The maximum depth of an atracurium neuromuscular block antagonized by edrophonium to effect adequate recovery.

BACKGROUND: The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium. METHODS: In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio > or = 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium. RESULTS: In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio > or = 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > or = 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 +/- 3% (mean +/- SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 +/- 0.33 mg.kg-1 (mean +/- SD). CONCLUSIONS: There is a maximum level of neuromuscular block that can be antagonized by edrophonium to effect adequate recovery. The level corresponds approximately to the reappearance of the fourth response to TOF stimulation. It is probably safest to wait until this level of block occurs before edrophonium is given for reversal. Earlier administration will not hasten recovery.

Pharmacokinetics of alcuronium in children with acyanotic and cyanotic cardiac disease undergoing cardiopulmonary bypass surgery.

The aim of this study was to determine the pharmacokinetic parameters for alcuronium in children with cyanotic or acyanotic congenital cardiac disease undergoing cardiopulmonary bypass surgery and to compare these parameters with previously reported values in children and adults with normal cardiac function. Seven children with acyanotic disease and seven with cyanotic disease were studied. Alcuronium (base) was administered in an initial dosage of 0.25 mg.kg-1 with additional doses as needed to maintain paralysis. Using time averaged data, cyanotic children had lower mean clearance, elimination half-life and volume of distribution at steady state than the acyanotic children; none of these differences was, however, statistically significant. In this study, children with acyanotic and cyanotic cardiac disease undergoing bypass, had a diminished clearance (P < 0.05) and a smaller volume of distribution (P < 0.05) than normal children and a shorter elimination half-life (P < 0.05) than adults. Onset of cardiopulmonary bypass caused an immediate marked decrease in alcuronium plasma concentrations which remained low in the acyanotic children at the completion of bypass.

Delayed onset of alcuronium effect in children with cyanotic congenital heart disease.

The effect of alcuronium dichloride (0.3 mg/kg) was studied in seven normal children (Group A), nine with acyanotic congenital heart disease (Group B) and eight with cyanotic disease (Group C). The onset of action was recorded using an integrated electromyograph and blood samples taken for later estimation of plasma concentrations of the drug. The mean time (SD) taken to 75% suppression of twitch height was 1.3(0.8), 1.7(1.0) and 3.8(2.8) minutes, respectively, in each of the three groups. This was significantly slower in Group C compared with both other groups (P < 0.05). While six of the Group A patients and seven from Group B reached 95% paralysis within ten minutes, only two of the cyanosed children achieved this level of relaxation. However, if times to 95% relaxation were extrapolated, there was no significant difference between the groups at 4.5(3.9), 5.8(5.7) and 10.9(6.5) minutes respectively. There was a weak but statistically significant relationship between haematocrit and time to 75% blockade. Maximum twitch depression was similar in all three groups with plasma concentrations at this time being 1.6(0.7), 1.8(0.5) and 2.3(1.4) micrograms/ml respectively. Again, there was no statistically significant difference between these values. These results confirm that the clinical onset of relaxation is delayed in children with cyanotic congenital heart disease, possibly because of delayed distribution of alcuronium.