Objective: Mivacurium produces a prolonged neuromuscular block (NMB) in anuric patients (13), in spite of its rapid hydrolysis by pseudocholinesterase (PChE) which is independent of renal function (17). In the present study the pharmacodynamics and the cardiovascular effects of a bolus dose of mivacurium (0.15 mg/kg) in relation to impairment of renal function were evaluated.
Methods: 60 patients (ASA class 2-4) were assigned to one of three groups according to the degree of renal dysfunction. Creatinine clearance (Krea-Cl) as a measure of renal function was calculated using weight, age, sex and serum creatinine concentrations. Group C (control): Krea-Cl > 50 ml/min; group P (preterminal): 20 ml/min < Krea-Cl < 50 ml/min; group T (terminal): Krea-Cl < 20 ml/min. PChE activity and dibucaine numbers were assessed preoperatively. Neuromuscular transmission (Train-of-Four) was monitored using electromyography (Relaxograph, Datex Inc.) with stimulation of the ulnar nerve. The response was recorded from the hypothenar muscle. Five minutes after induction of anaesthesia with propofol and fentanyl, 0.15 mg/kg mivacurium was given i.v. over 30 s. 150 s later patients were intubated. Anaesthesia was maintained by propofol (2-10 mg/kg/h) and fentanyl (0-5 micrograms/kg/h) infusion. Patients were ventilated with oxygen/nitrous oxide (FiO2 = 0.35). As soon as T1 recovered to 5% or more, mivacurium was administered continuously and this part of the study was finished. Times of onset (onset 10; onsetmax), maximal neuromuscular block (NMBmax), neuromuscular block when intubation was started (NMBTubus), and duration 5% (dur 5) were calculated. Arterial blood pressure and heart rate were recorded before anaesthesia, after induction of anaesthesia, 2-times after mivacurium application, and after intubation. All data were compared using Kruskal-Wallis test corrected for multiple comparisons, Friedman test, or chi 2-test (*: p < 0.05). Logarithms of dur 5 and PChEd were correlated using linear regression.
Results: Demographic data were comparable between all groups. PChEd was 3.7 (3.0/4.1) kU/l in group C, 3.2 (2.2/4.8) kU/l in group P, and 3.5 (2.5/4.0) kU/l in group T, respectively. There were no differences between groups, neither in the NMBmax, in NMBTubus, or in onset times. But dur 5 was significantly longer in patients with renal impairment, both preterminal and also end-stage (medians: 11 min in group K, 16 min in group P, 17 min in group T). Emphasis, however, is put on the broad range between 5 and 47 min of dur 5 in group P, and between 6 and 53 min in patients of group T which is clinically more important than the differences in the median values. Dur 5 correlates with PChEd (p = 0.0001). Intubation conditions were excellent (relaxed vocal cords, easy passage of the tube, without coughing) in approximately 70% of all 59 patients without significant differences between groups. In 8 patients conditions were poor (successful intubation, inspite of moderately adducted vocal cords, but moderate coughing after passage of the endotracheal tube). There were no clinically relevant hemodynamic changes in each group in the time between injection of 0.15 mg/kg mivacurium slowly and intubation 2.5 min later.
Discussion: Our findings suggest that 0.15 mg/kg mivacurium is an effective and safe intubation dose in healthy patients as well as in patients with renal impairment, inspite of a prolonged duration in patients with renal impairment. Low PChE in some, but not in all patients with a renal dysfunction indicates involvement of impaired hepatic function. There was a close correlation between the PChEd and dur 5. Therefore mivacurium dosage should be reduced in patients with compromised renal function, mainly if there are additional systemic, especially hepatic diseases. Thus, in patients with impaired renal function, relaxometry may be of high valu