Edrophonium and human plasma cholinesterase combination for antagonism of mivacurium-induced neuromuscular block.

We have compared the reversal characteristics of mivacurium after administration of an edrophonium-plasma cholinesterase (PCHE) combination with that produced by each antagonist alone. Forty ASA I adults were given mivacurium 0.15 mg kg-1 during fentanyl-thiopentone-nitrous oxide-isoflurane anaesthesia. TOF stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height (T1) reached 10% of its initial control value, patients were allocated randomly to one of four groups (n = 10 in each). Neuromuscular function in patients in group 1 (control group) was allowed to recover spontaneously. Patients in groups 2-4, respectively, received edrophonium 1 mg kg-1 (group ED), exogenous PCHE equivalent to activity present in 25 ml kg-1 of human plasma (group PCHE) or edrophonium 1 mg kg-1 with exogenous human PCHE equivalent to the activity present in 25 ml kg-1 of human plasma (combination group). The time to attain a TOF ratio of 0.75 in the combination group was 4.6 (SD 0.9) min. This was shorter (P < 0.01) than that observed in patients in the control (16.8 (3.3) min), ED (8.9 (3.6) min) and PCHE (9.3 (1.6) min) groups. There was no difference in recovery indices between groups ED and PCHE. We have demonstrated that the edrophonium-PCHE combination significantly accelerated recovery of mivacurium-induced block compared with that observed with the use of individual antagonists.

Enzymatic versus pharmacologic antagonism of profound mivacurium- induced neuromuscular blockade.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is hydrolyzed by butyrylcholinesterase. The use of butyrylcholinesterase for antagonism of profound mivacurium-induced blockade has not been studied in humans. In part 1 of this two-part study, the authors examined the relationship between the posttetanic count (PTC) and recovery from profound mivacurium-induced blockade. In part 2, an attempt was made to antagonize a quantified level of profound mivacurium-induced blockade using either butyrylcholinesterase, edrophonium, or neostigmine. METHODS: Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg.kg-1 mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. They were randomly assigned to eight groups. Neuromuscular function was monitored by recording the mechanomyographic response of the adductor pollicis to PTC and train-of-four (TOF) stimulation in all patients except those in group 1 where the TOF was the only pattern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOF) until TOF ratio (the amplitude of the fourth evoked response as a fraction of the first evoked response T4/T1) had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 31 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously until TOF ratio had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously, until TOF ratio had reached 0.75 (group 2; control-PTC). In part 2, the antagonism of mivacurium-induced profound (PTC > or = 1; groups 3-6) and 90% block (groups 7-8) of twitch height were investigated in another 56 patients. Groups 3 and 7 received neostigmine 0.06 mg.kg-1 whereas groups 4 and 8 received edrophonium 1 mg.kg-1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml.kg-1 of human plasma, respectively. RESULTS: Neither butyrylcholinesterase nor edrophonium shortened the times from first PTC response to TOF = 0.75 compared to group 2. Neostigmine resulted in prolongation of recovery time. There was a linear relationship (r = -0.80; P = 0.00001) between PTC and time of onset of TOF response. CONCLUSIONS: There appears to be no clinical advantage in attempting to antagonize profound mivacurium-induced neuromuscular blockade.

Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine.

We have examined the effects of different benzyl-isoquinolinium and steroidal neuromuscular blocking compounds on plasma concentrations of histamine, heart rate and arterial pressure in surgical patients. A single, rapid (5-s) bolus of mivacurium 0.2 mg kg-1, atracurium 0.6 mg kg-1, tubocurarine 0.5 mg kg-1, vecuronium 0.1 mg kg-1 or rocuronium 0.6 mg kg-1 was administered to 75 patients (n = 15 in each group). Anaesthesia was induced with thiopentone 6 mg kg-1 i.v. and maintained with isoflurane and 70% nitrous oxide in oxygen. Venous blood samples were obtained before induction, 1 min after thiopentone and 1, 3 and 5 min after administration of the neuromuscular blocking drug. Mivacurium, atracurium and tubocurarine caused 370%, 234% and 252% increases in plasma histamine concentrations at 1 min, respectively. Corresponding values at 3 min were 223%, 148% and 157%, respectively. These changes were significant (P < 0.01) at 1 and 3 min. In contrast, the rocuronium and vecuronium groups had no significant changes in either plasma histamine concentrations or haemodynamic variables.

Comparative potency of steroidal neuromuscular blocking drugs and isobolographic analysis of the interaction between rocuronium and other aminosteroids.

We have determined the relative potency of rocuronium, pancuronium, pipecuronium and vecuronium, and examined the nature of the interaction of rocuronium with the other three steroidal neuromuscular blocking drugs. We studied the dose-response relationships of each drug and their combination with rocuronium in 200 ASA I or II patients during propofol-fentanyl-nitrous oxide-oxygen anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to single twitch stimulation of the ulnar nerve at 10-s intervals. The dose-response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess the combined effect of equipotent doses of rocuronium and vecuronium, pipecuronium or pancuronium and to define the type of interaction between these drugs. The isobolograms were constructed by plotting single-drug ED50 points on the dose co-ordinates, and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the twitch height for rocuronium, pancuronium, pipecuronium and vecuronium were 144.8 (95% confidence intervals 140.4-149.3), 32.4 (31.7-32.9), 27.1 (26.5-27.6) and 23.7 (22.7-24.8) micrograms kg-1, respectively. Corresponding doses producing 95% depression (ED95) of twitch height were, respectively, 322.1 (307.5-337.3), 58.1 (56.2-60.1), 48.7 (46.9-50.5) and 39.9 (38.4-41.4) micrograms kg-1. Based on the estimate of ED50, the relative potency was 1:4.5:5.4:6, respectively. The interaction between rocuronium and vecuronium, pipecuronium or pancuronium was found to be additive.

Airway protection by the laryngeal mask airway in children.

The pediatric laryngeal mask airway (LMA) is a scale-down version of the adult form, and no direct postmortem specimen work has been performed so far. There are several anatomical differences between pediatric and adult airways, and hence, the scale-down version of the adult LMA is not necessarily water-tight in pediatric patients. We performed a prospective study to assess airway protection by the LMA in pediatric patients, using methylence blue (injected in the pharynx outside the LMA) and the fibreoptic bronchoscope to view the inside of the mask, to detect any leakage of the dye. Fifty Patients (40 boys and 10 girls) aged 1-10 years (mean 4.5 yr) were studied. All patients underwent surgery below the level of the umbilicus, under light general anesthesia combined with caudal epidural block. All patients were allowed to breath spontaneously over an Ayre's T-piece. Dye staining of the inside of the mask was detected in 5 patients (10%). The esophageal opening was visualized within the mask in 3 patients (6%). No serious complications occurred in any of our patients.