Effects of environmental temperature on pharmacokinetics of and clinical response to xylazine in goats

Abstract

The clinical use of xylazine may result in morbidity and mortality in small ruminants, and it was suspected that exposure to changes in environmental temperature may contribute to these effects. Xylazine hydrochloride was administered intravenously at a dose of 0.1 mg/kg to a group of six indigenous domestic goats with a mean body mass of 28.2 kg. Xylazine was administered at a room temperature of 14°C and relative humidity of 33%, at 24°C and a relative humidity of 55%, and at 34°C with a relative humidity of 65%. The following variables were evaluated: clinical behaviour, cardiopulmonary function, haematology, acid-base balance, plasma glucose and insulin, body temperature, and the pharmacokinetic characteristics of xylazine. Xylazine administration resulted in transient restlessness, followed by sedation, muscle relaxation, and salivation. The onset of these clinical signs was not influenced by environmental conditions. Administration of xylazine resulted in a transient increase in respiratory rate in the 24 and 34°C environments. In the 14°C environment, the respiratory rate decreased significantly (p<0.05) from baseline and continued to decrease for the full duration of the 60 minutes observation period. Heart rate decreased in all three environments, but this decrease was only significant in the 14°C environment for the duration of the observation period. Changes in haemoglobin concentration, haematocrit, red blood cell count and mean red blood cell volume were significantly (p<0.05) different 15 minutes after xylazine administration and continued to be so for the duration of the observation period. Total serum protein changed significantly (p<0.05) in the 24° and 34°C environments from 15 minutes after xylazine administration. The white cell count changed significantly (p<0.05) from 15 minutes after xylazine administration for the duration of the observation period in all three environments. Significant (p<0.05) changes occurred after xylazine administration in acid-base balance and arterial blood gas variables independent of environmental conditions. Arterial pH and the partial pressure of oxygen decreased significantly within 5 minutes of xylazine administration, and the partial pressure of carbon dioxide, total carbon dioxide and base excess increased significantly (p<0.05). Environmental conditions had no observable on plasma glucose and insulin concentration. Significant (p<0.05) changes occurred in all three environments. Environmental conditions had no influence on body temperature in the control (untreated) animals. Following the administration of xylazine, the body temperature of the goats in the 14 and 24°C environments was significantly (p<0.05) lower than that of the goats in the 34°C environment. The maximum decrease in oesophageal temperature of 1.57°C was observed 60 minutes after xy1azine administration to goats maintained in the 14°C environment. Environmental conditions had no influence on all of the pharrnacokinetic parameters of xylazine hydrochloride evaluated. It is concluded that apart from changes in body temperature, changes that occurred in clinical and pharmacokinetic variables after xylazine administration, were independent of the three environmental temperature and humidity conditions.