Pharmacokinetics and pharmacodynamics of the three isomers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function.

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)

Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the chiral mixture in hepatic cirrhosis.

We have studied the pharmokinetics of cis-trans, trans-trans and cis-cis mivacurium in 10 healthy subjects and 11 patients with mild or moderate hepatic cirrhosis, during nitrous oxide-oxygen-isoflurane anaesthesia. Mivacurium 15 micrograms kg-1 min-1 was infused for 10 min (total dose 0.15 mg kg-1) and the plasma concentration of the three isomers measured at regular intervals for 190 min. The electromyographic response to the drug was also measured. Compartmental analysis of the resulting isomer profiles was undertaken: one- and two-compartment models were fitted to derive clearance, volume of distribution and half-life. Clearance of the cis-trans and trans-trans isomers was reduced significantly in the cirrhotic compared with the healthy group: cis-trans (median (range)) 44 (15-121) ml kg-1 min-1 vs 95 (57-213) ml kg-1 min-1 (P < 0.05); trans-trans 32 (12-64) ml kg-1 min-1 vs 70 (34-101) ml kg-1 min-1 (P < 0.05). The difference in the clearance of the cis-cis isomer in the cirrhotic (4.2 (2.9-12.1) ml kg-1 min-1) compared with the healthy group (5.2 (2.9-8.9) ml kg-1 min-1) was not significant with this sample size. Clearance of each isomer correlated significantly with plasma cholinesterase activity: cis-trans r = 0.73, P < 0.001; trans-trans r = 0.69, P < 0.001; cis-cis r = 0.48, P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacodynamics of mivacurium chloride in patients with hepatic cirrhosis.

Ten healthy patients and 25 patients with cirrhosis of the liver (10 Child's A, 10 Child's B and 5 Child's C) received a bolus dose of mivacurium chloride 150 micrograms kg-1. The electromyographic response was monitored throughout anaesthesia until recovery of the first twitch of the train-of-four (TOF) (T1/T0) to at least 85% and the TOF ratio (T4:T1) to at least 80%. There was no significant difference between the two groups in the onset of neuromuscular block, but recovery was prolonged in the cirrhotic group compared with the healthy patients (respective mean times to recovery of T1/T0: to 5% = 20.2 vs 11.2 min (P < 0.05); to 10% = 23.8 vs 13.4 min (P < 0.005); to 25% = 28.4 vs 16.6 min (P < 0.005); to 50% = 41.1 vs 20.1 min (P < 0.005); to 75% = 43.8 vs 24.9 min (P < 0.005). Recovery of T4:T1 to 70% = 48.1 vs 27.4 min (P < 0.005)). Recovery was most prolonged in the Child's C patients. Mean plasma cholinesterase activity was less in the cirrhotic compared with the healthy group (mean 582 (SD 254) iu litre-1 vs 1125 (303) iu litre-1) (P < 0.001) and there was a significant negative correlation between plasma cholinesterase activity and all the indices of recovery (P < 0.001 for all except recovery index (P < 0.01)). We conclude that patients with hepatic cirrhosis may be sensitive to mivacurium, which could be explained, at least in part, by the lesser plasma cholinesterase activity.

Use of EMLA cream for skin anaesthesia prior to epidural insertion in labour.

The efficacy of the use of EMLA cream to provide skin anaesthesia prior to the insertion of 16 G Tuohy needles was assessed. Sixty women in labour were randomly allocated to receive either EMLA cream over the proposed epidural site for a minimum period of 5 min (mean 9.1 min), a skin bleb and subcutaneous injection of lignocaine 2% (1 ml), or a skin bleb with additional lignocaine 2% (2 ml) infiltrated into the supra- and interspinous ligaments using a 23 G needle. Once the epidural catheter was sited, using a standard technique, 10 cm visual analogue pain scales were completed independently by the patient, by a blinded midwife and by the anaesthetist siting the epidural. Patients' perception of pain was not significantly different in any of the three groups, although the mean pain score was least in the group receiving full infiltration. The anaesthetists consistently underestimated the patients' perception of pain.

Profound desaturation following vomiting on induction. A case for routine pre-oxygenation.

Whilst participating in a clinical trial, a patient vomited during induction of anaesthesia. Subsequent analysis of the continuous record of oxygen saturation showed precipitous desaturation.

Effect of changes in heart rate on pressure half time in normally functioning mitral valve prostheses.

To test the validity of a relation between the pressure half time and the diastolic time interval, previously shown in a pulse duplication system, eight patients with prosthetic mitral valves and permanent pacemaker systems were studied. Recordings were made from the apex by continuous wave or pulsed Doppler echocardiography at heart rates between 75 and 150 beats/min. The pressure half time was found to be closely correlated with the diastolic time interval although there was individual variation and in three prostheses the pressure half time attained a plateau when the diastolic time interval was more than 300 ms. It is likely that the orifice area is the main controller of pressure half time where there is stenosis of the prosthesis, but that other factors such as ventricular or atrial compliance and the diastolic time interval may modify or obscure the effect of orifice area in normally functioning prosthetic valves.