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:10.1097/00000539-199504000-00018

Cited by 67 publications

(30 citation statements)

References 18 publications

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“…Remifentanil was not used in any of these cases. Elimination of vecuronium and rocuronium in cases of hepatic cirrhosis and other severe liver dysfunction is reduced, especially in patients with repeated injections and a long infusion time [38,39,40,41]. Although plasma cholinesterase levels are reduced in pregnancy and hepatic disease and there have been reports of prolonged neuromuscular blockade after a second dose in cases of AFLP, succinylcholine is still recommended as the muscle relaxant for rapid-sequence induction [42].…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of Acute Fatty Liver of Pregnancy: Twenty-Eight Cases and Discussion of Anesthesia

Zhou

Zhang

2013

Gynecol Obstet Invest

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Aims: To summarize the clinical features, perioperative management and maternal and neonatal outcomes of patients with acute fatty liver of pregnancy (AFLP) and to discuss the management of anesthesia in these patients. Methods: This study was a retrospective review over a period of 5 years and 9 months; 28 cases from the Shanghai Public Health Clinical Center were included. Records were reviewed for symptoms, signs, laboratory findings, clinical courses, perioperative management and maternal and neonatal outcomes. Results: Of the AFLP cases analyzed in the present study, 75.0% occurred in primipara and 63.3% occurred with male fetuses. Prodromic symptoms included the sudden onset of fatigue, nausea, vomiting, anorexia and jaundice. Laboratory results indicated liver function abnormalities, coagulopathy, hypoglycemia, leukocytosis and negative urine bilirubin. There were 2 maternal deaths (7.1%) without fetal deaths. Cesarean sections were performed in 16 cases under neuraxial anesthesia and in 12 cases under general anesthesia with rapid-sequence induction. Conclusion: Early diagnosis, prompt delivery and intensive supportive treatment are critical for improving the prognosis of AFLP. Anesthesia selection should be individualized and general anesthesia with rapid-sequence induction may be the best choice for patients with severe coagulopathy.

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Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of Acute Fatty Liver of Pregnancy: Twenty-Eight Cases and Discussion of Anesthesia

Zhou

Zhang

2013

Gynecol Obstet Invest

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“…The latter finding may depend on an increased V dss of ropivacaine. The V dss of other drugs, such as rocuronium 79 and propofol, 80 is also increased in patients with hepatic dysfunction. When repeated doses 25 or continuous infusions are used, the accumulation of both bupivacaine and ropivacaine and of their metabolites needs to be considered, and doses should be reduced accordingly.…”

Section: Patient-related Factors To Be Considered When Large Doses Ofmentioning

confidence: 99%

Maximum recommended doses of local anesthetics: A multifactorial concept

Rosenberg

Veering

Urmey

2004

Regional Anesthesia and Pain Medicine

297

265

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The current recommendations regarding maximum doses of local anesthetics presented in textbooks, or by the responsible pharmaceutical companies, are not evidence based (ie, determined by randomized and controlled studies). Rather, decisions on recommending certain maximum local anesthetic doses have been made in part by extrapolations from animal experiments, clinical experiences from the use of various doses and measurement of blood concentrations, case reports of local anesthetic toxicity, and pharmacokinetic results. The common occurrence of central nervous system toxicity symptoms when large lidocaine doses were used in infiltration anesthesia led to the recommendation of just 200 mg as the maximum dose, which has remained unchanged for more than 50 years. In most cases, there is no scientific justification for presenting exact milligram doses or mg/kg doses as maximum dose recommendations. Instead, only clinically adequate and safe doses (ranges) that are block specific are justified, taking into consideration the site of local anesthetic injection and patient-related factors such as age, organ dysfunctions, and pregnancy, which may influence the effect and the pharmacokinetics of the local anesthetic. Epinephrine in concentrations of 2.5 to 5 microg/mL should be added to the local anesthetic solution when large doses are administered, providing there are no contraindications for the use of epinephrine. As a rule, conditions (eg, end-stage pregnancy, high age in epidural, or spinal block) or diseases (uremia) that may increase the rate of the initial uptake of the local anesthetic are indications to reduce the dose in comparison to one normally used for young, healthy, and nonpregnant adults. On the other hand, the reduced clearance of local anesthetics associated with renal, hepatic, and cardiac diseases is the most important reason to reduce the dose for repeated or continuous administration. The magnitude of the reduction should be related to the expected influence of the pharmacodynamic or pharmacokinetic change.

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“…The authors concluded that, as the drug is thought to be eliminated mainly by biliary excretion, biliary excretion of the drug is perhaps preserved in cirrhosis. [73] Nevertheless, a study of long term bismuth administration to cirrhotic rats found substantial plasma and tissue accumulation of bismuth over a 70-day period, due to reduced biliary and renal eliminationP4] The authors concluded that patients with cirrhosis may therefore be at risk of a similar accumulation of bismuth and of other metals sharing common mechanisms of disposition.…”

Section: Biliary Excretionmentioning

confidence: 99%

Clinical Pharmacokinetic and Pharmacodynamic Considerations in Patients with Liver Disease

Morgan

McLean

1995

Clinical Pharmacokinetics

193

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The effects of liver disease on pharmacokinetics and pharmacodynamics are highly variable, and difficult to predict as the mechanisms of these effects are not well understood. Since the majority of the published literature is concerned with cirrhotic liver disease, this review also focuses mainly on this area. Four different theories have been proposed to account for the effects of chronic liver disease with cirrhosis on hepatic drug elimination: the sick cell theory; the intact hepatocyte theory; the impaired drug uptake theory; and the oxygen limitation theory. While some data in support of each of the first 2 theories have been published recently, a large amount of clinical data would appear to refute both of these theories. These clinical data are substantially consistent with the latter 2 theories, which regard the decreased permeability of the capillarised sinusoid as the critical feature in cirrhosis. Further work is required to determine the applicability of each of these theories. In cirrhosis, drug glucuronidation is spared relative to oxidative drug metabolism; however, in advanced cirrhosis this pathway may also be impaired substantially. There is evidence that in cirrhosis other conjugation pathways may also be impaired to variable degrees. Growing evidence suggests that biliary drug excretion is impaired in cirrhosis. Recent studies with several racemic drugs indicate that the disease can have different effects on the hepatic elimination of individual enantiomers, which may lead to a change in the concentration-response relationships of racemic drugs in cirrhosis. A major finding which has emerged in recent years is that, even with moderate degrees of hepatic impairment, there is a decrease in clearance of drugs or active metabolites normally cleared by the kidney. The effect on renal clearance of unbound drug may be masked if there is a concomitant decrease in plasma protein binding of the drug. Neither serum creatinine levels nor creatinine clearance are useful markers of the renal dysfunction associated with cirrhosis. Both may greatly overestimate renal function in patients with cirrhosis due to increased fractional renal tubular secretion of creatinine. Altered receptor sensitivity has been observed with some drugs in cirrhosis, while for other drugs there is no change in pharmacodynamics. Precise determination of drug dosage in cirrhosis requires information on changes in pharmacodynamics and plasma protein binding in addition to changes in drug elimination. Pharmacokinetic investigations in a variety of chronic liver diseases without cirrhosis (e.g. carcinoma, schistosomiasis and viral hepatitis) suggest that in the absence of cirrhosis, impairment of drug elimination is not sufficient to warrant reduction of drug dosage. However, if cirrhosis is present, 'safe' drug use requires an awareness of the possibility of multiple interactions between changes in hepatic and renal disposition and pharmacodynamics. In chronic liver disease with cirrhosis, dosage reduction is the general rule regardless...

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

Cited by 67 publications

References 18 publications

Retrospective Analysis of Acute Fatty Liver of Pregnancy: Twenty-Eight Cases and Discussion of Anesthesia

Retrospective Analysis of Acute Fatty Liver of Pregnancy: Twenty-Eight Cases and Discussion of Anesthesia

Maximum recommended doses of local anesthetics: A multifactorial concept

Clinical Pharmacokinetic and Pharmacodynamic Considerations in Patients with Liver Disease

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