HALOTHANE SELECTIVELY INHIBITS NONSHIVERING THERMOGENESIS - POSSIBLE IMPLICATIONS FOR THERMOREGULATION DURING ANESTHESIA OF INFANTS

Background: During halothane anesthesia, infants fail to increase oxyg en consumption in response to a cold stimulus in the form of an increa se in temperature gradient between body and environment. Based on rece nt observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshiveri ng thermogenesis during halothane anesthesia. Methods: The rate of oxy gen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environment al temperature of approximate to 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced b y 3% halothane and maintained by 1.5% halothane. One experimental seri es with spontaneously breathing hamsters and a second control series w ith spontaneously breathing rats and with rats whose lungs were mechan ically ventilated were conducted. Results: Norepinephrine injection le d to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% dec rease in resting metabolic rate (P<0.05) and a 70% inhibition of the t hermogenic response to norepinephrine (P<0.001). The halothane concent ration yielding half-maximal inhibitory effect was estimated to be les s than 1.0%. After the animals had recovered from halothane anesthesia , a completely restored thermogenic response to norepinephrine was obs erved. The inhibitory effect of halothane also was observed in hamster s maintained at normothermia and was therefore not secondary to the sl ight hypothermia that otherwise developed during anesthesia, In a seri es of control experiments, it was confirmed that rats also showed larg e thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the the rmogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilate d, and where blood gases were kept at virtually normal levels, the the rmogenic response to norepinephrine was found to be similarly markedly inhibited. Conclusions: A much diminished or abolished thermogenic re sponse to injected norepinephrine was demonstrated in halothane-anesth etized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiol ogically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.