Journal: Anaesthesia 62(11):1114-1120, 2007. 30 References
Reprint: Dept of Anaesthesiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Prof AF Merry)
Faculty Disclosure: Abstracted by L. Easley, who has nothing to disclose.
The implications of chronobiology for anesthesia have been recognized, but are often neglected. The authors have undertaken a study of the influence of time of day on the duration of neuromuscular blockade produced by standard doses of rocuronium. This prospective, observational study was conducted with reference to the good clinical research practice (GCRP) guidelines for pharmacodynamics studies of neuromuscular blocking agents. Potential participants were identified from acute and elective surgical lists between February 2004 and May 2006.
The dosing regimen of rocuronium was designed to allow the measurement of neuromuscular recovery without affecting normal clinical management of the patient and was based on fat-free mass (FFM). Neuromuscular function was measured quantitatively every 15 sec by accelerometry at the adductor pollicis throughout the procedure by train-of-four stimulation. The primary outcome variable (T1) was the time, in minutes, from the administration of an induction dose of rocuronium until recovery of neuromuscular function to a predefined endpoint. When longer periods of neuromuscular blockade (NMB) were required, a second dose, equal to 20% of the induction dose, and if necessary a third standard dose of 10 mg, were administered.
Forty-nine participants provided usable data from at least one dose in procedures occurring between 08:00 and 02:00. There was a clear relationship between duration of action and the time of day of administration, with maximum duration of 50 min falling between 08:00 and 11:00 and minimum duration of 29 min between 14:00 and 17:00. There was strong evidence that duration of T1 was dependent on the dose of neuromuscular blocking drug and the duration of action (T1) was dependent on time of day. A trend towards a time of day effect similar to that evident in T1 was also observed in the duration of the 20% FFM dose with the peak and trough occurring at the same times.
The time of day of administration influences the duration of neuromuscular blockade produced by rocuronium. The standard FFM weight-related dose administered in the morning lasts an average 17.4 min longer than if administered in the afternoon. These findings are consistent with data previously published for the neuromuscular blocker pancuronium. There are several theoretical reasons why time of day may influence duration of NMB. The circadian clock could influence drug metabolism, neuromuscular function or receptor expression directly. Circadian clock control of core (rectal) temperature causes a daily variation of up to 0.8°C, with highest temperature in the afternoon and lowest in the early morning.
This study demonstrated a clinically significant time of day effect on the duration of action of rocuronium. As a rule of thumb, clinicians should expect the duration of NMB with rocuronium to be one-third shorter in the afternoon than in the morning or evening. |
