Übelkeit und Erbrechen nach Narkosen: Besseres Verständnis und Vorgehen, Teil I

Postoperative Nausea and Vomiting: Improved Understanding and Better Strategies, Part I

In Germany about 10 millions surgeries are performed under general anesthesia annually. Without prevention, approximately every third patient suffers postoperative nausea and vomiting (PONV) [1] [2] [3]. Often, patients experiencing PONV rate these side effects as more troublesome than postoperative pain [4] [5]. It is thus unsurprising that prevention of PONV increases patient satisfaction [6]. Vomiting poses a risk for aspiration of gastric content and is associated with complications such as wound dehiscence, esophageal ruptures, and subcutaneous emphysema; vomiting has also been described as a cause of bilateral pneumothorax [7] [8]. Moreover, PONV leads to delayed discharge from the postanesthetic care unit and is a major reason for unanticipated admissions following ambulatory anesthesia [9]. The resulting costs for the German health system are estimated to be in the range of several 100 million euro annually [10] [11].

In the last ten years, more than 1000 randomized, controlled trials were published about the prevention and treatment of PONV. The most common method of preventing PONV is administration of antiemetics such as serotonin (5-hydroxytryptamine) receptor-3 antagonists (e. g. ondansetron), dexamethasone, and droperidol. Alternatively, avoiding or reducing the use of emetogenic anesthetics reduces the incidence of PONV too. This includes the use of propofol instead of volatile anesthetics and air instead of nitrous oxide [12] [13]. These well known facts raise the question as to whether there are any new insights with meaningful clinical implications. This question can be answered with a clear „yes” for many aspects.

Risk scores: Palazzo and Evans were the first to describe a multivariate method to estimate the risk of PONV 14. In the years following, several risk models were developed 4 15 16 17 18. While some scores are based on complex calculations, simplified risk scores allow a valid and objective assessment of the patient’s risk for PONV at the bedside 19 20 21. The patient’s risk seems to be determined mainly by patient- and anesthesia-specific factors and is less influenced by the type of surgery. This explains why the type of surgery and the patient’s history of PONV alone are insufficient to identify patients at risk and why the simplified risk score from Apfel et al. provides a better prediction rate 22. Meta-analyses: Although an immense number of studies have been published on PONV, Martin Tramèr was the first to use meta-analyses to provide point estimates for efficacy based on the best available evidence 23 24. Further, Kranke et al. and Eberhart et al. demonstrated that efficacy of dimenhydrinate (Vomex A® or Dramamine®) and of the transdermal scopolamine patch is similar to other antiemetics 25 26. However, we need to caution that the frequently reported „number-needed-to-treat”, which is often used as the major efficacy measure in meta-analysis, is highly dependent on the patient’s risk and, thus, is not a reliable measure to compare the efficacy of antiemetics administered prophylactically 27. IMPACT: The limited effectiveness of single antiemetics 23 led investigators to study how the effectiveness might be improved by combining the antiemetics in numerous ways 28. However, no study had an adequate design and power to compare the efficacy of the most important antiemetic strategies and all their possible combinations. A quantum leap, however, was achieved with the International Multi-center Protocol to quantify the efficacy of Antiemetic strategies in a Controlled Trial of factorial design. (IMPACT) 29. The results, published last year in the New England Journal of Medicine, demonstrated that all antiemetic interventions (including total intravenous anesthesia, TIVA) reduce the risk for PONV by about one-fourth (i. e. ∼ 26 %) and, thus, are similarly effective 30. Moreover, they act independently and can be combined freely. Finally, the relative reduction-in-risk in PONV was independent of the presence of proven or alleged risk factors, so that the absolute reduction in risk is proportionally related to the patient’s risk.

In this issue you will find the opinion of four experts. A close look will reveal that these expert opinions have more similarities than differences. All agree

that prophylaxis is neither medically nor economically justifiable in the vast majority of patients with a low risk of PONV 30, that a combination of antiemetic strategies is warranted in patients at a very high risk for PONV 30 31, that metoclopramide (Reglan®, Paspertin®) should not be used as a first line antiemetic because the majority of studies demonstrated that it has no or very limited efficacy 32, and that dexamethasone given early after induction of general anesthesia appears to be a cost-effective alternative with high efficacy and few side-effects 32 33.

As you will see, Apfel [34], Kranke [35], and Eberhart [36] suggest a risk-adapted approach, where the extent (number) of prophylactic interventions is basically guided by an objective risk assessment of the patient [30]. In contrast, Tramèr’s risk assessment is based on a rather subjective risk assessment, which is surprising in the light of the published evidence that risk scores are validated models for risk assessment [37]. Further, Tramèr favors the „All or Nothing-Principle”, i. e. either no prophylaxis or all available antiemetic strategies given at the same time. This opinion is surprising too given the fact that the IMPACT study demonstrated that a single antiemetic intervention is well justified at a slightly increased risk (e. g. 40 %) while further interventions will be less effective on the grounds that the risk is already reduced by the first intervention [30]. But please, read for yourself …

Literatur

• 1 Gan T J. Postoperative nausea and vomiting - can it be eliminated?.  JAMA. 2002;  287 1233-1236
• 2 Kovac A L. Prevention and treatment of postoperative nausea and vomiting.  Drugs. 2000;  59 213-243
• 3 Watcha M. Postoperative nausea and emesis.  Anesthesiol Clin North Am. 2002;  20 709-722
• 4 Koivuranta M, Laara E, Snare L, Alahuhta S. A survey of postoperative nausea and vomiting.  Anaesthesia. 1997;  52 443-449
• 5 Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients.  Anesth Analg. 1999;  89 652-658
• 6 Darkow T, Gora-Harper M L, Goulson D T, Record K E. Impact of antiemetic selection on postoperative nausea and vomiting and patient satisfaction.  Pharmacotherapy. 2001;  21 540-548
• 7 Schumann R, Polaner D M. Massive subcutaneous emphysema and sudden airway compromise after postoperative vomiting.  Anesth Analg. 1999;  89 796-797
• 8 Bremner W G, Kumar C M. Delayed surgical emphysema, pneumomediastinum and bilateral pneumothoraces after postoperative vomiting.  Br J Anaesth. 1993;  71 296-297
• 9 Gold B S, Lecky J H, Neuhaus J M. Unanticipated admission to the hospital following ambulatory surgery.  Jama-Journal of the American Medical Association. 1989;  262 3008-3010
• 10 Hill R P, Lubarsky D A, Phillips-Bute B, Fortney J T, Creed M R, Glass P S, Gan T J. Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo.  Anesthesiology. 2000;  92 958-967
• 11 Watcha M F. The cost-effective management of postoperative nausea and vomiting.  Anesthesiology. 2000;  92 931-933
• 12 Apfel C C, Kranke P, Katz M H, Goepfert C, Papenfuss T, Rauch S, Heineck R, Greim C A, Roewer N. Volatile anaesthetics may be the main cause for early but not delayed postoperative nausea and vomiting: a randomized controlled trial of factorial design.  British Journal of Anaesthesia. 2002;  88 659-668
• 13 Divatia J V, Vaidya J S, Badwe R A, Hawaldar R W. Omission of nitrous oxide during anesthesia reduces the incidence of postoperative nausea and vomiting. A meta-analysis.  Anesthesiology. 1996;  85 1055-1062
• 14 Palazzo M, Evans R. Logistic regression analysis of fixed patient factors for postoperative sickness: a model for risk assessment.  Br J Anaesth. 1993;  70 135-140
• 15 Apfel C C, Greim C A, Haubitz I, Goepfert C, Usadel J, Sefrin P, Roewer N. A risk score to predict the probability of postoperative vomiting in adults.  Acta Anaesthesiol Scand. 1998;  42 495-501
• 16 Apfel C C, Laara E, Koivuranta M, Greim C A, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: Conclusions from cross-validations between two centers.  Anesthesiology. 1999;  91 693-700
• 17 Sinclair D R, Chung F, Mezei G. Can postoperative nausea and vomiting be predicted?.  Anesthesiology. 1999;  91 109-118
• 18 Junger A, Hartmann B, Benson M, Schindler E, Dietrich G, Jost A, Beye-Basse A, Hempelmann G. The use of an anesthesia information management system for prediction of antiemetic rescue treatment at the postanesthesia care unit.  Anesth Analg. 2001;  92 1203-1209
• 19 Eberhart L H, Hogel J, Seeling W, Staack A M, Geldner G, Georgieff M. Evaluation of three risk scores to predict postoperative nausea and vomiting.  Acta Anaesthesiol Scand. 2000;  44 480-488
• 20 Apfel C C, Kranke P, Eberhart L HJ, Roos I A, Roewer N. A comparison of predicting models for postoperative nausea and vomiting.  Br J Anaesth. 2002;  88 234-240
• 21 Pierre S, Benais H, Pouymayou J. Apfel's simplified score may favourably predict the risk of postoperative nausea and vomiting.  Can J Anesth. 2002;  49 237-242
• 22 Apfel C C, Kranke P, Eberhart L H. Comparison of surgical site and patient's history with a simplified risk score for the prediction of postoperative nausea and vomiting.  Anaesthesia. 2004;  59 1078-1082
• 23 Tramèr M R. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part I. Efficacy and harm of antiemetic interventions, and methodological issues.  Acta Anaesthesiol Scand. 2001;  45 4-13
• 24 Tramèr M R. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda.  Acta Anaesthesiol Scand. 2001;  45 14-19
• 25 Kranke P, Morin A M, Roewer N, Eberhart L H. Dimenhydrinate for prophylaxis of postoperative nausea and vomiting: a meta-analysis of randomized controlled trials.  Acta Anaesthesiol Scand. 2002;  46 238-244
• 26 Kranke P, Morin A M, Roewer N, Wulf H, Eberhart L H. The efficacy and safety of transdermal scopolamine for the prevention of postoperative nausea and vomiting: a quantitative systematic review.  Anesth Analg. 2002;  95 133-143
• 27 Apfel C C, Roewer N. Postoperative Übelkeit und Erbrechen.  Anaesthesist. 2004;  53 377-389
• 28 Scuderi P E, James R L, Harris L, Mims G R, III. Multimodal antiemetic management prevents early postoperative vomiting after outpatient laparoscopy.  Anesth Analg. 2000;  91 1408-1414
• 29 Apfel C C, Korttila K, Abdalla M, Biedler A, Kranke P, Pocock S J, Roewer N. An international multicenter protocol to assess the single and combined benefits of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2 factorial design (IMPACT).  Control Clin Trials. 2003;  24 736-751
• 30 Apfel C C, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock S J, Trenkler S, Kredel M, Biedler A, Sessler D I, Roewer N. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.  New Engl J Med. 2004;  350 2441-2451
• 31 Eberhart L HJ, Mauch M, Morin A M, Wulf H, Geldner G. Impact of a multimodal anti-emetic prophylaxis on patient satisfaction in high-risk patients for postoperative nausea and vomiting.  Anaesthesia. 2002;  57 1022-1027
• 32 Henzi I, Walder B, Tramèr M R. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies.  Br J Anaesth. 1999;  83 761-771
• 33 Henzi I, Walder B, Tramèr M R. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review.  Anesth Analg. 2000;  90 186-194
• 34 Apfel C C. A risk-dependent evidence-based strategy to prevent postoperative nausea and vomiting.  Anaesth Intensivmed Notfallth Schmerzth . 2005;  in press
• 35 Kranke P, Eberhart L H. Übelkeit und Erbrechen nach Narkosen: Was ist gesichert in Prophylaxe und Therapie?.  Anaesth Intensivmed Notfallth Schmerzth. 2005;  in press
• 36 Putzke C, Eberhart L H, Steinfeld T, Kranke P. Übelkeit und Erbrechen in der postoperativen Phase (PONV) - Bedeutung und multimodale Therapie.  Anaesth Intensivmed Notfallth Schmerzth. 2005;  in press
• 37 Tramèr M R. Pharmakologische PONV-Kontrolle: Prophylaxe oder Therapie?.  Anaesth Intensivmed Notfallth Schmerzth. 2005;  in press