Postoperative Nausea and Vomiting: Prevention and Treatment

1
Postoperative Nausea and VomitingPrevention and
Treatment

• Phillip E. Scuderi, M.D.
• Department of Anesthesiology
• Wake Forest University School of Medicine
• Winston-Salem, NC 27157-1009

2
Topics

• Risk factors
• Pharmacologic approaches to management
• Adjuvants (nonpharmacologic)
• Efficacy versus outcome
• Prevention versus treatment
• Postdischarge nausea and vomiting
• Multimodal management

3
Risk Factors

• Non-anesthetic factors
• Anesthetic related factors
• Postoperative factors

4
Risk Factors
Non-anesthetic Factors

• Age
• Gender
• Body habitus
• Hx motion sickness
• Hx PONV
• Anxiety
• Concomitant disease
• Operative procedure
• Duration of surgery

5
Risk Factors
Anesthetic Related Factors

• Preanesthetic medication
• Gastric distension
• Gastric suctioning
• Anesthetic technique
• Anesthetic agents

6
Risk Factors
Postoperative Factors

• Pain
• Dizziness
• Ambulation
• Oral intake
• Opioids

7
Postoperative Nausea and VomitingAnesthetic
Related Factors

• Nitrous oxide
• Volatile anesthetics
• NMB reversal
• Propofol

8
Risk FactorsNitrous Oxide and PONV
9
Risk FactorsNitrous 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 199676186-193
10
Risk FactorsVolatile anesthetics
Compared to propofol
Apfel et al. BJA 200288659-668
11
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 199982379-386
12
Risk Factors Propofol and PONV
Analysis by NNT
13
Risk Factors Antiemetic Effects of Propofol
14
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 199370135-40.
Koivuranta M, Läärä E, Snåre L, Alahuhta S. A
survey of postoperative nausea and vomiting.
Anaesthesia 199752443-49.
Apfel CC, Greim CA, Haubitz I, et al. A risk
score to predict the probability of postoperative
vomiting in adults. Acta Anaesthesiol Scand
199842495-501.
15
Risk Factors
Logistic Regression

• Younger age
• Nonsmoking history
• Female
• Hx of motion sickness
• Hx of PONV
• Increased duration of operation

16
Risk Factors
Simplified Scoring System

• Female
• Nonsmoking history
• Hx of motion sickness or PONV
• Use of postoperative opioids

Incidence of PONV
Apfel CC et al. Anesthesiology 199991693-700.
17
Management of PONVPharmacological Approaches

• Medications
• Dose response
• Comparative efficacy
• Combination therapy
• Timing of administration

18
Currently Available Medications

• 5HT3 (serotonin) antagonists - ondansetron
• Butyrophenones - droperidol
• Benzamides - metoclopramide
• Antihistamines - promethazine, dimenhydrinate
• Steroids - dexamethasone
• Phenothiazines- promethazine, prochlorperazine
• Anticholinergics scopolamine

19
5HT3 Antagonists and PONV
Approved for PONV indication
20
Prevention of PONVOndansetron Versus Placebo
All patients, 0 - 24 hrs



p 0.010 p lt 0.001
McKenzie et al. Anesthesiology 19937821-28
21
Ondansetron Dose ResponsePrevention
Numbers Needed to be Treated

• Only 4 mg and 8 mg were significantly different
  than placebo
• No further improvement with doses gt8 mg

Tramer et al. Anesthesiology 1997871277-1289
22
Treatment of PONVOndansetron Versus Placebo






p lt 0.001
Scuderi et al. Anesthesiology 1993782-5 Hantler
et al. Anesthesiology 199277A16
23
Ondansetron Dose ResponseTreatment
Numbers Needed to be Treated

• All three doses significantly different than
  placebo
• No significant difference in antiemetic efficacy
  between the three doses of ondansetron

Tramer et al. BMJ 19973141088-1092
24
Breakthrough PONVRepeat Dosing With Ondansetron
p 0.074 p 0.342


Kovac et al. J. Clin Anesth 199911453-459
25
Prevention of PONVDolasetron Versus Placebo


















p lt 0.0003 compared to placebo
Graczyk et al. Anesth Analg 199784325-330
26
Treatment of PONVDolasetron Versus Placebo
















p lt 0.001 compared to placebo
Kovac et al. Anesth Analg 199785546-552
27
Prevention of PONVOndansetron Versus Dolasetron







p lt 0.05 versus placebo and dolasetron 25 mg
p lt 0.05 versus placebo only
Korttila K et al. Acta Anaesthesiol Scand
199741914-922
28
Prevention of PONVOndansetron Versus Dolasetron
Postoperative Vomiting
No statistically significant differences among
the groups
Zarate E, et al. Anesth Analg 2000901352-1358
29
Prevention of PONVOndansetron Versus Dolasetron
Postoperative Nausea
No statistically significant differences among
the groups
Zarate E, et al. Anesth Analg 2000901352-1358
30
Prevention of PONVOndansetron Versus Droperidol
Complete Response








p lt 0 .05 compared to placebo p lt 0.05
compared to ondansetron 4 mg p ,lt0.05 compared
to droperidol 0.625 mg
Fortney et al. Anesth Analg 199886731-738
31
Prevention of PONVOndansetron Versus Droperidol
No Nausea
p lt 0 .05 compared to placebo p lt 0.05
compared to droperidol 0.625 mg and
ondansetron 4 mg
?

?
?
Fortney et al. Anesth Analg 199886731-738
32
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 2002A-1196
33
DroperidolFDA 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)

34
Putting It in Perspective
35
Prevention of PONVMetoclopramide

• 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
199983761-771
36
Prevention of PONVDexamethasone

• 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 200090186-194
Eberhart LH. Morin AM. Georgieff M. Dexamethasone
for prophylaxis of postoperative nausea and
vomiting. A meta-analysis of randomized
controlled studies. Anaesthesist. 2000 49713-20
37
Prevention of PONVDexamethasone

• Dose ranging
• Major gynecological surgery

P lt0.05 compared with placebo and 1.25 mg
Liu K, et al. Anesth Analg 1999891316-1318
38
Prevention of PONVScopolamine
Undefined control event rate
Kranke, et al. Anesth Analg 200295133-143
39
Prevention of PONVScopolamine
Defined control event rate
Kranke, et al. Anesth Analg 200295133-143
40
Prevention of PONVScopolamine
Adverse Events
Kranke, et al. Anesth Analg 200295133-143
41
Prevention of PONVDimenhydrinate
Kranke, et al. Acta Anaesth Scand 200246238-244
42
Prevention of PONVCombination Therapy
Ondansetron/Dexamethasone

• McKenzie R, et al. Comparison of ondansetron with
  ondansetron plus dexamethasone in the prevention
  of postoperative nausea and vomiting. Anesth
  Analg 199479961-964
• Lopez-Olaondo L, et al. Combination of
  ondansetron and dexamethasone in the prophylaxis
  of postoperative nausea and vomiting. BJA
  199676835-840
• Eberhart LH. Morin AM. Georgieff M. Dexamethasone
  for prophylaxis of postoperative nausea and
  vomiting. A meta-analysis of randomized
  controlled studies. Anaesthesist. 2000 49713-20

43
Prevention of PONVCombination Therapy
Ondansetron/Droperidol

• Pueyo FJ, et al. Combination of ondansetron and
  droperidol in the prophylaxis of postoperative
  nausea and vomiting. Anesth Analg 199683117-122
• McKenzie R, et al. Droperidol/ondansetron
  combination controls nausea and vomiting after
  tubal banding. Anesth Analg 1996831218-1222
• Klockgether-Radke A, et al. Ondansetron,
  droperidol and their combination for the
  prevention of post-operative vomiting in
  children. Eur J Anesthesiology. 199714362-367
• 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.
  2000441252-7

44
Prevention of PONVCombination Therapy
Which Combination?
Ashraf et al. Anesthesiology 2001 95A-41
45
Prevention of PONVCombination Therapy
Tang, et al. Anesthesiology 2001 95A43
46
Prevention of PONVTiming of Administration
Ondansetron

• Sun et al. The effect of timing on ondansetron
  administration in outpatients undergoing
  otolaryngologic surgery. Anesth Analg
  199784331-336
• Chen et al. The effect of timing of dolasetron
  administration on its efficacy as a prophylactic
  antiemetic in the ambulatory setting. Anesth
  Analg 200193906-911
• Wang et al. The effect of timing of dexamethasone
  administration on its efficacy as a prophylactic
  antiemetic for postoperative nausea and vomiting.
  Anesth Analg 200091136-139

Dolasetron
Dexamethasone
47
Timing of AdministrationDexamethasone
Compared to Group 3 Compared to Group 2
Wang et al. Anesth Analg 200091136-139
48
Management of PONVAdjuvants (Nonpharmacologic)

• P-6 acupuncture point stimulation
• Supplemental oxygen
• Aggressive perioperative rehydration
• Preemptive analgesia

49
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
  200192629-35.

50
P-6 Acupuncture Point Stimulation
Control of Nausea
compared to sham compared to placebo
Zarate E, et al. Anesth Analg 200192629-35
51
Supplemental Oxygen

• Greif R, Laciny S, Rapf B, et al. Supplemental
  oxygen reduces the incidence of postoperative
  nausea and vomiting. Anesthesiology
  1999911246-52.
• 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 200192112-17.

52
Supplemental Oxygen
Greif et al. Anesthesiology 1999911246-1252
53
Supplemental Oxygen
Goll et al. Anesth Analg 200192112-117
54
Intravenous Fluid Therapy
Incidence of Postop Nausea

High Infusion 20 ml/kg Low Infusion 2 ml/kg
Yogendran S, et al. Anesth Analg 199580682-686
55
Pain and PONV
56
Efficacy Versus Outcome

57
Surrogate End PointsAre They Meaningful

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

Fisher. Anesthesiology 199481795-796
58
Measures of Outcome

• Mortality
• Morbidity
• Patient satisfaction
• Cost

59
Risk of Mortality and Adverse Outcome in a
Tertiary Care Population
Patient Safety in Anesthesia Practice. Morel and
Eichorn (ed)
60
Complications of PONV

• Electrolyte imbalance
• Tension on sutures, evisceration
• Venous hypertension, bleeding
• Aspiration
• Delayed discharge (outpatients)
• Dehydration
• Unanticipated admission

61
Unanticipated Admissions
Overall Admission Rate 0.01 PONV Admission Rate
0.002
Gold et al. JAMA 19892623008-3010
62
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 19958294-101
63
Subject Preference Following Surgery
Preoperative
Orkin FK. Anesth Analg 199274S225
64
Patient Preference Following Surgery
Preoperative
Macario et al. Anesth Analg, 199989652-658
65
Patient Satisfaction With Outpatient Surgery
Postoperative
Tarazi and Philip. Am J Anesthesiology
199825154-157
66
Efficacy Versus Outcome
If efficacy is an appropriate endpoint when
evaluating analgesics, why not when evaluating
antiemetics?
67
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
68
Frequency of PACU Treatment by Risk Factors and
Group
Scuderi et al. Anesthesiology. 199990360-371
69
Efficacy of Prophylaxis Overall
Scuderi et al. Anesthesiology. 199990360-371
70
Efficacy of Prophylaxis - Group E
Scuderi et al. Anesthesiology. 199990360-371
71
Outcomes - Treatment vs Prophylaxis Patient
Satisfaction, Time to Discharge
Scuderi et al. Anesthesiology. 199990360-371
72
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
73
Post Discharge Nausea and Vomiting

• Incidence
• Severity
• Contributing factors
• Prevention
• Treatment

74
Post Discharge Symptoms Following Ambulatory
Surgery
Wu CL, et al. Anesthesiology 200296994-1003
75
Strabismus SurgeryPostdischarge Vomiting
Significantly different from metoclopramide
(p0.003) and placebo (p0.025)
Scuderi PE, et al. JCA 19979551-558
76
68
Scuderi PE, et al. JCA 19979551-558
77
Postdischarge VomitingOndansetron versus Placebo
Scuderi PE, et al. Anesthesiology 200093A37
78
Postdischarge VomitingOndansetron versus Placebo
plt0.05
Gan TJ, et al. Anesth Analg 2002941199-1200
79
Multimodal Management of PONVHypothesis

• 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 200091408-414
80
Multimodal Management of PONVResults
Scuderi at al. Anesth Analg 200091408-414
Group I vs II Group I vs III Group II vs III
81
Multimodal Management of PONVSimplified
Algorithm

• I. INDUCTION
• A. PreO2
• B. Propofol 2 - 4 mg/kg
• C. Opioid prn
• D. Neuromuscular blockade prn
• C. Droperidol 10 mcg/kg
• D. Decadron 4 - 8 mg

• II. MAINTENANCE
• A. Propofol 50 mcg/kg/min
• B. Potent inhalation agent
• C. Nitrous oxide prn
• E. NMB reversal prn
• III. EMERGENCE
• A. Ondansetron 1 mg IV
• B. Suction oropharynx
• C. Extubate when awake

82
Multimodal Management of PONVSimplified
Algorithm
Cost Analysis
83
Multimodal Management of PONVConclusions

• Elimination of PONV in outpatients is possible
  with multi-modal management
• Algorithm may be institution and/or procedure
  specific
• Identification of the optimal management
  algorithm may require several iterations
• Elimination of PONV may not improve objective
  measures of outcome

84
General Recommendations

• Use generic drugs for routine prophylaxis
• Treat breakthrough symptoms with 5HT3 antagonists
• Dont 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