Combined I.V. Bolus and Infusion of Pancuronium Bromide

Abstract

SUMMARYAn i.v. bolus and concomitant infusion of pancuronium is proposed for use in prolonged anaesthesia. Plasma concentrations of pancuronium were measured in 16 patients receiving this regime. The desired steady-state concentration of 0.2 fig ml" 1 was achieved in most instances at approximately 45 min. Following the bolus, the neuromuscular twitch response decreased to low values or was abolished completely. Thereafter the response remained relatively constant or increased in intensity consistent with the mean steady-state plasma concentrations of 0.214 y.g ml" 1 (SEM 0.012) maintained by the infusion. When the infusion was stopped, the mean twitch height was 23% of control and increased thereafter at approximately 1 % per min, while plasma concentrations decreased by half in 69 min. One patient with renal artery stenoses exhibited complete neuromuscular blockade at a steady-state plasma concentration of 0.29 (zgml" 1 ; following cessation of infusion the twitch response was detected after 30 min (plasma concentration 0.20 (ig ml"" 1 ) and recovery was uneventful. Plasma clearance and apparent volume of distribution of pancuronium used to calculate the dosage regime were found not to differ significantly from those reported for a single dose. Following cessation of infusion, plasma concentrations declined in either a mono-or bi-exponential form depending on the ratio of the hybrid disposition rate constants (P/a). In all instances a twocompartment open model was used to describe the time course of the plasma concentrations.The continuous administration of a non-depolarizing muscle relaxant to produce sustained neuromuscular blockade was employed first by Evans and Spencer Gray (1953). Following an initial, rapid infusion of gallamine, a slower infusion at the rate of 1 mg min" 1 was used, and the effects on abdominal muscular relaxation and spontaneous ventilation were observed. Ryan (1964) employed a similar procedure for tubocurarine, based on the rate of disappearance and accumulation of the drug in anaesthetized man. Following an initial bolus dose (usually 15 mg) of tubocurarine, neuromuscular blockade was maintained by a constant infusion at a rate equivalent to the bolus dose per hour. By clinical assessment, the rate of infusion "remained remarkably constant in the majority of cases", although a few patients required a reduction in infusion rate during the 3rd and 4th hours.Miller and Eger (1976) determined the potency ratios of tubocurarine and pancuronium. Following a bolus dose, a continuously changing rate of infusion was administered to produce a constant 90% reduction of twitch tension. Plasma concentrations of drug(s) were not measured. For their study, calcula- tions were based on differences in the amount administered over different periods during the infusion of each relaxant. From the difference in potency ratios based on dose requirements for the first and last 30-min periods of observation, it was concluded that potency values determined by single injection techniques did not describe ad...

Relative Potency of Org NC45, Pancuronium, Alcuronium and Tubocurarine in Anaesthetized Man

“…The relative potency of pancuronium, alcuronium and tubocurarine found in this study is in accord with previous animal studies (Cass et al, 1976;Booij et al, 1980) and human studies (Lund and Stovner, 1970;Donlon, Ali and Savarese, 1974) and with clinical experience (Baird and Reid, 1967;Baird, 1968;Crul, 1970;Levin and Dillon, 1971). Somogyi, Shanks and Triggs (1978) calculated the amount of a bolus injection of pancuronium producing an almost complete block to be 62.5 ng kg" 1 body weight. This is almost identical with our finding (62.2 ±4.9 (xg kg-1 )-The relative potency of Org NC 45 to pancuronium (1.7) in this study differs from that reported by Agoston and others (1980), who found the drugs to be equipotent.…”

Relative Potency of Org Nc 45, Pancuronium, Alcuronium and Tubocurarine in Anaesthetized Man

“…The relative potency of pancuronium, alcuronium and tubocurarine found in this study is in accord with previous animal studies (Cass et al, 1976;Booij et al, 1980) and human studies (Lund and Stovner, 1970;Donlon, Ali and Savarese, 1974) and with clinical experience (Baird and Reid, 1967;Baird, 1968;Crul, 1970;Levin and Dillon, 1971). Somogyi, Shanks and Triggs (1978) calculated the amount of a bolus injection of pancuronium producing an almost complete block to be 62.5 ng kg" 1 body weight. This is almost identical with our finding (62.2 ±4.9 (xg kg-1 )-The relative potency of Org NC 45 to pancuronium (1.7) in this study differs from that reported by Agoston and others (1980), who found the drugs to be equipotent.…”