An overview of intravenous amisulpride as a new therapeutic option for the prophylaxis and treatment of postoperative nausea and vomiting.

Introduction: Current therapies of postoperative nausea and vomiting (PONV) are based on a combination of antiemetics from different pharmacological classes. Dopamine receptor antagonists are one of the cornerstones of such multimodal antiemetic approach, with droperidol being the best studied representative of this group. Droperidol's use has significantly declined after the FDA's black-box warning in 2001 due to its QT-prolonging properties. Amisulpride is a promising antiemetic agent which could fill this gap.Areas covered: In this review, the authors discuss the pharmacological profile as well as clinical safety and efficacy of intravenous amisulpride and its relevance in the management of PONV. The article is based on a Medline, ClinicalTrials.gov, and Cochrane Library search for studies on amisulpride conducted so far.Expert opinion: Promising clinical results on Barhemsys®, an intravenous formulation of amisulpride, make it a potential future drug of choice from the dopamine receptor antagonist group, replacing droperidol after its safety concerns. Amisulpride's success on the market will mostly be determined by its cost-effectiveness and it will likely find a brighter use on the US-market, where the black-box warning led to droperidol's withdrawal, while in many European countries, droperidol is still being used as an antiemetic.

Impact of medical training and clinical experience on the assessment of oxygenation and hypoxaemia after general anaesthesia: an observational study.

In Germany it is common practice to use pulse oximetry and supplementary oxygen only on request in patients breathing spontaneously transferred to the post-anaesthesia care unit (PACU) following surgery under general anaesthesia. The main aim was to study the influence of medical training and clinical experience on assessing SpO(2) and detecting hypoxaemia in these patients. The second aim was to do a preliminary assessment whether this practice can be found in countries other than Germany. Anaesthetists, nurses and medical students estimated SpO(2) in patients breathing room air at the end of transfer to the PACU following surgery (including all major surgical fields) under general anaesthesia. Estimated SpO(2) was compared to SpO(2) measured by pulse oximetry. A survey was carried out among European anaesthesists concerning the use of pulse oximetry and supplementary oxygen during patient transfer to the PACU. Hypoxaemia (SpO(2) < 90 %) occurred in 154 (13.5 %) out of 1,138 patients. Anaesthetists, nurses, and medical students identified only 25, 23, and 21 patients of those as being hypoxaemic, respectively. Clinical experience did not improve detection of hypoxaemia both in anaesthetists (p = 0.63) and nurses (p = 0.18). Use of pulse oximetry and supplemental oxygen during patient transfer to the PACU in European countries differs to a large extent. It seems to be applied only on request in many hospitals. Considering the uncertainty about deleterious effects of transient, short lasting hypoxaemia routine use of pulse oximetry is advocated for patient transfer to the PACU.

Activity-based cost analysis of opioid-related nausea and vomiting among inpatients.

OBJECTIVE: Nausea and/or vomiting (N/V) are frequent side effects of opioid drugs. These are of major concerns to patients and caregivers and only few studies have focused on their economical costs. DESIGN: This is a prospective, nonproduct-related, activity-based evaluation of personnel and material costs of opioid-related N/V among inpatients. SETTING: Data were obtained from surgical, general medicine, and palliative care wards at 16 German hospitals of different size, healthcare mandate, and ownership. PATIENTS, PARTICIPANTS: According to predefined criteria, of 462 documented N/V events, 340 were diagnosed as opioid related. INTERVENTIONS: Elicited activities and pharmacological interventions for N/V episodes followed local standards. MAIN OUTCOME MEASURE: Both materials used and the time engaged to treat patients with N/V were documented on an "ad hoc" activity recording form. The total cost of an opioid-related N/V episode was calculated based on standard wages of the involved personnel and standard costs of the inherent materials used. RESULTS: Mean staff tenure time for handling an episode of N/V was 26.2 ± 19.8 minutes (nausea 16.9 ± 28.7 minutes; nausea + vomiting: 33.4 ± 26.8 minutes). In the German context, this corresponds to average personnel costs of €18.06 ± 13.64. Material cost contributes to another €13.49 ±13.38 of costs mainly depending on acquisition costs of antiemetic drugs. CONCLUSIONS: N/V showed to have impact on workload of nurses and (to lesser extent) physicians and economic burden of €31 ± 22 for each N/V episode. In view of these results, the potential costs of strategies to minimize the incidence of N/V (use of antiemetics and/or the use of new analgesics) should be outweighed against the incurred costs of N/V.

Quantifying prognosis with risk predictions.

Prognosis is a forecast, based on present observations in a patient, of their probable outcome from disease, surgery and so on. Research methods for the development of risk probabilities may not be familiar to some anaesthesiologists. We briefly describe methods for identifying risk factors and risk scores. A probability prediction rule assigns a risk probability to a patient for the occurrence of a specific event. Probability reflects the continuum between absolute certainty (Pi = 1) and certified impossibility (Pi = 0). Biomarkers and clinical covariates that modify risk are known as risk factors. The Pi as modified by risk factors can be estimated by identifying the risk factors and their weighting; these are usually obtained by stepwise logistic regression. The accuracy of probabilistic predictors can be separated into the concepts of 'overall performance', 'discrimination' and 'calibration'. Overall performance is the mathematical distance between predictions and outcomes. Discrimination is the ability of the predictor to rank order observations with different outcomes. Calibration is the correctness of prediction probabilities on an absolute scale. Statistical methods include the Brier score, coefficient of determination (Nagelkerke R2), C-statistic and regression calibration. External validation is the comparison of the actual outcomes to the predicted outcomes in a new and independent patient sample. External validation uses the statistical methods of overall performance, discrimination and calibration and is uniformly recommended before acceptance of the prediction model. Evidence from randomised controlled clinical trials should be obtained to show the effectiveness of risk scores for altering patient management and patient outcomes.

[Postoperative nausea and vomiting (PONV) - recommendations for risk assessment, prophylaxis and therapy - results of an expert panel meeting]. / 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.

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.

[Postoperative nausea and vomiting. Identification of patients with risk factors for PONV]. / Für wen ist PU & E relevant--und wer ist ein Risikopatient?

This review discusses the clinical relevance of risk stratification to determine measures to prevent postoperative nausea and vomiting. The key question is whether PU&E is a problem related only to a small group of risk patients and whether risk stratification is a reasonable approach to deal with this problem. The application of risk scores to predict PU&E has been strongly advocated in the past years. These tools suggest that PU&E is mainly a problem of a small and well defined group of patients that can be identified and clearly separated from patients with no risk for PU&E. The need for applying these risk scores was based on the assumption that efficiency of antiemetic intervention mainly depends on the baseline risk for PU&E and that these are only justified at an increased risk (e.g. PU&E-risk > 60 %) where the number needed to treat is about 5 or lower. PU&E, on the other hand, are distressing and annoying symptoms for the patient. PU&E is a limiting factor for any approach to speed postoperative recovery and thus incompatible with so called fast-track rehabilitation programs. Thus, PU&E is relevant not only for high-risk patients but also for the great majority of patients with an intermediate risk for PU&E. The latter group, e.g. patients with a predicted risk to suffer from PU&E between 20 and 60 %, account for more than 80 % of all patients undergoing risk evaluation. Considering the high impact of PU&E for the individual patient, the small incidence of patients where the occurrence of PU&E can be ruled out with appropriate high probability, and finally the availability of several effective antiemetic measures all with a marked low incidence of side-effects, the authors of this review advocate a liberal policy for prophylactic administration of antiemetics. Prophylaxis against PU&E should be as self-evident as measures to limit postoperative pain. Omitting antiemetic prevention should only be considered if the estimated risk for PU&E is extremely low. All other patients in whom PU&E cannot be ruled out with high confidence should receive routine antiemetic prophylaxis.

[Postoperative nausea and vomiting: rational algorithms for prevention and treatment based on current evidence]. / Wie gehe ich im Alltag vor? Prophylaxe- und Therapiealgorithmen.

Postoperative nausea and vomiting (PONV) constitutes a major unpleasant symptom in the postoperative period. The prevention of PONV is judged equally important as the prevention of postoperative pain. Therefore, a working PONV-algorithm should be as self-evident as the approach to prevent and treat postoperative pain. None of the currently available pharmacological interventions is able to totally abolish PONV. However, using a multimodal approach with the combination of various antiemetic interventions, a substantial reduction or even elimination of PONV is already feasible. As a rule of thumb, each effective antiemetic intervention will lead to a relative risk reduction of approximately 30 %. Well documented interventions in terms of the aforementioned efficacy are the administration of ondansetron 4 mg, dexamethasone 4 mg, droperidol 1,25mg and dimenhydrinate 62 mg, as well oral Aprepitant. Metoclopramide may play a role for instance in a multimodal approach. Apart from the administration of antiemetics, the avoidance of inhalational anaesthetics by using propofol is associated with a comparable risk reduction. In general, using a risk-dependent approach, e.g. based on a simplified risk score, allows to avoid administering antiemetics to patients at low risk. However, due to the difficulties associated with the implementation of risk-score based algorithms and the inherent weaknesses of clinical risk scores to predict PONV in an individual patient, a general (multimodal) approach seem to be justified as well. Considering the fact that the currently available antiemetics are associated with few side effects, the administration of prophylactic antiemetics should not be associated with a high hurdle in the clinical setting. In case of any doubts regarding the individual risk, it seems justified to expand the (multimodal) prophylaxis rather than to wait until PONV occurs and impairs patient comfort.

Recent advances, trends and economic considerations in the risk assessment, prevention and treatment of postoperative nausea and vomiting.

During the last two decades there have been considerable achievements regarding the management of postoperative nausea and vomiting (PONV). Due to the importance of these symptoms in the aim to streamline clinical processes and to improve patient satisfaction, the debate on the best strategies and also research that focuses on PONV continues. This review summarises the recent developments with respect to the management of PONV. Following a brief review on what is already known on the risk assessment, prevention and treatment of PONV, newer trends in the pharmacological prevention (dexamethasone, neurokinin-1 antagonists, multimodal prevention) will be discussed as well as new insights regarding the value of algorithms for the prevention of PONV. Further, pharmacogenetically based algorithms (according to the metaboliser status) as well as new treatment strategies (dexamethasone, multimodal treatment) will be covered. No drug so far can achieve a reduction of PONV of more than one third. Furthermore, all clinical studies consistently demonstrated that a combination treatment has a simple additive effect without any relevant interaction between different drugs or classes of drugs. The relative reduction of approximately 30% can also be expected from dexamethasone and it is likely that the substances presently in development and in an early clinical use (e.g., neurokinin-1 antagonists) will not represent the new panacea. However, they will probably replenish the existing antiemetic portfolio to better cope with high risk patients. Stratified prevention using pharmacogenetic knowledge is still in the early stages. Algorithms need to be customized to the local settings in order to prove efficient. Treatment remains a most important pillar and there is evidence that the principles of combining antiemetics to prolong effects and improve protection can be similarly applied to treatment. Recent developments in the area of PONV are more related to implementing the already existing evidence than based on the introduction of new molecules. New molecules replenish the pharmacological antiemetic portfolio, which is needed due to the limited efficacy of any single agent available so far. The new neurokinin-1 receptor antagonist, aprepitant, and the long lasting 5-HT(3) receptor antagonist palonosetron are the latest developments in this context. Treatment is most important and can also be regarded as a secondary prevention. Due to limited efficacy of single treatment interventions, combination therapy may gain more widespread use in the future.

Cost analyses of remifentanil, mivacurium and ropivacaine - a systematic review.

Remifentanil, mivacurium and ropivacaine are the latest innovations in clinical anaesthesia and have gained increasing importance in daily practise due to their unique pharmacodynamic and pharmacokinetic properties. However, drug acquisition costs for these agents are considerably higher in most countries than for comparable substances. This review provides a systematic, critical appraisal of pharmacoeconomic studies with remifentanil, mivacurium and ropivacaine, primarily based on prospective, randomised trials. Results from analyses using cost-minimising techniques stress the issue of the higher drug acquisition costs. However, studies using a more sophisticated method (e.g., cost-effectiveness analysis) indicate comparable costs or even financial advantage in favour of the newer investigative drugs remifentanil, mivacurium and ropivacaine.