ABSTRACT
Abstract Background: Postoperative Nausea and Vomiting (PONV) is a common complication of general anesthesia. Several kinds of antiemetics, including 5-Hydroxytryptamine3 (5-HT3) receptor antagonists, and Neurokinin-1 (NK-1) receptor antagonists have been used to treat PONV. Objectives: To compare the antiemetic effect of NK-1 receptor antagonists, including fosaprepitant. Data sources: Online databases (PubMed, MEDLINE, Scopus, The Cochrane Library databases) were used. Study eligibility criteria, participants, and interventions: Randomized Controlled Trials (RCTs) performed in patients over 18 years with ASA-PS of I‒III, aimed to assess the efficacy of antiemetics including NK-1 receptor antagonists and 5-HT3 receptor antagonists, and compared the incidence of PONV were included. Study appraisal and synthesis methods: All statistical assessments were conducted by a random effect approach, and odds ratios and 95% Confidence Intervals were calculated. Results: Aprepitant 40 mg and 80 mg significantly reduced the incidence of vomiting 0‒24 hours postoperatively (Odds Ratio [OR = 0.40]; 95% Confidence Interval [95% CI 0.30‒0.54]; p < 0.001, and OR = 0.32; 95% CI 0.19‒0.56; p < 0.001). Fosaprepitant could also reduce the incidence of vomiting significantly both 0‒24 and 0‒48 hours postoperatively (OR = 0.07; 95% CI 0.02‒0.24; p < 0.001 and OR = 0.07; 95% CI 0.02‒0.23; p < 0.001). Limitations: Risk factors for PONV are not considered, RCTs using multiple antiemetics are included, RCTs for fosaprepitant is small, and some bias may be present. Conclusions and implications of key findings: Aprepitant and fosaprepitant can be effective prophylactic antiemetics for postoperative vomiting. However, more studies are required for higher-quality meta-analyses. Systematic review registration number: CRD42019120188.
Resumo Histórico: Náusea e Vômito no Pós-Operatório (NVPO) é um evento adverso frequente da anestesia geral. Várias classes de antieméticos, incluindo antagonistas do receptor 5-Hidroxitriptamina3 (5-HT3) e antagonistas do receptor da Neurocinina-1 (NK-1), têm sido utilizados para tratar a NVPO. Objetivo: Comparar o efeito antiemético dos antagonistas do receptor NK-1, incluindo o fosaprepitanto. Fontes de dados: Foram utilizadas bases de dados on-line (PubMed, MEDLINE, Scopus, The Cochrane Library). Critérios de elegibilidade do estudo, participantes e intervenções: Foram incluídos Estudos Clínicos Randomizados (ECR) realizados em pacientes acima de 18 anos classificação ASA I a III, com o objetivo de avaliar a eficácia de antieméticos que incluíssem antagonistas do receptor NK-1 e antagonistas do receptor 5-HT3, e que comparassem a incidência de NVPO. Métodos de avaliação e síntese do estudo: Todas as avaliações estatísticas foram realizadas por abordagem de efeito aleatório e foram calculadas razões de chances e Intervalos de Confiança de 95%. Resultados: As doses de 40 mg e 80 mg de aprepitanto reduziram significantemente a incidência de vômito no período de 0 a 24 horas pós-operatórias (razão de chances [OR = 0,40]; Intervalo de Confiança de 95% [95% IC] 0,30-0,54; p < 0,001 e OR = 0,32; 95% IC 0,19-0,56; p < 0,001). O fosaprepitanto pode também reduzir significantemente a incidência de vômito tanto de 0-24 horas como no período de 0-48 horas pós-operatórias (OR = 0,07; 95% IC 0,02-0,24; p < 0,001 e OR = 0,07; 95% IC 0,02-0,23; p < 0,001). Limitações: Os fatores de risco para NVPO não foram analisados, ECRs usando múltiplos antieméticos foram incluídos, ECRs para fosaprepitanto tinham amostras pequenas, podendo haver algum viés. Conclusões e implicações dos principais achados: Aprepitanto e fosaprepitanto podem ser drogas antieméticas profiláticas efetivas para vômito no pós-operatório. No entanto, são necessários mais estudos para elaboração de meta-análises de melhor qualidade. Número de registro da revisão sistemática: CRD42019120188.
Subject(s)
Humans , Postoperative Nausea and Vomiting/prevention & control , Neurokinin-1 Receptor Antagonists/administration & dosage , Antiemetics/administration & dosage , Randomized Controlled Trials as Topic , Morpholines/administration & dosage , Morpholines/pharmacology , Incidence , Postoperative Nausea and Vomiting/epidemiology , Serotonin 5-HT3 Receptor Antagonists/administration & dosage , Serotonin 5-HT3 Receptor Antagonists/pharmacology , Neurokinin-1 Receptor Antagonists/pharmacology , Anesthesia, General/adverse effects , Anesthesia, General/methods , Antiemetics/pharmacologyABSTRACT
The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.