Effect of remifentanil on requirements for propofol administered by use of a target-controlled infusion system for maintaining anesthesia in dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of lidocaine on the minimum alveolar concentration of sevoflurane in dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of remifentanil on the minimum alveolar concentration of isoflurane in dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

Pharmacokinetics of synthetic atrial natriuretic peptides in normal men.

The kinetics of atrial natriuretic peptides (ANP) and the kinetic profile of their effect on blood pressure and renal hemodynamic and electrolyte excretion were investigated in 20 salt-loaded healthy volunteers during and after constant rate infusion. At steady state, mean plasma concentrations of ANP were measured at 210, 430, and 2990 pg/ml and mean systemic clearance was 2.6, 2.5, and 1.7 L/min for ANP infusion rates of 0.5, 1, and 5 micrograms/min, respectively, which corresponds to the clearance rate of other vasoactive peptide hormones. The apparent volume of distribution averaged 17 L and the mean half-life was 4.5 minutes. ANP induced dose-related effects on systemic and renal hemodynamic, as well as urinary electrolyte excretion, albeit with a time lag between onset and full effect.

Cancer chronotherapeutics: experimental, theoretical, and clinical aspects.

The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

Infusão contínua de lidocaína em diferentes taxas no controle de arritmias induzidas pela administração de adrenalina em cães anestesiados com isofluorano

Avaliaram-se os efeitos da infusão de diferentes doses de lidocaína sobre o ritmo cardíaco, em cães anestesiados com isofluorano que receberam doses crescentes de adrenalina. Foram utilizados 10 cães, cada qual anestesiado quatro vezes, respeitando-se um intervalo de duas semanas. A indução anestésica foi realizada com propofol, 8mg/kg, e a manutenção com isofluorano a 1,5 CAM. Os animais foram distribuídos em quatro grupos, que receberam bolus de lidocaína, 1mg/kg, seguido pela infusão de lidocaína nas taxas de 50μg/kg/h (G50), 100μg/kg/h (G100) e 200μg/kg/h (G200). O grupo-controle (GC) recebeu bolus e infusão de NaCl a 0,9%. As variáveis foram mensuradas 30 minutos após a indução, e em seguida, iniciadas as infusões. Após 10 minutos do princípio dos tratamentos, colheram-se novamente os dados e iniciou-se a infusão de adrenalina, 1μg/kg/min. em intervalos de 10 minutos, realizou-se nova colheita de dados e acrescentou-se 1μg/kg/min na taxa de infusão de adrenalina, até atingir 5μg/kg/min. Comparativamente ao GC, ocorreu redução do aparecimento de batimentos de origem não sinusal e bloqueios atrioventriculares de segundo grau nos grupos tratados com lidocaína. Concluiu-se que a associação de lidocaína à anestesia com isofluorano diminuiu o aparecimento de irregularidades no ritmo cardíaco.

The effects of 2 levels of the inspired oxygen fraction on blood gas variables in propofol-anesthetized dogs with high intracranial pressure

The influence of 2 different levels of the inspired oxygen fraction (FiO(2)) on blood gas variables was evaluated in dogs with high intracranial pressure (ICP) during propofol anesthesia (induction followed by a continuous rate infusion [CRI] of 0.6 mg/kg/min) and intermittent positive pressure ventilation (IPPV). Eight adult mongrel dogs were anesthetized on 2 occasions, 21 d apart, and received oxygen at an FiO(2) of 1.0 (G100) or 0.6 (G60) in a randomized crossover fashion. A fiberoptic catheter was implanted on the surface of the right cerebral cortex for assessment of the ICP. An increase in the ICP was induced by temporary ligation of the jugular vein 50 min after induction of anesthesia and immediately after baseline measurement of the ICP. Blood gas measurements were taken 20 min later and then at 15-min intervals for 1 h. Numerical data were submitted to Morrison's multivariate statistical methods. The ICP, the cerebral perfusion pressure and the mean arterial pressure did not differ significantly between FiO(2) levels or measurement times after jugular ligation. The only blood gas values that differed significantly (P < 0.05) were the arterial oxygen partial pressure, which was greater with G100 than with G60 throughout the procedure, and the venous haemoglobin saturation, that was greater with G100 than with G60 at M0. There were no significant differences between FiO(2) levels or measurement times in the following blood gas variables: arterial carbon dioxide partial pressure, arterial hemoglobin saturation, base deficit, bicarbonate concentration, pH, venous oxygen partial pressure, venous carbon dioxide partial pressure and the arterial-to-end-tidal carbon dioxide difference.

Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine

Objective-To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M-2) antagonist, methoctramine, in anesthetized horses.Animals-6 horses.Procedure-Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 mug/kg, IV) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 mug/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period.Results-Methoctramine was given at a total cumulative dose of 30 mug/kg to 4 horses, whereas 2 horses received 10 mug/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups.Conclusions and Clinical Relevance-Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M-2 antagonists may represent a safe alternative for treatment of horses with intraoperative bracycardia.

Effects of glycopyrrolate on cardiorespiratory function in horses anesthetized with halothane and xylazine

Objective-To evaluate cardiopulmonary effects of glycopyrrolate in horses anesthetized with halothane and xylazine.Animals-6 horses.Procedure-Horses were allocated to 2 treatment groups in a randomized complete block design. Anesthesia was maintained in mechanically ventilated horses by administration of halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV). Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of glycopyrrolate or saline (0.9% NaCl) solution. Glycopyrrolate (2.5 mug/kg, IV) was administered at 10-minute intervals until heart rate (HR) increased at least 30% above baseline or a maximum cumulative dose of 75 mug/kg had been injected. Recovery characteristics and intestinal auscultation scores were evaluated for 24 hours after the end of anesthesia.Results-Cumulative dose of glycopyrrolate administered to 5 horses was 5 mug/kg, whereas 1 horse received 75 mug/kg. The positive chronotropic effects of glycopyrrolate were accompanied by an increase in cardiac output, arterial blood pressure, and tissue oxygen delivery. Whereas HR increased by 53% above baseline values at 20 minutes after the last glycopyrrolate injection, cardiac output and mean arterial pressure increased by 38% and 31%, respectively. Glycopyrrolate administration was associated with impaction of the large colon in I horse and low intestinal auscultation scores lasting 24 hours in 3 horses.Conclusions and Clinical Relevance-The positive chronotropic effects of glycopyrrolate resulted in improvement of hemodynamic function in horses anesthetized with halothane and xylazine. However, prolonged intestinal stasis and colic may limit its use during anesthesia.

Effects of the opiold remifentanil on the arrhythmogenicity of epinephrine in halothane-anesthetized dogs

Opioids may exert a protective effect against ventricular arrhythmias via a vagally mediated mechanism. This study evaluated the effects of the opioid remifentanil on arrhythmogenicity of epinephrine during halothane anesthesia. Eight dogs were assigned to 2 treatments in a randomized crossover design, with 1-week intervals between treatments. Anesthesia was maintained with 1.3% end-tidal halothane in oxygen and mechanical ventilation to maintain eucapnia. A constant rate infusion of remifentanil (0.72 mu g/kg/min) was administered throughout the study in the experimental treatment, while control animals received physiologic saline as placebo. The arrhythmogenic dose of epinephrine (ADE), defined as 4 premature ventricular complexes (PVCs) within 15 s, was determined by administering progressively increasing infusion rates of epinephrine (2.5, 5.0, and 10 mu g/kg/min), allowing 20 min intervals between each infusion rate. In both treatments, epinephrine infusions induced bradyarrhythmias and atrioventricular conduction disturbances, which were followed by escape beats and PVCs. In the remifentanil treatment, mean s ADE values (11.3 +/- 4.9 mu g/kg) did not differ from values observed in control animals (9.9 +/- 6.1 mu g/kg). on the basis of the ADE model for assessing the arrhythmogenity of drugs during halothane anesthesia, the present study did not demonstrate a protective effect of remifentanil (0.72 mu g/kg/min) against ventricular arrhythmias in dogs.