Comparison of dexmedetomidine or ondansetron with haloperidol for treatment of postoperative delirium in trauma patients admitted to intensive care unit: randomized controlled trial

This study was designed to compare the effect of dexmedetomidine or ondansetron with haloperidol, as a control, for the treatment of postoperative delirium in trauma patients. A total of 96 adult trauma patients diagnosed with postoperative delirium were randomized into three equal groups. Patients were given either 1 microg/kg dexmedetomidine [Dexmed group] or 4 mg ondansetron [Ondan group] or 5 mg haloperidol [Halo group], administered twice daily for 3 consecutive days. Number of delirious patients, patients who needed [rescue haloperidol] and the total amount of [rescue haloperidol] during study period was calculated. At the end of the study, the number of remaining delirious patients was 3, 6, and 2 in Dexmed,Ondan, and Halo groups, respectively, without statistical significance. During the study period, there was no significant difference in the number of patients who needed [rescue haloperidol] between Dexmed and Halo groups [5 vs. 3; p = 0.7]. However, the difference was significantly higher in Ondan group compared to Halo group [11 vs. 3; p = 0.03]. The mean total [rescue haloperidol] dose was significantly higher in Ondan group compared to Halo group [p < 0.001], but there was no difference between Dexmed and Halo groups [p = 0.07]. At the same time of delirium assessment, mean arterial blood pressure and mean score on Visual Analog Scale were not statistically different between Dexmed or Ondan group versus Halo group. No serious adverse events were reported. Dexmedetomidine is a potential alternative treatment for postoperative delirium in trauma patients admitted to ICU

Ondansetron reducing pain on injection of etomidate: a controlled randomized study / Ondansetrona reduz a dor da injeção de etomidato: estudo randômico controlado / El ondansetrón reduce el dolor de la inyección de etomidato: estudio aleatorizado controlado

Introduction: Etomidate causes pain when injected intravenously. In this study we sought to determine if pretreatment by ondansetron reduces the pain on injection of etomidate. Methods: In this randomized, double blinded, placebo-controlled clinical trial, 20 patients of both sexes aged between 18 and 50 years of American Society of Anesthesiologists (ASA) physical status class I or II, whom were candidates for various elective surgical procedures and need more than one intravenous access were enrolled in the study. On arrival to the operating room two 22 gauge cannulas were inserted into veins on the dorsum of both hands. Following the infusion of 100 mL normal saline into both intravenous lines, using an elastic band, venous drainage of hands was occluded at midarm. The patients were administered 8 mg (2 mL) of ondansetron into one hand and 2 mL of 0.9% saline into the other hand at the same time. The elastic band was removed after 1 min and 2 mg (1 mL) of etomidate was administered at the same rate simultaneously into intravenous lines. The patients were asked to give a score of pain based on a verbal analog scale (VAS) to each hand. Results: A total number of 20 patients were studied (male = 55%, female = 45%). The mean age of the participants was 37.5 ± 13.1 years old and the mean weight was 67.7 ± 7.3 kg. The mean VAS for injection pain of etomidate after pre-administration of intravenous ondansetron was 1.5 ± 1.2 which was lower compared to pre-administration of placebo (3.2 ± 2.8, p < 0.05). Conclusion: This study illustrates that pre-treatment with intravenous ondansetron significantly reduces the pain on injection of etomidate. .

Justificativa e objetivo: etomidato causa dor quando administrado por via intravenosa. Neste estudo buscamos determinar se o pré-tratamento com ondansetrona reduz a dor causada pela injeção de etomidato. Métodos: neste estudo clínico randômico, duplo-cego e controlado por placebo, 20 pacientes de ambos os sexos, entre 18 e 50 anos, estado físico ASA I ou II, candidatos a procedimentos cirúrgicos eletivos que exigiam mais de um acesso intravenoso, foram incluídos. Ao darem entrada na sala de cirurgia, duas cânulas de calibre 22 foram inseridas nas veias do dorso de ambas as mãos. Após a infusão de 100 mL de solução salina normal em ambas as linhas de acesso intravenoso, a drenagem venosa das mãos foi ocluída até o meio do braço com o uso de um torniquete elástico. Os pacientes receberam 8 mg (2 mL) de ondansetrona em uma das mãos e 2 mL de solução salina a 0,9% na outra mão ao mesmo tempo. O torniquete foi removido após um minuto e 2 mg (1 mL) de etomidato foram administrados na mesma proporção simultaneamente nas linhas intravenosas. Pediu-se aos pacientes que dessem pontos à dor em cada mão, com base em uma escala verbal analógica (EVA). Resultados: avaliamos 20 pacientes (homens = 55%, mulheres = 45%). A média de idade e de peso foi de 37,5 ± 13,1 anos e 67,7 ±7,3 kg. A média do escore EVA para dor causada pela injeção de etomidato após a pré-administração de ondansetron IV foi de 1,5 ± 1,2, que foi menor em comparação com a pré-administração de placebo (3,2 ± 2,8, p < 0,05). Conclusão: este estudo mostra que o pré-tratamento com ondansetrona IV reduz significativamente a dor causada pela injeção de etomidato. .

Introducción: el etomidato causa dolor cuando es administrado por vía intravenosa. En este estudio buscamos determinar si el pretratamiento con ondansetrón reduce el dolor causado por la inyección de etomidato. Métodos: fueron incluidos en este estudio clínico aleatorizado, doble ciego y controlado por placebo, 20 pacientes de ambos sexos con edades entre 18 y 50 años, estado físico ASA I o II, candidatos a varios procedimientos quirúrgicos electivos, que exigían más de un acceso intravenoso. Al entrar en quirófano, se insertaron dos cánulas de calibre 22 en las venas del dorso de ambas manos. Después de la infusión de 100 mL de solución salina normal en ambas líneas de acceso intravenoso; usando un torniquete elástico, el drenaje venoso de las manos se cerró hasta la mitad del brazo. Los pacientes recibieron 8 mg (2 mL) de ondansetrón en una de las manos y 2 mL de solución salina al 0,9% en la otra mano al mismo tiempo. El torniquete fue retirado después de 1 min y 2 mg (1 mL) de etomidato se administró en la misma proporción simultáneamente en las líneas intravenosas. Se les solicitó a los pacientes que hiciesen una puntuación del dolor en cada mano, basándose en una escala verbal analógica (EVA). Resultados: evaluamos a un total de 20 pacientes (un 55% hombres y un 45% mujeres). La media de edad y del peso de los participantes fue de 37,5 ± 13,1 años y de 67,7 ±7,3/kg, respectivamente. El promedio de la puntuación EVA para el dolor causado por la inyección de etomidato después de la preadministración de ondansetrón iv fue de 1,5 ± 1,2, siendo menor en comparación con la preadministración de placebo (3,2 ± 2,8; p < 0,05). Conclusión: este estudio demuestra que el pretratamiento con ondansetrón iv reduce ...

Can you stop this shivering, doctor?

Postoperative shivering and feeling of cold associated with it is rated as worse than pain by some patients. It has been a problem not only after general anesthesia, but also during and after spinal anesthesia. This editorial compliments an original article in this issue of 'Anesthesia, Pain and Intensive Care' on comparison of three different drugs for the treatment of postoperative shivering, and draws attention towards pathogenesis of shivering and its control. Shivering is not a point in time event and its cessation with pharmacological intervention does not guarantee against its recurrence

prospective, randomized, double-blind, comparative study of the efficacy of intravenous ondansetron and palonosetron for prevention of postoperative nausea and vomiting

Palonosetron is a second generation 5-Hydroxytryptamine-3 receptor antagonist with longer half life and higher receptor binding affinity than Ondansetron. To assess the efficacy and safety profile of intravenous palonosetron compared to the ondansetron for prevention of post-operative nausea and vomiting [PONV] under general anesthesia. A prospective, randomized, placebo-controlled, double-blind study was conducted in 90 patients aged 20-60 years, undergoing major surgeries. Group I [n=30] received placebo injection; Group II [n=30] received inj. ondansetron 8 mg and Group III [n=30] received inj. palonosetron 0.075 mg IV. In the operating room, the study drugs were given IV in equal volume of 4ml, before inducing the patients. In postoperative period each patient was observed for retching, nausea and/or vomiting at 30 min; and then at 1, 2, 6, 12 and 24 hours. Any side effects intra-operatively and post-operatively were recorded. The number of patients, who remained vomiting free in the first 24 hours after surgery was 56.6%, 80% and 86% in the placebo, Ondansetron and Palonosetron groups respectively. The difference with placebo was highly significant for ondansetron [p < 0.05], and highly significant for palonosetron [p=0.009]. The difference in vomiting between Ondansetron and Palaonosetron was not significant but the incidence of nausea was significantly less common in the Palonosetron group than the Ondansetron group [16.7% vs. 43.4%, p=0.006]. We conclude that the second generation 5-HT3 antagonist, palonosetron is significantly more effective against PONV than ondansetron. It has a particularly more pronounced and prolonged effect on postoperative nausea

Influence of ondansetron on the antitumor activity and lung toxicity of bleomycin

Bleomycin [BLM] is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Moderate nausea and vomiting occur in virtually all patients taken BLM. Ondansetron [OND] is a highly selective 5-HT3 receptor antagonist with significant antiemetic activity. This study was conducted to investigate the effect of OND administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma [EAC] cells. Ondansetron did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-HT and increase in the contractility of tracheal smooth muscles induced by ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in GSH level. Pretreatment with ondansetron decreased lipid peroxidation and normalized GSH level and hence enhanced the percent survival of rats. The results of the present study indicate that OND did not modify the antitumor effect of BLM but ameliorated the increase in some biochemical markers associated with BLM-induced lung toxicity

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.

Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats.

Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.

5-HT3 receptors in selective animal models of cognition.

Role of 5-HT3 receptors in cholinergic hypofunctional models of cognitive impairment in the elevated plus maze model and a passive avoidance model is studied. Cognitive impairment was caused by scopolamine (1 mg/kg, ip) in mice and 5-HT3 ligands mCPBG (1 and 5 mg/kg, ip) and ondansetron (0.5 and 5 mg/kg, ip) were administered before the pre-learning phase to study the effects on acquisition, while post-learning administration was used to determine the effects on consolidation. Ondansetron improved acquisition and retention in cholinergic hypofunctional models while mCPBG potentiated selected impaired cognitive indices. The results indicate the role of 5-HT3 receptors in cognition and that an ideal evaluation of 5-HT3 ligands in cognition should distinguish true cognitive effects from locomotor, motivational and emotional effects.

Serotonergic mechanism in imipramine induced antinociception in rat tail flick test.

Substantial evidence has accumulated that spinally projecting serotonergic neurons modulate nociception. However, the exact receptor subtypes that mediate the antinociceptive response of serotonin within the spinal cord continue to be a subject of debate. Therefore, we explored the effect of serotonergic system on imipramine induced antinociception by using 5-Hydroxytryptamine-3 (5HT3) receptor antagonist ondansetron and 5-Hydroxytryptamine-2 (5HT2) receptor antagonist mianserine, and depletion of brain 5-Hydroxytryptamine (5HT) with p-chlorophenyl alanine (PCPA). Male wistar strain rats were pretreated with either ondansetron (0.5 mg/kg, i.p.) or mianserine (1 mg/kg, i.p.). After 15 minutes, rats received injection of imipramine (10 mg/kg). Nociception was assessed by tail-flick method. Imipramine (2 mg, 5 mg, 10 mg, and 20 mg/kg) produce antinociceptive response in the dose dependent manner. Prior treatment with 5HT3 antagonist, Ondansetron and 5HT2 antagonist, mianserine reduce the antinociceptive response of imipramine. In PCPA treated rats imipramine (10 mg/kg) failed to produce antinociception. These results indicate that the 5HT plays an important role in imipramine induced antinociception.

Effect of the 5-HT3 receptor antagonist ondansetron on amphetamine-induced hyperactivity and stereotypy in rats.

The effects of different doses of ondansetron (0.1, 0.5, 1, 2 mg/kg) administered intra-peritoneally were studied on amphetamine-induced hyperactivity and stereotypy in wistar rats. Ondansetron was administered 30 minutes prior to d-amphetamine (3 mg/kg, i.p.). Ondansetron in doses of 0.5 and 1 mg/kg significantly decreased the mean number of head dippings and crossings in the hole board test and in doses of 0.1 and 0.5 mg/kg significantly decreased the average stereotypic score. Since the hyperactivity and stereotypy are dopamine mediated, the effect of ondansetron to reduce these states suggests a potential role for ondansetron in conditions with dopamine excess.

Inhibidores de serotonina en el tratamiento de la náusea y el vómito provocados por el tratamiento con quimioterapia antineoplásica / Serotonine inhibitors in the treatment of nausea and vomit provoked for the treatment with antineoplasic chemotherapy

El desarrollo de fármacos antieméticos es una de las áreas más estudiadas en la investigación oncológica. Los avances terapéuticos en este campo pueden resultar en mejoría inmediata de la calidad de vida de los pacientes en tratamiento con quimioterapia antineoplásica. Hace 15 años, los pacientes que recibían tratamiento altamente emetógeno tenían entre 10 y 15 episodios de vómito en las primera 24 horas posquimioterapia. En la actualidad esto se ha reducido de manera significativa y los mecanismos de producción de vómito anticipatorio resultan mejor controlados. Los inhibidores de serotonina representan una línea de tratamiento para la náusea y el vómito en los pacientes con cáncer, pero además han permitido un mayor conocimiento de la fisiopatología de estos trastornos, así como la mejor comprensión de los mecanismos fisiológicos de producción del vómito. A la luz de los distintos tipos de antieméticos, los inhibidores de serotonina representan un alternativa viable en los pacientes que no se benefician con otros tipos de antieméticos. Aunque su eficacia se ha demostrado en diversos estudios, se ha impugnado su uso de forma extensa por su alto costo; sin embargo, el avance en la mejoría de la calidad de vida de los pacientes oncológicos no está sujeto a discusión, por los escasos efectos adversos que provocan y su amplio perfil de seguridad