Respiratory, cardiovascular and metabolic effects of etorphine, with and without butorphanol, in white Rhinoceros (Ceratotherium Simum)

Abstract

This thesis presents data that increases our understanding of the pathophysiological effects of etorphine in the white rhinoceros (Ceratotherium simum). This iconic species is poached for its horn throughout southern Africa and must be managed strategically for its protection. Management procedures require chemical immobilisation, and the ultrapotent µ (mu) opioid receptor agonist, etorphine, is one of the few drugs available for rhinoceros immobilisation. However, since etorphine was first introduced in the mid-20th century, veterinarians have observed severe side effects in white rhinoceros during immobilisation, the most serious of which is, arguably, hypoxaemia. Although uncommon, mortalities have occurred.1 An understanding of the mechanisms by which etorphine causes these derangements will inform efforts to develop preventative or therapeutic strategies that will increase the safety of chemical immobilisation for the white rhinoceros, thus contributing to its conservation. Previous studies have evaluated heart rate (fH), systemic arterial pressure (SAP), arterial blood gases and acid-base status, minute ventilation (VE), plasma catecholamine concentrations, metabolic rate, and tremors, among other variables.2-7 However, a comprehensive understanding of the effects of etorphine requires measurement of pulmonary pressures, cardiac output (Qt), and mixed venous blood gases and acid-base status as well. To this end, my colleagues and I developed and refined an ultrasound-guided technique for pulmonary arterial catheterisation in the white rhinoceros. In other species, pulmonary arterial catheters (PAC) are inserted through a percutaneous introducer into the jugular vein; the tip is passed through the right heart and into the pulmonary artery. Ultrasound examination suggested that percutaneous access to the jugular vein is impractical in white rhinoceros. However, my colleagues and I found that in this species the introducer can be inserted instead into the linguofacial vein, a branch of the jugular vein, and designed a PAC long enough to reach the pulmonary artery. Pilot testing of a custom-built PAC in boma-habituated white rhinoceros immobilised with etorphine and azaperone, followed by butorphanol intravenously (IV), afforded me the opportunity to assess some of the cardiopulmonary effects of a supplemental, IV bolus of etorphine. I observed an increase in mean pulmonary arterial pressure (mPAP), Qt, and fH and a decrease in arterial oxygen partial pressure (PaO2) following an etorphine bolus. Based on normal values in the white rhinoceros and the horse, or values calculated allometrically for the white rhinoceros, these variables were already pathologically increased (mPAP, Qt, fH) or decreased (PaO2), and the bolus worsened these physiological derangements. The development and refinement of the pulmonary arterial catheterisation technique, and the data on the effects of an etorphine bolus are detailed in Chapter 2. After increasing the PAC length to enable measurement of pulmonary arterial occlusion pressure (PAOP), my colleagues and I conducted further research in six boma-habituated, sub-adult, male white rhinoceros. Using a crossover design, each rhinoceros was administered each of two treatments (i.e., two study phases) in random order: etorphine intramuscularly (IM) followed by saline IV (treatment ES), or etorphine IM followed by butorphanol IV (treatment EB). Once a rhinoceros was positioned in lateral recumbency (time = 0 minutes [t = 0]), 30 minutes was allotted for instrumentation, which included pulmonary and systemic arterial catheterisation and connection to a custom breathing system. Baseline data were collected at t = 30, saline or butorphanol was administered at t = 37, and data were collected again at t = 40 and 50. Chapter 3 presents data from ES and examines changes over time. As reported in previous studies, etorphine produced severe hypoxaemia and hypercapnia, and VE was lower than normal, expected VE calculated allometrically.2 I found that over time, physiological variables remained relatively constant after etorphine administration, with a few exceptions. Mixed venous oxygen partial pressure (PῡO2), arterial oxygen content (CaO2), and mixed venous oxygen content (CῡO2) increased (i.e., improved); tidal volume (VT) decreased (i.e., worsened), and tremor score and mixed venous lactate concentration decreased (i.e., improved). Oxygen consumption (VO2) initially decreased (i.e., improved) then increased somewhat. (However, some of these differences lost significance after correction for multiple comparisons; refer to Chapters 3 and 4.) Values for mPAP, PAOP, mean SAP (mSAP), Qt, VO2, and plasma noradrenaline concentrations were higher than ‘normal’, assessed by comparison to values measured in other species (or those calculated allometrically), consistent with sympathetic outflow. Chapter 4 examines changes over time in EB and compares ES and EB. I found that butorphanol decreased (i.e., improved) pulmonary pressures, mSAP, Qt, fH, pulmonary artery and rectal temperatures (T), arterial carbon dioxide partial pressure (PaCO2), VO2, carbon dioxide production (VCO2), oxygen extraction ratio (OER), shunt fraction (Qs/Qt), noradrenaline concentration, tremor score, and haemoglobin (Hb) concentration ([Hb]); it also decreased (i.e., worsened) VT. Butorphanol increased (i.e., improved) pulmonary vascular resistance (PVR), PaO2, PῡO2, CaO2, CῡO2, minute ventilation body temperature and pressure, saturated with water vapour (VEBTPS), and respiratory rate (fR). These differences were either changes from baseline in EB or differences at one or more sampling points between ES and EB.