Neurokinin-1 receptor antagonists for postoperative nausea and vomiting: a systematic review and meta-analysis / Antagonistas do receptor da neurocinina-1 no tratamento de náusea e vômito no pós-operatório: Revisão sistemática e meta-análise

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.

Benefits of ginger in the control of chemotherapy-induced nausea and vomiting / Beneficios del jengibre en el control de náusea y vómito inducidos por la quimioterapia / Benefícios do gengibre no controle da náusea e vômito induzidos pela quimioterapia

ABSTRACT Objectives: To identify and discuss scientific evidence of the effects of ginger use on the management of chemotherapy-induced nausea and vomiting. Methods: This is an integrative reviewperformed by Ganong's reference. Results: We included 24 studies, highlighting three thematic categories, namely 1) antiemetic action of ginger - nausea (13 articles; of these, nine significant) and emesis (10 studies; of these, six significant); 2) action in the control of nausea (11 articles; of these, six significant) and vomiting (8 articles; of these, three significant) in the acute phase; 3) action in the control of nausea (6 articles; of these, three significant) and vomiting (6 articles; of these, three significant) in the delayed phase. There were divergences of the methods used. Final considerations: This complementary therapy has low cost and easy access, but no statistical confirmation of its effectiveness in the management of nausea and vomiting in cancer patients was found.

RESUMEN Objetivos: Identificar y discutir evidencias científicas de los efectos del uso del jengibre en el manejo de la náusea y vomito inducidos por la quimioterapia. Métodos: Se trata de revisión integranterealizada por el referencial Ganong. Resultados: Han sido incluidos 24 estudios, destacándose 3 categorías temáticas: 1) acción antiemética del jengibre - ha sido evaluada la náusea (13 artículos [9 significativos]) y emesis (10 estudios [6 significativos]); 2) acción en el control de la náusea (11 artículos [6 significativos]) y vomito (8 artículos [3 significativos]) en la fase aguda; 3) acción en el control de la náusea (6 artículos [3 significativos]) y vomito (6 artículos [3 significativos]) en la fase tardía. Hubo divergencias de los métodos utilizados. Consideraciones finales: Esa terapia complementar ha sido de bajo costo y fácil acceso, pero no ha sido encontrada confirmación estadística de su efectividad en el manejo de la náusea y vomito en pacientes oncológicos.

RESUMO Objetivos: Identificar e discutir evidências científicas dos efeitos do uso do gengibre no manejo da náusea e vômito induzidos pela quimioterapia. Métodos: Trata-se de revisão integrativabaseada no referencial de Ganong. Resultados: Foram incluídos 24 estudos, destacando-se 3 categorias temáticas, a saber, 1) ação antiemética do gengibre - foi avaliada a náusea (13 artigos; destes, 9 significativos) e êmese (10 estudos; destes, 6 significativos); 2) ação no controle da náusea (11 artigos; destes, 6 significativos) e vômito (8 artigos; destes, 3 significativos) na fase aguda; 3) ação no controle da náusea (6 artigos; destes, 3 significativos) e vômito (6 artigos; destes, 3 significativos) na fase tardia. Houve divergências dos métodos utilizados. Considerações finais: Essa terapia complementar é de baixo custo e fácil acesso, mas não foi encontrada confirmação estatística de sua efetividade no manejo da náusea e vômito em pacientes oncológicos.

Effects of metoclopramide on the expression of metalloproteinases and interleukins in left colonic anastomoses. An experimental study

PURPOSE : To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. METHODS : Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. RESULTS : On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1β, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1β, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. CONCLUSION : Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs.

Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study

Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.

In vivo antipyretic, antiemetic, in vitro membrane stabilization, antimicrobial, and cytotoxic activities of different extracts from Spilanthes paniculata leaves

BACKGROUND: The study was conducted to evaluate the in vitro antimicrobial activity, cytotoxic, and membrane stabilization activities, and in vivo antiemetic and antipyretic potentials of ethanolic extract, n-hexane and ethyl acetate soluble fractions of Spilanthes paniculata leaves for the first time widely used in the traditional treatments in Bangladesh. RESULTS: In antipyretic activity assay, a significant reduction (P < 0.05) was observed in the temperature in the mice tested. At dose 400 mg/kg-body weight, the n-hexane soluble fraction showed the effect (36.7 ± 0.63°C ) as like as the standard (dose 150 mg/kg-body weight) after 5 h of administration. Extracts showed significant (P < 0.001) potential when tested for the antiemetic activity compared to the standard, metoclopramide. At dose 50 mg/kg-body weight, the standard showed 67.23% inhibition, whereas n-hexane and ethyl acetate soluble fractions showed 37.53% and 24.93% inhibition of emesis respectively at dose 400 mg/kg-body weight. In antimicrobial activity assay, the n-hexane soluble fraction (400 µg/disc) showed salient activity against the tested organisms. It exerts highest activity against Salmonella typhi (16.9 mm zone of inhibition); besides, crude, and ethyl acetate extracts showed resistance to Bacillus cereus and Bacillus subtilis, and Vibrio cholera respectively. All the extracts were tested for lysis of the erythrocytes. At the concentration of 1mg/ml, ethanol extract, and n-hexane and ethyl acetate soluble fractions significantly inhibited hypotonic solution induced lysis of the human red blood cell (HRBC) (27.406 ± 3.57, 46.034 ± 3.251, and 30.72 ± 5.679% respectively); where standard drug acetylsalicylic acid (concentration 0.1 mg/ml) showed 77.276 ± 0.321% inhibition. In case of heat induced HRBC hemolysis, the plant extracts also showed significant activity (34.21 ± 4.72, 21.81 ± 3.08, and 27.62 ± 8.79% inhibition respectively). In the brine shrimp lethality bioassay, the n-hexane fraction showed potent (LC50 value 48.978 µg/ml) activity, whereas ethyl acetate fraction showed mild (LC50 value 216.77 µg/ml) cytotoxic activity. CONCLUSIONS: Our results showed that the n-hexane extract has better effects than the other in all trials. In the context, it can be said that the leaves of S. paniculata possess remarkable pharmacological effects, and justify its folkloric use as antimicrobial, antipyretic, anti-inflammatory, and antiemetic agent. Therefore, further research may be suggested to find possible mode of action of the plant part.

Effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis / Efeitos da bromoprida na cicatrização de anastomoses no cólon esquerdo de ratos sob sepse abdominal induzida

PURPOSE: To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. METHODS: Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. RESULTS: On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. CONCLUSION: In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery.

OBJETIVO: Avaliar os efeitos da bromoprida sobre a cicatrização de anastomoses de cólon esquerdo de ratos na presença de sepse abdominal. MÉTODOS: Quarenta ratos distribuídos em grupos contendo 20 animais para administração de bromoprida ou salina. Cada grupo foi dividido em subgrupos contendo dez animais, para eutanásia no terceiro ou no sétimo dia de pós-operatório. A indução da sepse foi realizada pelo método de ligadura e punção do ceco. Foi realizada ressecção de um segmento do cólon esquerdo e anastomose término-terminal. À re-laparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, força de ruptura, concentração de hidroxiprolina e histomorfometria do colágeno. RESULTADOS: No 3° DPO, as anastomoses dos animais tratados com bromoprida apresentaram menor força de ruptura (p=0,02) e maior redução da concentração de hidroxiprolina (p=0,04) que os animais controle. Não houve diferença estatística quanto a estes parâmetros no 7° DPO. O conteúdo de colágeno foi semelhante entre os subgrupos. CONCLUSÃO: Na presença de sepse abdominal, o uso da bromoprida esteve associado à diminuição da força de ruptura e da concentração de hidroxiprolina das anastomoses do cólon esquerdo de ratos no 3° DPO.

Effects of bromopride on abdominal wall healing with induced peritoneal sepsis after segmental colectomy and colonic anastomosis in rats / Efeitos da bromoprida na cicatrização da parede abdominal com sepse peritoneal induzida e submetidos à ressecção segmentar e anastomose do cólon esquerdo em ratos

PURPOSE: Evaluate the effects of bromopride on abdominal wall healing of rats with induced peritoneal sepsis after segmental colectomy and colonic anastomosis. METHODS: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of bromopride (bromopride group - B) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (GB3 and GC3) or seventh postoperative day (GB7 and GC7). It was analyzed the following characteristics: breaking strength of the abdominal wall's wound; surgical and histopathological features of the abdominal wall; and clinical features of the rats. RESULTS: There was no difference between the groups in relation to the weight of the rats and the breaking strength of the abdominal wall's wound. The GB7 group presented less edema and less quantity of fibrin during histopathological evaluation compared to the GC7 group. CONCLUSION: Bromopride did not have harmful effects on the healing of abdominal wall in rats.

OBJETIVO: Avaliar o efeito da bromoprida, na cicatrização da ferida operatória da parede abdominal de ratos com sepse peritoneal experimentalmente induzida e submetidos a ressecção segmentar e anastomose de cólon esquerdo. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para administração de bromoprida (grupo bromoprida- B) ou solução de NaCl 0,9 por cento (grupo controle - C). Cada grupo foi dividido em subgrupos contendo 10 animais, para eutanásia no terceiro (GB3 e GC3) ou sétimo dia (GB7 e GE7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da eutanásia foram avaliadas as características cirúrgicas da cavidade abdominal e clínicas dos ratos. Foram coletados segmentos da parede para a avaliação histopatológica e de resistência tênsil da ferida operatória. RESULTADOS: Não houve diferenças entre os pesos dos ratos e resistência tênsil da ferida operatória nos dois grupos. Em relação a análise histopatológica, o grupo GB7 apresentou menos edema e menos fibrina que o grupo GC7. Não houve outras diferenças. CONCLUSÃO: A utilização de bromoprida não resultou em distúrbios ou retardo da cicatrização no grupo de ratos submetidos à laparotomia e anastomose término-terminal em condições de sepse peritoneal.

A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy.

OBJECTIVE: To study the efficacy of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy. STUDY DESIGN: Double blind randomized controlled trial. SETTING: Department of Obstetrics and Gynecology, Thammasat Hospital, Faculty of Medicine, Thammasat University. MATERIAL AND METHOD: Between January 2005 and December 2005, 170 pregnant women who attended at antenatal clinic Thammasat University Hospital with the symptoms of nausea and vomiting in pregnancy were randomly allocated into group A (n = 85) and group B (n = 85). The patients in group A received one capsule of ginger twice daily (one capsule contained 0.5 gm of ginger powder) while the patients in group B received the identical capsule of 50 mg dimenhydrinate twice daily. The visual analogue nausea scores (VANS) and vomiting times were evaluated at day 0-7 of the treatment. RESULTS: There was no significant difference in the visual analogue nausea scores (VANS) between group A and group B in day 1-7 of the treatment. The vomiting episodes of group A were greater than group B during the first and second day of the treatment with statistically significant difference. No difference in vomiting episodes during the day 3-7 of treatment was found in both groups. There was a statistically significant difference in the side effect of drowsiness after treatment in group B greater (77.64%) than group A (5.88%) (p < 0.01). CONCLUSION: From the presented data, ginger is as effective as dimenhydrinate in the treatment of nausea and vomiting during pregnancy and has fewer side effects.

Combination of Antiemetics for the Prevention of Postoperative Nausea and Vomiting in High-Risk Patients

It was previously reported that the Korean predictive model could be used to identify patients at high risk of postoperative nausea and vomiting (PONV). This study investigated whether PONV in the high-risk and very high-risk patients identified by the Korean predictive model could be prevented by multiple prophylactic antiemetics. A total of 2,456 patients were selected from our previous PONV study and assigned to the control group, and 374 new patients were recruited consecutively to the treatment group. Patients in each group were subdivided into two risk groups according to the Korean predictive model: high-risk group and very high-risk group. Patients in the treatment group received an antiemetic combination of dexamethasone 5 mg (minutes after induction) and ondansetron 4 mg (30 min before the end of surgery). The incidences of PONV were examined at two hours after the surgery in the postanesthetic care unit and, additionally, at 24 hr after the surgery in the ward, and were analyzed for any differences between the control and treatment groups. The overall incidence of PONV decreased significantly from 52.1% to 23.0% (p< or =0.001) after antiemetic prophylaxis. Specifically, the incidence decreased from 47.3% to 19.4% (p< or =0.001) in the high-risk group and from 61.3% to 28.3% (p< or =0.001) in the very high-risk group. Both groups showed a similar degree of relative risk reductions: 59.0% vs. 53.8% in the high-risk and very high-risk groups, respectively. The results of our study showed that the antiemetic prophylaxis with the combination of dexamethasone and ondansetron was effective in reducing the occurrence of PONV in both high-risk and very high-risk patients.

Imipramine in persistent vomiting.

A 21-year-old female presented with persistent vomiting for last 3 years. She had all the investigations done including gastroscopy but there was no abnormality detected. She was tried earlier with medicines prescribed in a medical college or a private nursing home. The cause of vomiting was thought of psychogenic. She was advised imipramine 25 mg thrice daily and responded to the treatment favourably.

The efficacy of ginger in prevention of postoperative nausea and vomiting after major gynecologic surgery.

OBJECTIVE: To study the efficacy of ginger in prevention of nausea and vomiting after major gynecologic surgery. STUDY DESIGN: Double blind randomized controlled trial. SETTING: Department of Obstetrics and Gynecology, Thammasat University Hospital, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand. MATERIAL AND METHOD: From March 2005 to April 2006, 120 patients who underwent major gynecologic surgery were randomized into group A (n = 60) and group B (n = 60). The patients in group A received two capsules of ginger taken one hour before the procedure (one capsule contains 0.5 gram of ginger powder). The patients in group B received the placebo. The visual analog nausea score (VANS) and frequency of vomiting were evaluated at 0, 2, 6, 12, and 24 hours after the operation. RESULTS: The results demonstrated the statistically significant differences in nausea between group A (48.3%) and group B (66.7%). The VANS was lower in group A compared to group B at 2, 6, 12, and 24 hours. The most statistically significant differences occurred at 2 and 6 hour. The incidence and frequency of vomiting in group A were lower than group B. Side effects caused by ginger were not detected. CONCLUSION: Ginger has efficacy in prevention of nausea and vomiting after major gynecologic surgery.

Antiemetic effect of ondansetron and dexamethasone in gynecologic malignant patients receiving chemotherapy.

OBJECTIVES: To evaluate the antiemetic effect of a single dose of ondansetron and dexamethasone as a prophylaxis for chemotherapy induced acute nausea and emesis and factors associated with the control of acute nausea and emesis. MATERIAL AND METHOD: Patients who received single dose of 8 mg ondansetron and 20 mg dexamethasone as a prophylaxis for chemotherapy induced nausea and emesis at Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital, between October 2004 and April 2006 were identified. The assessment record of the drug efficacy had been evaluated in the first 24 hours after the start of chemotherapy in terms of control of vomiting, and nausea. Age of the patients, history of alcohol intake, type of cancer, regimen of chemotherapy and course of chemotherapy were analysed as possible factors associated with the control of nausea and emesis. RESULTS: Seventy-eight gynecologic-cancer patients receiving 353 cycles of chemotherapy were evaluated in this study. Completed control of acute vomiting and nausea were 68% and 57.2% respectively. Complete control of acute vomiting and nausea were 56.9% and 45.4% in patients of < or = 45 years compared to 78.8% and 68.7% in those with > 45 years. Complete control of acute vomiting and nausea were 59.2% and 48.7% in those receiving cisplatin-containing regimens compared to 86.7% and 75.2% in non-cisplatin containing regimens. Univariable and multivariable analysis showed that younger patients and those who received cisplatin-containing regimens had significant lower rates of complete control of both nausea and emesis. Patients receiving the first three courses of chemotherapy had significantly higher rate of complete control of nausea but not emesis as compared to those receiving chemotherapy after the third course. CONCLUSION: A single intravenous dose of 8 mg of ondansetron and 20 mg of dexamethasone had good control of acute nausea and vomiting only in those who received non-cisplatin containing regimens and those older than 45 years.

Avaliaçäo da funçäo renal de cäes sob dois protocolos para administraçäo da cisplatina / Renal function evaluation in dogs under two protocols for cisplatin administration

OBJETIVO: Avaliar a funçäo renal de cäes sadios, sob dois protocolos para administraçäo de cisplatina. MÉTODOS: Todos os animais foram submetidos a três sessöes de quimioterapia com cisplatina (60mg/m², iv) a intervalos de 21 dias. Foi realizada fluidoterapia com soluçäo de cloreto de sódio a 0,9 por cento, (25mL/kg/hora,iv), durante duas horas e, após administraçäo de cisplatina, por mais uma hora. Os animais do grupo 2 receberam furosemida (2mg/kg, iv) 20 minutos antes da administraçäo da cisplatina. A avaliaçäo da funçäo renal foi feita por exame clinico, urinálise, concentraçöes séricas de uréia e creatinina, clearance de creatinina, excreçäo fracionada de sódio e de potássio e razäo proteína: creatinina urinária. As avaliaçöes foram feitas imediatamente antes e 1, 2, 5, e 21 dias após cada uma das três sessöes de quimioterapia. RESULTADOS: Mantiveram-se dentro da normalidade, näo sendo detectados sinais de lesöes ou insuficiência renal. Os animais que näo receberam furosemida sofreram aumento gradativo nas concentraçöes séricas de creatinina e diminuiçäo no clearance da mesma. CONCLUSÄO: O regime de fluidoterapia empregado mostra ser efetivo em minimizar a açäo nefrotóxica da cisplatina e benefício adicional importante é obtido pela administraçäo de furosemida.

Dispepsia funcional / Functional dyspepsia

As micoses superficisis säo as infecçöes mais comuns do tegumento cutâneo, envolvendo as partes queratinizadas, semiqueratinizadas, mucosas e os anexos pêlos e unhas.(au)

Post-operative nausea and vomiting in out-patient gynecologic laparoscopy: a comparison of thiopental-nitrous oxide, propofol-nitrous oxide and total intravenous anesthesia using propofol.

An intravenous anesthetic drug, propofol was considered to pose antiemetic action. A randomized controlled trial was conducted to evaluate whether propofol could effectively reduce post-operative nausea and vomiting (PONV) compared to thiopental-nitrous oxide (N2O). One-hundred and eight patients undergoing outpatient gynecologic laparoscopy were assigned to receive 3 techniques of anesthesia; thiopental-N2O (T/N), propofol-N2O (P/N) and total intravenous anesthesia (TIVA) using propofol (P/P). The results showed that in the early period (0-5 hours), post-operative nausea in T/N, P/N and P/P groups was 72 per cent, 44 per cent and 31 per cent, respectively (P = 0.002), and post-operative vomiting was 58 per cent, 36 per cent and 11 per cent respectively (P = 0.00014). Patients in the P/N and P/P groups experienced nausea less frequently than the T/N group [relative risk (RR) = 0.62, (95% CI 0.41-0.93) and RR = 0.42 (0.25-0.72) respectively]. Patients in the P/N and P/P groups experienced vomiting less frequently than the T/N group [RR = 0.62 (0.37-1.04) and RR = 0.19 (0.07-0.5) respectively]. Two patients in the T/N group were admitted because of severe nausea and vomiting. In conclusion, TIVA using propofol and propofol-N2O anesthesia can significantly reduce the incidence of PONV in the early period. Concerning the economic crisis of the country as well as the quality of care, propofol-N2O would be the most appropriate anesthetic of choice.

Estudio comparativo de granisetron versus metroclopramida/dexametasona en el tratamiento de emesis inducida por cisplatino / Granisetron versus metoclopramide/dexamethasone comparative study in emesis treatment for cisplatin therapy

El vómito y la náusea inducida por agentes citotóxicos frecuentemente limita la utilización de agentes efectivos pero emetizantes como el cisplatino. Este fue un estudio comparativo de Granisetron versus metoclopramida más dexametasona que evaluó la eficacia y efectos colaterales en las primeras 24 horas en ambos grupos. Se incluyeron 40 pacientes con diagnóstico de cáncer candidatos a recibir cisplatino a una dosis mayor de 49 mg/m2 con hoja de consentimiento informado. Se excluyeron pacientes que hubieran tenido náusea o vómito previo al tratamiento. Se administró Granisetron 40 m g/kg diluido en 20 mL de la solución salina para infusión intravenosa de cinco minutos previo a cisplatino en un grupo y en el otro se administró dexametasona 12 mg diluidos en 50 mL de solución salina para infusión de 30 minutos y metoclopramida 3 mg/kg I.V. en 30 minutos seguido de 4 mg/kg en infusión intravenosa para 8 hrs. Se consideró respuesta completa cuando los pacientes no tuvieron vómito ni náusea o sólo náusea leve. Hubo veintiún pacientes en el grupo de Granisetron y 19 en el grupo de tratamiento estándar. Obtuvimos respuesta completa (RC) del 66.6 por ciento en el grupo de Granisetron vs 73.68 por ciento en el grupo control, se presentó 20 por ciento de extrapiramidalismo de intensidad moderada en el grupo control (p=0.89), mientras que sólo el 9.5 por ciento del grupo de Granisetron presentó cefalea. Granisetron fue tan eficaz como la combinación con metoclopramida con la ventaja de tener muy pocos efectos adversos.

Cinarizina e as labirintopatias / Cinnarizine and labyrinth diseases

Uma revisäo dos resultados de vßrios estudos clÝnicos com a cinarizina no tratamento de diversos distúrbios vestibulares Ú apresentada. De acordo com estes resultados clÝnicos, o uso adequado de cinarizina Ú um procedimento terapÛutico seguro e muito eficaz na remissÒo da vertigem e outros tipos de tontura de variada etiologia e de origem vestibular perifÚrica ou central.

Dose-dependent response of central dopaminergic systems to metoclopramide in mice.

Metoclopramide (5 to 40 mg/kg, i.p.) induces catalepsy and antagonised apomorphine induced cage climbing behaviour in mice. This further indicate its postsynaptic striatal and mesolimbic D 2 dopamine (DA) receptor blocking activity. Metoclopramide at 1.25 and 2.5 mg/kg, i.p. induced stereotyped cage climbing behaviour in mice. Pretreatment with haloperidol and alpha-methyl-p-tyrosine significantly antagonised metoclopramide (1.25 and 2.5 mg/kg)-induced stereotyped cage climbing behaviour. Metoclopramide at these doses induces stereotyped cage climbing behaviour by releasing DA from the mesolimbic dopaminergic neurons with resultant activation of the postsynaptic mesolimbic D 2 DA receptors by the released DA. DA releasing action of metoclopramide (1.25 and 2.5 mg/kg, i.p.) and the subsequent induction of the stereotyped cage climbing behaviour by these doses of metoclopramide is explained on the basis of selective blockade of the presynaptic D 2 DA autoreceptors by these doses of metoclopramide.

The influence of gastrokinetics and inhibitors of acid secretion on motor responses of the gastric fundus to acetylcholine

The influence of eight gastrokinetics and six inhibitors of acid secretion used routinely in gastrointestinal prescriptions were verified, through dose-response curves to acetylcholine, on longitudinal muscular gastric fundus secretions of 70 rats. Some drugs increased the fundic motor response, and few others decreased the affinity of the fundi for acetylcholine. The results of the present paper may contribute to the knowledge of the effect of these drugs on gastric motility