E.N. Robertson

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.

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.

Intradermal Histamine Release by 3 Muscle Relaxants

The induration and redness caused by intradermal injections of equipotent doses of atracurium, vecuronium and d‐tubocurarine were measured in six healthy, male volunteers. Atracurium and d‐tubocurarine were almost indistinguishable in their reactions. Vecuronium caused a significantly smaller response than both atracurium and d‐tubocurarine. We therefore suggest that of these three drugs, vecuronium may cause the least histamine release and is, perhaps, the drug of choice in patients with a history of asthma or allergy.

Time-course of action of rocuronium 0.3 mg.kg-1 in children with and without endstage renal failure.

Background: 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.

Suxamethonium administration prolongs the duration of action of subsequent rocuronium.

Background and aim: Rocuronium may be given to patients for intubation and also after they have received suxamethonium for intubation. The neuromuscular profile of rocuronium given after recovery from suxamethonium may not be identical to that when rocuronium has been given alone. The neuromuscular effects of suxamethonium and rocuronium, and their effects on intraocular pressure (IOP), heart rate (HR) and arterial pressure were also recorded. Methods: Thirty patients were randomly allocated to receive either 0.6 mg kg−1 rocuronium (n = 15) or 1 mg kg−1 suxamethonium (n = 15) for intubation. Anaesthesia was first induced using propofol 2.5 mg kg−1 and fentanyl 2 μg kg−1 and maintained with propofol 6-12 mg kg−1 h−1. The response of the thumb to supramaximal train-of-four (TOF) ulnar nerve stimulation at the wrist was measured using a mechanomyograph. In the suxamethonium group, when the first twitch of the TOF had recovered to 90%, rocuronium 0.6 mg kg−1 was administered. Before administration of relaxant, baseline readings of HR, arterial pressure and IOP were measured until stable, then the appropriate relaxant administered. Thereafter, all readings were repeated at 30, 90, 150, 210 and 270 s. Tracheal intubation was performed 300 s after the intubating dose and all recordings repeated 30 s later. Mechanomyographic monitoring was continued until 70% TOF recovery. Results: Suxamethonium had a more rapid onset than rocuronium (49 s vs. 74 s, P < 0.0001). The onset time of rocuronium after suxamethonium was significantly reduced (56 s) and the time to recover to a TOF of 70% following rocuronium was increased by previous suxamethonium administration (47 vs. 58 min, P < 0.05). Suxamethonium caused a marked rise in IOP (>30%) and HR (>10%) while rocuronium had little effect on either. Conclusion: Previous suxamethonium administration decreases the onset time and increases the duration of action of rocuronium. Unlike suxamethonium, rocuronium has few cardiovascular effects and causes little change in IOP.