The Effect of Nitrous Oxide on the Dose-Response Relationship of Rocuronium

Abstract

It has been generally assumed that nitrous oxide (N(2)O) enhances the effects of nondepolarizing muscle relaxants only weakly if at all. More recent evidence suggests that drug potency may be more intense under N(2)O anesthesia compared with total IV anesthesia (TIVA). However, the magnitude of this effect has not been well defined. We measured the 50% effective dose of rocuronium in 35 patients receiving N(2)O-propofol-opioid anesthesia and a comparable group receiving TIVA. A single dose of rocuronium was given to each patient and drug potency was calculated for each individual from the Hill equation assuming a log-dose/logit slope of 4.5. In both groups, the relaxant was administered 15 min after induction of anesthesia. Neuromuscular function was measured using electromyography with single stimuli at 0.10 Hz. We measured a 50% effective dose of 0.209 +/- 0.051 mg/kg during TIVA and of 0.166 +/- 0.041 mg/kg during N(2)O anesthesia, a decrease of 20% (P < 0.001). The clinical importance of this effect must be considered modest; however, estimates of potency that are usually obtained during N(2)O anesthesia may underestimate drug requirements at the time of induction of anesthesia.

Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial

“…Other previous studies using bolus techniques in the assessment of the pharmacodynamics have yielded similar results as compared to Kopman et al [5] Nitrous oxide has been shown to slightly affect the potency of both vecuronium [6] and mivacurium [4]. However, the duration of nitrous oxide administration before muscle relaxant was only 15 min in these rocuronium and mivacurium studies and 5 min in the vecuronium study [4-6].…”

“…The study group of Kopman et al [5] used the single-dose technique for the quantition of the nitrous oxide-rocuronium interaction. They estimated the value of the mean effective dose 50% (ED 50 ) assuming that the dose-effect relation of rocuronium has a constant slope of 4.5 in a log-dose/logit plot.…”

“…Volatile anesthetics do not seem to affect the pharmacokinetics of muscle relaxants, and it is generally assumed that nitrous oxide has no effect on the pharmacokinetics of muscle relaxants [16-20]. It has been proposed that nitrous oxide affects the neuromuscular junction directly and independently of its rate of accumulation in the muscle [4] or by altering the transfer of muscle relaxants to the site of action [5]. In fact the saturation of muscle tissue with nitrous oxide is less than 30% complete after 15 min of nitrous oxide anesthesia thus supporting the idea of an accumulation-independent effect of nitrous oxide on neuromuscular junction [4].…”

Neostigmine injected 5 minutes after low-dose rocuronium accelerates the recovery of neuromuscular function

“…Presumably, N 2 Opropofol-opioid anesthesia, as was used in our study, might have only slightly, if at all, increased the duration of the block. Kopman et al found that estimates of potency that are usually obtained during N 2 O anesthesia may underestimate drug requirements at the time of induction of anesthesia [12]. Intubations were successfully performed 120 to 180 seconds after injection in all patients, which is significantly longer than after the regular intubation dose of rocuronium 0.6 mg/kg.…”

ORIGINAL ARTICLE: Potency and recovery characteristics of rocuronium mixed with sodium bicarbonate

“…Pain on injection of rocuronium is common, occurring in 80% of awake patients [2]. Several methods have been reported for reducing the pain on injection, including treatment with fentanyl [3], lidocaine [4–9], ondansetron [6], sodium bicarbonate 8.4% [7–10], magnesium sulphate [8] and ketamine [11]. The mixture of rocuronium with 8.4% bicarbonate results in the production of carbon dioxide [12].…”