Anesthesiology
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Randomized Controlled Trial Clinical Trial
Prolonged antagonism of opioid action with intravenous nalmefene in man.
To identify the opioid antagonist activity of nalmefene and to determine its duration in man, six healthy male subjects were pretreated on separate days with a saline placebo, 0.5 mg, 1 mg, or 2 mg nalmefene intravenously in a randomized double-blind fashion. Opioid challenges with fentanyl, 2 micrograms/kg, then were administered 1, 2, 4, 6, and 8 h afterward. Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 rebreathing, while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test. ⋯ The antagonist effects of the lowest nalmefene dose, 0.5 mg, persisted for about 4 h, at which time VE60 was 64% of control. Fentanyl administration produced consistent increases in pain tolerance (44-55% above control) throughout the experiment. Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly.(ABSTRACT TRUNCATED AT 250 WORDS)
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The ability of sufentanil to suppress noxiously evoked activity of wide dynamic range (WDR) neurons was studied in decerebrate, spinal-cord-transected cats. Sufentanil, 2.5 micrograms (n = 7) or 5.0 micrograms (n = 7), when administered spinally, produced a significant, dose-dependent suppression of noxiously evoked (51 degrees C radiant heat stimulus) activity of WDR neurons in the dorsal horn of the spinal cord. Spontaneous recovery from sufentanil suppression was not seen for up to 2 h. ⋯ Intravenous sufentanil, 5.0 micrograms/kg (n = 4), produced significant but short-lasting depression of noxiously evoked WDR neuron activity. A comparison of the results of this study with data from a previous fentanyl study suggests that sufentanil may be more appropriate than fentanyl for spinal or epidural administration because of a possible longer duration of action. However, the lesser degree of naloxone reversal seen in this study may suggest that, clinically, reversal of sufentanil effects may be more difficult.
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The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. ⋯ PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.
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Clinical Trial Controlled Clinical Trial
Influence of naloxone infusion on analgesia and respiratory depression following epidural morphine.
The influence of two different concentrations of iv naloxone infusion on the analgesia and adverse effects of epidural morphine were compared in a double-blind, placebo-controlled study. Forty-five patients undergoing gallbladder surgery were provided postoperative analgesia by 4 mg epidural morphine; they then received an iv infusion over a 12-h period consisting of either 5 micrograms X kg-1 X h-1 naloxone, 10 micrograms X kg-1 X h-1 naloxone, or saline. Pain relief was assessed by hourly visual analog scoring (VAS) and by direct questioning of the patient. ⋯ Complete reversal of analgesia was not seen in any patient. A dose-related stimulatory effect on respiratory frequency was noted in the groups receiving naloxone. PaCO2 values also were better in these groups as compared to values in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)