Anesthesiology
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The ability of edrophonium to reverse the nondepolarizing neuromuscular blockade produced by pancuronium was studied in 40 adult patients during light nitrous oxide--enflurane anesthesia. Antagonism of paralysis was attempted when the train-of-four fade ratio had spontaneous recovered in various extents. ⋯ When the train-of-four count was three or fewer visible twitches, the response to endrophonium was unpredictable. No evidence of recurarization was seen.
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Using extracellular single-unit recording techniques, effects of intravenously administered lidocaine on dorsal-horn nociceptive neurons were studied in cats made decerebrate whose spinal cords had been transected. Thirty-seven neurons in Rexed lamina V responding to high-threshold mechanical and noxious thermal stimuli (radiant heat, using Hardy-Wolff-Goodell dolorimeter) were studied. Lidocaine hydrochloride, 2.5, 5, and 10 mg/kg, iv, produced dose-related suppression of both spontaneous activity and responses of these neurons to noxious thermal stimulation. ⋯ Plasma lidocaine concentrations 5 min after lidocaine, 5 mg/kg, averaged 3.6 +/- 0.7 microgram/ml. These data support the clinical impression that intravenously administered lidocaine produces analgesia at plasma concentrations of 3--10 microgram/ml. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons.
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To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular blockade and associated plasma concentrations following equipotent doses of pancuronium using three methods of pancuronium administration: the isolated-arm technique in conscious volunteers (n = 4), and the bolus intravenous injection (n = 7) and continuous-infusion methods (n = 3) in anesthetized patients. Although maximum depressions of twitch tension were similar (85 +/- 11,91 +/- 6, and 92 +/- 4 per cent, respectively) with the three techniques, times to recovery from neuromuscular blockade differed significantly, being 10 +/- 2 min with the isolated-arm technique, 23 +/- 7 min with the bolus-injection technique, and 46 +/- 5 min with the continuous-infusion method. ⋯ At 25 and 75 per cent recovery, mean plasma concentrations were 0.07 +/- 0.01 and 0.04 +/- 0.01 microgram/ml in the isolated arm; 0.13 +/- 0.04 and 0.09 +/- 0.02 microgram/ml after bolus injection, and 0.20 +/- 0.04 and 0.11 microgram/ml during continuous infusion, respectively. It is concluded that the relationship between plasma concentration of pancuronium and magnitude of neuromuscular blockade depends on the method of pancuronium administration.
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Comparative Study
Dose-response and plasma concentration-response relationships of pancuronium in man.
The dose-response and plasma concentration-response relationships for pancuronium in man were studied during its intravenous administration to eight patients at a rate of 1.62 microgram/kg/min. The (log) dose-response relationships resulted in a sigmoid curve that was linear in its central range. At 20, 50 and 80 per cent paralysis the cumulative dosages (mean +/- SEM) were 0.04 (+/- 0.01), 0.06 (+/- 0.01), and 0.08 (+/- 0.02) mg/kg, respectively. ⋯ Using data for the entire response range during recovery from paralysis, the mean effective plasma concentration of pancuronium for a 50 per cent response was 0.20 microgram/ml. Recovery from blockade to 95 per cent paralysis (5 per cent of control twitch height) was associated with a plasma concentration of 0.25 microgram/ml, a value in agreement with plasma concentrations obtained following a single bolus administration of pancuronium, 6 mg, to 30 patients. For 27 patients the rate of decline of paralysis from 80 to 20 per cent showed a highly statistically significant relationship to the apparent rate of decline in the plasma concentrations of pancuronium.