Anesthesiology
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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.
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Following the observation that mice manifest a characteristic withdrawal syndrome after an hour of exposure to nitrous oxide, the authors reasoned that there might be a very rapidly developing tolerance to nitrous oxide. Thus, they determined the inspired concentrations that cause loss of the righting reflex in mice (i.e, the ED50), in the presence of 1 atm of oxygen, of: 1) nitrous oxide alone; 2) cyclopropane alone; 3) nitrous oxide plus 13.6 atm helium; 4) ethylene plus 13.6 atm helium. In each instance the ED50 was determined after averages of 6,34 and 64 min of exposure to the anesthetic agents. ⋯ For ethylene plus helium the ED50 increased from 1.21 +/- 0.033 atm at 6 min to 1.31 +/- 0.039 atm at 64 min, indicating the development of acute tolerance. Neither cyclopropane alone nor nitrous oxide plus helium caused acute tolerance. This absence of tolerance may have resulted from a slower development of an alveolar anesthetic concentration.