rocuronium and Liver-Diseases

Neuromuscular blocking agents have always shown wide inter-individual variability when it comes to their duration of action. This prevents clinicians from anticipating the evolution of the neuromuscular block for any given patient. With this study, we aimed to assess the nature of the relationships existing between different time course parameters used to describe paralysis onset and offset.. Sixty American Society of Anesthesiologists (ASA) score III-IV anaesthetised patients were randomised to receive a single equipotent dose (2ED95) of either rocuronium, mivacurium or atracurium. We used acceleromyography to monitor neuromuscular transmission. We described the relationships between the time-interval measurements of: onset, the first response (T1) reappearance, T1 25% of control, train-of-four ratio 0.25 and 0.75. Pearson correlation coefficients were calculated.. We found no significant relationships between onset and any of the four parameters used to describe the offset. On the other hand, we showed strong and highly significant linear relationships between all the parameters describing the offset for each of the muscle relaxants studied (correlation coefficients ranging from 0.850 to 0.992).. We evidenced strong linear correlations between the four offset time course parameters of spontaneous recovery after a single neuromuscular blocking agents (NMBAs) bolus. Such relationships open up new clinical perspectives concerning quantitative neuromuscular transmission monitoring: the scope of individual valuable anticipation of the patient's recovery.

Topics: Aged; Aged, 80 and over; Androstanols; Anesthesia Recovery Period; Anesthesia, General; Atracurium; Calibration; Coronary Artery Bypass; Electromyography; Female; Humans; Isoquinolines; Kidney Diseases; Liver Diseases; Male; Middle Aged; Mivacurium; Monitoring, Intraoperative; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Time Factors; Treatment Outcome

A prospective controlled study was designed to observe the pharmacodynamics of rocuronium in cholestatic patients with or without hepatocellular injury.. Sixty patients undergoing abdominal surgery were allocated into three groups: group I had 20 cholestatic patients with hepatocellular injury; group II had 20 cholestatic patients without hepatocellular injury, and group III (control group) had 20 patients without hepatic disease. Anesthetized with propofol and fentanyl, all patients received rocuronium 0.6 mg/kg for initial dose followed by intermittent repeated administration of rocuronium 0.15 mg/kg. The twitch high of adductor pollicis muscle was monitored by acceleromyography. The onset time of the initial dose, the duration time of the initial and the repeated doses, and the recovery index were observed.. The onset and the duration time of the initial dose had no significant difference among the three groups (P<0.05). After administration of the 5th dose, the duration time of the repeated doses was significantly prolonged than that of the 2nd dose in group I (31+/-8 versus 22+/-4 min) and group II (28+/-5 versus 21+/-4 min) (P<0.05), but not in group III (P>0.05). The recovery index of rocuronium was longer in group I (48+/-13 min) and group II (46+/-9 min) than that in group III (24+/-5 min) (P<0.05).. Cholestatic patients experience prolonged duration time and longer recovery index after repeated use of rocuronium, despite normal onset time after the initial dose.

Topics: Adult; Androstanols; Cholestasis; Drug Administration Schedule; Electromyography; Female; Humans; Liver; Liver Diseases; Male; Middle Aged; Muscle, Skeletal; Neuromuscular Nondepolarizing Agents; Prospective Studies; Rocuronium; Time Factors

To develop a rapid online test of graft liver function during liver transplantation.. Prospective, observational study.. University hospital transplant unit.. 17 adult patients with end-stage liver disease who underwent liver transplantation surgery.. Rocuronium infusion dose requirements and plasma concentrations to maintain constant levels of neuromuscular paralysis during three phases of liver transplantation and their relationship with early postoperative liver function tests were studied.. Infusion dose requirements of rocuronium, assay of rocuronium plasma concentrations using gas chromatography-mass spectrometry, and intensity of neuromuscular blockade were measured.. A 24% decrease in rocuronium infusion requirements was observed during the an-hepatic phase. Rocuronium requirement during the neohepatic phase was increased only modestly or remained unchanged in 14 of the 16 patients who had normal graft function in the immediate postoperative period. Rocuronium plasma concentrations for maintaining constant levels of paralysis were significantly lower during the neohepatic phase than during the paleohepatic and anhepatic phases, indicating that there is likely to be a change in pharmacodynamics during this phase. Significant reduction in rocuronium infusion requirements during the neohepatic phase was observed in the only patient who had poor graft function in the early postoperative stage, suggesting that the reduced infusion requirement to maintain a constant neuromuscular paralysis may be related to the functional state of the graft liver after reperfusion.. A significant reduction in rocuronium infusion requirement during the neohepatic phase may be suggestive of impaired organ function after reperfusion of the graft liver. Rocuronium may serve as a potential online indicator of graft liver function during liver transplantation by measurement of its infusion requirements during transplantation.

Topics: Adolescent; Adult; Analysis of Variance; Androstanols; Dose-Response Relationship, Drug; Female; Gas Chromatography-Mass Spectrometry; Humans; Infusions, Intravenous; Liver Diseases; Liver Function Tests; Liver Transplantation; Male; Middle Aged; Monitoring, Intraoperative; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Postoperative Period; Prospective Studies; Rocuronium

Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The authors determined the pharmacokinetics of rocuronium during liver transplantation and examined whether variability in pharmacokinetics could explain variability in recovery of neuromuscular function.. Twenty patients undergoing liver transplantation were given rocuronium, 600 microg/kg, after induction of anesthesia and again after perfusion of the transplanted liver. Plasma was sampled to determine rocuronium concentrations. Pharmacokinetic models were fit to rocuronium concentrations versus time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to account for changes in hepatic function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four twitches of the orbicularis oculi was determined.. During the paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml x kg(-1) x min(-1) and was not influenced by the magnitude of preexisting liver disease (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase [ALT], and aspartate transaminase [AST]). During the neohepatic period, the typical value of Cl varied as a function of the duration of warm ischemia of the hepatic allograft and was 2.72 ml x kg(-1) x min(-1) for a patient with an average 60-min period of warm ischemia; time to neuromuscular recovery varied as a function of Cl.. Despite prolonged hypothermic ischemia, the newly transplanted liver eliminates rocuronium as well as the diseased native liver (and comparably with historical control values). However, some patients had decreased rocuronium Cl during the neohepatic period, apparently a result of prolonged graft warm ischemia. The authors' finding of preservation of hepatic drug elimination in the hepatic allograft is consistent with limited data for other drugs evaluated during anesthesia.

Topics: Adult; Aged; Androstanols; Anesthesia, General; Female; Humans; Liver; Liver Diseases; Liver Transplantation; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Perfusion; Rocuronium; Time Factors

Sugammadex rapidly reverses neuromuscular blockade (NMB) induced by rocuronium. NMB induced by rocuronium is prolonged in patients with liver dysfunction, because the drug is mainly excreted into the bile. However, the efficacy and safety of sugammadex in terms of reversing rocuronium-induced NMB in patients with liver dysfunction undergoing hepatic surgery have not been evaluated. This observational study investigated the efficacy and safety of sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery.. Remifentanil/propofol anesthesia was administered to 31 patients: 15 patients in the control group, and 16 patients from a group with liver dysfunction. Rocuronium (0.6 mg/kg) was administered, followed by continuous infusion. The enrolled patients were then subdivided into two groups according to the dose of sugammadex. In the first group a single dose of sugammadex (2.0 mg/kg) was given at the reappearance of the second twitch (T2). In the second group a single dose of sugammadex (4.0 mg/kg) was given at the first twitch response if T2 did not reappear in 15 minutes after stopping rocuronium. The primary outcome was time from administration of sugammadex to recovery of a train-of-four ratio to 0.9.. The dose of rocuronium required in the liver dysfunction group was lower than that in the control group (6.2 vs. 8.2 μg/kg/min, p = 0.002). The mean time from the administration of sugammadex to recovery of the train-of-four ratio to 0.9 was not significantly different between the liver dysfunction group and the control group (2.2 minutes vs. 2.0 minutes in the 2 mg/kg administration group, p = 0.44 and 1.9 minutes vs. 1.7 minutes in the 4 mg/kg administration group, p = 0.70, respectively). No evidence of recurarization was observed in any of the patients. Most of the adverse events were found to be mild and such events were not related to the use of sugammadex. None of the patients was eliminated from the study because of an adverse event. One patient died due to cholestatic liver cirrhosis because of repeated hepatic surgery.. Sugammadex can rapidly reverse NMB after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Sugammadex was found to be safe and well tolerated. However, further studies of sugammadex under similar conditions should be conducted involving a large number of patients with liver dysfunction undergoing hepatic surgery.

Topics: Aged; Androstanols; Female; gamma-Cyclodextrins; Humans; Liver; Liver Diseases; Male; Middle Aged; Neuromuscular Blocking Agents; Rocuronium; Sugammadex

Topics: Adult; Androstanols; Anesthesia Recovery Period; Budd-Chiari Syndrome; Female; gamma-Cyclodextrins; Hepatitis C; Humans; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Male; Middle Aged; Monitoring, Intraoperative; Neuromuscular Nondepolarizing Agents; Portasystemic Shunt, Transjugular Intrahepatic; Rocuronium; Sugammadex

We examine two cases of prolonged neuromuscular blockade (NMB) after cardiac surgery. To the best of our knowledge, these are the first reported cases of complete paralysis lasting more than ten hours after surgery.. We attribute the extended durations of NMB (more than ten hours) to high doses of NMB drugs in combination with magnesium sulphate and moderate renal failure. Advanced age, hepatic disease, aminoglycoside exposure, hypocalcemia, and possible interaction between rocuronium and pancuronium may have played minor roles.. We should avoid administering large doses of NMB agents, even in the context of planned postoperative ventilation. If NMB is not monitored intraoperatively in patients who are at risk of prolonged NMB, then train-of-four response should be measured in the intensive care unit. Adequate sedation should be provided until proper recovery of neuromuscular function is documented.

Topics: Acute Kidney Injury; Aged; Aminoglycosides; Androstanols; Anesthesia Recovery Period; Aorta; Aortic Valve; Cardiac Surgical Procedures; Coronary Artery Bypass; Drug Interactions; Female; Heart Valve Prosthesis Implantation; Humans; Hypocalcemia; Liver Diseases; Magnesium Sulfate; Mitral Valve; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Pancuronium; Paralysis; Rocuronium

Neuromuscular blocking drugs can be divided into those that are: (i) excreted entirely by the kidney; (ii) predominantly by the kidney but also by the liver; (iii) mainly by the liver but also by the kidney or; (iv) removed by other metabolic pathways. Rocuronium is mainly excreted by the liver and pharmacokinetic and pharmacodynamic studies in humans suggest that its duration of action may be prolonged to a greater extent in patients with hepatic disease than in patients with renal disease. The effect is likely to be modest and not a contra-indication to its use.

Topics: Androstanols; Animals; Humans; Kidney; Liver; Liver Diseases; Neuromuscular Nondepolarizing Agents; Renal Insufficiency; Rocuronium