rocuronium and Renal-Insufficiency

How to titrate rocuronium under the specific conditions such as hepatic/renal failure, hypothermia, acidosis, and baby/aged, obese, with antibiotics, type of anesthetics, operation site and continuous infusion was discussed.

Topics: Acidosis; Age Factors; Androstanols; Anesthetics; Anti-Bacterial Agents; Drug Interactions; Humans; Hypothermia; Liver Failure; Neuromuscular Nondepolarizing Agents; Obesity; Renal Insufficiency; Rocuronium; Time Factors

Topics: Androstanols; Cardiovascular System; Humans; Nerve Block; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Renal Insufficiency; Rocuronium; Time Factors

Mivacurium is a short-acting nondepolarising muscle relaxant of the benzylisoquinoline type undergoing rapid breakdown by plasma cholinesterase. With 2.5 fold ED95, tracheal intubation can be accomplished within 2-3 min following injection. The ensuing DUR 25% (i.e. time from injection to 25% recovery of control twitch tension) is three times as long as with succinylcholine and about half as long as with equipotent doses of atracurium and vecuronium. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to a moderate histamine release following doses of 3-4 times the ED95. In patients with end stage liver or renal disease as well as in patients with atypical plasma cholinesterase the duration of action of mivacurium is prolonged. Rocuronium is a steroidal non-depolarising neuromuscular blocking agent chemically related to vecuronium. Compared with the latter, rocuronium is less potent, has a shorter onset of action, and no cumulative effects. Adequate intubating conditions are achieved within 60 to 90 s after i.v. injection of twice the ED95. Its elimination from the blood occurs primarily via liver uptake, while renal elimination is about 10 to 30%. Slight vagolytic effects are reported following injection of 0.6 mg/kg rocuronium, while histamine release is unlikely to occur. Atracurium is a mixture of ten stereoisomers. One of them, cis-atracurium, is five times as potent as the chiral mixture while having a similar pharmacodynamic and kinetic profile. It does not cause significant histamine release or clinically relevant cardiovascular effects at doses up to 8 times the ED95. Laudanosine release seems to be less with cis-atracurium than with atracurium.

Topics: Androstanols; Anesthesia, Endotracheal; Anesthesia, General; Atracurium; Biotransformation; Dose-Response Relationship, Drug; Humans; Isoquinolines; Liver Failure; Metabolic Clearance Rate; Mivacurium; Neuromuscular Nondepolarizing Agents; Preanesthetic Medication; Renal Insufficiency; Rocuronium

A new aminosteroidal neuromuscular blocking agent, rocuronium bromide, has recently been introduced into clinical practice. Its main advantage over other currently used drugs of this kind is its fast onset of action, which could render rocuronium the muscle relaxant of choice for rapid facilitation of tracheal intubation. A further advantage of the new compound over vecuronium bromide is the less extensive formation of breakdown products, reducing the contribution of active metabolites to the neuromuscular blocking effects of the parent compound. Thorough knowledge of the pharmacokinetics of any new drug is highly desirable for the anaesthesiologist because absorption, distribution to the tissue, as well as elimination by biotransformation and excretion, are closely related to its effects. Due to its chemical relationship to other aminosteroidal neuromuscular blocking agents such as pancuronium bromide or vecuronium, rocuronium is expected to display pharmacokinetic behaviour similar to that of its predecessors. Hepatic and renal disease may prolong the effect of rocuronium, but to a lesser extent than seen with pancuronium or vecuronium, because the plasma clearance of rocuronium is not significantly influenced by dysfunction of the liver or kidneys. On the contrary, in elderly or hypothermic patients the reduction in plasma clearance results in a prolonged duration of the action of rocuronium. All information on the pharmacokinetics of this new nondepolarising neuromuscular blocking agent which has been made available to date is presented in this review, with a discussion of the significance of these data for clinical use of the drug.

Topics: Adult; Aged; Androstanols; Child; Child, Preschool; Critical Care; Female; Humans; Hypothermia; Infant; Liver Cirrhosis; Neuromuscular Nondepolarizing Agents; Pregnancy; Renal Insufficiency; Rocuronium

This study clarifies the relationship between the neuromuscular blocking effects of rocuronium 0.6 mg kg(-1) and its pharmacokinetics in patients with renal failure.. Seventeen healthy patients and 17 patients with renal failure were studied under propofol anaesthesia in this prospective open label study. Rocuronium 0.6 mg kg(-1) was given after induction of anaesthesia. The train-of-four mechano-myographic response of the thumb to supramaximal stimulation of the ulnar nerve at 2 Hz every 12 s was measured. Venous blood samples (4 mL) were obtained at 0, 2, 4, 7, 10, 15, 20, 30, 60, 120, 180, 240 and 360 min after relaxant administration. Samples were centrifuged, separated and stored at -20 degrees C until plasma levels of rocuronium and its metabolites were measured. Two- and three-exponential equations were used to describe the pharmacokinetic data in each group and these were compared to each other using the Wilcoxon signed rank sum test as was the pharmacodynamic data. P < 0.05 was significant.. Onset of block was similar in both groups. Clinical duration and the time to recovery of the train-of-four to 70% were prolonged in the renal failure group compared to control; 49 vs. 32 min (P < 0.004, 95% confidential, interval 17, difference 5-28) and 88 vs. 55 min (P < 0.001, 95% confidential interval 33, difference 17-50), respectively. Clearance of rocuronium was reduced by 39% in the renal failure patients compared to control, with an 84% increase in the mean residence time. The volume of distribution was unaffected by renal failure.. The duration of action of a bolus dose of 0.6 mg kg(-1) rocuronium is increased significantly in patients with end-stage renal failure compared to healthy controls. This increase may be due to a decreased clearance of rocuronium, the disease process causing the renal failure and/or the medication which patients with renal failure need in their treatment.

Topics: Adolescent; Adult; Aged; Androstanols; Biotransformation; Electric Stimulation; Female; Humans; Kidney Function Tests; Male; Middle Aged; Models, Biological; Monitoring, Intraoperative; Nerve Block; Neuromuscular Nondepolarizing Agents; Renal Insufficiency; Rocuronium

This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1)).. Sugammadex 4 mg kg(-1) was administered at 1-2 post-tetanic counts for reversal of rocuronium NMB. Primary efficacy variable was time from sugammadex to recovery to train-of-four (T4/T1) ratio 0.9. Equivalence between groups was demonstrated if two-sided 95% CI for difference in recovery times was within -1 to +1 min interval. Pharmacokinetics of rocuronium and overall safety were assessed.. The intent-to-treat group comprised 67 patients (renal n=35; control n=32). Median (95% CI) time from sugammadex to recovery to T4/T1 ratio 0.9 was 3.1 (2.4-4.6) and 1.9 (1.6-2.8) min for renal patients vs controls. Estimated median (95% CI) difference between groups was 1.3 (0.6-2.4) min; thus equivalence bounds were not met. One control patient experienced acceleromyography-determined NMB recurrence, possibly as a result of premature sugammadex (4 mg kg(-1)) administration, with no clinical evidence of NMB recurrence observed. Rocuronium, encapsulated by Sugammadex, was detectable in plasma at day 7 in 6 patients. Bioanalytical data for sugammadex were collected but could not be used for pharmacokinetics.. Sugammadex 4 mg kg(-1) provided rapid reversal of deep rocuronium-induced NMB in renal and control patients. However, considering the prolonged sugammadex-rocuronium complex exposure in patients with severe renal impairment, current safety experience is insufficient to support recommended use of sugammadex in this population.. NCT00702715.

Topics: Androstanols; Blood Pressure; Female; gamma-Cyclodextrins; Heart Rate; Humans; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Pain; Renal Insufficiency; Rocuronium; Sugammadex; Treatment Outcome

Topics: Androstanols; Female; Humans; Intubation, Intratracheal; Metabolic Clearance Rate; Neuromuscular Nondepolarizing Agents; Renal Insufficiency; 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