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 legal guardian.
Thirty adults, aged 23–62 yr with ASA physical class II–III, with a history of burn trauma [>15% total body surface area (TBSA)], were studied during the hyperdynamic phase (>72 h after injury). During this period, all of the patients were minimally ambulatory, mostly bed-ridden, and continued to lose weight, but had no significant ongoing ventilatory problems. A control group of 31 patients without burns, matched for age, sex, and weight, was also studied. All patients had a Mallampatti airway class 1 or 2 with no evidence of potential difficulty for either mask ventilation or tracheal intubation.
Patients with 35% above or below the normal body weight, having an artificial pacemaker or a history of allergic reaction to neuromuscular blocking agents were excluded, and those with any history of hepatic, renal, neuromuscular or thyroid disease, electrolyte imbalance, myasthenia gravis, or the use of drugs that might affect neuromuscular transmission such as gentamicin. Subjects were also excluded if pregnant or requiring a rapid sequence procedure.
One hour before the anticipated induction of anaesthesia, an 18 or 20 G i.v. catheter was inserted. On arrival in the operating theatre, midazolam 0.01 mg kg−1 i.v. was given. In the operating theatre, routine monitors, including ECG, non-invasive arterial pressure, and pulse oximeter, were applied. Pre-oxygenation with 100% oxygen by a facemask for 3 min was initiated.
Whenever possible, the adductor pollicis area without any burn injury was chosen for monitoring twitch response. To maintain muscle blood flow and venous return, the monitoring arm was kept free from inflation of non-invasive arterial pressure cuff, or infusion of i.v. fluids. The arm used for neuromuscular monitoring was placed on a wooden board for immobilization. The thumb was left freely movable, whereas the other fingers were loosely attached with a tape to the board so as not to distort the movement in the adductor pollicis muscle. Monitoring of neuromuscular block was performed with an acceleromyograph, TOF-Watch™ (NV Organon, Oss, The Netherlands). Before applying the electrodes, the skin was cleansed, degreased, and rubbed with an alcohol sponge. To stimulate the ulnar nerve, the two stimulating electrodes were placed in parallel above the flexor carpi ulnaris tendon on the volar aspect of the wrist and connected to the negative alligator clip distally and positive alligator proximally. An acceleration transducer was attached at the volar aspect of the distal phalanx of the thumb.
The same anaesthesia induction regimen was used in all patients and consisted of i.v. propofol 1.5–2.5 mg kg−1 and fentanyl 1–2 µg kg−1. After induction of anaesthesia and while TOF-Watch™ monitoring was being established, the airway was maintained with an oral airway and a facemask without intubation; ventilation was assisted with supplemental oxygen. The end-tidal CO2 was controlled within the normocarbic level during this period.
Additional midazolam 0.01 mg kg−1 and fentanyl 1 µg kg−1 were i.v. administered before TOF stimulation. TOF-Watch™ was programmed to deliver 50 mA single-twitch impulses at 0.1 Hz, 200 ms duration. To recruit the neuromuscular junction, the period of initial TOF-Watch™ calibration was followed by a tetanic stimulation for 10 s. This was succeeded by single-twitch stimuli (T1) for at least 1 min. After the establishment of stable response, the number on the screen was considered as the baseline. The time course of the onset and recovery of neuromuscular block was continuously assessed with the single-twitch response. The numbers displayed on the TOF-Watch™ screen were serially recorded.
All patients received mivacurium 0.2 mg kg−1 i.v. administered over 5 s after the induction of anaesthesia and establishment of a single twitch on the TOF-Watch™ monitor. Onset times were measured as the time from the beginning of drug administration to the appearance of first-twitch depression, 50%, 90%, and 100% twitch depressions of control height. The appearance of first-twitch depression was defined as >10-point decrement in measurements.
Anaesthesia was maintained with i.v. propofol 0.1–0.2 mg kg−1 min−1, 66% nitrous oxide in oxygen, and supplemental fentanyl 0.5–1 µg kg−1 bolus as needed. Core and peripheral skin temperatures were kept at ≥35°C and 32°C, respectively. Ventilation was adjusted to maintain end-tidal CO2 at 4.7–5.3 kPa. Spontaneous recovery from the maximal neuromuscular block to recovery of T1 to at least ≥0.8 was recorded. The clinical durations of action were specified as the times from the start of drug injection until 25%, 50%, and 75% T1 recovery (duration 25%, 50%, and 75%), respectively. The recovery parameters were recorded from the monitor screen using the pre-drug baseline as a control. The recovery index (time from 25% to 75% twitch recovery) was also calculated.
The assay for plasma PChE levels used a colorimetric technique, which measures a colour produced by cholinesterase in the patient plasma after adding Ellman's reagent.14
For the measurement of dibucaine number, cholinesterase activity is assayed the same way with and without dibucaine, which does not inhibit atypical PChE. The dibucaine number or the inhibition per cent (% inhibition)=(1−cholinesterase activity with dibucaine/cholinesterase without dibucaine)×100.
Sigma Plot ver. 11.0 (Systat Software, Inc., San Jose, CA, USA) was used for statistical analysis. All data are presented as mean (sd) or median with range (min–max) wherever appropriate. Differences in patient characteristics, PChE levels, and dibucaine numbers between the groups were compared with the Student t-test or Mann–Whitney rank-sum test as deemed appropriate. A repeated measure of anova with Bonferroni's post hoc test was used for differences in onset times and duration of action between burn and control groups. Spearman's correlation (r) evaluated the relationship between PChE activity and 50% twitch recovery. A value of P<0.05 was considered statistically significant.