiting after tubal banding. Anesth Analg 1996;83:1218-1222
    Klockgether-Radke A, et al. Ondansetron, droperidol and their combination
     for the prevention of post-operative vomiting in children. Eur J
     Anesthesiology. 1997;14:362-367
    Eberhart LH. Morin AM. Bothner U. Georgieff M. Droperidol and 5-ht3-
     receptor antagonists, alone or in combination, for prophylaxis of
     postoperative nausea and vomiting. A meta-analysis of randomized
     controlled trials. Acta Anaesthesiologica Scandinavica. 2000;44:1252-7
Prevention of PONV:
Combination Therapy
Which Combination?

               5-HT3 + drop      5-HT3 + dex
     Event       N    Rate         N         Rate      P-value        OR
  Early
   Nausea       138   17%         260        11%          0.12         1.6
   Vomiting     318    1%         419         1%          1.00         1.0
  Late
    Nausea      358   27%         623       21%*          0.02         1.4
    Vomiting    443    9%         813         9%          1.00         0.9


                              Ashraf et al. Anesthesiology 2001; 95:A-41
Prevention of PONV:
Combination Therapy

                   Placebo   Metoclopramide        Dolasetron      Ondansetron
  Predischarge
    nausea (%)       13            7                     3               3
    vomiting (%)     0             0                     0               0
    rescue (%)       0             0                     0               0
  Postdischarge
    nausea (%)       13           10                     7               3
    vomiting (%)     0             0                     0               0
    rescue (%)       0             0                     0               0


                                       Tang, et al. Anesthesiology 2001; 95:A43
Prevention of PONV:
Timing of Administration
Ondansetron
   Sun et al. The effect of timing on ondansetron administration in outpatients
    undergoing otolaryngologic surgery. Anesth Analg 1997;84:331-336

Dolasetron
   Chen et al. The effect of timing of dolasetron administration on its efficacy
    as a prophylactic antiemetic in the ambulatory setting. Anesth Analg
    2001;93:906-911

Dexamethasone
   Wang et al. The effect of timing of dexamethasone administration on its
    efficacy as a prophylactic antiemetic for postoperative nausea and vomiting.
    Anesth Analg 2000;91;136-139
Timing of Administration:
Dexamethasone
                             Group 1             Group 2             Group 3
                            (Preinduction)     (Postextubation)      (Placebo)
 0 – 2 hr
    nausea (%)                   10                  25                 33
    vomiting (%)                  5                  20                 20
    total (%)                   15*†                 45                 53
 2 – 24 hr
    nausea (%)                   15                  18                 30
    vomiting (%)                 10                  10                 25
    total (%)                   25*                 28*                 55

    * Compared to Group 3
    † Compared to Group 2               Wang et al. Anesth Analg 2000;91;136-139
Management of PONV:
Adjuvants (Nonpharmacologic)


     P-6 acupuncture point stimulation
     Supplemental oxygen
     Aggressive perioperative rehydration
     Preemptive analgesia
P-6 Acupuncture Point Stimulation
    Zarate E, Mingus M, White PF, Chiu JW,
     Scuderi PE, et al. The use of transcutaneous
     acupoint electrical stimulation for preventing
     nausea and vomiting after laparoscopic surgery.
     Anesth Analg 2001;92:629-35.
P-6 Acupuncture Point Stimulation
Control of Nausea
                            TAES            Sham               Placebo
    PACU                    25                 17                   28
    45 min                  36                 51                   32
    90 min                  27*                51                   33
    120 min                  27                40                   41
    4 hr                    26*                52                   35
    6 hr                    22*†               47                   43
    9 hr                    18*†               42                   47
    * compared to sham
    † compared to placebo     Zarate E, et al. Anesth Analg 2001;92:629-35
Supplemental Oxygen
   Greif R, Laciny S, Rapf B, et al. Supplemental
    oxygen reduces the incidence of postoperative
    nausea and vomiting. Anesthesiology
    1999;91:1246-52.
   Goll V, Ozan A, Greif R, et al. Ondansetron is no
    more effective than supplemental intraoperative
    oxygen for prevention of postoperative nausea
    and vomiting. Anesth Analg 2001;92:112-17.
Supplemental Oxygen
                           30 % Oxygen        80% Oxygen        P Value
  Male/Female                 57/62               41/71          0.110
  0-6 hr    PONV (%)           15.1                 8            0.141
            nausea (%)         15.1                 8            0.077
            vomiting (%)        1.7                 0            0.169
  6-24 hr   PONV (%)           22.2               19.9           0.045
            nausea (%)         17.6                8.9           0.066
            vomiting (%)        5.9                1.8           0.108
  0-24 hr   PONV (%)           30.3                17            0.027
            nausea (%)         27.7                16            0.034
            vomiting (%)        5.9                1.8           0.108

                           Greif et al. Anesthesiology 1999;91:1246-1252
Supplemental Oxygen
                             30 % Oxygen      80% Oxygen        Ondansetron
 Patients (female)               80                79                71
 0-6 hr      PONV (%)            36                20                27
             nausea (%)          35                20                27
             vomiting (%)        19                 9                14
 6-24 hr     PONV (%)            13                 4                 6
              nausea (%)         11                 4                 6
              vomiting (%)        9                 4                 1
 0-24 hr     PONV (%)            44                22*               30
             nausea (%)          41                22*               30
             vomiting (%)        26                10*               15

                                  Goll et al. Anesth Analg 2001;92:112-117
Intravenous Fluid Therapy
Incidence of Postop Nausea
                    20
                                           Low Infusion     High Infusion
                    15
      Incidence %




                    10


                    5
                                                                                *
                    0
                         30 min   60 min                  DIS               Day 1
                                             Time
High Infusion = 20 ml/kg
                                  Yogendran S, et al. Anesth Analg 1995;80:682-686
Low Infusion = 2 ml/kg
Pain and PONV

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Efficacy Versus Outcome
Surrogate End Points
Are They Meaningful


  Appropriate end points
     Duration of PACU stay
     Incidence of unplanned admissions
     Patient satisfaction

                  Fisher. Anesthesiology 1994;81:795-796
Measures of Outcome

        Mortality

        Morbidity

        Patient   satisfaction

        Cost
Risk of Mortality and Adverse Outcome
in a Tertiary Care Population

     Adverse outcomes                               1:125

     Death (all causes)                             1:500

     Anesthesia provider error causing adverse      1:1,500
     outcome
     Risk of death (anesthesia cause only)          1:250,000



                    Patient Safety in Anesthesia Practice. Morel and Eichorn (ed)
Complications of PONV
     Electrolyte imbalance
     Tension on sutures, evisceration
     Venous hypertension, bleeding
     Aspiration
     Delayed discharge (outpatients)
     Dehydration
     Unanticipated admission
Unanticipated Admissions
                  Reasons for Admission   Number Percent
                  Pain                      18      19
                  Bleeding                  18      19
                  Intractable Vomiting      17      18
                  Perforated Uterus          7      7
                  Extensive Surgery         6       6
                  Urinary Retention         5       5
                  Additional Surgery        4       4




 Overall Admission Rate = 0.01
 PONV Admission Rate = 0.002              Gold et al. JAMA 1989;262:3008-3010
Cost Savings From the
Management of PONV

 Analysis of strategies to decrease postanesthesia care
 unit costs:
     1. Supplies and medications account for 2% of PACU charges
     2. Personnel account for almost all PACU charges
     3. PACU staffing is determined by peak PACU patient load
     4. Peak PACU patient load is determined by OR scheduling
     5. Elimination of PONV would decrease PACU stay by less than
        4.8% which would not be sufficient to decrease the level of
        PACU staffing



                             Dexter et al. Anesthesiology 1995;82:94-101
 Subject Preference Following Surgery
Preoperative
                             Levels                        Preference
     Mental Acuity   awake   drowsy      asleep                5%
     Pain            none     mild     moderate                18%
     Emetic Sxs      none    nausea    vomiting                40%
     Muscle Aches     no      yes                              11%
     Dysphoria        no      yes                              16%
     Cost            none     $15         $35       $50        10%


                               Orkin FK. Anesth Analg 1992;74:S225
Patient Preference Following Surgery
Preoperative
                       Mean    Relative Value             Ranking (%)
       Outcome         Rank     (out of 100)      First     Second      Third
   Vomiting            2.55         18.5           24         31         23
   Gagging             2.95         18.6           22         20         24
   Pain                3.46         16.8           22         16         16
   Nausea              4.05         12.5            6         18         14
   Recall w/o pain     4.87         13.8           20         6           4
   Shivering           5.39         7.3             1         6           7
   Residual weakness   5.43         7.2             5         4          11
   Sore Throat         8.04         3.2             0         0           0
   Somnolence          8.18         2.9             0         0           0
   Normal              10.00        0.2             0         0           0
                                  Macario et al. Anesth Analg, 1999;89:652-658
Patient Satisfaction With Outpatient Surgery
Postoperative
                                   Considered
                                                    Ranking in     Rank Order
              Factor                 Factor
                                                    Top 5 (%)       of top 5
                                   Important
  Preoperative
       Avoidance of Delays              86               45             5
       Starting IV smoothly             95               53             4
  Intraoperative
       Friendliness of OR Staff         97               67             1
  Postoperative
       Management of Postop pain        96               62             3
       Surgeon’s PACU visit             96               63             2
       Treatment of PONV                90               31

                            Tarazi and Philip. Am J Anesthesiology 1998;25:154-157
Efficacy Versus Outcome



   If efficacy is an appropriate endpoint when
   evaluating analgesics, why not when evaluating
   antiemetics?
Prevention Versus Treatment
Question:
   Does routine* administration of prophylactic
   antiemetics improve outcome when compared to
   rapid symptomatic treatment of postoperative
   nausea and/or vomiting?

   *Routine: habitual or mechanical (i.e., mindless)
   performance of an established procedure
Frequency of PACU Treatment
by Risk Factors and Group
                                                           PACU TREATMENT
                         RISK FACTORS                     REQUIRED BY GROUP
                            Prior       Emetogenic
    Subgroup   Gender      History      Procedure1         Ondansetron        Placebo
       A        Male         Yes            Yes                0%              50%
       B        Male         Yes            No                 25%             38%
       C        Male         No             Yes                7%              25%
       D        Male         No             No                 16%             16%
       E       Female        Yes            Yes                38%             57%
       F       Female        Yes            No                 45%             53%
       G       Female        No             Yes                29%             31%
       H       Female        No             No                 14%             17%

1
  Emetogenic procedures - laparoscopy, strabismus surgery, middle ear surgery, herniography,
tonsillectomy, adenoidectomy, uvulopalatopharyngoplasty

                                                     Scuderi et al. Anesthesiology. 1999;90:360-371
Efficacy of Prophylaxis – Overall

                                Ondansetron           Placebo        p-value


      Total                         285                 290

      Nausea Score PACU Entry
        median, 75th, 90th         0, 0, 0              0,0,2         0.54

      No Tx Required (%)         204 (71.6)          179 (61.7)       0.01

      Treatment Required
         Nausea (%)              64 (22.5)            70 (24.1)        0.63
         Vomiting (%)             17 (6.0)            41 (14.1)       0.001
         Total (%)                81 (28)             111 (38)         0.01

      Nausea Score @ TX
        median, 75th, 90th         5,8,10              6,9,10
        nausea score >0 (%)        (100)               (96.4)         0.14




                                             Scuderi et al. Anesthesiology. 1999;90:360-371
Efficacy of Prophylaxis - Group E

                             Ondansetron            Placebo        p-value


   Total                         58                    60

   Nausea Score PACU Entry
     median, 75th, 90th         0,0,4                 0,0,6          0.49

   No Tx Required (%)          36 (62)               26 (43)        0.045

         ent
   Treatm Required
      Nausea (%  )             17 (29)              21 (35)
      Vom iting (% )            5 (9)               13 (22)
      Total (% )               22 (38)              34 (57)         0.045




                                         Scuderi et al. Anesthesiology. 1999;90:360-371
Outcomes - Treatment vs Prophylaxis
Patient Satisfaction, Time to Discharge

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                           Scuderi et al. Anesthesiology. 1999;90:360-371
Prevention Versus Treatment

Answer:
  Routine administration of prophylactic antiemetics does
  reduce the incidence of emesis both before and after
  discharge; however, it does not improve “objective”
  measures of outcome following outpatient surgery except
  in patients at the highest risk for symptoms
Post Discharge Nausea and Vomiting

       Incidence
       Severity
       Contributing   factors
       Prevention
       Treatment
Post Discharge Symptoms Following
Ambulatory Surgery
         Symptom            Incidence (%)
     Pain                         45
     Nausea                       17
     Vomiting                      8
     Headache                     17
     Drowsiness                   42
     Dizziness                    18
     Fatigue                      21

              Wu CL, et al. Anesthesiology 2002;96:994-1003
Strabismus Surgery
Postdischarge Vomiting


                        Ondansetron     Droperidol     Metoclopramide        Placebo


Patients                     40             40                 40               40


Predischarge emesis        2 (5%)*        2 (5%)*          13 (33%)         10 (25%)


Postdischarge emesis      10 (25%)       10 (25%)           8 (20%)         10 (25%)




      *Significantly different from metoclopramide (p=0.003) and placebo (p=0.025)

                                              Scuderi PE, et al. JCA 1997;9:551-558
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                                   Scuderi PE, et al. JCA 1997;9:551-558
Postdischarge Vomiting:
Ondansetron versus Placebo
                                Ondansetron            Placebo         P-value
                                  (n = 70)             (n = 70)
  Predischarge
   Patients with emesis           6 (8.6 %)           4 (5.7%)          0.75
   Patients rescued               7 (10%)             6 (8.6%)          1.00
   Emesis (post rescue)           1 (1.4%)            1 (1.4%)          1.00
  Postdischarge
   Patients with emesis           6 (8.6%)            9 (12.9%)         0.59
     Relative risk (95% CI)   0.667 (0.46; 5.70)
   Time to first emesis
      Median hr (range)           17 (1, 20)          5 (1, 16)         0.05
      MeanSEM                   13.8  3.0           5.9  1.7

                                  Scuderi PE, et al. Anesthesiology 2000;93:A37
Postdischarge Vomiting:
Ondansetron versus Placebo

                        ODT           Placebo            P-value

 patients               30                30

 Predischarge emesis    3%               0%                 n.s

 Predischarge nausea    40%              37%                n.s

 Postdischarge emesis   3%*              23%               0.02

 Postdischarge nausea   30%              50%               0.11

    * p<0.05
                              Gan TJ, et al. Anesth Analg 2002;94:1199-1200
Multimodal Management of PONV:
Hypothesis


 A   multi-modal approach to the management
   of PONV can result in a zero incidence of
   vomiting (and perhaps nausea) in the
   immediate postoperative period (i.e.,
   PACU)


                   Scuderi at al. Anesth Analg 2000;91:408-414
 Multimodal Management of PONV:
 Results
                                               Group I       Group II       Group III        P values
                                            Multimodal     Ondansetron      Placebo
Patients                                              60         42            37
Hx Risk Factors (%)                                   48         64            65             0.17*†
Tx required (%)                                       2          24            41           <0.0001*†
Vomiting before discharge (%)                         0          7             22         0.67* 0.003†
Vomiting after discharge (%)                          12         21            32          0.27* 0.02†
Satisfaction with PONV (%)                        100           100            92             0.05†‡
Satisfaction score <10 (%)                            5          6             37        1.00* 0.0013‡
Time to discharge ready (mean)                    128           162            192      0.0015*; 0.0001†

 *Group I vs II; † Group I vs III; Group II vs III‡        Scuderi at al. Anesth Analg 2000;91:408-414
Multimodal Management of PONV:
Simplified Algorithm
I. INDUCTION                        II. MAINTENANCE
    A. PreO2                            A. Propofol 50 mcg/kg/min
    B. Propofol 2 - 4 mg/kg             B. Potent inhalation agent
    C. Opioid prn                       C. Nitrous oxide prn
    D. Neuromuscular blockade prn       E. NMB reversal prn
    C. Droperidol 10 mcg/kg
    D. Decadron 4 - 8 mg            III. EMERGENCE
                                        A. Ondansetron 1 mg IV
                                        B. Suction oropharynx
                                        C. Extubate when awake
Multimodal Management of PONV:
Simplified Algorithm
  Cost Analysis
                                      COST ($)

  Case duration              1 hour       2 hours   3 hours

  Droperidol (10 mcg/kg)     $2.10        $2.10     $2.10

  Dexamethasone (8 mg)       $1.30        $1.30     $1.30

  Ondansetron (1 mg)         $4.00        $4.00     $4.00

  Propofol (50 mcg/kg/min)   $7.50        $15.00    $22.50

  Total Cost                 $14.90       $22.40    $29.90
Multimodal Management of PONV:
Conclusions

 Eliminationof PONV in outpatients is possible with
  multi-modal management

 Algorithm   may be institution and/or procedure specific

 Identificationof the optimal management algorithm may
  require several iterations

 Elimination of PONV may not improve objective
  measures of outcome
General Recommendations
 Use generic drugs for “routine” prophylaxis
 Treat breakthrough symptoms with 5HT3 antagonists
 Don’t repeat dose with 5HT3 antagonists
 Treat with different classes of antiemetics
 For high risk patients use combination prophylaxis
 Consider propofol infusion as part of anesthetic
 Prevent and control pain
 Consider post-discharge therapy

								
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