Minimum Anesthetic Concentration Of Halothane Research Articles

Effects of halothane on the electroencephalogram of the chicken.

Little is known about the effects of inhalant anaesthetics on the avian electroencephalogram (EEG). The effects of halothane on the avian EEG are of interest, as this agent has been widely used to study nociception and analgesia in mammals. The objective of this study was to characterize the effects of halothane anaesthesia on the EEG of the chicken. Twelve female Hyline Brown chickens aged 8–10 weeks were anaesthetized with halothane in oxygen. For each bird, anaesthesia was progressively increased from 1–1.5 to 2 times the Minimum Anesthetic Concentration (MAC), then progressively decreased again. At each concentration, a sample of EEG was recorded after a 10‐min stabilization period. The mean Total Power (PTOT), Median Frequency (F50) and 95% Spectral Edge Frequency (F95) were calculated at each halothane MAC, along with the Burst Suppression Ratio (BSR). Burst suppression was rare and BSR did not differ between halothane concentrations. Increasing halothane concentration from 1 to 2 MAC resulted in a decrease in F50 and increase in PTOT, while F95 increased when MAC was reduced from 1.5 to 1. The results indicate dose‐dependent spectral EEG changes consistent with deepening anaesthesia in response to increasing halothane MAC. As burst suppression was rare, even at 1.5 or 2 times MAC, halothane may be a suitable anaesthetic agent for use in future studies exploring EEG activity in anaesthetized birds.

Chronic desipramine treatment desensitizes the rat to anesthetic and antinociceptive effects of the alpha2-adrenergic agonist dexmedetomidine.

The effects of long-term administration of the tricyclic antidepressant agent desipramine on the hypnotic, antinociceptive, anesthetic-sparing, and central norepinephrine turnover suppressant action of short-term dexmedetomidine, a highly selective alpha2-adrenergic agonist, were studied in rats. Rats were given a 3- or 4-week course of twice daily administration of desipramine, 10 mg/kg, or saline. The effect of a hypnotic dose of dexmedetomidine, 250 microg/kg given intraperitoneally, on the duration of loss of righting reflex was determined. The tail flick latency response was determined before and after 50 microg/kg dexmedetomidine. The minimum anesthetic concentration of halothane and the central norepinephrine turnover rate were determined before and after administration of 30 microg/kg dexmedetomidine. Changes in the affinity and density of the alpha2-adrenergic receptor in locus coeruleus and spinal cord also were determined. Treatment with desipramine decreased dexmedetomidine-induced loss of righting reflex duration by 67% and eliminated the antinociceptive effect of dexmedetomidine. Dexmedetomidine produced a 55% decrease in minimum anesthetic concentration in the control group but no reduction in desipramine-treated rats. Desipramine did not change the receptor density or binding affinity of alpha2 receptors at the site for hypnotic (locus coeruleus) or antinociceptive (spinal cord) responses. No decrement in the central norepinephrine turnover rate was noted in the locus coeruleus of dexmedetomidine after 3 weeks of treatment with desipramine. The alpha1-adrenergic antagonist prazosin at 1 or 5 mg/kg completely (minimum anesthetic concentration reduction), almost completely (antinociceptive), or partially (hypnotic) restored responsiveness to normal. These data indicate that treatment with desipramine induces hyporesponsiveness to the hypnotic, analgesic, and minimum anesthetic concentration-reducing, but not to the suppression of central norepinephrine turnover, properties of dexmedetomidine. The hyporesponsiveness appears to involve an alpha1-adrenergic mechanism.

Modulating role of dopamine on anesthetic requirements

The influence of dopamine on halothane anesthetic requirements was determined in mice. Halothane anesthetic requirement was defined as the minimum anesthetic concentration (MAC) that prevented 50% animals from moving in response to a supramaximal stimulus. Levodopa (L-DOPA) dose-dependently decreased halothane MAC to a maximum of 49% of control; over the same dose range L-DOPA increased striatal dopamine nearly 4-fold. The MAC-reducing effect of L-DOPA was attenuated by selective antagonism of the D 2 dopamine receptor with YM-09151-2 while selective blockade of the D 1 dopamine receptor with SCH-23390 did not alter L-DOPA's effect on the MAC for halothane. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased striatal dopamine by 82% and increased the MAC for halothane by 27%. Repletion of striatal dopamine with L-DOPA, in MPTP-treated mice, restored the MAC for halothane back to the control state. The regression line derived from the plot of hatothane MAC versus striatal dopamine content shows a highly significant correlation between the two variables (r 2 = 0.94). These are the first results to suggest that anesthetic requirements can be modulated directly and precisely by increasing or decreasing the content of a single neurotransmitter in the central nervous system.

Enhancement of Anesthetic Effect of Halothane by Spiradoline, A Selective ??-Agonist

Reduction in the anesthetic requirement of halothane by narcotics has been studied extensively in humans and animals. Problems of respiratory depression, cardiovascular depression, muscle rigidity, and abuse potential make narcotics less than ideal as supplements to general anesthesia with inhalational agents. Spiradoline, a clinical candidate, is a highly potent and selective kappa-agonist. As such it was considered important to study the effects of spiradoline on the minimum anesthetic concentration (MAC) of halothane required to block responses to noxious stimulation. The results of these experiments in rats showed a dose and plasma concentration-dependent reduction in halothane MAC over a wide range of subcutaneous doses of spiradoline (0.03 to 300 mg/kg). A maximum MAC reduction of 70% was obtained. Plasma levels of spiradoline (6 to 1800 ng/ml) were linearly related to dose. Measurement of blood pressure, heart rate, and PCO2 determined over the course of each experiment showed minor variations which would be acceptable if observed in a clinical setting. It is concluded that spiradoline has promise as an anesthetic supplement.

Effects of U-50488H, a selective kappa-analgesic, on the minimum anesthetic concentration (MAC) of halothane in the rat.

The effects of U-50488H, a selective kappa-analgesic, on the minimum anesthetic concentration (MAC) of an inhalational agent (halothane) were studied in the rat. U-50488H was given subcutaneously in doses of 3, 10, and 30 mg/kg body weight. The maximal MAC reduction was about 60%. The potency ratio of U-50488H to morphine in this model was comparable with potency ratios in other analgesic assays. In separate experiments, the percent reduction in halothane MAC with U-50488H at 30 mg/kg was determined during the infusion of naloxone (5 micrograms X kg-1 X min-1 and 1 mg X kg-1 X min-1) at doses shown to have reversed a 70% reduction in MAC by 10 mg/kg of morphine. Only when naloxone was infused at 1 mg X kg-1 X min-1 was there a significant reversal of the U-50488H-induced reduction in halothane MAC. This observation suggests that the reduction in MAC of halothane with U-50488H was not mediated by a mu-receptor. In conclusion, through the use of a selective pharmacologic tool that stimulates kappa-receptors we have demonstrated potential utility of kappa-analgesics as supplements to general anesthesia.