Pentobarbital-morphine anesthetic interactions in terms of intensity of noxious stimulation required for arousal

Previous reports suggest that the outcome (synergism, antagonism, summation) of opioid-barbiturate interactions may depend on the depth of anesthesia. One aim of the present study was to determine whether pentobarbital, alone and in combination with morphine, blocks awakening caused by noxious stimulation in a dose-related manner: the more intense the noxious stimulation, the more pentobarbital is required to suppress the response. A second aim of the study was to determine whether the pentobarbital-morphine anesthetic interaction depends on the depth of anesthesia measured in terms of intensity of noxious stimulation required for behavioral arousal (recovery of the righting reflex).

Experiments were performed on rats, with the measure of anesthetic effect being suppression of the righting reflex. The noxious stimulus was pressure on the tail at four levels of intensity: 0.0, 0.25, 2.5, and 3.3 kg, generated with an Analgesy-Meter. Pentobarbital and morphine were injected intravenously via chronically implanted catheters. Dose-response curves for pentobarbital given alone and in combination with morphine were determined (by probit analysis) separately for each of the pressure levels.

Pentobarbital, alone and in combination with morphine, blocked awakening caused by noxious stimulation of different intensities in a dose-related fashion so that more anesthetic was required to block awakening with more intense stimulation. The pentobarbital ED50 values were: 12.0, 19.5, 22.7, and 24.3 mg/kg for 0.0, 0.25, 2.5, and 3.3 kg pressure, respectively. The addition of morphine (1 mg/kg) reduced the pentobarbital ED50 values for 0.0, 0.25, and 2.5 kg pressure by 34% (P < 0.0001), 39% (P < 0.0001), and 21% (P < 0.005), respectively. No change was seen in the pentobarbital ED50 value at the maximal (3.3 kg) pressure level.

The results suggest that the depth of anesthesia can be measured in terms of intensity of noxious stimulation required for arousal and that the outcome of barbiturate-opioid anesthetic interaction depends on the depth of anesthesia.