rocuronium and Kidney-Failure--Chronic

Topics: Androstanols; gamma-Cyclodextrins; Humans; Kidney Failure, Chronic; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Prospective Studies; Retrospective Studies; Rocuronium; Sugammadex

Sugammadex, a cyclodextrin, is a novel agent designed to encapsulate selectively steroidal neuromuscular blocking agents such as rocuronium and vecuronium as well. One molecule of sugammadex is able to encapsulate only one molecule of muscle relaxant. This original pharmacological property allows a very rapid reversal of muscle paralysis. After sugammadex injection, a train of four ratio higher than 0.9 is obtained in less than 5 minutes in all the patients whatever the degree of muscle paralysis at the time of reversal and even when anesthesia is maintained with halogenated agents. However, in order to preserve this efficacy, the dose of sugammadex needs to be adjusted to the degree of muscle paralysis at the time of reversal : 2 mg/kg after obtaining 2 responses at the adductor pollicis muscle after a train of four stimulation, 4 mg/kg with a post-tetanic count between 1 and 3 responses, and 12 to 16 mg/kg in case of rescue reversal (3 to 15 minutes after 0.6 to 1.2 mg/kg rocuronium). Even if the original property of sugammadex lets us think that per-operative neuromuscular transmission monitoring would not be furthermore useful, the assessment of the exact degree of muscle paralysis before reversal is mandatory for choosing the right dose of sugammadex.

Topics: Algorithms; Androstanols; Anesthesia Recovery Period; Clinical Trials, Phase III as Topic; Contraindications; Electrodiagnosis; gamma-Cyclodextrins; Humans; Kidney Failure, Chronic; Muscle Relaxation; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Postoperative Complications; Randomized Controlled Trials as Topic; Respiratory Paralysis; Rocuronium; Sugammadex; Vecuronium Bromide

Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal failure and healthy controls.. Fifteen ASA class II-III renal patients [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 ASA I-II controls (CL(CR) > or =80 ml min(-1)) were included. After induction of anaesthesia, a single i.v. dose of rocuronium 0.6 mg kg(-1) was given, followed by a single i.v. dose of sugammadex 2.0 mg kg(-1) at reappearance of the second twitch of the train-of-four response. Plasma concentrations of rocuronium and sugammadex were estimated and PK variables determined using non-compartmental analyses. Percentages of sugammadex and rocuronium excreted in the urine were measured.. PK data were obtained from 26 patients. Mean total plasma clearance (CL) of sugammadex was 5.5 ml min(-1) in renal patients and 95.2 ml min(-1) in controls (P<0.05). Rocuronium CL was 41.8 ml min(-1) in renal patients and 167 ml min(-1) in controls (P<0.05). The median amount of sugammadex and rocuronium excreted in the urine over 72 h in renal patients was 29% and 4%, respectively, and 73% and 42% over 24 h in controls.. Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed. The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex. Urinary excretion of both drugs was reduced in renal patients.

Topics: Adult; Aged; Aged, 80 and over; Androstanols; Anesthesia, General; gamma-Cyclodextrins; Humans; Kidney Failure, Chronic; Middle Aged; Neuromuscular Nondepolarizing Agents; Renal Dialysis; Rocuronium; Sugammadex

Sugammadex, a modified gamma-cyclodextrin, is the first selective relaxant binding agent that specifically encapsulates the steroidal neuromuscular blocking agent, rocuronium. The action of rocuronium is prolonged in patients with renal failure. As sugammadex is primarily cleared renally, this phase III trial investigated the efficacy and safety of sugammadex for reversal of rocuronium-induced neuromuscular block (NMB) in patients with end-stage renal failure.. Thirty adult patients were studied: 15 renally impaired [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 controls (CL(CR)>80 ml min(-1)). Anaesthesia was induced and maintained using i.v. opiates and propofol. Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) nerve stimulation. Rocuronium (0.6 mg kg(-1)) was given, followed by a single i.v. dose of sugammadex (2.0 mg kg(-1)) at reappearance of the second twitch of the TOF. The primary efficacy variable was time from administration of sugammadex to recovery of the TOF ratio to 0.9. Safety variables included clinical evidence of reoccurrence of NMB.. After sugammadex administration, the mean (sd) time to recovery of the TOF ratio to 0.9 was 2.0 (0.72) min in renal patients and 1.65 (0.63) min in controls (NS). Recurrence of NMB was not observed in any patient. No sugammadex-related serious adverse events were reported.. Sugammadex administered at reappearance of T(2) rapidly and effectively reverses NMB induced by rocuronium in renal failure and healthy patients. Sugammadex was well tolerated by all patients. Further safety studies on sugammadex in patients with severe renal impairment are warranted.

Topics: Adult; Aged; Aged, 80 and over; Androstanols; Anesthesia Recovery Period; Anesthesia, General; Female; gamma-Cyclodextrins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

We studied the onset and duration of action and pharmacokinetics of rocuronium bromide during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium (0.6 mg kg-1) in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block and duration of clinical relaxation (DUR25) were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min, respectively, for patients with and without renal failure. The time for train-of-four ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) mL kg-1 min-1 and 3.7 (1.4) mL kg-1 min-1, respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) (P < 0.05). The differences in other kinetic parameters were not significant.

Topics: Androstanols; Anesthesia; Chromatography, High Pressure Liquid; Humans; Kidney Failure, Chronic; Muscle Relaxation; Neuromuscular Nondepolarizing Agents; Rocuronium

Topics: Cohort Studies; Humans; Kidney Failure, Chronic; Rocuronium; Sugammadex

Topics: Cohort Studies; Humans; Kidney Failure, Chronic; Rocuronium; Sugammadex

Topics: Accidents, Traffic; Brain Contusion; Brain Injuries, Traumatic; Disease Management; Humans; Intubation, Intratracheal; Kidney Failure, Chronic; Male; Middle Aged; Neurologic Examination; Neuromuscular Nondepolarizing Agents; Rocuronium; Subarachnoid Hemorrhage, Traumatic; Sugammadex

Sugammadex is a modified gamma cyclodextrin that encapsulates rocuronium. We report the successful use of sugammadex in the management of an elderly man with end-stage renal failure who sustained an infiltration of subcutaneous rocuronium during rapid sequence induction of general anesthesia. Given the erratic absorption of subcutaneous rocuronium from the tissue, sugammadex was chosen to reverse the neuromuscular block at the end of the procedure. This report demonstrates the efficacy of sugammadex to reverse neuromuscular block in elderly patients with poor renal function. Moreover, the duration of action for sugammadex was sufficient to neutralize the ongoing absorption of subcutaneous rocuronium.

Topics: Aged; Biopsy; Endoscopy, Gastrointestinal; Gastroesophageal Reflux; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Rocuronium; Sugammadex; Treatment Outcome

Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure.. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function.. A prospective clinical trial.. Two university hospitals, from 1 October 2011 to 31 January 2012.. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) <30 ml min] and 20 control patients (ClCr >90 ml min).. Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h.. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8.. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed.. In patients with renal failure, sugammadex (4 mg kg) effectively and safely reversed profound rocuronium induced neuromuscular block, but the recovery was slower than healthy patients.. Clinicaltrials.gov identifier NCT01785758.

Topics: Accelerometry; Adult; Androstanols; Case-Control Studies; Female; gamma-Cyclodextrins; Hospitals, University; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Prospective Studies; Rocuronium; Sugammadex; Time Factors

Postoperative curarization in patients has been established. Nevertheless, extremely prolonged neuromuscular blockades are rare. We report the case of a prolonged neuromuscular blockade (lasting 10 hours) following a single dose of rocuronium, in an elderly patient with severe renal failure. We have studied the possible causes of prolonged curarization, and discussed the interest of the use of sugammadex in such cases.

Topics: Aged, 80 and over; Androstanols; Diabetes Mellitus, Type 2; Female; gamma-Cyclodextrins; Humans; Kidney Failure, Chronic; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Postoperative Complications; Rocuronium; Sugammadex

It is known that the duration of rocuronium action can be prolonged in elderly patients and that such action shows important interindividual variability. We report a case of prolonged neuromuscular block lasting 11 h, in a woman subjected to kidney transplantation. The possible causes of such prolonged action, inherent to the drug, or related to external factors, are commented.

Topics: Androstanols; Diuresis; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Nephrectomy; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Preanesthetic Medication; Rocuronium; Sclerosis

The elderly represent a wide and increasing patient population and significant numbers of elderly patients have chronic renal disease. This study aimed to investigate the neuromuscular effects of 0.6 mg kg(-1) rocuronium under propofol anaesthesia in young adults and elderly patients with or without renal failure.. The neuromuscular effects of rocuronium 0.6 mg kg(-1) under propofol anaesthesia were investigated in 40 patients with renal failure undergoing arteriovenous shunt surgery, of whom 20 were young adults (18-50 yr) and 20 were elderly (>65 yr) and in 40 patients with normal renal function undergoing peripheral venous surgery, of whom 20 were young adults and 20 were elderly. Neuromuscular transmission was monitored using acceleromyography. The times to recovery of the twitch (T1) to 25%, 50%, 75% and 90% and of the train-of-four ratio to 70%, and the recovery index were recorded.. The times to recovery of the first twitch to 25%, 50%, 75% and 90% and train-of-four to 70% and recovery index were found to be prolonged in both young and elderly patients with renal failure compared to those with normal renal function (e.g. T1 25%: 58.4 +/- 20.2 and 80.1 +/- 23.7 min vs. 32.8 +/- 5.6 and 46.3 +/- 9.0 min, respectively) (P < 0.05). These parameters were also prolonged in the elderly when compared with young adults in both the renal failure and the non-renal failure groups.. The neuromuscular effects of 0.6 mg kg(-1) rocuronium under propofol anaesthesia were markedly prolonged in young and elderly renal failure patients compared to patients with normal renal function, and also in elderly patients with normal renal function compared with young adults.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Androstanols; Anesthetics, Intravenous; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Propofol; Rocuronium; Young Adult

The neuromuscular effects of a bolus dose of rocuronium 0.6 mg kg(-1) under propofol anaesthesia in renal failure patients are prolonged compared to healthy patients. The present study aims to describe the neuromuscular effects of 0.3 mg kg(-1) rocuronium under propofol anaesthesia in patients with renal failure and to compare these effects with healthy control patients.. With institutional approval and informed consent, 18 healthy patients and 18 patients with renal failure took part in this prospective open label study. The renal failure patients were undergoing either renal transplantation or insertion of a shunt. Rocuronium 0.3 mg kg(-1) was given intravenously after induction of anaesthesia with propofol 1-2 mg kg(-1) and fentanyl 2 microg kg(-1). Propofol 6-12 mg kg(-1) h(-1) was used for maintenance of anaesthesia. Four acceleromyographic responses of the thumb after supramaximal stimulation of the ulnar nerve using surface electrodes at 2 Hz every 15 s were measured and recorded. The onset time, the time to recovery of the first twitch to 25% recovery and the time to a train-of-four ratio of 0.7 were all recorded. Wilcoxon rank sum testing was used to compare the pharmacodynamics and to see if medication, gender or electrolytes influenced the duration of the block. P < 0.05 was significant.. No statistical differences were seen in the neuromuscular blocking effects of rocuronium between the two groups but there was a significant difference (P < 0.00001) in the variability of the total duration of the block.. Rocuronium 0.3 mg kg(-1) is suitable for use in patients with renal failure when endotracheal intubation and neuromuscular block for a short period of time are needed. Tracheal intubation is facilitated within 4 min and the block can be antagonized within 20 min.

Topics: Adult; Androstanols; Anesthesia, Intravenous; Anesthetics, Intravenous; Female; Humans; Intubation, Intratracheal; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Propofol; Rocuronium; Time Factors

The time-course of the neuromuscular effects of rocuronium 0.3 mg.kg-1 during nitrous oxide-halothane anaesthesia in children with and without renal failure is unknown. This study compared the neuromuscular blocking effects in these groups.. The study was approved by the Hospital Ethical Committee. In the control group, 14 healthy children without renal disease were scheduled for various elective surgical procedures. Sixteen children with endstage renal failure, 14 of whom were already on renal dialysis, were scheduled for (re)placement of dialysis catheters (n=14) or for renal transplantation (n=2). Anaesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Acceleromyographic thumb adduction after supramaximal ulnar nerve stimulation was recorded using train-of-four stimulation every 15 s. The onset time, the time to recovery of the first twitch to 25% or 75% and to recovery of a train-of-four ratio of 0.7 after rocuronium 0.3 mg.kg-1 were measured. Statistical analysis was performed with Student's t-test. P < 0.05 was considered statistically significant.. The onset time was longer in children with renal failure (139 s, SD=71) than in control children (87 s, SD=43) (P=0.02). There were no significant differences in the duration of action of rocuronium between children without renal failure and in 15 out of 16 children with renal failure.. In children with renal failure, aged over 1 year, a single bolus dose of rocuronium 0.3 mg.kg-1 does not cause a prolonged block, but has a slower onset than in healthy children.

Topics: Androstanols; Anesthesia, General; Anesthetics, Inhalation; Case-Control Studies; Child, Preschool; Halothane; Humans; Infant; Kidney Failure, Chronic; Neuromuscular Nondepolarizing Agents; Nitrous Oxide; Rocuronium; Time Factors

An end-stage renal failure patient, receiving chronic treatment with the anticonvulsants, sodium valproate and primidone, showed accelerated recovery with enhanced elimination (T1/2(z) = 52 min) and clearance (Cl = 14.4 ml min-1 kg-1) of rocuronium. The pharmacokinetic and pharmacodynamic effects of rocuronium in this patient are compared with those published for healthy and renal failure patients. Increased hepatic binding of rocuronium rather than metabolism is suggested as the possible cause of this effect.

Topics: Adult; Androstanols; Anticonvulsants; Drug Interactions; Humans; Kidney Failure, Chronic; Male; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Primidone; Rocuronium; Valproic Acid

Topics: Adult; Androstanols; Cadaver; Drug Interactions; Epilepsy, Tonic-Clonic; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Metabolic Clearance Rate; Neuromuscular Nondepolarizing Agents; Phenytoin; Rocuronium; Time Factors

We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg-1 in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block, duration of clinical relaxation (T1(25)) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kg-1 min-1 and 3.7 (1.4) ml kg-1 min-1, respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) P < 0.05). The differences in other kinetic parameters were not significant. We conclude that the effects of rocuronium may be prolonged in patients with renal disease, because of a decreased clearance of the drug.

Topics: Adult; Androstanols; Anesthesia, Inhalation; Female; Humans; Isoflurane; Kidney Failure, Chronic; Male; Middle Aged; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Rocuronium; Time Factors

The pharmacodynamics of an initial dose of 0.6 mg.kg-1 rocuronium followed by three maintenance doses of 0.15 mg.kg-1 were studied during nitrous oxide/oxygen/isoflurane anaesthesia in patients with normal renal function (n = 12) and chronic renal failure (n = 12). The mean (SD) duration (min) of block after the initial dose was 28.0 (5.5) and 25.6 (11.7) respectively. The mean (SD) duration (min) of the effect of the three maintenance doses was 15.3 (4.0) and 14.2 (7.0); 17.3 (3.2) and 17.4 (8.7); 18.1 (2.8) and 19.1 (10.1) for the normal and renal failure patients respectively. The induced and spontaneous recovery indices were 3.7 (0.7) and 17.1 (6.9) in the normal group compared with 3.9 (0.5) and 19.0 (12.5) in the renal failure group and these values did not differ between the two groups. In this small study rocuronium appears to be suitable for patients with chronic renal failure. There is no evidence of prolonged block even when the drug is given in repeated doses for maintenance.

Topics: Adolescent; Adult; Aged; Androstanols; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Rocuronium; Time Factors

To determine the effect of end-stage renal disease on the pharmacokinetics of reocuronium bromide (ORG 9426), a new nondepolarizing monoquaternary steroidal neuromuscular blocking drug, the authors administered 600 micrograms/kg rocuronium (2 x ED95) intravenously to ten patients undergoing cadaver renal transplantation and ten healthy patients undergoing elective minor surgery (controls). All patients were anesthetized with nitrous oxide (50-70% in oxygen) and isoflurane (end-tidal concentrations of 1.2 +/- 0.5% and 0.8 +/- 0.2%, mean +/- SD, for control and transplant groups, respectively). Plasma concentrations of rocuronium were determined by capillary gas chromatography. A population-based pharmacokinetic analysis (NONMEM) was used to determine typical values, standard errors, and interindividual variability for the pharmacokinetic parameters and to determine whether these values differed between control and renal transplant patients. Total plasma clearance (2.89 +/- 0.25 ml.kg-1.min-1, mean +/- SE) and volume of the central compartment (76.9 +/- 10.6 ml/kg) did not differ between control and renal transplant patients, whereas volume of distribution at steady state was greater in renal transplant patients (264 +/- 19 ml/kg) than in control patients (207 +/- 14 ml/kg). This resulted in a longer elimination half life in renal transplant patients (97.2 +/- 17.3 min) compared to controls (70.9 +/- 4.7 min). The authors conclude that renal failure and renal transplantation alter the distribution but not the clearance of rocuronium.

Topics: Adult; Aged; Androstanols; Female; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Reference Values; Rocuronium