Jan Wallenborn

Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomised double blind multicentre trial

Abstract Objectives To determine whether 10 mg, 25 mg, or 50 mg metoclopramide combined with 8 mg dexamethasone, given intraoperatively, is more effective in preventing postoperative nausea and vomiting than 8 mg dexamethasone alone, and to assess benefit in relation to adverse drug reactions. Design Four-armed, parallel group, double blind, randomised controlled clinical trial. Setting Four clinics of a university hospital and four district hospitals in Germany. Participants 3140 patients who received balanced or regional anaesthesia during surgery. Main outcome measures Postoperative nausea and vomiting within 24 hours of surgery (primary end point); occurrence of adverse reactions. Results Cumulative incidences (95% confidence intervals) of postoperative nausea and vomiting were 23.1% (20.2% to 26.0%), 20.6% (17.8% to 23.4%), 17.2% (14.6% to 19.8%), and 14.5% (12.0% to 17.0%) for 0 mg, 10 mg, 25 mg, and 50 mg metoclopramide. In the secondary analysis, 25 mg and 50 mg metoclopramide were equally effective at preventing early nausea (0-12 hours), but only 50 mg reduced late nausea and vomiting (> 12 hours). The most frequent adverse drug reactions were hypotension and tachycardia, with cumulative incidences of 8.8% (6.8% to 10.8%), 11.2% (9.0% to 13.4%), 12.9% (10.5% to 15.3%), and 17.9% (15.2% to 20.6%) for 0 mg, 10 mg, 25 mg, and 50 mg metoclopramide. Conclusion The addition of 50 mg metoclopramide to 8 mg dexamethasone (given intraoperatively) is an effective, safe, and cheap way to prevent postoperative nausea and vomiting. A reduced dose of 25 mg metoclopramide intraoperatively, with additional postoperative prophylaxis in high risk patients, may be equally effective and cause fewer adverse drug reactions. Trial registration Current Controlled Trials ISRCTN31625370

Nausea and Vomiting After Surgery Under General Anesthesia: An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment

BACKGROUND The German-language recommendations for the management of postoperative nausea and vomiting (PONV) have been revised by an expert committee. Major aspects of this revision are presented here in the form of an evidence-based review article. METHODS The literature was systematically reviewed with the goal of revising the existing recommendations. New evidence-based recommendations for the management of PONV were developed, approved by consensus, and graded according to the scheme of the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS The relevant risk factors for PONV include female sex, nonsmoker status, prior history of PONV, motion sickness, use of opioids during and after surgery, use of inhalational anesthetics and nitrous oxide, and the duration of anesthesia. PONV scoring systems provide a rough assessment of risk that can serve as the basis for a risk-adapted approach. Risk-adapted prophylaxis, however, has not been shown to provide any greater benefit than fixed (combination) prophylaxis, and PONV risk scores have inherent limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two approaches to manage PONV is chosen, high-risk patients must be given multimodal prophylaxis, involving both the avoidance of known risk factors and the application of multiple validated and effective antiemetic interventions. PONV should be treated as soon as it arises, to minimize patient discomfort, the risk of medical complications, and the costs involved. CONCLUSION PONV lowers patient satisfaction but is treatable. The effective, evidence-based measures of preventing and treating it should be implemented in routine practice.

Do Variations in the 5-ht3a and 5-ht3b Serotonin Receptor Genes ( htr3a and htr3b ) Influence the Occurrence of Postoperative Vomiting?

BACKGROUND: Postoperative nausea and vomiting are unpleasant side effects of general anesthesia. Besides known risk factors (female gender, nonsmoker, history, and opioids), a genetic influence of the serotonin receptor system on the development of nausea and vomiting has repeatedly been proposed. In this pilot study, we therefore investigated the genes of the serotonin receptor subunits A and B (HTR3A and HTR3B) for genetic variants. METHODS: We included 95 patients who had suffered from postoperative vomiting (POV) after general anesthesia and 94 control patients. After DNA isolation, the entire HTR3A and HTR3B coding regions, the 5′ flanking regions, and exon/intron boundaries were screened for genetic variants. Correlation of identified genetic variants with POV was determined by logistic regression. RESULTS: We identified 16 different variants in the HTR3A gene and 19 in the HTR3B gene. By using a multivariate logistic regression model that also included classical risk factors, the HTR3A variant c1377A>G was associated with a significantly higher risk (odds ratio [OR] 2.972; 95% confidence interval [CI] 1.466–6.021; P = 0.003) and the HTR3B variants c5+201_+202delCA (OR 0.421; 95% CI 0.257–0.69; P = 0.001) and c6-137C>T (OR 0.034; 95% CI 0.003–0.332; P = 0.004) were associated with a lower risk for POV. However, all significant genetic variants were located in noncoding regions of their gene. CONCLUSIONS: Genetic variations in the HTR3A and HTR3B gene seem to be associated with the individual risk of developing POV. How strong their influence is within the multifactorial genesis of POV needs to be investigated in additional studies with an appropriate sample size.

I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial

BACKGROUND Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis. METHODS Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery. RESULTS Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects. CONCLUSIONS APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.

Comparative evaluation of Bispectral Index and Narcotrend Index in children below 5 years of age

Background:  The use of electroencephalogram (EEG) monitoring devices for assessing the depth of hypnosis is most difficult in children under 5 years of age.

Übelkeit und Erbrechen nach Operationen in Allgemeinanästhesie – Empfehlungen zur Risikoeinschätzung, Prophylaxe und Therapie

BACKGROUND The aim was to update recommendations concerning the management of postoperative nausea and vomiting (PONV) for German speaking countries. METHODS An expert panel produced evidence-based, consented statements graded according to the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS Relevant risk factors for PONV include female gender, non-smoking status, history of PONV, history of motion sickness, use of intra- and postoperative opioids, volatile anesthetics and nitrous oxide. PONV scoring systems allow for an approximative risk assessment as a basis for a risk adapted approach. Since a risk-adapted prophylaxis vs. a risk-independent, fixed (combined) prophylaxis has not yet proven superior and because of inherent limitations of PONV scoring systems a fixed prophylaxis may be favourable. Regardless of the strategy for prophylaxis of PONV, high risk patients must be given a multimodal prophylaxis by avoiding known risk factors and applying multiple validated and effective antiemetic interventions. In the case of PONV immediate treatment is indicated due to its relevance for patients as well as the economic and medicolegal implications PONV may have. CONCLUSIONS Given the impact of PONV on patient satisfaction and the availability of effective and safe measures to prevent and treat PONV, further efforts should be taken to actually implement present evidence in order to improve patient?s outcome following surgical procedures.

Palonosetron Hydrochloride in the Prevention and Treatment of Postoperative Nausea and Vomiting

On the strength of two phase III clinical trials, palonosetron hydrochloride was granted FDA approval in March 2008 for the prevention of postoperative nausea and vomiting (PONV) in the period up to 24 hours after surgery. Palonosetron is superior to the established first-generation 5-hydroxytryptamin-3 receptor antagonists (5-HT3-RAs) in respect of pharmacokinetic data such as a high receptor binding affinity (pKi = 10.45) and a prolonged mean elimination half-life (40 hours). Clinically, palonosetron 0.075 mg was superior to placebo within the 0 to 24 h period usually investigated. A pooled data analysis of the complete response (CR) rates revealed efficacy in the 0 to 24 h period (when compared to placebo CR = 1.67 [1.38–2.02; P < 0.001, n = 370]) and between 24–72 h after surgery (CR = 1.29 [1.10–1.51; P = 0.002, n = 273]). Overall, the effect of palonosetron in reducing delayed vomiting was not as promising as expected. In the approval studies for PONV the rates of AEs including headache (3%), constipation (2%) and prolongation of the QTc interval (5%) were indistinguishable between palonosetron and placebo. In studies on chemotherapy-induced nausea and vomiting, palonosetron increased the QTc interval (between one and three ms) to a lesser extent than ondansetron or dolasetron (5 ms). The safety profile of palonosetron therefore seems to be favourable so far, making it a preferred perioperative antiemetic in the geriatric population or in multimorbid patients. However, further studies are needed to permit general recommendations, and we still lack comparative trials with older (and less expensive) 5-HT3-RAs, trials with combined PONV prophylaxis, and trials in the paediatric population.

Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients.

Context: Sleep deprivation is a common problem on intensive care units (ICUs) influencing not only cognition, but also cellular functions. An appropriate sleep-wake cycle should therefore be maintained to improve patients’ outcome. Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-sedated. Aims: The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam. Settings and Design: Monocentric, randomized, double-blinded trial. Materials and Methods: A total of 66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n = 34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus dose (0.015 mg/kg). Differences between groups were evaluated using a standardized sleep diary and the bispectral index (BIS). Statistical Analysis Used: Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was considered to be statistically significant. Results: Sleep quality and the frequency of awakenings were significantly better in the propofol group (Pg). In the same group lower BIS values were recorded (median BIS propofol 74.05, flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration. Conclusions: Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-sedated was superior to flunitrazepam regarding sleep quality and sleep structure.

Effects of clonidine and superficial cervical plexus block on hemodynamic stability after carotid endarterectomy.

OBJECTIVES To evaluate the effects of 2 interventions (intravenous clonidine and superficial cervical block) on hemodynamic stability after carotid endarterectomy and to identify variables associated with hemodynamic instability. DESIGN Prospective, observational study, sequential enrollment. SETTING University hospital. PARTICIPANTS Two hundred seventy-five patients undergoing elective carotid endarterectomy under general anesthesia. INTERVENTIONS Group NN (n = 50) received no intervention. In group CN (n = 85), 3 mug/kg of clonidine were administered intravenously 30 minutes before the end of the operation. Group CB (n = 140) additionally received a superficial cervical plexus block (SCB) with 20 mL of naropine 0.5% before the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Clonidine alone (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.45-3.76) and clonidine combined with an SCB (OR, 4.99; 95% CI, 3.19-7.82) resulted in a significant increase in hemodynamic stability after CEA (p < 0.001) from 53.3% (NN) to 70.0% (CN) and 83.3% (CB), respectively. The need for rescue medication decreased from 40.0% to 17.6% and 13.6% (p < 0.001). Both interventions significantly reduced the need for postoperative opioid analgesics (p < 0.01). Logistic regression analysis showed preoperative systolic blood pressure values greater than 170 mmHg (OR, 3.23; 95% CI, 1.76-5.93), previous cardiac interventions (OR, 3.3; 95% CI, 1.54-7.11), and the need for rescue medication in the awakening period (OR, 5.8; 95% CI, 2.88-11.52) to be independent risk factors for postoperative hemodynamic instability (p < or = 0.002). CONCLUSIONS Intravenous clonidine and superficial cervical block significantly improve cardiovascular stability after carotid endarterectomy. Patients with pre-existing excessive hypertension and previous coronary interventions must be considered a high-risk group.

[Postoperative nausea and vomiting--what's new in anti-emetic pharmacotherapy?].

Neurokinin-1 receptor antagonists represent a new approach in the prevention of postoperative nausea and vomiting (PONV) and show an efficacy comparable with those of common antiemetics with some evidence for superiority with regard to vomiting. Currently, only aprepitant is available as an oral preparation. Palonosetron is a new representative of the serotonin-3 receptor antagonists but without the hoped for superiority on the 2nd and 3rd postoperative days. However, available data do suggest that palanosetron does not prolong the OT (c) interval. When using 5-HT (3)-receptor antagonists for the prevention of PONV, anaesthetists should be aware of negative interactions with analgesics. Low-dose droperidol has regained approval and should be considered as first choice among the current available neuroleptics.