SOGC CLINICAL PRACTICE GUIDELINE SOGC CLINICAL PRACTICE GUIDELINE Guideline for the Management of Postoperative Nausea and Vomiting
2. When the choice is available, patients should be advised that the
risk of PONV decreases when regional rather than general
This guideline has been approved by Executive and Council of the
Society of Obstetricians and Gynaecologists of Canada.
3. The perioperative use of opioids should be minimized. Surgeons
should evaluate the risks/benefits of opioid administration in light
4. Prophylactic antiemetics should be administered to patients with
moderate or high risk of developing PONV. (II-1A)
5. In patients with a high risk of developing PONV, combination
antiemetic therapy should be considered. (III-B)
6. Acupoint electrical stimulation may be used as an alternative or
adjuvant therapy for prevention of PONV. (II-1A)
Objective: To provide recommendations for the management of
postoperative nausea and vomiting (PONV), which may affect as
7. For patients with PONV who did not receive prophylaxis or in
whom prophylaxis failed, antiemetic treatment should beadministered as soon as feasible. (III-A)
Methods and Evidence: Medline, PubMed, and the Cochrane
Database were searched for articles published in English from
8. When prophylaxis with one drug has failed, a repeat dose of this
1995 to 2007. Recognizing that we must work as a team to
drug should not be initiated as a rescue therapy; instead, a drug
optimize the care of our patients perioperatively, this guideline was
from a different class of antiemetic drugs should be
written in partnership with anaesthesiologists. Options: The areas of clinical practice considered in formulating this
9. As patients who undergo surgery in surgical daycare units may
guideline are prevention and prophylaxis, treatment, both medical
have PONV after they are discharged, they should be given
and alternative, and patient education. Outcomes: Implementation of this guideline should optimize the
10. Patients at high risk of developing PDNV should be provided with
prevention of and prophylaxis against PONV and the prompt
treatment of women who suffer from PONV following gynaecologic
J Obstet Gynaecol Can 2008;30(7):600–607
surgery. Increased awareness of options for management shouldhelp minimize the effects of PONV. INTRODUCTION Benefits, Harms, and Costs: PONV results not only in increased
patient discomfort and dissatisfaction but also in increased costsrelated to length of hospital stay. Cost of medications to prevent
Postoperative nausea and vomiting, defined as nausea
and treat PONV must be weighed against improved surgical
and/or vomiting occurring within 24 hours after sur-
experience for the patient and decreased costs to the system.
gery, affects between 20% and 30% of patients.1–4 As many
Values: Recommendations were made according to the guidelines
as 70% to 80% of patients at high risk may be affected.5 The
developed by the Canadian Task Force on Preventive Health
etiology of PONV is thought to be multifactorial, involving
individual, anaesthetic, and surgical risk factors.2,5,6 PONV
results in increased patient discomfort and dissatisfaction6
1. Physicians should be aware of the risk factors associated with
PONV, and the baseline risks should be reduced whenever
and in increased costs related to length of hospital stay. One
study revealed that the time to discharge was increased by25% in patients with PONV.7 Serious medical complica-tions such as pulmonary aspiration, although uncommon,are also associated with vomiting.6
Key Words: Postoperative nausea, postoperative vomiting This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the SOGC.
l JULY JOGC JUILLET 2008 Guideline for the Management of Postoperative Nausea and Vomiting Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on Preventive Health Care
Evidence obtained from at least one properly randomized
A. There is good evidence to recommend the clinical preventive
II-1: Evidence from well-designed controlled trials without
B. There is fair evidence to recommend the clinical preventive
II-2: Evidence from well-designed cohort (prospective or
C. The existing evidence is conflicting and does not allow to
retrospective) or case-control studies, preferably from more
make a recommendation for or against use of the clinical
preventive action; however, other factors may influencedecision-making
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
D. There is fair evidence to recommend against the clinical
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
E. There is good evidence to recommend against the clinical
III: Opinions of respected authorities, based on clinical
L. There is insufficient evidence (in quantity or quality) to make
experience, descriptive studies, or reports of expert
a recommendation; however, other factors may influence
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Forceon Preventive Health Care.75†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The CanadianTask Force on Preventive Health Care.75
PONV is a significant problem for patients: in one study,
afferent pathways involved in stimulating the vomiting cen-
patients were more concerned about PONV than about
postoperative pain8; in another, patients were willing to
spend up to US $100 for an effective antiemetic treatment.9
2. the vagal mucosal pathway in the gastrointestinal system,
Several thousand studies examining PONV have been pub-lished, and several hundred new papers are published each
3. neuronal pathways from the vestibular system,
year on the topic. Guidelines for the prevention and man-
4. reflex afferent pathways from the cerebral cortex C2,3,
agement of PONV have been published by anaesthetic
Management of PONV for gynaecological patients in mosthospitals continues to be on an ad hoc basis. The aim of
Stimulation of one of these afferent pathways can activate
these guidelines is to provide information on the manage-
ment of PONV in gynaecological patients.
dopaminergic, histaminergic, or serotonergic receptors. PHYSIOLOGY OF NAUSEA AND VOMITING MANAGEMENT OF PONV
Primary control of nausea and vomiting arises from the
Reduction in Baseline Risk Factors
vomiting centre, located in the medulla. The five primary
Blanket use of PONV prophylaxis is not cost-effective andunnecessarily risks drug-related adverse effects. Mostguidelines are in agreement that patients at low risk forPONV are unlikely to benefit from prophylaxis and that itshould be reserved for patients at moderate to high risk. ABBREVIATIONS
Patients with no more than one risk factor are considered
low risk. Identifying patient risks remains a challenge.
Apfel et al.13 devised a simplified risk score for predicting
PONV. They concluded that there are 4 main risk factors:
NSAIDs nonsteroidal anti-inflammatory drugs
2. prior history of motion sickness or PONV,
JULY JOGC JUILLET 2008 l SOGC CLINICAL PRACTICE GUIDELINE Recommendations
4. the use of postoperative opioids.
2. When the choice is available, patients should be advised
that the risk of PONV decreases when regional rather
The estimated probability of PONV was 10%, 21%, 39%,
than general anaesthesia is administered. (III-A)
and 78% with 0, 1, 2, 3, and 4 risk factors, respectively.
3. The perioperative use of opioids should be minimized.
Surgeons should evaluate the risks/benefits of opioid
Risk Factors for PONV
administration in light of the increased risk of PONV. (III-B)
These can de divided into 3 main groups: • Patient-specific: female sex8,13; non-smoker13,14; Pharmacological Prophylaxis
history of PONV or motion sickness.13–15
Prophylactic doses and timing for the administration of
• Anaesthetic: use of volatile anaesthetics within 0 to
2 hours16; use of nitrous oxide17; use of intraoperative
Serotonin (5-HT3) receptor antagonists exert their effects in
and postoperative opioids13,18–21; high doses of
the chemoreceptor trigger zone and at vagal afferents in the
gastrointestinal tract. Ondansetron was the first of this class
• Surgical: duration of surgery, with each 30-minute
of drug to be marketed; others include dolasetron,
increase in duration increasing the risk of PONV by
In 2003, an expert panel agreed that there was no evidence
of any difference in the efficacy and safety profiles of the
1. Physicians should be aware of the risk factors associated
different 5-HT3 receptor antagonists in the prophylaxis
with PONV, and the baseline risks should be reduced
against PONV.10 Ondansetron 4 mg has a NNT of 7 for the
prevention of nausea and 6 for the prevention of vomiting. The number needed to harm with a single dose of
Optimization in the Perioperative Period
ondansetron is 36 for headache, 31 for increased liver
A number of perioperative factors have been shown to
Dexamethasone, a corticosteroid, administered at a dose of8–10 mg IV, prevents PONV with a NNT of 4.38 Smaller
When possible, regional anaesthetic should be administered
doses of 2.5–5 mg have been shown to be as effective13,40
as general anaesthetic is associated with an 11-fold
The precise mode of action is not well understood, but may
increased risk of PONV.22 When general anaesthetic is
be due to the release of endorphins that elevate mood and
required, the use of propofol as the induction agent is effec-
stimulate appetite.16 There are no reports of adverse effects
tive in reducing early PONV incidence when compared
in the doses used for the management of PONV.38
with other induction agents. The number needed to treatwith propofol to reduce PONV is approximately 5.23
Droperidol blocks dopamine receptors in the CTZ. Theefficacy of droperidol is equivalent to that of ondansetron,
Avoidance of intraoperative and postoperative opioids has
with a NNT of 5 for prevention of PONV. The FDA issued
been shown to reduce PONV. Moiniche et al. showed that
a “black box” warning about droperidol, stating that it may
treatment with NSAIDs as compared with opioids
cause death associated with QT prolongation and torsades
decreased the risk of PONV.20 The use of supplemental
de pointes. In Canada, droperidol is still available but its use
oxygen perioperatively has been shown to reduce PONV by
50%.24,25 possibly by reducing gastrointestinal hypoxia. However, there is conflicting evidence, and a recent study
Metoclopramide blocks dopamine receptors in the CTZ
by Turan et al. demonstrated no benefit associated with
and vomiting centre. It also shortens bowel transit time and
in high doses blocks serotonin receptors. When used instandard clinical doses of 10 mg, metoclopramide was
Perioperative intravenous fluid administration has been
found to be ineffective for PONV prophylaxis.49 A dose of
shown to reduce PONV.27,28 The mechanism is unclear but
50 mg intravenous metoclopramide has been shown to sig-
may be related to the release of serotonin due to decreased
nificantly reduce late (> 12 hours) PONV, but the side
intestinal perfusion, which can be caused by the drop in sys-
effect profile is unsatisfactory.47 The guidelines produced
tolic blood pressure seen with some induction agents.
by Gan et al. do not recommend metoclopramide as a
Neostigmine, a reversal agent for non-depolarising muscle
relaxants, is associated with increased PONV, especially in
Dimenhydrinate, a commonly used antihistaminic, has sim-
large doses (> 2.5 mg),29 and should be avoided if possible.
ilar efficacy to 5-HT3 receptor antagonists.43 Its efficacy is
l JULY JOGC JUILLET 2008 Guideline for the Management of Postoperative Nausea and Vomiting Table 2. Prophylactic doses and timing for the administration of antiemetics
Headache, lightheadedness, elevatedliver enzymes
Headache, lightheadedness, elevatedliver enzymes
Headache, lightheadedness, elevatedliver enzymes
Headache, lightheadedness, elevatedliver enzymes
Vaginal itching or anal irritation with IVbolus
Sedation, dizziness, anxiety,hypotension, EPS
Sedation, dry mouth, blurred vision,dizziness, urinary retention
disturbances; CNS effects in elderlypatients, renal or hepatic impairment
Before induction, morning ofsurgery, 1 tablet
presumably due to the high concentration of histamine and
antiemetic properties found in over-the-counter sleeping
muscarinic cholinergic receptors within the vestibular
medication) and 10 mg pyridoxine hydrochloride (vitamin
B6), in a delayed release formulation. Pyridoxine may haveintrinsic antiemetic properties and also may be synergistic
Promethazine and prochlorperazine belong to a group of
with the antinauseant property of antihistamines.54–56
drugs known as phenothiazines, which act primarily via a
Diclectin has been used since the 1950s and is considered to
central antidopaminergic mechanism in the CTZ. The use
be a safe treatment for nausea and vomiting associated with
of these drugs has decreased because of their significant
pregnancy.57 The International Cochrane Collaboration has
side effects: sedation, dizziness, and extrapyramidal
systematically reviewed randomized trials of Diclectin and
concluded that it safely provides considerable relief for nau-
Scopolamine is an anticholinergic that blocks emetic
muscarinic receptors in the cerebral cortex.51 It is veryeffective, with a NNT of 3.8 for prevention of PONV.52 Its
Aprepitant was the first neurokinin-1 (NK-1) receptor
use is limited because of its two- to four-hour onset of
antagonist approved for the treatment of PONV. This drug
effect and side effect profile as listed above.
blocks NK1 receptors in the central and peripheral nervoussystems thus preventing emesis. In one study, patients given
A recent publication has shown Diclectin to be as effective
oral aprepitant alone or in combination with intravenous
as ondansetron for the prevention of late postoperative
ondansetron had significantly fewer emetic episodes than
vomiting in women undergoing laparoscopic tubal ligation,
those given ondansetron alone.59 In a report of combined
data from 2 large trials, oral aprepitant 40 mg was superior
Diclectin is an antiemetic medication that contains 10 mg
to intravenous ondansetron 4 mg for the prevention of
doxylamine succinate (a common antihistamine with
PONV.60 Complete response (no nausea, vomiting, or need
JULY JOGC JUILLET 2008 l SOGC CLINICAL PRACTICE GUIDELINE
for rescue therapy) was achieved in 37.9% of the aprepitant
group compared with 31.2% of the ondansetron group. Itsacquisition cost is relatively high, making it less appealing as
Acupuncture has been shown to be effective in the manage-
ment of PONV. Coloma et al.65 compared acustimulationwith ondansetron for the treatment of established PONV
None of the available agents is entirely effective for pre-
in outpatient laparoscopic surgery patients. They concluded
venting PONV, particularly for high-risk patients. As there
that acustimulation may be a satisfactory alternative to
are four major receptor systems involved in the etiology of
ondansetron for established PONV, and that ondansetron
PONV, a combination of agents that act on different recep-
seems to enhance the efficacy of acustimulation for treat-
tors results in better prophylaxis.61,62 The most commonly
studied combinations have included 5-HT3 receptor antag-onists with droperidol or dexamethasone, and both are
Ginger root is a commonly used non-medical therapy
equally efficacious.63,64 The Figure illustrates a proposed
but is not effective for PONV prophylaxis.66 Similarly,
cannabinoids have not been confirmed to be effective in the
4. Prophylactic antiemetics should be administered to
patients with moderate or high risk of developingPONV. (II-1 A)
6. Acupoint electrical stimulation may be used as an
5. In patients with a high risk of developing PONV, combi-
alternative or adjuvant therapy for prevention of
nation antiemetic therapy should be considered. (III-B)
l JULY JOGC JUILLET 2008 Guideline for the Management of Postoperative Nausea and Vomiting Rescue Treatment for PONV
In a study by Gan et al.73 4 mg IV ondansetron for PONV
In the presence of persistent nausea and vomiting, possible
prophylaxis was administered. Patients were then random-
contributing factors, such as patient-controlled morphine
ized to receive either ondansetron oral disintegrating tablet
analgesia, presence of blood in the pharynx, or an abdomi-
(ODT) 8 mg or placebo immediately before discharge from
nal obstruction, should be excluded before rescue therapy
the ambulatory surgery centre and again 12 hours later.
Patients who received ondansetron ODT had less severe
When prophylaxis with one drug has failed, a repeat dose of
nausea and fewer vomiting episodes (3% vs. 23%) after
this drug should not be initiated as a rescue therapy. Instead
a drug from a different class of antiemetics should be
Al-Sadi et al.74 assessed the efficacy of acupuncture as a pro-
administered.67 However, if the PONV occurs more than 6
phylactic antiemetic. They found a significant difference
hours after surgery, repeat dosing of the initial prophylactic
between groups before and after discharge, with the pla-
drug may be considered. Repeat doses of dexamethasone
cebo group four times more likely to have post-discharge
and transdermal scopolamine should not be administered
nausea and vomiting than the acupuncture group. Recommendations
If a patient has received no prophylaxis, treatment with a
9. As patients who undergo surgery in surgical daycare units
5-HT3 receptor antagonist may be considered.68 Rescue
may have PONV after they are discharged, they should
treatment doses for 5-HT3 receptor antagonists are
be given instructions for its management. (III-B)
approximately 25% the dose of those used for prophylaxis(e.g., 1 mg ondansetron).
10. Patients at high risk of developing PDNV should be
7. For patients with PONV who did not receive prophylaxis
or in whom prophylaxis failed, antiemetic treatment
1. Kovac AL. Prevention and treatment of postoperative nausea and vomiting.
should be administered as soon as feasible. (III-A)
2. Watcha MF, White PF. Postoperative nausea and vomiting: its aetiology,
8. When prophylaxis with one drug has failed, a repeat dose
treatment and prevention. Anesthesiology 1992; 77;162–84
of this drug should not be initiated as a rescue therapy;
3. Leman J. Surgical and patient factors involved in postoperative nausea and
instead, a drug from a different class of antiemetic drugs
vomiting. Br J Anaesth 1992; 69(Suppl 1):S24–32.
4. Cohen MM, Duncan PG, DeBoer DP, Tweed WA. The postoperative
interview; assessing risk factors for nausea and vomiting. Anesth Analg1994;78:7–16. Post-discharge Nausea and Vomiting
5. Camu F, Lauwers MH, Verbessem D. Incidence and aetiology of
PDNV is nausea and/or vomiting that occur after discharge
postoperative nausea and vomiting. Eur J Anaesthesiol 1992; 9(Suppl
from the health care facility, but within the 24-hour period
immediately following surgery. Post-discharge nausea and
6. Palazzo MG, Strunin L. Anaesthesia and emesis: 1. Etiology, Can Anaesth
vomiting that occurs after the initial 24-hour postoperative
7. Chung F, Mezei F. Factors contributing to a prolonged stay after
period is considered delayed PDNV.69 Post-discharge nau-
ambulatory surgery. Anesth Analg 1999;89:1352–9.
sea and vomiting is becoming more common as more
8. Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia
patients are being operated on in an ambulatory setting, and
outcomes are important to avoid? Anesth Analg 1999;89:652–8.
it has been reported in 35% to 50% of patients.70,71
9. Gan T, Sloan F, Dear Gde L, El-Moalem HE, Lubarsky DA. How much
are patients willing to pay to avoid postoperative nausea and vomiting?
In a recent meta-analysis, the NNT to prevent post dis-
charge nausea following ambulatory surgery was 12.9, 12.2,
10. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, et al.
and 5.2 following the prophylactic administration of
Consensus guidelines for managing postoperative nausea and vomiting.
ondansetron 4 mg, dexamethasone, and a combination of
two antiemetics, respectively. For post-discharge vomiting,
11. TramPr MR. A rational approach to the control of postoperative nausea and
the NNT was 13.8 for ondansetron 4 mg and 5 for combi-
vomiting: evidence from systemic reviews. I. Efficacy and harm ofantiemetic interventions, and methodological issues. Acta Anaesthesiol
nation treatment. These results suggest that ondansetron
alone should not be used routinely in ambulatory patients at
12. Tramèr MR. A rational approach to the control of postoperative nausea and
low risk and that patients at high risk are best managed with
vomiting: evidence from systemic reviews. II. Recommendations for
prevention and treatment and research agenda. Acta Anaesthesiol Scand2001;45:14–9.
Optimal management of PDNV is unsupported by scien-
13. Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk
tific evidence, and the choice of medication for PDNV is
score for predicting postoperative nausea and vomiting. Anesthesiology
JULY JOGC JUILLET 2008 l SOGC CLINICAL PRACTICE GUIDELINE
14. Koivuranta M, Laara E, Snare L, Alahuhta S. A survey of postoperative
32. Graczyk SG, McKenzie R, Kallar S, Hickok CB, Melson T, Morrill B, et al.
nausea and vomiting. Anaesthesia 1997;52:443–9.
Intravenous dolasetron for the prevention of postoperative nausea andvomiting after outpatient laparoscopic gynecologic surgery. Anesth Analg
15. Sinclair DR, Chung F, Mezei G. Can postoperative nausea and vomiting be
predicted? Anesthesiology 1999;91:109–18.
33. Wilson AJ, Diemunsch P, Lindeque BG, Scheinin H, Helbo-Hansen HS,
16. Apfel CC, Kranke P, Katz MH, Goepfert C, Papenfuss T, Rauch S, et al.
Kroeks MV, et al. Single-dose IV granisetron in the prevention of
Volatile anaesthetics may be the main cause of early but not delayed
postoperative nausea and vomiting. Br J Anaesth 1996;76:515–8.
postoperative vomiting: a randomized controlled trial of factorial design. Br J Anaesth 2002;88:659–68.
34. Cieslak GD, Watcha MF, Phillips MB, Pennant JH. The dose response
relation and cost-effectiveness of granisetron for the prophylaxis of
17. TramPr M, Moore A, McQuay H. Omitting nitrous oxide in general
pediatric postoperative emesis. Anesthesiology 1996;85:1076–85.
anaesthesia: meta-analysis of intraoperative awareness and postoperativeemesis in randomized controlled trials. Br J Anaesth 1996;76:186–93.
35. Mikawa K, Takao Y, Nishina K, Shiga M, Maekawa N, Obara H. Optimal
dose of granisetron for prophylaxis against postoperative emesis after
18. Apfel CC, Kranke P, Eberhart LH, Roos A, Roewer N. Comparison of
gynaecological surgery. Anesth Analg 1997;85:652–6.
predictive models for postoperative nausea and vomiting. Br J Anaesth2002;88:234–40.
36. Domino KB, Anderson EA, Polissar NL, Posner KL. Comparative efficacy
and safety of ondansetron, droperidol, and metoclopramide for preventing
19. Sukhani R, Vazquez J, Pappas AL, Frey K, Aasen M, Slogoff S. Recovery
postoperative nausea and vomiting: a meta-analysis. Anesth Analg
after propofol with and without intraoperative fentanyl in patients
undergoing ambulatory gynecologic laparoscopy. Anesth Analg1996;83:975–81.
37. Fortney JT, Gan TJ, Graczyk S, Wetchler B, Melson T, Khalil S, et al.
A comparison of the efficacy, safety, and patient satisfaction of ondansetron
20. Mriniche S, Rrmsing J, Dahl JB, TramPr MR. Nonsteroidal
versus droperidol as antiemetics for elective outpatient surgical procedures:
anti-inflammatory drugs and the risk of operative site bleeding after
S3A-409 and S3A-410 Study Groups. Anesth Analg 1998;86:731–8.
tonsillectomy: a quantitative systematic review. Anesth Analg2003;96:68–77.
38. Henzi I, Walder B, TramPr MR. Dexamethasone for the prevention of
postoperative nausea and vomiting: a quantitative systematic review. Anesth
21. Polati E, Verlato G, Finco G, Mosaner W, Grosso S, Gottin L, et al.
Ondansetron versus metoclopramide in the treatment of postoperativenausea and vomiting. Anesth Analg 1997;85:395–9.
39. Liu K, Hsu CC, Chia YY. The effective dose of dexamethasone for
antiemesis after major gynecological surgery. Anesth Analg 1999;89:1316–8.
22. Sinclair DR, Chung F, Mezei G. Can postoperative nausea and vomiting be
predicted? Anesthesiology 1999;91:109–18.
40. Wang JJ, Ho ST, Lee SC, Liu YC, Ho CM. The use of dexamethasone for
preventing postoperative nausea and vomiting in females undergoing
23. Visser K, Hassink EA, Bonsel GJ, Moen J, Kalkman CJ. Randomized
thyroidectomy: a dose-ranging study. Anesth Analg 2000;91:1404–7.
controlled trial of total intravenous anesthesia with propofol versusinhalation anesthesia with isoflurane-nitrous oxide: postoperative nausea
41. Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone
with vomiting and economic analysis. Anesthesiology 2001;95:616–26.
administration on its efficacy as a prophylactic antiemetic for postoperativenausea and vomiting. Anesth Analg 2000;91:136–9.
24. Greif R, Laciny S, Rapf B, Hickle RS, Sessler DI. Supplemental oxygen
reduces the incidence of postoperative nausea and vomiting. Anesthesiology
42. Henzi I, Sonderegger J, Tramèr MR. Efficacy, dose response, and adverse
effects of droperidol for prevention of postoperative nausea and vomiting. Can J Anesth 2000;47:537–51.
25. Goll V, Akça O, Greif R, Freitag H, Arkiliç CF, Scheck T, et al.
Ondansetron is no more effective than supplemental intraoperative oxygen
43. Kranke P, Morin AM, Roewer N, Eberhart LH. Dimenhydrinate for
for prevention of postoperative nausea and vomiting. Anesth Analg
prophylaxis of postoperative nausea and vomiting: a metaanalysis of
randomized controlled trials. Acta Anaesthesiol Scand 2002;46:238–44.
26. Turan A, Apfel CC, Kumpch M, Danzeisen O, Eberhart LH, Forst H, et al.
44. Khalil S, Philbrook L, Rabb M, Wells L, Aves T, Villanueva G, et al.
Does the efficacy of supplemental oxygen for the prevention of
Ondansetron / promethazine combination or promethazine alone reduces
postoperative nausea and vomiting depend on the measured outcome,
nausea and vomiting after middle ear surgery. J Clin Anesth
observational period or site of surgery? Anaesthesia 2006;61:628–33.
45. Kranke P, Morin AM, Roewer N, Wells L, Aves T, Villanueva G, et al.
27. Holte K, Klarskov B, Christensen DS, Lund C, Nielsen KG, Bie P, et al.
The efficacy and safety of transdermal scopolamine for the prevention of
Liberal versus restrictive fluid administration to improve recovery after
postoperative nausea and vomiting: a quantitative systematic review. Anesth
laparoscopic cholecystectomy. Ann Surg 2004;240:892–9.
28. Magner JJ, McCaul C, Carton E, Gardiner J, Buggy D. Effect of intravenous
46. Bailey PL, Streisand JB, Pace NL, Bubbers SJ, East KA, Mulder S, et al.
crystalloid infusion on postoperative nausea and vomiting after
Transdermal scopolamine reduces nausea and vomiting after outpatient
gynaecological laparoscopy: comparison of 30 and 10 ml kg. Br J Anaesth
laparoscopy. Anesthesiology 1990;72:977–80.
47. Wallenborn J, Gelbrich G, Bulst D, Behrends K, Wallenborn H, Rohrbach
29. Tramèr MR, Fuchs-Buder T. Omitting reversal of neuromuscular blockade:
A, et al. Prevention of postoperative nausea and vomiting by
effect on postoperative nausea and vomiting and risk of residual paralysis:
metoclopramide combined with dexamethasone: randomized double blind
a systemic review. Br J Anaesth 1999;82:379–86.
multicentre trial. BMJ 2006;333:324.
30. Tramèr MR, Reynolds DJM, Moore RA, McQuay HJ. Efficacy,
48. Habib AS, Gan TJ. Evidence-based management of postoperative nausea
dose-response, and safety of ondansetron in prevention of postoperative
and vomiting: a review. Can J Anesth 2004;51:326–41.
nausea and vomiting: a qualitative systematic review of randomizedplacebo-controlled trials. Anesthesiology 1997;87:1277–89.
49. Rowbotham DJ. Current management of postoperative nausea and
vomiting. Br J Anaesth 1992;69:46S–59S.
31. Sun R, Klein KW, White PF. The effect of timing of ondansetron
administration in outpatients undergoing otolaryngologic surgery. Anesth
50. Wilhelm SM, Dehoorne-Smith ML, Kale-Pradhan PB. Prevention of
postoperative nausea and vomiting. Ann Pharmacother 2007;41:68–78.
l JULY JOGC JUILLET 2008 Guideline for the Management of Postoperative Nausea and Vomiting
51. Lerman J. Surgical and patient factors involved in postoperative nausea and
64. Habib AS, El-Moalem HE, Gan TJ. The efficacy of the 5-HT3 receptor
vomiting. Br J Anaesth 1992;69:24S–32S.
antagonists combined with droperidol for PONV prophylaxis is similar totheir combination with dexamethasone. A meta-analysis of randomized
52. Kranke P, Morin AM, Roewer N, Wulf H, Eberhart LH. The efficacy and
controlled trials. Can J Anesth 2004;51:311–19.
safety of transdermal scopolamine for the prevention of postoperativenausea and vomiting: a quantitative systematic review. Anesth Analg
65. Coloma M, White PF, Ogunnaike BO, Markowitz SD, Brown PM, Lee AQ,
et al. Comparison of acustimulation and ondansetron for the treatment of
53. Reeve B. Prophylactic Diclectin reduces the incidence of postoperative
established postoperative nausea and vomiting. Anesthesiology
vomiting. Can J Anesth 2005;52:55–61.
54. Ornstein M, Einarson A, Koren G. Bendectin/diclectin for morning
66. Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting:
sickness: a Canadian follow-up of an American tragedy (Editorial). Reprod
a systematic review of randomized clinical trials. Br J Anaesth
55. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. Vitamin B6 is effective
67. Hill RP, Soppitt AJ, Gan TJ. The effectiveness of rescue antiemetics in
therapy for nausea and vomiting of pregnancy: a randomized, double-blind
patients who received a prophylactic antiemetic. Anesth Analg 2000;90:S8
placebo-controlled study. Obstet Gynecol 1991;78:33–6.
56. Vutyavanich T, Wongtra-ngan S, Ruangsri RA. Pyridoxine for nausea and
68. Tramèr M, Moore RA, Reynolds DJM, McQuay HJ. A quantitative systemic
vomiting of pregnancy: a randomized, double-blind, placebo-controlled
review of ondansetron in treatment of established postoperative nausea and
trial. Am J Obstet Gynecol 1995;173:881–4.
57. Brent R. The Bendectin Saga: another American tragedy (Brent ’80);
69. American Society of PeriAnesthesia Nurses PONV/PDNV Strategic Work
(Editorial). Teratology 1983;27:283–6.
Team. ASPAN’S evidence-based clinical practice guideline for the
58. Jewell MD, Debendox (Bendectin) for nausea in pregnancy. In: Enkin MW,
prevention and/or management of PONV/PDNV. J Perianesth Nurs
Keirse MJ, Renfrew MJ, Neilson JP, eds. Pregnancy and Childbirth Module.
Disk issue 1. Cochrane Database of Systematic Reviews: Review No 03351,
70. Carroll NV, Miederhoff P, Cox FM, Hirsch JD. Postoperative nausea and
30 April 1993. Oxford: Cochrane Updates on Disk 1994.
vomiting after discharge from outpatient surgery centers. Anesth Analg
59. Gesztesi Z, Scuderi PE, White PF, Wright W, Wender RH, D’Angelo R,
et al. Substance P (Neurokinin 1) antagonist prevents postoperative
71. Gan TJ. Postoperative nausea and vomiting: Can it be eliminated? JAMA
vomiting after abdominal hysterectomy procedures. Anesthesiology
72. Polati E, Verlato G, Finco G, Mosaner W, Grosso S, Gottin L, et al.
60. Diemuncsh PA, Apfel C, Phillip B, Gan TJ, Reiss TR. NK1 antagonist
Ondansetron versus metoclopramide in the treatment of postoperative
aprepitant vs. ondansetron for prevention of PONV: combined data from
nausea and vomiting. Anesth Analg 1997;85:395–9.
2 large trials (abstract A125). Presented at: American Society ofAnesthesiologists 2006 Annual Meeting, Chicago, IL, October 14–18, 2006.
73. Gan TJ, Franiak R, Reeves J. Ondansetron orally disintegrating tablet versus
61. Habib AS, Gan TJ. Combination therapy for postoperative nausea and
placebo for the prevention of postdischarge nausea and vomiting after
vomiting—a more effective prophylaxis? Ambul Surg 2001;9:59–71.
ambulatory surgery. Anesth Analg 2002;94:1199-200.
62. Habib AS, Gan TJ. Combination antiemetic. What is the evidence? Int
74. al-Sadi M, Newman B, Julious SA. Acupuncture in the prevention of
Anesthesiol Clin Fall 2003;41:119–44.
postoperative nausea and vomiting. Anaesthesia 1997;52:658-61.
63. Sanchez-Ledesma MJ, Lopez-Olaondo L, Pueyo FJ, Carrascosa F, Ortega A.
75. Woolf SH, Battista RN, Anderson GM, Logan AG, Eel W. Canadian Task
A comparison of three antiemetic combinations for the prevention of
force on Preventive Health Care. New grades for recommendations from
postoperative nausea and vomiting. Anesth Analg 2002;95:1590–5.
the Canadian Task force on Preventive Health Care. CMAJ 2003;169:207–8.
JULY JOGC JUILLET 2008 l
488 F.3d 1377, *; 2007 U.S. App. LEXIS 11886, **; PFIZER, INC., Plaintiff-Appellee, v. APOTEX, INC. (formerly known as Tor- Pharm, Inc.) Defendant-Appellant. 2006-1261 UNITED STATES COURT OF APPEALS FOR THE FEDERAL CIRCUIT 488 F.3d 1377; 2007 U.S. App. LEXIS 11886; 82 U.S.P.Q.2D (BNA) 1852 May 21, 2007, Decided May 21, 2007, Filed PRIOR HISTORY: [**1] Appealed from
MATERIAL SAFETY DATA SHEET State of the art ingredients ∙ fast friendly service SECTION 1 :: PRODUCT IDENTIFICATION Chemical Name : Caffeine, anhydrous INCI : Caffeine SECTION 2 :: DATA ON COMPONENTS Molecular Weight : 194.19 Chemical Characterization : C2-H10-N4-O2 FEMA number : 2224 TSV Level : 10 mg/m3 Caffeine is regulated as a nuisance particulate, not otherwise class