Christian C. Apfel

A simplified Risk score for predicting postoperative nausea and vomiting : Conclusions from Cross-validations between two centers

BACKGROUND Recently, two centers have independently developed a risk score for predicting postoperative nausea and vomiting (PONV). This study investigated (1) whether risk scores are valid across centers and (2) whether risk scores based on logistic regression coefficients can be simplified without loss of discriminating power. METHODS Adult patients from two centers (Oulu, Finland: n = 520, and Wuerzburg, Germany: n = 2202) received inhalational anesthesia (without antiemetic prophylaxis) for various types of surgery. PONV was defined as nausea or vomiting within 24 h of surgery. Risk scores to estimate the probability of PONV were obtained by fitting logistic regression models. Simplified risk scores were constructed based on the number of risk factors that were found significant in the logistic regression analyses. Original and simplified scores were cross-validated. A combined data set was created to estimate a potential center effect and to construct a final risk score. The discriminating power of each score was assessed using the area under the receiver operating characteristic curves. RESULTS Risk scores derived from one center were able to predict PONV from the other center (area under the curve = 0.65-0.75). Simplification did not essentially weaken the discriminating power (area under the curve = 0.63-0.73). No center effect could be detected in a combined data set (odds ratio = 1.06, 95% confidence interval = 0.71-1.59). The final score consisted of four predictors: female gender, history of motion sickness (MS) or PONV, nonsmoking, and the use of postoperative opioids. If none, one, two, three, or four of these risk factors were present, the incidences of PONV were 10%, 21%, 39%, 61% and 79%. CONCLUSIONS The risk scores derived from one center proved valid in the other and could be simplified without significant loss of discriminating power. Therefore, it appears that this risk score has broad applicability in predicting PONV in adult patients undergoing inhalational anesthesia for various types of surgery. For patients with at least two out of these four identified predictors a prophylactic antiemetic strategy should be considered.

Society for Ambulatory Anesthesia Guidelines for the Management of Postoperative Nausea and Vomiting

The present guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in postoperative nausea and vomiting (PONV) under the auspices of The Society of Ambulatory Anesthesia. The panel critically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. In brief, these guidelines identify risk factors for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic monotherapy and combination therapy regimens for PONV prophylaxis; recommend approaches for treatment of PONV when it occurs; and provide an algorithm for the management of individuals at increased risk for PONV.

Consensus Guidelines for the Management of Postoperative Nausea and Vomiting

The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

Evidence-based analysis of risk factors for postoperative nausea and vomiting

BACKGROUND /st> In assessing a patients risk for postoperative nausea and vomiting (PONV), it is important to know which risk factors are independent predictors, and which factors are not relevant for predicting PONV. METHODS /st> We conducted a systematic review of prospective studies (n>500 patients) that applied multivariate logistic regression analyses to identify independent predictors of PONV. Odds ratios (ORs) of individual studies were pooled to calculate a more accurate overall point estimate for each predictor. RESULTS /st> We identified 22 studies (n=95 154). Female gender was the strongest patient-specific predictor (OR 2.57, 95% confidence interval 2.32-2.84), followed by the history of PONV/motion sickness (2.09, 1.90-2.29), non-smoking status (1.82, 1.68-1.98), history of motion sickness (1.77, 1.55-2.04), and age (0.88 per decade, 0.84-0.92). The use of volatile anaesthetics was the strongest anaesthesia-related predictor (1.82, 1.56-2.13), followed by the duration of anaesthesia (1.46 h(-1), 1.30-1.63), postoperative opioid use (1.39, 1.20-1.60), and nitrous oxide (1.45, 1.06-1.98). Evidence for the effect of type of surgery is conflicting as reference groups differed widely and funnel plots suggested significant publication bias. Evidence for other potential risk factors was insufficient (e.g. preoperative fasting) or negative (e.g. menstrual cycle). CONCLUSIONS /st> The most reliable independent predictors of PONV were female gender, history of PONV or motion sickness, non-smoker, younger age, duration of anaesthesia with volatile anaesthetics, and postoperative opioids. There is no or insufficient evidence for a number of commonly held factors, such as preoperative fasting, menstrual cycle, and surgery type, and using these factors may be counterproductive in assessing a patients risk for PONV.

How to study postoperative nausea and vomiting.

Anesthesiological journals are flooded by innumerable studies of postoperative nausea and vomiting (PONV). Nevertheless, PONV remains a continuing problem with an average incidence of 20–30%. This paper should provide essential information for the design, conduct, and presentation of these studies. It should also increase comparability among future studies and help clinicians in assessing and reading the literature on PONV.

Who is at risk for postdischarge nausea and vomiting after ambulatory surgery

Background: About one in four patients suffers from postoperative nausea and vomiting. Fortunately, risk scores have been developed to better manage this outcome in hospitalized patients, but there is currently no risk score for postdischarge nausea and vomiting (PDNV) in ambulatory surgical patients. Methods: We conducted a prospective multicenter study of 2,170 adults undergoing general anesthesia at ambulatory surgery centers in the United States from 2007 to 2008. PDNV was assessed from discharge until the end of the second postoperative day. Logistic regression analysis was applied to a development dataset and the area under the receiver operating characteristic curve was calculated in a validation dataset. Results: The overall incidence of PDNV was 37%. Logistic regression analysis of the development dataset (n = 1,913) identified five independent predictors (odds ratio; 95% CI): female gender (1.54; 1.22 to 1.94), age less than 50 yr (2.17; 1.75 to 2.69), history of nausea and/or vomiting after previous anesthesia (1.50; 1.19 to 1.88), opioid administration in the postanesthesia care unit (1.93; 1.53 to 2.43), and nausea in the postanesthesia care unit (3.14; 2.44–4.04). In the validation dataset (n = 257), zero, one, two, three, four, and five of these factors were associated with a PDNV incidence of 7%, 20%, 28%, 53%, 60%, and 89%, respectively, and an area under the receiver operating characteristic curve of 0.72 (0.69 to 0.73). Conclusions: PDNV affects a substantial number of patients after ambulatory surgery. We developed and validated a simplified risk score to identify patients who would benefit from long-acting prophylactic antiemetics at discharge from the ambulatory care center.

A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting

BACKGROUND: Antiemetics currently in use are not totally effective. Neurokinin-1 receptor antagonists are a new class of antiemetic that have shown promise for chemotherapy-induced nausea and vomiting. This is the first study evaluating the efficacy and tolerability of the neurokinin-1 receptor antagonist, aprepitant, for the prevention of postoperative nausea and vomiting. METHODS: In this multicenter, double-blind trial, we randomly assigned 805 patients receiving general anesthesia for open abdominal surgery to a preoperative dose of aprepitant 40 mg orally, aprepitant 125 mg orally, or ondansetron 4 mg IV. Vomiting, nausea, and use of rescue therapy were assessed over 48 h after surgery. Treatments were compared using logistic regression. RESULTS: Incidence rates for the primary end point (complete response [no vomiting and no use of rescue] over 0–24 h after surgery, tested for superiority of aprepitant) were not different across groups (45% with aprepitant 40 mg, 43% with aprepitant 125 mg, and 42% with ondansetron). The incidence of no vomiting (0–24 h) was higher with aprepitant 40 mg (90%) and aprepitant 125 mg (95%) versus ondansetron (74%) (P < 0.001 for both comparisons), although between-treatment use of rescue and nausea control was not different. Both aprepitant doses also had higher incidences of no vomiting over 0–48 h (P < 0.001). No statistically significant differences were seen among the side effect profiles of the treatments. CONCLUSIONS: Aprepitant was superior to ondansetron for prevention of vomiting in the first 24 and 48 h, but no significant differences were observed between aprepitant and ondansetron for nausea control, use of rescue, or complete response.

A Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo in Preventing Postoperative Nausea and Vomiting Over a 72-hour Period

BACKGROUND: We designed this multicenter, randomized, double-blind study to assess the efficacy and safety of three doses of palonosetron, compared with placebo, on the incidence and severity of postoperative nausea and vomiting (PONV) in inpatients for 72 h after surgery. METHODS: Female patients undergoing either elective gynecological or breast surgery were stratified according to two additional PONV risk factors: nonsmoking status and history of PONV and/or motion sickness. Five hundred forty-four patients with one or both of these risk factors were randomized to receive one of the three doses of IV palonosetron (0.025 mg, 0.050 mg, 0.075 mg) or placebo immediately before induction of anesthesia. The primary efficacy end-point was complete response (CR: no emesis and no use of rescue medications) evaluated at the 0–24 and 24–72 h time intervals after surgery. RESULTS: CR rates for placebo and palonosetron 0.075 mg were 36% and 56% for 0–24 h (P = 0.001), 52% and 70% for 24–72 h (P = 0.002) and 36% and 52% (P = 0.010) for the 0–72 h postoperative interval. Palonosetron 0.075 mg was associated with less intense nausea (e.g., toward “mild” or “none”) versus placebo during the 0–24 h (P < 0.001) time interval and significantly delayed median time to emesis (P = 0.002) and treatment failure (P = 0.004). Although CR rates for both the 0.025 mg and 0.050 mg palonosetron doses were not statistically superior to placebo for the 0–24 h or 24–72 h periods, both lower doses reduced nausea severity during the 0–24 h period (P = 0.040 and P = 0.004). CONCLUSION: A single 0.075-mg IV dose of palonosetron effectively reduced the severity of nausea and delayed the time to emesis and treatment failure in the inpatient surgical setting; lower doses were not as effective.

Prevention of pain on injection of propofol: systematic review and meta-analysis.

Objective To systematically determine the most efficacious approach for preventing pain on injection of propofol. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Cochrane Library, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers. Study selection Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults. Results Data were analysed from 177 randomised controlled trials totalling 25 260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions. Conclusions The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.

Risk assessment of postoperative nausea and vomiting.

It is generally accepted that emetic sequelae such as postoperative nausea, postoperative vomiting, and postoperative nausea and vomiting (PONV) are of multifactorial origin and that the incidence of PONV after balanced anesthesia—despite the advances in the last decades—is still between 20% and 30%. Anaesthetic factors such as volatile anesthetics and opioids, the type of surgery, and patient-related factors are all thought to have a major impact on PONV. Thus, for a long time it was assumed that prediction of PONV is difficult, if not impossible, as PONV was believed to be influenced by too many factors. However, there is now sufficient evidence that the risk for emetic sequelae after balanced anesthesia in adults can be predicted by a risk score derived from a limited number of risk factors. In order to reduce the incidence of PONV, antiemetic strategies such as choosing a less emetogenic anesthetic technique, applying antiemetics, or both by a multimodal approach can be applied. Because nonselective routine prophylactic antiemetic treatment may not improve patient outcome when applied to all patients, the use of a risk-adapted prophylactic strategy would be the most rational approach. These issues have been discussed in a review by Everett in the Spring 2002 issue of this journal. However, very recently there have been some additional insights and advances that will be updated in this chapter. Thus, this review provides an update on risk factors for PONV. It will explain how risk models—based on “true” risk factors—could be developed. Further, the applicability but also the limitations of predictive models will be discussed. In addition, a brief summary of antiemetic strategies needs to be discussed. Finally, a risk-dependent antiemetic strategy— based on current evidence and easily implemented in daily clinical practice—will be suggested.