The influence of body temperature on MAC of halothane in the rabbit determined using controlled mechanical and heat stimulation

Abstract

The determination of the minimum alveolar concentration (MAC) of any inhalation anaesthetic requires repeated application of the stimulus. The investigation of the influence of body temperature on MAC in the same animal, requires even more applications of the stimulus. The use of what is commonly known as a "supramaximal stimulus", beyond which there is no increase in MAC with any further increase in stimulus intensity, is generally held to provide for the reproducibility of MAC. However, there are many conflicting reports with regard to the MAC values obtained using "supramaximal stimuli" and with the interpretation of results.

In this study the unreliability of the "supramaximal stimulus", in the form of tail clamping using a haemostat for the determination of MAC of halothane in the rabbit, was established. The use of this technique was demonstrated, both grossly and histologically, to cause severe trauma and lacerations that may have altered the sensitivity of the sensory mechanisms as indicated by the great variability in the values of MAC obtained on subsequent determinations in the same animal. Also, the technique appeared to disregard modern physiological concepts on receptor thresholds, inflammation and hyperalgesia.

Therefore, it was decided to explore more reliable techniques of stimulation. Controlled mechanical and heat stimulators were devised and used for the determination of MAC of halothane in the rabbit as the body temperature was manipulated to test the effect of environmental heating or cooling on MAC.

The mechanical stimulator is a form of pincer driven by compressed air, and is operated from a control panel with a manual trigger. It is capable of delivering a precise stimulus at a preselected pressure to the target site (ear pinna). The stimulus was calculated in terms of Newtons per unit surface area after calibration of the device using gram weights. The heat stimulator was designed to deliver a controlled, preset focal heat stimulus from a heat lamp for a preselected duration The device is V operated through a system of electronic circuits controlling the temperature and time. With both stimulators, a just noxious level of stimulation was applied.

The mechanical and heat stimulators shared some common advantages over the established clamping techniques used for the determination of MAC. Firstly, both of them were shown to be capable of delivering precise stimuli in terms of amount, duration and rate of application. The control of such components of the stimulus is essential for the reproducibility and interpretation of results, particularly in the ever growing field of comparative studies. Secondly, the stimulus applied by both stimulators was recordable. This allows for the calculation and the calibration of the applied stimulus and, together with the electronically measured and recorded movement response, it was also possible to calculate the response time.

At normothermia, the MAC values of halothane determined in the rabbit usingnondestructive stimuli from either stimulator were found to be consistent and reproducible. Hyperthermia (rectal temperature of 40.6 °C +/- 0.3 (SD) was demonstrated to cause a significant increase in MAC of halothane (12.3% per 1°C rise in body temperature) when determined using a mechanical stimulus of 1.37 +/- 0.04 (SD) N/mm^. On the other hand, no significant difference was detected in MAC determined using a focal heat stimulus of 54.35 °C +/- 0.09 (SD) in hyperthermic rabbits (41.6 °C +/- 0.4 (SD). Hypothermia of 4 °C was shown to reduce the MAC of halothane in the rabbit by 50% (12.8% per 1 °C drop in body temperature) to a focal heat stimulus of 54.3 °C, and by 35.1% (9 % per 1 °C decrease in body temperature) to a mechanical stimulus of 1.39 - 1.41 N/mm^. By extrapolation of results, it was predicted that the "anaesthetising body temperature", at which no halothane would be required to abolish movement response to such stimuli, would be 31.0 °C and 27.7 °C for the heat and mechanical stimuli respectively. It is concluded that, normal doses of potent anaesthetics similar to halothane should probably be considerably reduced in hypothermic rabbits, which must be closely monitored for signs of overdose.

In the initial stages of this study some problems were encountered regarding the determination of MAC in hyperthermic rabbits due to the difficulty in the control of animal heating. As a result a section of this thesis was devoted to the establishment of a controlled and reliable heating and cooling protocol, with some emphasis on selected cardiopulmonary parameters and some stimulus-related responses. A body temperature of 42.0 °C appeared to represent a critical temperature in the rabbit above which the normal physiological responses are interfered with and also above that temperature, induced cooling was ineffective in reducing the body temperature.

Stimulus-related responses, other than movement, included changes in arterial blood pressure, apnoea and hyperpnoea. Such responses, particularly those of the arterial blood pressure, showed both quantitative and qualitative inconsistency. Therefore it was concluded that these responses are not reliable end points for the determination of MAC in the rabbit. On the other hand, the provoked movement of the head and or limbs, remains unchallenged as the most reliable end point for the determination of MAC.