Plasma Concentrations of Laudanosine, but Not of Atracurium, Are Increased during the Anhepatic Phase of Orthotopic Liver Transplantation in Pigs

Pittet, Jean–François; Tassonyi, E.; Schopfer, C.; Morel, Denis R.; Mentha, Gilles; Fathi, Marc; Coultre, C. Le; Steinig, D.A.; Benakis, A.

doi:10.1097/00000542-199001000-00024

Cited by 27 publications

(9 citation statements)

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“…This was confirmed by the study of Foldes and Deery (10) in which the plasma protein binding of atracurium was reported to be about 80%. The finding of a previous study (6) showed that the potency of atracurium was approximately 7 times lower in pig than in man. For this reason, correspondingly larger doses were administered to pigs in the present study.…”

Section: Discussionmentioning

confidence: 81%

Pharmacokinetics of atracurium besylate in the pig after a single i.v. injection

Schopfer

Pittet

Morel

et al. 1989

Eur. J. Drug Metab. Pharmacokinet.

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A pharmacokinetic study of atracurium besylate was performed in the pig after a single i.v. bolus injection of 2 mg/kg, the dose needed to produce surgical neuromuscular blockade. The plasma concentration values were obtained by high performance liquid chromatography. Using a two-compartment pharmacokinetic model, the elimination half life was found to be 28.6 +/- 6.3 min (mean +/- SEM), the total volume of distribution 341 +/- 56 ml/kg and the plasma clearance 8.7 +/- 1.1 ml/min/kg. Although the doses required to obtain a satisfactory neuromuscular blockade as well as the plasma level, volume of distribution and plasma clearance values were higher in the pig than in man, the distribution and elimination half-lives were similar to those recently reported.

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Section: Discussionmentioning

confidence: 81%

Pharmacokinetics of atracurium besylate in the pig after a single i.v. injection

Schopfer

Pittet

Morel

et al. 1989

Eur. J. Drug Metab. Pharmacokinet.

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“…However, the main metabolite, laudanosine, may accumulate in the presence of hepatic impairment and can produce central nervous system excitation. 19 This has never been described to our knowledge following atracurium for intubation.…”

Section: Discussionmentioning

confidence: 93%

Use of remifentanil in a patient with chronic hepatic failure

Dumont

Picard

Martí

et al. 1998

British Journal of Anaesthesia

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SummaryWe describe a 73-yr-old woman anaesthetized for a laminectomy. She suffered from hepatic failure with mild encephalopathy complicated by several exacerbations associated with sedative and opioid therapy. The challenge for anaesthesia management was to provide adequate analgesia and avoid causing hepatic encephalopathy during and after the surgery. We used remifentanil to provide intraoperative and postoperative analgesia, because it has a short duration of action and does not require hepatic metabolism. We closely monitored the respiratory and the neurological status throughout the administration and conclude that remifentanil can provide perioperative analgesia in patients at risk Remifentanil is licensed in Switzerland for use as an analgesic in the immediate postoperative period, with the supervision of staff trained in the recognition and treatment of the respiratory effects of powerful opioids. Case reportA 73-yr-old woman suffered from a painful arachnoid cyst at the thoracic level, with a Brown-Séquard syndrome. She was being treated with tramadol (Tramal, Grünenthal), morphine (MST Continus, Mundipharma) and ibuprofen (Brufen, Knoll Pharmaceuticals). She had a 10-yr history of hepatitis C complicated by cirrhosis with frequent minor episodes of memory loss, mild confusion and irritability. She had experienced three episodes of severe hepatic encephalopathy in the preceding eight months, associated with administration of sedative or opioid drugs. The first one was precipitated by a minor gastric ulcer haemorrhage and diazepam (Valium, Roche) medication. The two other episodes occurred without gastrointestinal haemorrhage, but in association with morphine or tramadol administration. Each episode resolved satisfactorily with lactulose, a low protein diet and removal of the likely precipitating drugs. The clinical features of these episodes and EEG findings were characteristic of hepatic encephalopathy rather than simple opioid intoxication.In order to alleviate her continuous pain, and reduce the drug treatment, surgical resection of the cyst was planned. The patient did not receive premedication. Anaesthesia was induced with propofol 2 mg kg 91 (Disoprivan, Zeneca), remifentanil 1 g kg 91 (Ultiva, Glaxo Welcome) and intubation was facilitated by atracurium 0.5 mg kg 91 (Tracrium, Glaxo Welcome). Anaesthesia was maintained with 50% nitrous oxide/oxygen, isoflurane 0.5-0.8 MAC (Forene, Abbott) and remifentanil infusion at a rate of 0.25 to 0.5 g kg 91 min 91 . The monitoring included ECG, arterial pressure by the radial artery catheter, pulse oximetry, rectal temperature, and anaesthetic gas and carbon dioxide analysis. One hour before operation the patient received platelet concentrates and fresh frozen plasma to correct the blood coagulation defect. Intraoperatively 2 litres of crystalloid (glucose 5%-NaCl 0.45 %) were administered. After induction of anaesthesia, a decrease in arterial pressure to 85/40 mm Hg necessitated administration of i.v. ephedrine 10 mg to restore the arterial pressure to th...

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“…3 and 4). These metabolic phenomena may be either caused by atracurium itself or by its major metabolite laudanosine the clearance of which is known to depend on liver function (Canfell et al 1986;Pittet et al 1990).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Hepatic Microsomal Drug Metabolism by Atracurium Administration in the Rat

Böhrer

Schmidt

Bach

et al. 1993

Pharmacology & Toxicology

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The muscle relaxant atracurium is known to undergo extrahepatic degradation via Hofmann elimination and ester hydrolysis. The purpose of the present study was to evaluate the effects of atracurium on hepatic P450-dependent enzyme activities. Thirty-two male Sprague-Dawley rats were anaesthetized, mechanically ventilated, and randomly allocated to one of four study groups: group 1 received saline, group 2 atracurium, group 3 vecuronium, and group 4 pancuronium intravenously for a period of 3 hr. Equipotent doses of the muscle relaxants were applied; the doses had been obtained in a pilot study using evoked electromyography. At the end of the study period, the livers were removed and analyzed. All three muscle relaxants may lead to inhibition of hepatic drug metabolism. Atracurium influences hepatic P450, although it is predominantly degraded in extrahepatic tissues. Further studies are needed to evaluate the contribution of the major metabolite laudanosine to this inhibitory action.

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Plasma Concentrations of Laudanosine, but Not of Atracurium, Are Increased during the Anhepatic Phase of Orthotopic Liver Transplantation in Pigs

Cited by 27 publications

References 0 publications

Pharmacokinetics of atracurium besylate in the pig after a single i.v. injection

Pharmacokinetics of atracurium besylate in the pig after a single i.v. injection

Use of remifentanil in a patient with chronic hepatic failure

Inhibition of Hepatic Microsomal Drug Metabolism by Atracurium Administration in the Rat

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