Understanding the physiological basis for managing anaesthetic related cardiopulmonary side-effects in wildlife
Date
2017
Authors
Buss, Peter Erik
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Abstract
Immobilization of white rhinoceros (Ceratotherium simum) is a fundamental procedure used in the conservation of this threatened megaherbivore and allows for the capture, translocation and treatment of individuals. Immobilization also allows scientific investigation, which facilitates protection of this species. The potent opioids, including etorphine, are the only class of drugs which allow for a rapid and reversible immobilization, which is essential in the capture of rhinoceros. However, immobilization is associated with changes in respiratory and cardiovascular function which can result in high morbidity and mortalities. I therefore investigated the cardiorespiratory pathophysiological effects of etorphine and azaperone; pharmacological agents most often used in rhinoceros immobilization, and examined the effectiveness of butorphanol, a mixed agonist- antagonist opioid, in limiting these adverse effects. Reducing morbidity and mortality risks through an increased understanding and moderation of drug- induced cardiorespiratory changes in immobilized rhinoceros will contribute to future successes in managing this species.
In my first study, ten healthy captive white rhinoceros including four males and six females ranging in age from 3.5 to 15 yr were immobilized for a total of 13 procedures with etorphine plus azaperone, and administered butorphanol intravenously immediately after initial blood collection and physiological assessment. Respiratory and cardiovascular parameters, body temperature and arterial blood gases were monitored for 100 min. The results confirmed that severe hypoxaemia, hypercapnia, tachycardia and an increased alveolar-arterial (A-a) oxygen gradient occur in immobilized rhinoceros. Giving butorphanol appeared to decrease heart rate, increase arterial oxygen tension, and decrease the A-a gradient and respiratory rate. However as the study was observational, it could not be confirmed that these changes were caused by butorphanol. Despite the initial improvements in blood oxygen levels, the rhinoceros remained severely hypoxaemic and hypercapnic for the remainder of the procedure.
To further investigate the cardiorespiratory effects of butorphanol in immobilized rhinoceros, a randomised cross-over study design was used. Six healthy sub-adult male white rhinoceros were subjected to four drug interventions: 1) etorphine intramuscularly; 2) etorphine plus azaperone intramuscularly; 3) etorphine intramuscularly and post-induction butorphanol intravenously; and 4) etorphine plus azaperone intramuscularly, and post-induction butorphanol intravenously. The results from this study demonstrated that hypoxaemia and hypercapnia in etorphine-immobilized rhinoceros were not predominantly a result of a decrease in respiratory minute volume, as has been proposed in previous studies. Rather, an increase in metabolic oxygen consumption and carbon dioxide production, associated with muscle tremors, is suggested as the primary cause. In addition, a high alveolar-arterial oxygen gradient may have contributed to hypoxaemia and possibly also hypercapnia in immobilized rhinoceros. Although, decreased minute ventilation was not the fundamental cause of hypoxaemia and hypercapnia, low arterial oxygen partial pressure (PaCb) and high arterial carbon dioxide partial pressure (PaCC>2) did not stimulate ventilation, probably as a consequence of opioid-induced central and peripheral chemoreceptor inhibition. Butorphanol administered post-induction in etorphine-immobilized rhinoceros resulted in a moderate improvement in blood gases, although hypoxaemia and hypercapnia persisted. My results support the idea that improvements in PaC>2 and PaC02 after butorphanol administration resulted from reduced muscle tremors, metabolic oxygen consumption and carbon dioxide production rather than improved minute ventilation.
Cardiovascular changes in etorphine-immobilized rhinoceros included hypertension and tachycardia. The inclusion of azaperone with etorphine in the immobilizing drug combination reduced blood pressure to below normotensive values; however, heart rate remained elevated. The administration of butorphanol was followed by a reduction in heart rate with no clinical effect on blood pressures in etorphine-immobilized rhinoceros. Similarly, butorphanol did not change blood pressure but reduced tachycardia in individuals immobilized with etorphine plus azaperone.
In summary, butorphanol administration reduced hypoxaemia and hypercapnia in immobilized white rhinoceros as a result of decreased muscle tremors and oxygen consumption. Reduced oxygen consumption may mitigate hypoxic and hypercapnic mortality risks associated with immobilization, especially in rhinoceros compromised due to old age, nutritional stress or disease. My findings indicate that butorphanol administration allows rhinoceros to be immobilized for extended periods, which facilitates clinical procedures in injured individuals or managing orphaned calves. The reduction in tachycardia suggests that butorphanol may have a myocardial oxygen-sparing effect and may lower the risk of an adverse outcome associated with immobilization.
My recommendations for the immobilization of white rhinoceros to reduce the morbidity and mortality risks associated with etorphine-induced respiratory and cardiovascular changes include azaperone administration in combination with the potent opioid. The inclusion of azaperone reduces hypertension in etorphine- immobilized rhinoceros. However, 1 suggest that lower azaperone doses be considered compared to those used in my studies to moderate the decrease in blood pressure and possible complications associated with reduced tissue perfusion. Butorphanol should be administered intravenously to etorphine plus azaperone-immobilized-rhinoceros as soon as possible after induction to limit increased opioid-induced metabolic effects and improve hypoxaemia and hypercapnia. The administration of butorphanol also has the advantage of reducing tachycardia with a potential myocardial oxygen sparing effect in immobilized-rhinoceros. Butorphanol should be administered in repeated doses (5 to 10 x etorphine dose in mg) until limb muscle tremoring is reduced and possibly halted, and an elevated heart rate slows to less than 100 beats per minute or slower.
Future research should focus on improving alveolar gas exchange and reducing the sympathomimetic and hypermetabolic effects of the potent opioids in immobilized-rhinoceros, and not only just improving ventilation and blood pressure.
Description
A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the
degree of
Doctor of Philosophy.
Johannesburg, South Africa, 2017