J.J. Driessen

Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure

Background and objective: 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. Methods: 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°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. Results: 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. Conclusions: 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.

Continuous femoral nerve block after total knee arthroplasty

Background: A continuous femoral nerve block is frequently used as an adjunct therapy after total knee arthroplasty (TKA). However, there is still debate on its benefits.

Acceleromyography in neonates and small infants: baseline calibration and recovery of the responses after neuromuscular blockade with rocuronium

Background: We have evaluated the use of the TOF‐Guard® (TOF, train‐of‐four) acceleromyographic thumb responses to ulnar nerve stimulation in neonates and infants and the return of the responses after neuromuscular blockade. Methods: Baseline acceleromyographic recording of thumb adduction to ulnar nerve stimulation during volatile anaesthesia was performed in 22 babies aged less than 30 weeks. At the start of stimulation the automatic set‐up procedure of the TOF‐Guard® was used to see if a 100% control twitch height could be achieved. Irrespective of the ability to achieve a 100% control twitch height, TOF stimulation was used thereafter. When no automatic 100% control twitch could be reached, the transducer signal gain factor was set manually to obtain a 100% value. In 14 of the 22 children the recovery after neuromuscular blockade with rocuronium 0.3 mg kg−1 was recorded. Results: In nine of 22 patients a 100% baseline twitch height was obtained with the automatic set‐up. In the other 13 babies the TOF‐Guard® display indicated that the transducer signal was too low. The mean time to recovery of control twitch to 75% of baseline after rocuronium 0.3 mg kg−1 was 51 min (SD = 21) and the time to recovery of the TOF ratio to 70% was 49 min (SD = 19). The mean final twitch height and TOF after recovery from rocuronium blockade were 101% (SD = 15) and 92% (SD = 12), respectively. Conclusion: The recovery of the responses after neuromuscular blockade to near baseline values shows that acceleromyography can be used to measure neuromuscular block and recovery in neonates and infants.

Train-of-four ratio recovery often precedes twitch recovery when neuromuscular block is reversed by sugammadex

Background: Sugammadex reverses rocuronium‐induced neuromuscular block (NMB). In all published studies investigating sugammadex, the primary outcome parameter was a train‐of‐four (TOF) ratio of 0.9. The recovery time of T1 was not described. This retrospective investigation describes the recovery of T1 vs. TOF ratio after the reversal of NMB with sugammadex.

A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex

A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs predispose such patients to severe postoperative residual paralysis and respiratory complications. Sugammadex binds steroidal NMBDs and, therefore reverses a rocuronium or vecuronium-induced NMB, without interfering with cholinergic transmission. A rapid and complete recovery from profound NMB was achieved and no adverse events were observed. This case suggests that sugammadex is a safe and effective antagonist of a rocuronium induced NMB blockade in patients with myasthenia gravis.

Sugammadex in patients with myasthenia gravis.

Unterbuchner and colleagues [1] described in their case report the successful reversal of a rocuronium-induced neuromuscular block in a patient with myasthenia gravis. The authors suggest that more evidence is required to examine the use of sugammadex in patients with myasthenia gravis. We would like to report our experience with two patients (with mild generalised muscle weakness, class IIa in myasthenia gravis severity classification system by Osserman and Jenkins [2] and on chronic cholinesterase inhibitor medication) in which we reversed an intense rocuronium-induced neuromuscular block with sugammadex. Both patients were scheduled for short procedures and subsequently gave consent for publication. After inducing neuromuscular block with rocuronium (0.15 mg.kg, which is 25% of the standard dose required for tracheal intubation in normal patients), both patients developed an intense neuromuscular block [3]. At the end of the surgical procedure, monitoring of the neuromuscular function (TOF-Watch SX; MSD ⁄ Shering-Plough Ireland Ltd, Dublin, Ireland) showed no response of the train-of-four and a post-tetanic count was 0. We then reversed the block with 4.0 mg.kg sugammadex. The time from the administration of sugammadex to 90% recovery of the train-of-four ratio was 162 s for the first patient and 135 s for the second. No adverse changes were observed in arterial blood pressure, heart rate or ECG after the administration of sugammadex. The recovery of anaesthesia was uneventful and no signs of residual neuromuscular block or recurarisation were observed. Although there is controversy whether cholinesterase inhibitor medication should be continued until the time of the operation, if patients are reliant on their cholinesterase inhibitor medication it should probably be continued peri-operatively [4]. As sugammadex does not interfere with cholinergic homeostatic regulation, continuation of cholinesterase inhibitors pre-operatively does not affect the efficacy of the reversal of neuromuscular block by sugammadex and therefore optimal muscle function is preserved. Reversal of a rocuronium-induced neuromuscular block by sugammadex will eliminate the risk of residual neuromuscular blockade in these patients with their highly increased sensitivity to nondepolarizing neuromuscular blocking drugs. The combination of rocuronium and sugammadex may avoid the requirement for suxamethonium. Moreover, the use of sugammadex prevents the need for postoperative mechanical ventilation, often the consequence of using non-depolarizing neuromuscular blocking drugs. Reversal of rocuronium-induced intense neuromuscular block by sugammadex in our two patients with myasthenia gravis was rapid, efficient, and without signs of postoperative residual neuromuscular block. We emphasise that in these two patients reversal of the neuromuscular block was initiated at a level of intense neuromuscular block, in contrast to the case described by Unterbuchner and colleagues. These additional cases contribute additional evidence that the combination of rocuronium and sugammadex for neuromuscular block and its reversal is safe and beneficial in myasthenia gravis.

Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats

PurposeSugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex–rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugammadex on recovery of rocuronium-induced neuromuscular block in cats with clamped renal pedicles, as a model for acute renal failure.MethodsTwelve male cats were divided into two groups and anesthetized with medetomidine, ketamine, and alpha-chloralose. The cats were intubated and ventilated with a mixture of oxygen and air. Neuromuscular monitoring was performed by single twitch monitoring. Rocuronium 0.5xa0mg/kg i.v. was administered. After spontaneous recovery from neuromuscular block, both renal pedicles were ligated. A second dose of rocuronium 0.5xa0mg/kg i.v. was given. One minute after disappearance of the twitches, in Group 1 placebo (0.9% saline) and in Group 2 sugammadex 5.0xa0mg/kg i.v. was administered. Onset time, duration of neuromuscular block, and time to recovery to 25, 50, 75, and 90% were determined.ResultsAfter renal pedicle ligation, sugammadex reversed rocuronium-induced neuromuscular block significantly faster than spontaneous recovery. Mean time (SEM) to 90% recovery of the twitch response was 4.7 (0.25)xa0min (Group 2) versus 31.1 (5.0)xa0min (Group 1) (pxa0<xa00.0001). No signs of recurrence of neuromuscular block were observed for 90xa0min after complete twitch restoration. Sugammadex caused no significant cardiovascular effects.ConclusionSugammadex rapidly and effectively reversed rocuronium-induced neuromuscular block in anesthetized cats, even when both renal pedicles were ligated and renal elimination of the drugs was no longer possible.

Longer than expected-duration of caudal analgesia with two different doses of levobupivacaine in children undergoing hypospadias repair

OBJECTIVEnTo assess our study design and to obtain preliminary data for a dose-effect study on levobupivacaine for caudal analgesia in patients undergoing hypospadias repair.nnnSTUDY DESIGNnnon randomised, non-blinded pilot study.nnnMETHODnFor this non-randomized, non-blinded pilot study, 20 patients (median age 17 months, median weight 10.5xa0kg) were allocated to two groups receiving either 0.5xa0mLxa0kg(-1) levobupivacaine 0.125% (Group 0) or 0.5xa0mLxa0kg(-1) levobupivacaine 0.375% (Group 1) caudally after induction of anaesthesia for pain control. No further analgesia was given before, during or after the procedure. Pain scores (Childrens and Infants Postoperative Pain Scale) were recorded throughout the observation period, which lasted from the start of the procedure until hospital discharge on the following day.nnnRESULTSnGroup 0: six out of 10 patients remained pain free throughout the observation period. Group 1: six out of seven patients remained pain free throughout the observation period.nnnCONCLUSIONnBoth concentrations of levobupivacaine provided excellent analgesia throughout surgery. The postoperative analgesia with both doses of levobupivacaine was found to be significantly longer lasting than previously reported. The study design, with a tight and extensive observation scheme, proved to be feasible, but given the surprisingly long-lasting analgesia, the observation period needs to be extended in future studies.

The relation between skin temperature increase and sensory block height in spinal anaesthesia using infrared thermography

Background and objectives: To evaluate the feasibility of determining the extent of sympathetic blockade by skin temperature measurement with infrared thermography and relate the cranial extent of the temperature increase to that of the sensory block after spinal anaesthesia.

Isoflurane and Neuromuscular Blocking Drugs

Volatile anaesthetics influence the pharmacodynamics of neuromuscular blocking drugs. Several studies have shown concentration-dependent potentiating effects of halothane, enflurane and isoflurane on the potency and duration of action of non-depolarizing neuromuscular blocking drugs in humans (Miller et al. 1972; Ali and Savarese 1976; Folges et al. 1983; Rupp et al. 1984). These studies have mainly compared dose-response curves for neuromuscular blocking drugs during anaesthesia with different volatile anaesthetics. Based on measurement of ED50 and ED90 (effective dose for 50% and 90% depression of twitch height), the greatest potentiation was reported with en-flurane and the smallest with halothane.