EFEIFOS DO SULFATE DE MAGNESIO NA HEMODINAMICA CARDIOVASCULAR DE CAES ANESTESIADOS COM PENTOBARBITAL SODICO

Background and Objectives - A controversy exists in the literature regarding the effects of the acute administration of magnesium on the cardiovascular system of animals and humans. The purpose of this study was to evaluate the effects of hypermagnesemia on the cardiovascular hemodynamics of dogs. Methods - Sixteen mongrel dogs were anesthetized with pentobarbitone 30 mg.kg-1 and submitted to volume expansion with Ringer's solution (0.4 ml.kg-1.min-1 and mechanical ventilation with room air. In this model, the hemodynamic repercussions of the following drugs and doses were studied. pentobarbitone 5 mg.kg-1 Group 1, control - and the association of pentobarbitone and magnesium sulphate (MS), at the dose of 140 mg.kg-1 injected in 15 minutes, followed by an infusion of 80 mg.kg-1.h-1 - Group 2. The parameters studied were: heart rate, blood pressure, inferior vena cava pressure, cardiac index, systolic index and peripheral resistance index, evaluated at 5 different moments: 15(M1), 30(M2), 60(M3) and 75(M4) minutes after the first suppplementary dose of pentobarbitone and 15 minutes (M5) after the second supplementary dose. In Group 2, the moments M3, M4, M5 corresponded to 15, 30 and 60 minutes after the priming dose of magnesium sulphate. Results - Group 1 animals exhibited tachycardia since the beginning of the experiment. There was a decrease in the cardiac index, in the systolic index and an increase in the inferior vena cava pressure. Group 2 animals also exhibited tachycardia, but heart rate decreased after MS infusion. The blood pressure and the peripheral resistance index decreased. The systolic index increased and the cardiac index decreased only at the end of the experiment. Conclusions: The antiadrenergic effects of MS could have been responsible for the decrease in heart rate. The vasodilating effects of the magnesium induced the decrease in the peripheral resistance index. The systolic index increased, showing that myocardial depression did not occur.

Comparison of xylazine and medotomidine as premedicants for cats being anaesthetised with propofol-sevoflurane

The effects of premedicating cats with saline, xylazine or medetomidine before anaesthetising them with propofol-sevoflurane were compared. Twenty-four cats were randomly assigned to three groups of eight to receive either 0.25 ml of saline, 0.50 mg/kg of xylazine or 0.02 mg/kg of medetomidine intravenously, and anaesthesia was induced with propofol and maintained with sevoflurane. Medetomidine produced a greater reduction in the induction dose of propofol and fewer adverse postoperative effects than saline or xylazine. Hypoxaemia was observed after induction with propofol in the cats premedicated with saline and xylazine, but not in the cats given medetomidine. The cats treated with medetomidine and xylazine developed profound bradycardia. The blood pressure of the cats premedicated with saline and xylazine decreased, but the blood pressure of the cats premedicated with medetomidine was maintained. The cats premedicated with saline took longer to recover from anaesthesia than the other two groups.

La vía aérea, un reto en el servicio de urgencias indicaciones, manejo y complicaciones

INTRODUCCIÓN: El control rápido y seguro de la vía aérea es una de las habilidades más importantes que se debe tener para el manejo de pacientes críticamente enfermos y traumatizados en los departamentos de emergencias de todo el mundo, en nuestro medio no contamos con estadísticas que cuantifiquen el éxito y complicaciones en este aspecto. METODOLOGIA: Se realizo un estudio observacional, descriptivo, prospectivo, que recolecto los datos de las intubaciones realizadas en la sala de emergencias del Hospital Universitario Mayor “Mederi” por parte de especialistas en medicina de emergencias, medicina interna, médicos generales o personal en entrenamiento, durante el periodo comprendido entre noviembre de 2010 y junio de 2011. RESULTADOS: Se recolecto una muestra de 92 pacientes en el estudio, la causa mas frecuente de intubación orotraqueal fue falla respiratoria 77,2%, el éxito en el primer intento fue de 51,5%, se uso secuencia de intubación rápida como método de intubación en el 56,5% de los pacientes y se presento alguna complicación en el 61% de los pacientes. DISCUSIÓN: El éxito en la intubación orotraqueal es menor y las complicaciones superiores a los de países desarrollados, esto puede estar en relación con la falta del desarrollo de la medicina de emergencias y programas de entrenamiento formal en el manejo de la vía aérea.

Double-blind comparison of rectally administered diazepam to placebo for pediatric sedation: the cardiovascular response.

The sedative and cardiovascular effects of rectally administered diazepam (0.6 mg/kg) were compared to placebo in uncooperative children who required sedation during dental treatment. Twelve healthy preschool children, who required amalgam restorations, were treated during two standardized restorative appointments in a double-blind, crossover study. Blood pressure and pulse were obtained during four specified intervals during the appointment. The behavior of the children during the treatment visits was videotaped and later statistically analyzed using a kinesics/vocalization instrument. Behavioral ratings of cooperation were significantly improved during the treatment visit following diazepam. All interfering bodily movements, patient vocalizations and operator commands for the diazepam group were reduced significantly (p≤0.0001). No significant differences were observed for noninterfering behavioral response. Rectally administered diazepam did not alter blood pressure or pulse significantly in these sedated children when compared to the placebo. These findings indicate that rectal diazepam is an effective sedative agent with minimal effect on the cardiovascular system for the management of the young pediatric dental patient.

Midazolam for sedation before procedures

BACKGROUND: Midazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects. The drug can be administered by several routes including oral, intravenous, intranasal and intramuscular. OBJECTIVES: To determine the evidence on the effectiveness of midazolam for sedation when administered before a procedure (diagnostic or therapeutic). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL to January 2016), MEDLINE in Ovid (1966 to January 2016) and Ovid EMBASE (1980 to January 2016). We imposed no language restrictions. SELECTION CRITERIA: Randomized controlled trials in which midazolam, administered to participants of any age, by any route, at any dose or any time before any procedure (apart from dental procedures), was compared with placebo or other medications including sedatives and analgesics. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed risk of bias for each included study. We performed a separate analysis for each different drug comparison. MAIN RESULTS: We included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions. Intravenous midazolam versus diazepam (14 trials; 1069 participants)There was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I² = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence). Intravenous midazolam versus placebo (5 trials; 493 participants)One trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low-quality evidence). Oral midazolam versus chloral hydrate (4 trials; 268 participants)Midazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence). Oral midazolam versus placebo (3 trials; 176 participants)Midazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05). Intranasal midazolam versus placebo (2 trials; 149 participants)Midazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence). AUTHORS' CONCLUSIONS: We found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures.

The α5 neuronal nicotinic acetylcholine receptor subunits plays an important role in the sedative effects of ethanol but does not modulate consumption in mice

Alcohol use disorders (AUDs) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence. Here, we evaluate the role of 5* nAChR for ethanol-mediated behaviors using α5+/+ and α5-/- mice. We characterized the effect of hypnotic doses of ethanol and investigated drinking behavior using an adapted Drinking-in-the Dark (DID) paradigm that has been shown to induce high ethanol consumption in mice. We found the α5 subunit to be critical in mediating the sedative effects of ethanol. The α5-/- mice showed slower recovery from ethanol-induced sleep, as measured by loss of righting reflex. Additionally the α5-/- mice showed enhanced impairment to ethanol-induced ataxia. We found the initial sensitivity to ethanol and ethanol metabolism to be similar in both α5+/+ and α5-/- mice. Hence the enhanced sedation is likely due to a difference in the acute tolerance of ethanol in mice deficient of the α5 subunit. However the α5 subunit did not play a role in ethanol consumption for ethanol concentrations ranging from 5% to 30% in the DID paradigm. Additionally, varenicline (Chantix®) was effective in reducing ethanol intake in α5-/- mice. Together, our data suggest that the α5 nAChR subunit is important for the sedative hypnotic doses of ethanol but does not play a role in ethanol consumption. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.

Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L.

Citrus aurantium L. is commonly used as an alternative treatment for insomnia, anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v) extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and final aqueous (AF) fractions were obtained from HE by successive partitions. Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these preparations 30 min before the experiments for the evaluation of the sedative/hypnotic activity (sleeping time induced by sodium pentobarbital-SPB: 40 mg/kg, i.p.), anxiolytic activity (elevated plus maze-EPM) and anticonvulsant activity (induced by pentylenetetrazole-PTZ: 85 mg/kg, se or by maximal electroshock-MES: 50 mA, 0.11s, corneal). The results showed that EOP (0.5 g/kg) increased the latency period of tonic seizures in both convulsing experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg increased the sleeping time induced by barbiturates and the time spent in the open arms of the EPM. Specific tests indicated that the preparation, in both doses used, did not promote deficits in general activity or motor coordination. HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but were able to enhance the sleeping time induced by barbiturates. The results obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation model, are in accord with the ethnopharmacological use of Citrus aurantium L., which could be useful in primary medical care, after toxicological investigation.

Neurobehavioral effect of essential oil of Cymbopogon citratus in mice

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sedative and antinociceptive effects of romifidine and xylazine in Thoroughbred mares

Compararam-se os efeitos sedativos e antinociceptivos da romifidina (0,1mg/kg) e da xilazina (1,0mg/kg) em éguas da raça Puro Sangue Inglês. A sedação foi quantificada por meio da atividade locomotora espontânea (ALE) e altura da cabeça (AC) em baias individuais automatizadas para o estudo do comportamento. A antinocicepção foi avaliada utilizando uma lâmpada de irradiação de calor registrando-se a latência para o reflexo de retirada do membro (LRRM) e a latência para o reflexo do frêmito cutâneo (LRFC), em delineamento experimental em blocos ao acaso com 10 repetições. O efeito sedativo sobre a ALE foi de aparecimento mais rápido no grupo exposto à xilazina, ao passo que a ptose da cabeça foi mais prolongada no grupo que recebeu romifidina. A romifidina promoveu aumento da LRRM e LRFC e a xilazina não causou efeito antinociceptivo medido pela LRFC. O efeito antinociceptivo da romifidina foi mais pronunciado que o da xilazina.

Characterization of the antinociceptive and sedative effect of amitraz in horses

Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including α2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of α2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.