In recent years, attempts have been made to find a nondepolarizing muscle relaxant with a short enough onset to replace succinylcholine as the muscle relaxant of choice for rapid sequence induction. The onset time of new muscle relaxants has been measured mainly by mechanomyographically, electromyographically or, more recently, by acceleromyographically obtained responses of muscular sites, e.g., the adductor pollicis muscle. They are easily accessible, but not the site of interest for sufficient muscle relaxation at intubation: the larynx.
Furthermore, the pharmacodynamic data obtained by using different forms of neuromuscular monitoring can vary quite substantially (1,2). Thus, when comparing the onset time or the clinical duration of a specific neuromuscular blockade at various sites, care must be taken to use similar forms of neuromuscular monitoring, e.g., electromyography (EMG) at all sites.
EMG has long been a tool to measure responses of laryngeal muscles, especially in surgery of the thyroid gland, where damage to the recurrent laryngeal nerve is a potential hazard. Various electrodes have been used to obtain evoked electromyographic responses, such as hooked-wire electrodes endoscopically introduced into the adducting laryngeal muscles (cricothyroid posterior) (3) or, more recently, a less invasive, easily attachable laryngeal electrode (4). This form of monitoring proved reliable in obtaining reproducable electromyographic signals of the larynx.
The purpose of this study was to develop a method that uses the attachable laryngeal surface electrode to obtain electromyographic responses of the adducting laryngeal muscles, evoked by transcutaneous stimulation of the recurrent laryngeal nerve, and measure the onset of the neuromuscular blockade of rocuronium and mivacurium; this was compared with the onset at the adductor pollicis muscle using EMG via surface skin electrodes.
After approval of the institutional human investigation committee and obtaining written, informed consent, 40 patients, undergoing surgery of the thyroid gland, were included in the study. Pregnant women, patients with neuromuscular, hepatic, or renal disease, or patients receiving medications known to interact with neuromuscular blocking drugs were excluded. Standard anesthetic monitoring was used. Anesthesia was induced by using a perfusion of remifentanil at 0.5 μg · kg−1 · min−1. Two minutes later, a target-controlled infusion of propofol (target concentration: 4 μg/mL) was started, programmed to reach the target concentration within 30 s. After the induction of anesthesia, the patients were ventilated via a mask for 2 min and tracheally intubated by using a Woodbridge tube (Mallinckrodt, Northhampton, UK, size 7.0: female, size 8.0: male) with the surface laryngeal electrode attached 2 cm above the beginning of the cuff (Fig. 1). Care was taken to place the electrode amid the vocal cords for optimal electromyography (EMG) tracing. (Three days postoperatively, all patients were checked for recurrent laryngeal nerve function via indirect laryngoscopy by the otorhinolaryngology specialist; any lesion or damage to the vocal cords caused by the surface laryngeal electrode was also noted).
Anesthesia was maintained with target-controlled infusion of propofol (target concentration: 3 μg/mL) and remifentanil at 0.375 μg · kg−1 · min−1; mechanical ventilation was adjusted to achieve end-tidal CO2 pressure of 26–35 mm Hg.
After the induction and routine fixation of the tube, the laryngeal recurrent nerve was transcutaneously stimulated with an external nerve stimulator (Multiliner, Tönnies Company, Wuerzburg, Germany) at the notch of the thyroid cartilage, a method, apt to create maximal response of the adducting laryngeal muscles (5). The external nerve stimulator has a probe, which is attached at the neck just medially at the notch of the thyroid cartilage with an elastic band. It delivers a current between 0 and 70 mA. Single twitch-stimulation (0.1 Hz, pulse width: 0.2 ms) was performed on the left recurrent nerve to determine the supramaximal stimulation and recorded by using Multiliner software. The current was increased from 0 to the current with the maximal EMG-response (<70 mA) and then increased by 10 mA to assure supramaximal stimulation. The amplitudes of the compound action potential were measured and recorded (Fig. 2). After stimulation of the left ulnar nerve via Ag/AgCl-electrodes, evoked EMG single-twitch responses (0.1 Hz; pulse width: 0.2 ms) from the adductor pollicis muscle via Ag/AgCl-electrodes placed over the base of the thenar area were recorded; the automatic calibration of the Datex Relaxograph® NMT 100 (Datex Instrumentarium Corporation, Helsinki, Finland) was used to determine supramaximal stimulation (0–70 mA). After no change in the neuromuscular response could be detected on all three sites for at least 10 min, the patients received randomly, in a double-blinded fashion, either 0.2 mg/kg (2.5 × the 95% effective dose) of mivacurium (M-group) or 0.6 mg/kg (2 × the 95% effective dose) of rocuronium (R-group) IV, injected within 15 s into a fast-flowing infusion of lactated Ringer’s solution. No further dose of any muscle relaxant was applied.
The time from the end of the injection of the muscle relaxant to the first twitch depression and to 90% and the maximal twitch depression (Lag time, Onset 90, and Onset time) as well as the peak effect (%reduction of the maximal neuromuscular response) of the neuromuscular blockade was measured.
The results were expressed as mean ± SD and range; the anthropometric data of the two groups were compared by using Student’s t-tests. P < 0.05 was regarded as showing a significant difference. The pharmacodynamic variables were compared within the groups between the different monitoring sites by using one-paired-Student’s t-tests and two-paired-Student’s t-tests between the groups; in both comparisons, P < 0.05 was regarded as showing a significant difference.
The correlation between Lag time, Onset 90, Onset time, and peak effect of the two different muscular sites within the groups were analyzed by using test of Pearson;P < 0.05 was noted as showing a significant difference.
There were more men in the R-group than in the M-group; all other patient data were not significantly different (Table 1). Mean time of surgery was 2.5 ± 0.8 (1 to 4.5) h. In all patients, determination of the supramaximal stimulation on both sites of monitoring was successful.
In all patients, the laryngeal electrode was still attached to the tube at the time of extubation. No side effects caused by the transcutaneous stimulation of the recurrent nerve with mean of 40 (range: 25–55) mA, such as arrhythmias or skin irritation, were noted. The postoperative laryngoscopic examination performed by the otorhinolaryngology specialist did not show any alteration or damage of the vocal cords caused by the stimulation of the laryngeal electrode or the laryngeal electrode itself.
The mean amplitude of the EMG response of the laryngeal electrode at the adducting laryngeal muscles was 0.9 ± 0.5 (0.4 - 2) mV after supramaximal stimulation. The comparison of the pharmacodynamic data of rocuronium versus mivacurium showed that the lag times of 0.6 mg/kg-rocuronium were significantly shorter than the lag times of 0.2-mg/kg mivacurium at the larynx (P < 0.01) and the adductor pollicis (P < 0.01) (Table 2).
At the adductor pollicis muscle, the Onset 90 and the Onset time were significantly shorter in the R-group (P < 0.01) than in the M-group (Table 2).
At the laryngeal muscles, the Onset 90 and the Onset time, however, were not significantly different between rocuronium and mivacurium (Table 2).
The comparison of the onset of the neuromuscular blockade at the two monitoring sites within the two groups showed that, for both drugs, the Lag time, Onset 90 and Onset time were significantly shorter at the larynx than at the adductor pollicis (P < 0.01, Table 2).
There was a good correlation between the peak effects at the larynx and the adductor pollicis muscle for both drugs (r = 0.85 for mivacurium , P < 0.01, r = 0.91 for rocuronium;P < 0.01). There was no correlation of the Lag time, Onset 90, or Onset time of both drugs between the larynx and the adductor pollicis muscle.
This study shows that EMG-responses, evoked by transcutaneous stimulation of the recurrent laryngeal nerve and obtained by using a commercially available disposable laryngeal surface electrode, can be used to monitor the onset of neuromuscular block at the laryngeal muscles with various nondepolarizing muscle relaxants. The laryngeal electrode can be attached to any tube routinely used; in our study of patients undergoing thyroid surgery, a single-use Woodbridge tube was used.
The stimulation at the notch of the thyroid cartilage evoked steady and reproducable signals in all patients; this is in accordance with the investigation of Donati et al. (5), who showed that stimulation of that site offers the best results of selectively stimulating the adducting laryngeal muscles.
It cannot, however, be ruled out that parts of the abducting laryngeal muscles are stimulated as well, so the compound action potential results are a mixed response of all the laryngeal muscles innervated by the laryngeal nerve.
Care was taken to place the laryngeal electrode exactly between the vocal cords to assure the best EMG tracings; after the intubation, immediate transcutaneous stimulation of the recurrent laryngeal nerve was used to find the best position where maximal EMG responses could be obtained. Then, the tube was secured in place and measurements commenced. The EMG measurements at the adductor pollicis muscle were performed in routine fashion with the forearm kept in supine position by bandages.
Stimulation was performed as single-twitch at 0.1 Hz to avoid the decrease of the neuromuscular response shown at frequencies higher than 0.1 Hz (6).
Our investigation shows that, for both nondepolarizing muscle relaxants, the onset time at the larynx was faster than at the adductor pollicis muscle when EMG signals were compared. d’Honneur et al. (7) recently published a study of 16 patients, in which a special tube with integrated electrode for superficial EMG tracing evoked responses of the larynx; they compared the onset at the larynx with the diaphragm where EMG responses were obtained by using superficial skin electrodes. In that study, 1 mg/kg succinylcholine and 0.6 mg/kg rocuronium were compared. After the injection of rocuronium (n = 8), the peak effect at the larynx was 97% ± 3% and the onset time 124 ± 39 s. This is in accordance with our results in a greater number of patients (n = 20).
Onset time at different muscle groups with different sensitivities to muscle relaxants should be compared in such a way that the degree of the peak effect created by the chosen dose of muscle relaxant is similar. It seems that the onset time of different muscle relaxants at the larynx can only be properly compared when similar peak effects are obtained. In our study, the peak effects were more than 94% for both drugs at the two sites of monitoring and correlated well for each drug between the larynx and the adductor pollicis muscle. We must bear in mind that the main clinical purpose of measuring onset time at the larynx is to determine when safe intubation conditions occur; complete blockade of the adducting laryngeal muscles is important for these conditions, especially when newer nondepolarizing muscle relaxants are tested in search of a replacement for succinylcholine for rapid-sequence induction.
We conclude, that evoked EMG responses of the adducting laryngeal muscles via a surface electrode attached to a commercially available tube can easily be used to monitor the onset time of muscle relaxants at the larynx. When compared with evoked EMG signals from the adductor pollicis muscle, the laryngeal onset time of 0.2 mg/kg of mivacurium and 0.6 mg/kg of rocuronium was significantly shorter; there was no difference of the onset time at the larynx between the two muscle relaxants.
With this new method, we can not only easily obtain objective data of onset times of muscle relaxants at the larynx, we can also compare them with the onset time at the adductor pollicis muscle by using similar methods of evoked EMG-responses via surface electrodes.