mivacurium and Kidney-Failure--Chronic

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.. 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.. 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.. 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

Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Electromyography; Female; Hemodynamics; Humans; Intubation, Intratracheal; Isoquinolines; Kidney Failure, Chronic; Kidney Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Preanesthetic Medication; Prospective Studies; Risk Factors

We have studied the pharmacokinetics of cis-trans, trans-trans and cis-cis mivacurium in nine healthy patients (creatinine clearance 66-133 ml min-1), in seven patients with end-stage renal failure requiring dialysis (creatinine clearance 4-11 ml min-1) and in seven patients with impaired renal function (creatinine clearance 32-49 ml min-1), during thiopentone-fentanyl-midazolam-nitrous oxide-oxygen anaesthesia. Mivacurium chloride was infused at a rate of 15 micrograms kg-1 min-1 for 10 min, 7.5 micrograms kg-1 min-1 for a further 10 min, and then at a rate adjusted to maintain T1/T0 at 5%. The minimum duration of infusion was 60 min (range 60-235 min). The plasma concentration of the three isomers was measured at regular intervals throughout the infusion, and for up to 300 min after the infusion was stopped. Compartmental analysis of the resulting isomer profiles was undertaken: one- and two-compartment models were fitted to derive clearance, volume of distribution and terminal elimination half-life. Clearance of the cis-cis isomer was reduced significantly in the renal failure (median 2.4 (range 2.1-2.6) ml kg-1 min-1) and intermediate renal function groups (2.1 (2.0-2.9) ml kg-1 min-1), compared with healthy patients (3.8 (2.6-4.9) ml kg-1 min-1) (P < 0.01 in each case).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Female; Half-Life; Humans; Isomerism; Isoquinolines; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents

Topics: Adult; Female; Humans; Isoquinolines; Kidney Failure, Chronic; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Time Factors

We have determined the pharmacokinetics and duration of action of a bolus dose of mivacurium (0.15 mg kg-1) during isoflurane and nitrous oxide anaesthesia in nine patients with normal renal and liver function, nine patients undergoing cadaveric kidney transplantation and nine patients undergoing cadaveric liver transplantation. Total plasma concentrations of mivacurium were measured for 2.5 h after administration using a high-pressure liquid chromatographic assay. Plasma concentration vs time data for what were presumed to be the two active mivacurium isomers were analysed by a non-compartmental method based on statistical moments. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The mean time to recovery of 25% neuromuscular transmission, T25, was greater in the patients with liver failure (57.2 min) than in control patients (18.7 min). The volume of distribution at steady rate (Vdss) was comparable in the three groups. Patients with impaired liver function had significantly longer mean residence time and smaller plasma clearance than did patients with renal failure or control patients. There were significant negative correlations between plasma cholinesterase activity and both T25 (r = 0.79) and mean residence time (r = 0.62).

Topics: Adult; Cholinesterases; Female; Humans; Isomerism; Isoquinolines; Kidney; Kidney Failure, Chronic; Liver; Liver Failure; Male; Middle Aged; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Synaptic Transmission; Time Factors

Twenty anephric and 20 healthy patients received a bolus dose of mivacurium 150 micrograms kg-1. When the first EMG response (T1) of the train-of-four had recovered to 5% of control (T0), an infusion of mivacurium 10 micrograms kg-1 min-1 was started and adjusted to keep T1 at 5%. Ten patients in each group were given neostigmine 35 micrograms kg-1 when the infusion was stopped when T1/T0 had recovered to 20%; in the others recovery was spontaneous. After the bolus dose of mivacurium, mean (SD) depression of T1 was greater in the anephric group than in the normal group (98.4 (3.5) vs 96.8 (4.4)%; P less than 0.01) and recovery of T1/T0 to 5% was slower (15.3 (6.9) vs 9.8 (3.5) min; P less than 0.01). Anephric patients required a slower infusion rate (6.3 (1.9) vs 10.4 (2.8) micrograms kg-1 min-1; P less than 0.001). Neostigmine hastened recovery of both T1/T0 and T4/T1 in both groups. Spontaneous recovery of T1/T0 (from 25% to 75%) after the infusion was also slower in anephric patients (12.2 (8.2) vs 7.7 (1.2) min; P less than 0.05). Plasma cholinesterase activity was less in the anephric group (785 (207) vs 943 (217) iu litre-1; P less than 0.05) and there was a (negative) correlation overall between cholinesterase activity and time to 5% recovery of T1/T0 after the bolus dose (r = -0.42; P less than 0.02). We conclude that patients with chronic renal failure may require a reduced dose of mivacurium.

Topics: Adult; Blood Pressure; Butyrylcholinesterase; Cholinesterases; Drug Administration Schedule; Electromyography; Female; Heart Rate; Humans; Infusions, Intravenous; Isoquinolines; Kidney Failure, Chronic; Male; Middle Aged; Mivacurium; Neostigmine