Propofol-remifentanil or sevoflurane for children undergoing magnetic resonance imaging? A randomised study.

BACKGROUND: Magnetic resonance imaging (MRI) of children is generally performed under sedation or with general anaesthesia (GA), but the ideal regimen has not been found. The aim of this study was to see if propofol-remifentanil would be a suitable alternative for the maintenance of anaesthesia in this category of patients. PATIENTS AND METHODS: Children aged 1-10 years, American Society of Anesthesiologists physical status 1-2 were included. After induction with thiopental or sevoflurane, the children were randomised to maintenance of anaesthesia with an infusion of propofol and remifentanil (group PR) (56 µg/kg/min of propofol and 0.06 µg/kg/min of remifentanil) or with sevoflurane 1.3 MAC (group S). A binasal catheter was placed in group PR and a laryngeal mask airway in group S. The children breathed spontaneously. The Paediatric Anaesthesia Emergence Delirium (PAED) score (primary end point), the number of movements during MRI, and the length of stay in the recovery room (secondary endpoints) were recorded. RESULTS: Sixty children were included in each group. A lower level of emergence delirium (measured as a lower PAED score) was found in group PR compared with group S, and the children in group PR were discharged earlier from the recovery room than the children in group S. However, 15 children in group PR vs. 0 in group S moved during the scan (P < 0.001). CONCLUSION: The PR infusion ensured a satisfactory stay in the recovery room, but additional boluses were necessary during the MRI. Sevoflurane was reliable during the MRI, but emergence delirium was a concern.

Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically heterozygous for the usual and atypical plasma cholinesterase variants (UA).

BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase (pChe). The purpose of this study was to evaluate the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium in patients phenotypically heterozygous for the usual and the atypical pChe variant (UA). METHODS: Thirty-two patients were included in a dose-response study, in which the patients received one of four doses of mivacurium. An additional bolus dose of mivacurium, to a total of 0.1 mg kg-1, was given followed by a continuous infusion adjusted to maintain 91-99% neuromuscular block. The times to different levels of recovery following the infusion were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Twelve of the patients with an estimated duration of anaesthesia of more than 90 min were (randomly) selected for the pharmacokinetic part of the study. Venous samples were taken for determination of the three isomers of mivacurium. These results were compared with results from a previous study in phenotypically normal patients (UU). RESULTS: The estimated ED50 and ED95 were 24 and 69 microg kg-1, respectively. The median (range) infusion rate was 3.7 microg kg-1 min-1 (1.2-2.9) and the time to a TOF ratio of 0.7 was 29.8 min (16.1-44.8). The median clearances of the cis-cis, cis-trans and trans-trans isomers were 3.7, 29 and 28 ml kg-1 min-1, respectively. The elimination half-lives of the isomers were 45, 6.7 and 6.3 min, respectively. CONCLUSION: In patients heterozygous for the usual and the atypical variant (UA), the potency of mivacurium is higher, the infusion requirements lower and the rate of spontaneous recovery prolonged, compared with phenotypically normal patients. The clearances of the active isomers are significantly lower and the elimination half-lives longer in heterozygous patients than in phenotypically normal patients (UU). The pharmacokinetics of the inactive cis-cis isomer was not affected.

Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly patients.

BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase, and is therefore less dependent on liver metabolism and renal elimination than other neuromuscular blocking drugs. This might favor the use of mivacurium in elderly patients. The purpose of this study was to compare the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium and their metabolites in young adult and elderly patients. METHODS: Sixty-four patients were included in a dose-response study, in which 32 young adults and 32 elderly patients received one of four doses of mivacurium. An additional bolus dose of mivacurium to a total of 0.1 mg/kg was given followed by a continuous infusion adjusted to maintain a 91-99% neuromuscular block. The times to maximum block and different levels of recovery were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Thirty-two patients were randomly selected for the pharmacokinetic study. Venous samples were taken for determination of the three mivacurium isomers and the metabolites. RESULTS: The estimated ED95 were 0.053 and 0.061 mg/kg in young adults and elderly patients, respectively (NS). The median infusion rate did not differ, but duration to a TOF ratio of 0.7 was significantly longer in elderly patients than in young adult patients (21.0 vs. 16.5 min). No statistically significant difference between the age groups in clearance and elimination half-life of the isomers was seen. The half-lives of the metabolites were significantly prolonged in the elderly patients. CONCLUSION: There were no significant differences in the potency or infusion requirements between the adult and elderly patients, but the rate of recovery was significantly, though only moderately prolonged, in the elderly patients. No significant difference in clearance was seen but the elimination half-lives of the metabolites was longer in the elderly patients.

The influence of drug-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.

BACKGROUND: The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium. METHODS: Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography. RESULTS: Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol. CONCLUSION: A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.

[Infusion of mivacurium and atracurium guided by manual tactile evaluation]. / Infusion af mivacurium og atracurium styret ved hjaelp af manuel vurdering.

INTRODUCTION: The aim of this investigation was to compare the use of a continuous infusion of mivacurium or atracurium guided by tactile evaluation of the neuromuscular block. MATERIALS AND METHODS: Forty-five patients were randomly allocated to three groups of patients. Group M and MN received a bolus dose of mivacurium 0.15 mg/kg followed by a continuous infusion and group AN a bolus dose of atracurium 0.4 mg/kg followed by an infusion. RESULTS: The neuromuscular blockade recovered spontaneously in group M and was antagonised in group MN and AN. The level of block was quantified by tactile evaluation. The time to full recovery was significantly shorter in patients receiving mivacurium compared to patients given atracurium, 14.5, 12.0 and 18.0 min, respectively. Further, reversal with neostigmine significantly enhanced recovery following mivacurium. CONCLUSION: A continuous infusion of mivacurium and atracurium can easily be performed, guided by tactile evaluation of the neuromuscular block and the effect can be reversed by neostigmine.

Clinical importance of plasma cholinesterase for the anaesthetist.

Plasma cholinesterase is a glycoprotein synthesized in the liver and is found in plasma, liver, intestinal mucosa and other tissues. Six percent to 7% of patients in most surgical populations have an abnormal plasma cholinesterase activity and about 65% of all cases of prolonged neuromuscular blockade following succinylcholine are due to genetic factors. This review focuses on the causes and clinical significance of plasma cholinesterase for the hydrolyses of succinylcholine. Diagnosis and treatment of prolonged response to succinylcholine in phenotypically normal patients, heterozygous abnormal patients and patients homozygous for the atypical gene is mentioned. Also presented is the relationship between plasma cholinesterase and the new relaxant mivacurium, and bambuterol, a prodrug to terbutaline. Additionally, the recent developments in the identification of the plasma cholinesterase genotypes are presented.

[Anesthesia and porphyria]. / Anaestesi og porfyri.

The porphyrias are a group of disorders of haem metabolism. A knowledge of which anaesthetic can precipitate an acute attack of porphyria is important, since an accumulation of metabolites can result in life threatening symptoms, such as abdominal pain, vomiting, photophobia, neuropathy, bulbar paresis and respiratory failure. Treatment consists primarily of adequate calorie intake e.g. glucose, but is otherwise symptomatic. Anaesthetic drug recommendations are based both on animal experiments and patient experience, primarily case histories. An array of local anaesthetics, hypnotics, sedatives, neuroleptics, analgesics, muscle relaxants, inhalation anaesthetics and some antibiotics are reviewed. Patients with a history of porphyria should be in an optimal condition and maintain a high calorie intake perioperatively. The pre-operative fast should be a minimum and iv-glucose is advisable while fasting. There are anaesthetic agents that are safe for both regional and general anaesthesia.