Rocuronium is a non-depolarizing steroidal muscle relaxant with a short time to onset and of intermediate duration of action. The effects of an intravenous bolus dose of 600 ?g/kg of rocuronium in infants and children during halothane anesthesia have been previously described. Differences of response to neuromuscular blocking drugs occur in adults and children. Unfortunately, the time-course of rocuronium in children during isoflurane anesthesia has not been extensively evaluated. Because this anesthetic agent is commonly used in children, the time-course of the effect of rocuronium during isoflurane anesthesia needs to be further studied.

In addition, it has been suggested that age influences the neuromuscular response to muscle relaxants in children, but this has not been confirmed.

We performed the present study in order to evaluate the neuromuscular effect of 400, 600, and 800 ?g/kg of rocuronium administered to children during isoflurane anesthesia. We also assessed the relationship between the neuromuscular response and age (years) or weight (kg) of all children or children grouped by gender.

After approval by the Institutional Investigation Committee of the Hospital Infantil de México (Mexico City) and written informed parental consent, we studied 45 children aged 2–14 years, ASA physical status 1, undergoing elective surgery requiring tracheal intubation. No children were taking drugs known or suspected to interfere with neuromuscular transmission. No premedication was used in any patient. All children were randomly selected to receive either dose 400, 600, or 800 ?g/kg of rocuronium in a double-blind design.

On arrival at the operating room, children were monitored by means of ECG, pulse oxymetry and non-invasive blood pressure. Anesthesia was induced using atropine (10 ?g/kg), fentanyl (2 ?g/kg), and propofol (3 mg/kg). Normocapnia and normal body temperature (rectal or axillary) were maintained intra-operatively.

After induction of anesthesia, children were ventilated with 100% oxygen and neuromuscular function was monitored at the ulnar nerve using the TOF-guard neuromuscular transmission monitor (manufactured by Biometer International A/S, Odense, Denmark). The TOF-guard uses an accelometer (acceleration transducer) to measure the response to nerve stimulation and utilizes the Newtonian principle that acceleration is proportional to force. Using surgical tape, the acceleration transducer was attached to the flexor aspect of the freely mobile thumb and cutaneous electrodes to the ulnar nerve immediately proximal to the wrist joint. The TOF-guard was calibrated using its automatic start-up procedure and programmed to automatically deliver supramaximal train-of-four stimuli with square wave pulses of 0.2 msec duration to the ulnar nerve, in two phases. During the first, the stimuli was delivered every 15 sec from baseline to 5 min. Thereafter, the stimuli was delivered every 5 min from 5 min until complete recovery (T1:T0 = 100%) was observed. The response data were registered by one of the authors without knowledge of the dose of rocuronium.

The rocuronium (kindly donated by Organon-Teknika de México, Mexico City) was administered as a bolus dose into the T-connector of a rapidly running intravenous infusion. Simultaneously, the TOF-guard programmed sequence was initiated and the ratio of the height of the first response to the control height (T1:T0) was measured.

Finally, all children were intubated when either the T1:T0 reached 0% or there were no changes in the muscular relaxation present during a 1-min period. Endotracheal intubation condition was evaluated by another author also blinded for patient allocation group, using the four-score scale described by Fahey et al. Anesthesia was maintained after intubation with 1.5–2.0% isoflurane in 100% oxygen (flow rate of 4 L/min). Adequate anesthetic depth was judged by the lack of clinically significant changes in cardiovascular variables, i.e., heart rate and blood pressure, according to patient age. No additional drug was required during the anesthetic procedure.

For analysis, the response was also divided into two phases. The first was observed during the first 5 min and was used to compute the times to onset of action (TOA), while the second phase was from 5 min to complete recovery of neuromuscular function and was used to compute each time to spontaneous recovery of neuromuscular function (TSRNMF).

In order to obtain the TOA including time to 90 (B₉₀) and 99.9% (B₁₀₀) of relaxation or the TSRNMF including time to spontaneous recovery of 10 (T₁₀), 25 (T₂₅), 50 (T₅₀), 75 (T₇₅), and 90% (T₉₀) of neuromuscular function, T1:T0 response was fitted to time using SigmaPlot 4.01 (SPSS México, Mexico City) for Windows™ 95. The SigmaPlot curve fitter employs the Marquad-Levenberg algorithm to ascertain the parameters of the independent variable that provide the best fit between the equation and the data. The time-course of T1:T0 in each phase was considered to be sigmoidally related to time.

The model used was a four-parameter logistic equation where Y is the observed response and X, the time at which each response was registered. Additionally, a, b, c, and d are the four derived parameters where a = response at zero time, b = slope factor, c = time at which half maximal response is given, and d = maximal response.

The quality of fit of the pharmacodynamic (sigmoidal) model to the data was judged by the correlation coefficient automatically computed by SigmaPlot and by visual examination of both plots of observed vs. predicted response and plots of residuals (observed-predicted response) related to time.

All data were expressed as mean ± SD, median (ranges) and 95% confidence intervals for non-parametric data. The Fisher exact test was used for comparison of gender both among the three groups and in the general population. The comparisons of the TOA and the TSRNMF among the three doses were performed both parametrically by ANOVA and non-parametrically by the Kruskal-Wallis test followed by the Wilcoxon rank sum test to identify differences. Children were thereafter grouped by gender, and comparisons were performed by the Wilcoxon rank sum test to identify differences between males and females.

Linear regression analysis was performed between each TOA or TSRNF and the age or weight of all children. Thereafter, children were grouped by gender and linear regression analysis was performed between each TOA or TSRNMF and the age or weight previously significantly correlated while including all children. The 95% confidence intervals for the graphic linear relationship were automatically computed by SigmaPlot.

Multiple linear regression analysis was performed between each TOA or TSRNMF as the single quantitative dependent variable, and the age and weight of all children as quantitative explanatory variables. Finally, a two-tailed probability of p <0.05 was considered significant in each test or analysis.

In relation to the effect, the mean time-response courses of neuromuscular block and of spontaneous recovery of neuromuscular function observed with each dose of rocuronium. The TOA including B₉₀ and B₁₀₀ and TSRNMF including T₁₀, T₂₅, T₅₀, T₇₅, and T₉₀ from the three groups. The B₉₀ and B₁₀₀ were similar among groups, whereas all TSRNMF were similar between 600 and 800 ?g/kg of rocuronium, and significantly longer than those observed with 400 ?g/kg. In addition, all patients receiving 600 or 800 ?g/kg reached the maximal (100%) relaxation response, while three children in the 400 ?g/kg group reached 79, 96, and 98% inhibition, respectively, but were successfully intubated after 1 min of stabilization of muscular relaxation. The age and weight of the three children were 6, 2, and 8 years and 18, 9, and 21 kg, respectively. The three children were excluded for the comparisons of B₁₀₀, while only one was excluded for B₉₀ and T₁₀.