Analgetic Contribution of Sufentanil during Halothane Anesthesia

Abstract

DiFAZIO CA. Analgetic contribution of sufentanil during halothane anesthesia: a mechanism involving serotonin. Anesth Analg 1985;64:857-63.Catecholamine and serotonin concentrations in the cord, medulla, and hypothalamus were measured in rats after saline, after sufentanil sufficient to reduce the minimum alveolar concentration (MAC) of halothane by 30% or less, or after sufentanil sufficient to reduce the MAC of halothane by 80% or more. In the cord, high doses of sufentanil resulted in a 13.4% reduction (P < 0.05) in serotonin concentration compared to saline control and a 17.4% reduction ( P < 0.05) in serotonin concentration compared to low dosages of sufentanil. A 12.8% reduction ( P < 0.05) in medullary serotonin also was observed with high sufentanil compared to low sufentanil. Epinephrine decreased significantly in the hypothalamus at the high sufentanil dose. No other significant differences were found in catecholamine content. The experimental results support the hypothesis that sufentanit may contribute to an analgetic component of general anesthesia by modulating nociception via the release of 5-HT.Sufentanil is a substituted derivative of fentanyl that is more potent and less toxic than fentanyl or morphine (1). Recently sufentanil was shown to reduce the minimum alveolar concentration (MAC) of halothane by more than 90% in rats ( 2 ) .Evidence suggests that central monoamines may play an important role in the analgetic control of anesthesia, although this has not been clearly elucidated. Yaksh and Tyce showed that microinjections of morphine into the periaqueductal gray (PAG) evoked the release of serotonin from the spinal cord (3). These injections resulted in analgesia that could be reduced by inhibition of 5-HT terminals in the spinal cord (4). Wang showed that the direct intrathecal administration of serotonin resulted in antinociception (5) and mimicked the analgetic effect of morphine injected into the PAG, as reported by Yaksh and Tyce. When the PAG was electrically stimulated in human patients, Newfield et al. (6) found that halothane MAC was reduced by 73%. Ahtee showed that chronic morphine administration decreased 5-HT in rat brains (7).These findings suggest that the ability of narcotics to contribute to an analgetic component of general anesthesia may be related to modulation of nociception by the narcotic activation of 5-HT release in central nervous system tissues. To test this possibility further, we have measured concentrations of monoamines in nervous tissue in three groups of rats. One group, receiving only halothane anesthesia at 1 MAC, was designated as the control. The other two groups were designated as the low-dose and the high-dose sufentanil groups. The proposed mechanism of halothane MAC reduction by narcotics would be supported if our data showed a relationship between increased dosages of sufentanil and decreased levels of 5-HT in central nervous system tissue. MethodsHalothane MAC and reductions in halothane MAC were established as reported previously (2). Briefly, 19 S...