Prévention des nausées vomissements post opératoires

Pharmacological treatment of postoperative nausea and vomiting


Auteur :Martin R Tramèr, MD  DPhil

Consultant Anaesthetist Division of Anaesthesiology Department APSIC Geneva University Hospitals
CH-1211 Geneva 14 Switzerland
Tel 0041 22 382 74 41
Fax 0041 22 382 75 11


The importance of postoperative nausea and vomiting (PONV) has been generally underestimated, because it is self-limiting, never becomes chronic, and almost never kills. However, the impact of PONV on health care cost is not negligible. Ten percent of the population undergo a general anaesthetic every year 1, and about 30% of them suffer from PONV 2. This is 2,000,000 people in the UK every year. About 1% of patients undergoing ambulatory surgery are admitted overnight because of uncontrolled PONV 2.


When PONV happens, the anaesthetist is usually blamed, despite evidence that PONV results from factors that are related to anaesthesia, to surgery and to the patients themselves. Surgical patients prefer to suffer pain rather than PONV 3 and would be willing to pay considerable amounts of money for an effective antiemetic 4. A major obstacle to the development of an effective treatment has been the lack of a valid animal model for PONV. Extrapolation of data from animal research with highly emetogenic chemotherapy to PONV has been of limited value. Thus, anaesthetists have to rely on the results of clinical trials. Data on an almost infinite number of potentially useful antiemetic interventions have been published during the last 40 years. Despite this large body of literature, fundamental data on dose-responsiveness or adverse effect profile have remained unclear for most anitiemetics, and there has been no agreement on what constitutes a gold standard. Many trials are of small size and some of doubtful validity. As a consequence, anaesthetists have been using antiemetics irrationally.


The good news is that significant progress towards improved control of PONV has been achieved during recent years. Large amounts of the PONV literature have been systematically reviewed, critically appraised, and quantitatively synthesised 2. Today, we understand relative efficacy and harm of most antiemetic interventions.

Droperidol, for instance, a butyrophenone that has been withdrawn in some countries for apparent safety reasons 5, has a pronounced anti-nausea effect at doses that are so incredibly low that the occurrence of any relevant adverse effect becomes highly unlikely 6. Ondansetron, which was thought to represent the first universally effective antiemetic for PONV, was shown to have a limited effect just on vomiting 7. Metoclopramide, one of the most popular antiemetics for decades, showed no worthwhile efficacy 8. Perhaps the most important information from these systematic reviews was that none of the drugs tested could be regarded as a gold standard, and none was good enough to be used on its own; at best, they achieved a number-needed-to-treat to prevent PONV of about five compared with placebo in high-risk patients 2. Thus, in order to prevent PONV in one patient, five patients would need to receive that antiemetic prophylactically. However, systematic review also confirmed improved efficacy with “balanced antiemesis”, as, for instance, with the combination of a 5-HT3 receptor antagonist with droperidol or with dexamethasone, respectively 9.


As a further important step towards an improved control of PONV symptoms, anaesthetists have become increasingly aware of the emetogenic potency of some anaesthetic techniques. For a patient who must not vomit (she may be a non-smoker with a history of PONV, and she has wired jaws after maxillo-facial surgery), the anaesthetist may choose the intravenous anaesthetic propofol that was shown to be less emetogenic than volatiles, and may avoid drugs that are known to increase the risk of PONV such as nitrous oxide, physostigmine and opioids 10. Some of these modalities may be of limited or only short-lived efficacy, and not all are feasible in all circumstances. However, the combination of such simple measures clearly decrease the risk of PONV 11.

Modern anaesthesia tries to take advantage of this new knowledge; indeed, a multimodal PONV approach has been recommended recently 12. Thus, for optimal PONV prophylaxis in high-risk patients, anaesthetists would use a low emetogenic anaesthesia technique and administer an antiemetic cocktail before emergence. The cocktail may consist of a 5-HT3 receptor antagonist plus a dopamine antagonist (droperidol) plus dexamethasone.

Unfortunately, compared with the large amount of published data on prophylaxis of PONV, relatively little is known about the treatment of established PONV symptoms. Interestingly, for patients who suffer from PONV symptoms, rescue treatment with the expensive 5-HT3 receptor antagonists is efficacious at much lower doses than are necessary for successful prophylaxis 13. For ondansetron, for instance, the recommended prophylactic dose is 4 mg whereas mg for the treatment of established symptoms 1 mg is as efficacious as 4 or even 8 mg. Reasons for this improved therapeutic efficacy with low-dose 5-HT3 receptor antagonists remain unknown; however, it may be an argument in favour of therapy as compared to regular prophylaxis of PONV symptoms. For antiemetics other than 5-HT3 receptor antagonists there is a lack of evidence for their therapeutic efficacy; published and valid randomised trials are rare, small, or, for some drugs, completely lacking.

A further important clinical issue relates to opioid-induced nausea and vomiting. The typical target population would be patients undergoing major surgery, and receiving postoperatively morphine with a patient controlled analgesia (PCA) device. These patients are at a high risk of nausea, and some want their opioid-analgesia to be stopped. The only antiemetic that has been tested in several randomised controlled trials in this setting and that has shown consistent antiemetic efficacy is droperidol 14.

A randomised dose-finding study suggested that 2.5 mg of droperidol added to 100 mg of morphine provided satisfactory protection against morphine-induced nausea without increasing the risk of sedation or other droperidol-related adverse effects 15. Stability of a droperidol-morphine solution has been tested for a period of two weeks 16.

Despite considerable progress in PONV pharmacology during these recent years, research towards an optimal control of PONV symptoms is continuing. Old molecules that have been used for decades, often without a strong evidence base, are undergoing critical appraisal at last 17, and new compounds that have been shown to block yet another receptor system of the emesis pathways in animal models are currently undergoing clinical studies 18. Hopefully, these research activities will further improve the treatment of PONV.

Reference List

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17. Büttner M, Walder B, Von Elm ET, Tramèr MR. Is low-dose haloperidol a useful antiemetic? Meta-analysis of published and unpublished randomized trials. Anesthesiology (in press).

18. Gardner C, Perren M. Inhibition of anaesthetic-induced emesis by a NK1 or 5-HT3 receptor antagonist in the house musk shrew, Suncus murinus. Neuropharmacology 1998;37:1643-4.