The Pharmacokinetics and Neuromuscular Effects of Rocuronium Bromide in Patients with Liver Disease

Magorian, Toni; Wood, Paul; Caldwell, James E.; Fisher, Dennis M.; Segredo, Veronica; Szenohradszky, János; Sharma, Manohar; Gruenke, Larry D.; Miller, Ronald D.

doi:10.1213/00000539-199504000-00018

Cited by 16 publications

(19 citation statements)

References 18 publications

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“…Fisher et al showed that the clearance of rocuronium changed insignificantly during the paleohepatic and the anhepatic stages in patients undergoing liver transplantation (6). Studies comparing rocuronium with vecuronium showed that 2 agents are affected differently in liver disease (9,10). The less potent rocuronium was more dependent on redistribution than on metabolism for termination of action, and it was concluded that the liver does not play a dominant role in the termination of action of rocuronium.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Analysis of Rapacuronium and Its Metabolite During Liver Transplantation: An Assessment of Its Potential as a Pharmacodynamic Probe

Black

Gertler²,

Wright³

et al. 2003

Baylor University Medical Center Proceedings

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The liver extracts aminosteroidal neuromuscular blocking drugs. We hypothesized that the duration of action of these drugs might provide a pharmacodynamic probe for assessing graft function during orthotopic liver transplantation. The pharmacokinetics of rapacuronium and its active metabolite, ORG 9488, were prospectively studied in 11 patients. Rapacuronium (1.5 mg/kg) was administered at induction of anesthesia, 2 minutes after clamping the portal vein, and 5 minutes after reperfusion of the new graft. Blood samples were drawn at intervals, and an independent laboratory analyzed plasma for both rapacuronium and ORG 9488. Rapacuronium's pharmacokinetics were characterized for 3 stages of the transplant using NONMEM software to construct mixed-effects compartmental models. Rapacuronium plasma clearance during the first stage of orthotopic liver transplantation was 7.25 mL/kg/min. Clearance decreased by only 44% during the anhepatic stage, to 3.91 mL/kg/min, and remained decreased after reperfusion. This effect suggests that an alternate clearance pathway exists. The clearance for ORG 9488 was 13.5 mL/kg/min during the paleohepatic and anhepatic stages, but it decreased 83% on reperfusion, suggesting accumulation after reperfusion. This pharmacokinetic analysis suggests that rapacuronium may not be suitable for use as a pharmacodynamic probe.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Analysis of Rapacuronium and Its Metabolite During Liver Transplantation: An Assessment of Its Potential as a Pharmacodynamic Probe

Black

Gertler²,

Wright³

et al. 2003

Baylor University Medical Center Proceedings

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show abstract

“…Of the vecuronium excreted in bile, 50% was present as the 3-hydroxy metabolite in animals 66 . Hepatic elimination of rocuronium is reported to account for 80% of the injected dose 67 . Little if any metabolism of rocuronium apparently takes place and no metabolites were detected in liver, plasma, or urine.…”

Section: Nondepolarizing Neuromuscular Blocking Agentsmentioning

confidence: 99%

Potential Use of Pharmacological Markers to Quantitatively Assess Liver Function during Liver Transplantation Surgery

Gao

Ramzan

2000

Anaesth Intensive Care

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Early functioning of the transplanted liver is of crucial importance to the recipient. This function may be assessed by measuring the disposition of substances that are mainly eliminated via the liver. None of the agents currently used is ideal for this purpose. Measurement of mono-ethyleneglycinexylidide (MEGX) formation from lignocaine is useful and has been widely used in liver transplantation to assess liver graft function. MEGX formation can be affected by the use of drugs that influence liver perfusion or interfere with the CYP450 enzyme system. Indocyanine green clearance is a convenient method but both blood flow and hepatocellular function affect the test results. Tests of caffeine clearance, galactose elimination capacity and antipyrine clearance all require time-consuming, technically cumbersome and expensive serial blood sampling. The aminopyrine breath test is non-invasive, but gastric emptying and the patient's physical state affect results. The potential hazard of exposure to radioactive compounds limits the wide clinical use of both aminopyrine and erythromycin breath tests. Monitoring the rate of recovery from neuromuscular blockade induced by vecuronium and rocuronium can provide valuable information on liver function.

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“…The average plasma concentration measured at the first onset of steady state was 1.4 ± 0.4 μg/ml (95% CI 0.30-1.61), in accordance with the predicted values calculated using the Wierda model, which were measured under anesthesia with halothane and nitrous * Yutaka Oda yutakaodayutaka@gmail.com 1 Department of Anesthesiology, Osaka City Juso Hospital, 2-12-27, Nonaka-kita, Yodogawa-ku, Osaka 533-0034, Japan models. They found three-to four-fold inter-individual differences in the measured plasma concentration of rocuronium, and the Magorian model [10] could predict plasma concentration with acceptable values for both median PE and median absolute PE. Each of these reports could contribute to improve the quality of clinical practice by providing additional knowledge.…”

mentioning

confidence: 99%

“…Several pharmacokinetic models of rocuronium have been developed based on its plasma levels measured after bolus administration [5,[7][8][9][10]. Despite the smaller volume of distribution and shorter half-life compared with vecuronium [11], its applicability to continuous infusion is not clear.…”

mentioning

confidence: 99%

Rocuronium bromide: clinical application of single-dose pharmacokinetic models to continuous infusion

Oda¹

2017

J Anesth

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The Pharmacokinetics and Neuromuscular Effects of Rocuronium Bromide in Patients with Liver Disease

Cited by 16 publications

References 18 publications

Pharmacokinetic Analysis of Rapacuronium and Its Metabolite During Liver Transplantation: An Assessment of Its Potential as a Pharmacodynamic Probe

Pharmacokinetic Analysis of Rapacuronium and Its Metabolite During Liver Transplantation: An Assessment of Its Potential as a Pharmacodynamic Probe

Potential Use of Pharmacological Markers to Quantitatively Assess Liver Function during Liver Transplantation Surgery

Rocuronium bromide: clinical application of single-dose pharmacokinetic models to continuous infusion

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