The study protocol was reviewed and approved by the Institutional Ethics Committee for Human Research. After careful explanation and discussion, written informed consent was obtained from each patient or guardian. Adult patients with major burns (>20% TBSA), aged 18–59 yr, undergoing burn-related surgery, at 6–92 days after the injury, were studied. Ninety-three burned patients were recruited and assigned to either rocuronium priming 0.06+0.94 mg kg−1 (n=29) or rocuronium 1.0 mg kg−1 single bolus (n=29) groups. Rocuronium 1.5 mg kg−1 single bolus dose (n=35) in burns was studied as an additional group after data collection of priming and 1 mg kg−1 bolus were completed. Non-burned patients receiving either rocuronium priming 0.06+0.94 mg kg−1 (n=32) or rocuronium bolus dose of 1.0 mg kg−1 (n=29) served as controls. A bolus dose of rocuronium 1.5 mg kg−1 was not tested in the control group in view of the anticipated prolonged duration of paralysis.
Patient characteristics recorded included age, sex distribution, height in centimetres, weight in kilograms, American Society of Anesthesiologists physical status classification, types and extent of burn injury, and the number of days from the injury to the study. The studies were performed during the subacute hyperdynamic phase of injury when most of the patients were confined to bed and continued to lose weight, but had no serious respiratory problems requiring mechanical ventilation. Patients in whom difficulty in mask ventilation or tracheal intubation was anticipated were not recruited. Patients who were 30% above or below ideal body weight, with a cardiac pacemaker, or history of allergic reaction to neuromuscular blocking agents were excluded, as were those with evidence of hepatic, renal, neuromuscular, or endocrine disease, marked electrolyte imbalance, myasthenia gravis, or the use of drugs (e.g. anticonvulsants) that might affect neuromuscular transmission.
One hour before the anticipated induction of anaesthesia, an 18 or 20 gauge i.v. catheter was inserted. Routine monitors, including ECG, non-invasive blood pressure, and pulse oximetry, were applied in the operating theatre. The arm used for monitoring neuromuscular paralysis, free of blood pressure cuff or i.v. fluid infusion, was secured on an arm board, with the thumb left freely mobile, whereas the other fingers were loosely immobilized with tape. Neuromuscular block was monitored with an acceleromyography, TOF-Watch® (NV Organon, Oss, The Netherlands). To stimulate the ulnar nerve, two surface electrodes were placed in parallel over the flexor carpi ulnaris tendon and connected to the negative electrode distally and positive electrode proximally. The acceleration transducer was attached to the volar aspect of the distal phalanx of thumb.
Midazolam 2 mg was i.v. administered. Having informed the patient of the initiation of nerve stimulation, a brief period of initial TOF-Watch® calibration was followed by a tetanic stimulation for 10 s as a recruitment manoeuvre for the neuromuscular junction. This was followed by train-of-four (TOF) stimuli for 1 min. TOF-Watch® was programmed to deliver impulses at 2 Hz, pulse width 200 ms, square wave for 1.5 s, repeated every 15 s at 50 mA. After TOF stabilization, before the administration of normal saline or rocuronium priming, the first twitch response (T1) of the TOF was considered the baseline twitch height. The twitch responses shown in the TOF-Watch® monitor screen and the time of each twitch response, measured by a digital stopwatch, were recorded serially.
The study groups with burns received one of the three treatments. The priming group received rocuronium 0.06 mg kg−1 as the priming dose, followed 3 min later by rocuronium 0.94 mg kg−1 bolus over 5 s. The other group received normal saline 1 ml, mimicking the priming dose, followed 3 min later by a bolus dose of rocuronium 1.0 mg kg−1 given over 5 s. The third group of burned patients received rocuronium 1.5 mg kg−1. Control patients only received one of the two treatments, either rocuronium 0.06 mg kg−1 of rocuronium as the priming dose, followed 3 min later by rocuronium 0.94 mg kg−1 bolus, or normal saline 1 ml mimicking the priming dose, followed 3 min later by rocuronium 1.0 mg kg−1 bolus given over 5 s.
The same anaesthesia induction regimen was used in both the burned and the control groups. Approximately 2 min after priming (rocuronium or saline), anaesthesia was induced with i.v. propofol 2.0–2.5 mg kg−1
and fentanyl 1–2 µg kg−1
, followed 1 min later by the bolus of rocuronium 0.94 or 1.0. Burned patients in the rocuronium 1.5 mg kg−1
group received the rocuronium 1 min after propofol and fentanyl. The time from the beginning of rocuronium bolus administration to the earliest sign of twitch depression, and to 90%, and complete twitch depression of twitch height were noted. During this time, anaesthesia was maintained with an oral airway and facemask ventilation. The end-tidal CO2
was controlled within the normocarbic range during this period. An anaesthesiologist, unaware of the priming technique and dosage, performed tracheal intubation when the twitch suppression was completely ablated or maximal. The intubation was carried out by anaesthesiologists, experienced in the assessment of intubating condition, which was graded as excellent, good, or poor, as per the guidelines for Good Clinical Research Practice in Pharmacodynamic Studies of Neuromuscular Blocking Agents.10
SPSS version 11 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. All data are presented as mean (se) or median with range (min–max) whenever appropriate. Differences in patient characteristics among the groups were examined with one-way analysis of variance (anova). Non-parametric Kruskal–Wallis one-way anova with Dunn's post hoc method examined differences in onset times between priming and bolus groups in both burned and non-burned groups. Fisher's exact test compared intubating conditions among the groups. A value of P<0.05 was considered statistically significant.