Postoperative Nausea and Vomiting: Prevention and Treatment

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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

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Postoperative Nausea and VomitingPrevention and
Treatment

• http//www.wfubmc.edu/anesthesia
• pscuderi_at_wfubmc.edu

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Historical Perspective on PONV
Postoperative Nausea and Vomiting Its Etiology,
Treatment, and Prevention Mehernoor F. Watcha and
Paul F. White Anesthesiology 199277162-184
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Quality of Clinical Trials

• Appearance of control treatment
• Blinding of randomization process
• Blinding of patients and observers,
• Sample size estimate and power analysis
• Confidence intervals
• Statistical analyses
• Withdrawals
• Side effect discussions

Greenfield et al. Anesth Analg 200396S88
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Quality of Clinical Trials
Greenfield et al. Anesth Analg 200396S88
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Quality of Clinical Trials
Suggestions for Improvement

• Investigators
• Improve rigor of study protocols
• Improve quality of data analysis
• Peer Reviewers
• Process of randomization
• Power analysis
• Blinding

Greenfield et al. Anesth Analg 200396S88
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Critical Evaluation of Data

• Quality of individual clinical trials
• Type and adequacy of controls used
• Blinding process
• Sample size, power analysis
• Appropriateness of endpoints chosen
• Confidence limits particularly for negative
  studies
• Statistical analysis

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Critical Evaluation of Data

• Quality of individual clinical trials
• Evaluation of data in aggregate

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Evidence Based MedicineRating Scale

• Level of evidence based on study design
• I. Large randomized, controlled trial (ngt100
  per group)
• II. Systematic review
• III. Small randomized, controlled trial (nlt100
  per group)
• IV. Nonrandomized controlled trial or case
  report
• V. Expert opinion
• Strength of Recommendation based on expert
  opinion
• A. Good evidence to support the recommendation
• B. Fair evidence to support the recommendation
• C. Insufficient evidence to recommend for or
  against

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Critical Evaluation of Data

• Quality of individual clinical trials
• Evaluation of data in aggregate
• Estimation of treatment consequences

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Measures of Treatment Consequences

• Relative Risk Reduction
• The reduction of adverse events achieved by a
  treatment, expressed as a proportion of the
  control rate
• Odds Ratio
• The traditional expression of the relative
  likelihood of an outcome expressed as P/(1 - P)
  where P probability
• Absolute Risk Reduction
• The difference in event rates between the control
  and treatment groups
• Numbers Needed to be Treated (NNT)
• The number of patients who must be treated in
  order to prevent one adverse event. It is
  mathematically equivalent to the reciprocal of
  the absolute risk reduction.

Laupacis et al. NEJM 19883181728-1733
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Measures of Treatment Consequences
Laupacis et al. NEJM 19883181728-1733
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Topics

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

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Topics

• Risk factors

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Risk Factors

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

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Risk Factors
Non-anesthetic Factors

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

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Risk Factors
Anesthetic Related Factors

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

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Risk Factors
Postoperative Factors

• Pain
• Dizziness
• Ambulation
• Oral intake
• Opioids

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Risk FactorsPatient Specific
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.
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Risk FactorsPatient Specific
Logistic Regression

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

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Risk FactorsPatient Specific
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.
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Risk FactorsAnesthetic Related
Volatile Anesthetics
Compared to propofol
Apfel et al. BJA 200288659-668
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Risk FactorsAnesthetic Related
Nitrous Oxide and PONV
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Risk FactorsAnesthetic Related
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 199676186-193
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Risk FactorsSurgical Risk Factors
Duration of Surgery
Apfel et al. BJA 200288659-668 Sinclair et al.
Anesthesiology 1999 91109-118
Type of Surgery
Sinclair et al. Anesthesiology 1999
91109-118 Apfel et al. BJA 200288659-668 Fablin
g et al. Anesth Analg 200091358-361 Gan et al.
Anesthesiology 1996851036-1042
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Evidence Based MedicineRisk Factors for PONV in
Adults

• Patient-specific factors
• Female gender (I-A)
• Nonsmoking status (IV-A)
• History of PONV/motion sickness (IV-A)
• Anesthetic risk factors
• Use of volatile anesthetics (I-A)
• Nitrous oxide (II-A)
• Intraoperative opioids (II-A)
• Postoperative opioids (IV-A)
• Surgical risk factors
• Duration of surgery (IV-A)
• Type of surgery (IV-B)

Gan et al. et al. Anesth Analg 2003 9762-71
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Topics

• Risk factors
• Pharmacologic approaches to management

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Currently Available Medications

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

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Evidence Rating for Antiemetics
NNT
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Prevention of PONVOndansetron Versus Placebo
I-A
All patients, 0 - 24 hrs



p 0.010 p lt 0.001
McKenzie et al. Anesthesiology 19937821-28
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Ondansetron Dose ResponsePrevention
II-A
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
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Evidence Rating for Antiemetics
NNT
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Treatment of PONVOndansetron Versus Placebo
I-A






p lt 0.001
Scuderi et al. Anesthesiology 1993782-5 Hantler
et al. Anesthesiology 199277A16
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Ondansetron Dose ResponseTreatment
II-A
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
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVDolasetron Versus Placebo
I-A









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








p lt 0.001 compared to placebo
Kovac et al. Anesth Analg 199785546-552
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVGranisetron Versus Placebo
I-A
No Vomiting


p lt 0.001 compared to placebo
Wilson et al. BJA 199676515-518
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Prevention of PONVGranisetron Versus Placebo
No Nausea
I-A


p lt 0.001 compared to placebo
Wilson et al. BJA 199676515-518
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Prevention of PONVGranisetron Versus Placebo
I-A
Total Control


p lt 0.001 compared to placebo
Wilson et al. BJA 199676515-518
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Treatment of PONVGranisetron Versus Placebo
No Vomiting
I-A



p lt 0.001 compared to placebo
Taylor et al. JCA. 19979658-663
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Treatment of PONVGranisetron Versus Placebo
No Nausea
I-A



p lt 0.005 compared to placebo
Taylor et al. JCA. 19979658-663
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVOndansetron Versus Droperidol
Complete Response
I-A








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
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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
I-A
?

?
?
Fortney et al. Anesth Analg 199886731-738
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVDexamethasone
II-A

• 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
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVDimenhydrinate
II-A
Kranke, et al. Acta Anaesth Scand 200246238-244
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVPromethazine
III-B
No Vomiting

p lt 0.05 compared to placebo
Khalil et al. JCA 199911596-600
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Prevention of PONVPromethazine
III-B
No Nausea


p lt 0.05 compared to placebo
Khalil et al. JCA 199911596-600
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Prevention of PONVPromethazine
III-B
Total Response


p lt 0.05 compared to placebo
Khalil et al. JCA 199911596-600
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVMetoclopramide
II-A

• 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
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVScopolamine
II-A
Defined control event rate
Kranke, et al. Anesth Analg 200295133-143
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Prevention of PONVScopolamine
II-A
Adverse Events
Kranke, et al. Anesth Analg 200295133-143
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Evidence Rating for Antiemetics
NNT
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Prevention of PONVCombination Therapy
Ondansetron/Dexamethasone III-A

• 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. Anaesthetist. 2000 49713-20
  (meta analysis)

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Prevention of PONVCombination Therapy
Ondansetron/Droperidol III-A

• 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 5HT3-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

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Prevention of PONVCombination Therapy
Which Combination?
Ashraf et al. Anesthesiology 2001 95A-41
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Prevention of PONVTiming of Administration
Ondansetron III-A

• 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 III-A
Dexamethasone III-A
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Breakthrough PONVRepeat Dosing With Ondansetron
p 0.074 p 0.342
I-A


Kovac et al. J. Clin Anesth 199911453-459
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Topics

• Risk factors
• Pharmacologic approaches to management
• Adjuvants (nonpharmacologic)

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Management of PONVAdjuvants (Nonpharmacologic)

• P-6 acupuncture point stimulation III-A
• Supplemental oxygen III-C
• Aggressive perioperative rehydration III-A
• Preemptive analgesia IV-A

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Topics

• Risk factors
• Pharmacologic approaches to management
• Adjuvants (nonpharmacologic)
• Efficacy versus outcome

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Efficacy Versus Outcome
If efficacy alone is an appropriate endpoint when
evaluating analgesics, why isnt efficacy a valid
endpoint when evaluating antiemetics?
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Topics

• Risk factors
• Pharmacologic approaches to management
• Adjuvants (nonpharmacologic)
• Efficacy versus outcome
• Prevention versus treatment

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Prevention versus Treatment
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Frequency of PACU Treatment by Risk Factors and
Group
Scuderi et al. Anesthesiology. 199990360-371
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Prevention Versus Treatment
IA, IIIA
Routine administration of prophylactic
antiemetics does reduce the incidence of emesis
both before and after discharge however, it did
not improve any of the measures of outcome
following outpatient surgery except in patients
at the highest risk for symptoms.
Scuderi et al. Anesthesiology. 199990360-371
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Topics

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

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Post Discharge Symptoms Following Ambulatory
Surgery
Wu CL, et al. Anesthesiology 200296994-1003
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Postdischarge VomitingOndansetron Versus Placebo
III-A
plt0.05
Gan TJ, et al. Anesth Analg 2002941199-1200
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Topics

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

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Multimodal ManagementResults
III-A
Group I vs II Group I vs III Group II vs III
Scuderi at al. Anesth Analg 200091408-414
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Topics

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

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General Recommendations

• Use generic drugs for routine prophylaxis
• Treat breakthrough symptoms with 5HT3 antagonists
• Dont repeat dose with 5HT3 antagonists for
  failure
• Treat with different classes of antiemetics
• For high risk patients use combination
  prophylaxis
• Consider propofol infusion as part of anesthetic
• Prevent and control pain, hydrate aggressively
• Consider post-discharge therapy

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