Simultaneous determination of neuromuscular block at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscles

T. M. Hemmerling, J. Schmidt, C. Hanusa, T. Wolf and H. Schmitt

Department of Anaesthesiology, University Erlangen-Nuremberg, Germany*Corresponding author: Centre Hospitalier de l’Université de Montréal, Hotel-Dieu, Départment de l’anesthésie, 3840 Rue Saint-Urbain, Montréal (Quebec) H2W 1T8, Canada

Accepted for publication: July 13, 2000


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
We simultaneously determined the neuromuscular blocking effect of mivacurium 0.2 mg kg–1 at five muscles in 20 women undergoing gynaecological surgery. Evoked electromyographic responses were obtained using surface electromyography (EMG) at the adducting laryngeal muscles, the diaphragm (lateral to vertebrae T12/L1 or L1/L2) and the adductor pollicis muscle and acceleromyographic (AMG) responses were measured at the orbicularis oculi and the corrugator supercilii muscle. Onset time and times for the first twitch response (T1/T0) to return to 25, 75 and 90% at the adducting laryngeal muscles and the diaphragm were significantly (P<0.005) shorter than at the adductor pollicis, the corrugator supercilii or the orbicularis oculi muscles (mean (SD) onset time: 89 (26) s and 78 (17) s to 202 (45) s, 152 (41) s, 194 (40) s; T1/T0=25%: 10.4 (1.5) and 11.4 (1.2) min versus 20.5 (3.9), 15.9 (3.3), 16.3 (3.7) min; T1/T0=90%: 15.5 (1.6) and 16.1 (1.6) min versus 27.4 (4.6), 21.5 (3.8), 23.3 (5.1) min). Onset and clinical duration of neuromuscular block at the larynx and the diaphragm after mivacurium 0.2 mg kg–1 are shorter than in the peripheral muscles. Monitoring of neuromuscular block in the diaphragm was successfully used in all patients.

Br J Anaesth 2000; 85: 856–60

Keywords: neuromuscular block, mivaccurium; surgery, gynaecological


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In recent years, attempts have been made to measure onset and offset of neuromuscular block at various muscles The monitoring of the response of the larynx and the diaphragm to neuromuscular blocking drugs has enhanced our knowledge about the action of these agents and delivered more accurate data on the onset and clinical duration of neuromuscular block at those muscles. The determination of neuromuscular block by the introduction of a cuff-pressure technique for measurements at the larynx1 and electromyographic (EMG) monitoring of the diaphragm2 have replaced simple clinical observation in the study of neuromuscular block.3 The great inter-individual range of the pharmacodynamic profile of non-depolarizing neuromuscular blocking drugs makes the intra-individual comparison of onset and offset interesting.

We simultaneously determined the onset and offset of neuromuscular block produced by mivacurium 0.2 mg kg–1 at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscle using non-invasive, superficial electrodes. To record the diaphragmatic response, we modified the technique of skin EMG by placing the electrodes at the back of the patient, lateral to vertebrae T12/L1 or L1/L2, just inferior to the 12th rib, thus presenting a novel site for monitoring diaphragmatic neuromuscular block.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
After approval of the local ethics committee and written informed consent, 20 women undergoing gynaecological surgery were included in the study. Pregnant women, patients with neuromuscular, hepatic or renal disease and patients receiving medications known to interact with neuromuscular blocking drugs were excluded.

Anaesthesia was induced using alfentanil 20 µg kg–1 followed by a target-controlled infusion of propofol (target concentration 4 µg ml–1) programmed to reach the target concentration within 30 s. After induction of anaesthesia, the trachea was intubated through the mouth using a Woodbridge tube (Mallinckrodt, UK, size 7.0) with the surface laryngeal electrode (Magstim company, UK) attached 2 cm above the origin of the cuff. The electrode was placed between the vocal cords for optimal EMG tracing.4 Anaesthesia was maintained with a target-controlled infusion of propofol (target concentration 3 µg ml–1) and alfentanil in increments of 10 µg kg–1 given at the discretion of the anaesthetist; mechanical ventilation was adjusted to achieve an end-tidal carbon dioxide-pressure of 3.5–4.5 kPa.

Two Ag/AgCl-skin-electrodes were attached lateral to vertebrae T12/L1 or L1/L2 (wherever the maximum response was better) on the right paravertebral side of the back, inferior to the 12th rib, and placed 2 cm apart for monitoring of the response of the right diaphragmatic muscular crux to phrenic nerve stimulation5 (Fig. 1). One Ag/AgCl-electrode was used as a ground electrode and placed on the hip bone distant to the recording site.



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Fig 1 Position of the recording electrodes; marked are T 7, T 12, 12th rib; electrodes are placed 2 cm apart at T 12/L1 or L1/L2, wherever the response is better (the third electrode is the ground electrode).

 
The phrenic and recurrent laryngeal nerves were stimulated transcutaneously using one external bipolar nerve stimulator (Multiliner®, Tönnies company, Germany) on the right side at the inferolateral edge of the sternocleidomastoid muscle for the phrenic nerve. In addition, two Ag/AgCl electrodes were positioned over the notch of the thyroid cartilage on the same side for the recurrent laryngeal nerve.1 The stimulation site was selected, which produced only minimal or no concomitant stimulation of the brachial plexus. The probe of the external nerve stimulator is attached at the neck 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 right neck to determine the supramaximal stimulation and recorded using modified Multiliner® (Toennies, Germany) nerve conduction software. The current was increased from 0 mA to the current with the maximal EMG response and then increased by 10 mA to assure supramaximal stimulation. The amplitudes of the diaphragmatic and the laryngeal compound action potentials (peak-to-peak) were measured and recorded (Fig. 2). After stimulation of the right ulnar nerve using Ag/AgCl-electrodes attached to the forearm, 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).



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Fig 2 Compound action potential of the electromyographic response of the laryngeal muscles and the diaphragm for a representative patient; amplitude P1–P2 measured as muscular response (lines mark measurement points).

 
An AMG probe was placed on the medial part of the right superciliary arch was equipped with an AMG probe (TOFNMT-guard, eye-adapter, Organon Teknika, Finland) to record the neuromuscular response of the corrugator supercilii muscle. Another AMG probe was placed on the left upper eye lid to record evoked responses of the orbicularis oculi muscle.6 Stimulation of the upper branches of the facial nerves was performed on both sides using two Ag/AgCl-electrodes (size 1x1.5 cm) attached to the skin 2 cm anterior to the ear lobe. The automatic calibration set-up of the TOF-guardINMT (Organon Helsinki, Finland) was used to determine supramaximal stimulation on both sides (single twitch, 0.1 Hz). After no change in the neuromuscular response could be detected at all five sites for 10 min, the patients received mivacurium 0.2 mg kg–1, injected within 15 s into a fast-flowing infusion of Ringer solution. No further dose of neuromuscular blocking drug was given. Body temperature was measured at the forehead and kept above 35.6°C using a heating blanket (Bair Hugger, MN, USA).

The time from the end of injection of mivacurium to the first twitch depression (lag time), the maximum twitch depression (onset time) and the maximum block (%-reduction of the maximal neuromuscular response) were measured. To determine clinical duration of neuromuscular block, single-twitch responses every 15 s were used; time for the first twitch response (T1/T0) to return to 25, 75 and 90% was measured.

Statistical analysis
The results are expressed as mean (standard deviation (SD)) and range. The pharmacodynamic parameters were compared between the different monitoring sites using analysis of variance (ANOVA), followed by Fisher’s least significant difference strategy for multiple comparisons; P<0.05 was regarded as showing a significant difference.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In 20 female patients with a mean age of 44 (SD 16) yr (range 18–78 yr) and a mean weight of 64 (10) kg (46–81 kg), determination of the supramaximal stimulation at all five monitoring sites was successful. No side effects as a result of the simultaneous transcutaneous stimulation of the recurrent laryngeal and phrenic nerve with a mean current of 45 (6) mA (range 30–55 mA) such as arrhythmias or skin irritation were noted.

Mean maximum block was more than 98% at all sites. It was 99 (SD 4)% (range 88–100%) and 99 (4)% (range 82–100%) at the larynx and the diaphragm, respectively. The mean maximum block at the adductor pollicis, the corrugator supercilii and the orbicularis oculi muscle was 99 (2)% (93–100%), 99 (3)% (84–100%) and 98 (4)% (86–100%), respectively. There was no statistically significant difference between the muscles.

Onset times and clinical duration of neuromuscular block are presented in Figure 3A and Figure 3B. Lag time and onset time of neuromuscular block were significantly shorter at the larynx and the diaphragm than at the other muscles (P<0.005), without being significantly different between the diaphragm and the larynx or between the orbicularis oculi and the corrugator supercilii muscle.




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Fig 3 Onset and clinical duration of neuromuscular block after mivacurium 0.2 mg kg–1 Values are mean; error bars indicate standard deviation The larynx, the diaphragm and the adductor pollicis muscle monitored using EMG, the orbicularis oculi and the corrugator supercilii muscle are measured using AMG. (A) Lag time (black column) and onset time (white column): time from injection of mivacurium to the first and maximal effect; *P<0.005 versus larynx and diaphragm, #P<0.025, §P<0.005 versus adductor pollicis muscle, respectively. Mean time in box. (B) T1/T0=25% (white column), T1/T0=75% (black column), T1/T0=90% (striped column): time from injection to recovery of the twitch response to 25, 75 and 90%. *P<0.05 versus larynx and diaphragm, #P<0.005 versus larynx and diaphragm, §P<0.05 versus corrugator supercilii muscle.

 
The lag and onset time at the adductor pollicis muscle were significantly longer than the times at the corrugator supercilii muscle (P<0.025); although the lag time at the adductor pollicis muscle was significantly longer than the lag time at the orbicularis oculi muscle (P<0.005), the onset times at the adductor pollicis and the orbicularis oculi muscle did not differ statistically (202 versus 194 s). Time for the first twitch response (T1/T0) to return to 25, 75 and 90% was shorter for the larynx and the diaphragm than for the other muscles (P<0.05 versus the orbicularis oculi and the corrugator supercilii muscle, P<0.005 versus the adductor pollicis muscle).

The clinical duration of neuromuscular block at the corrugator supercilii muscle was significantly shorter than at the adductor pollicis muscle (P<0.05), but not statistically different from the clinical duration at the orbicularis oculi muscle.


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The simultaneous determination of neuromuscular block after mivacurium 0.2 mg kg–1 at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscle revealed that onset at the respiratory muscles (larynx, diaphragm) reaches a mean maximum block of 99% after 80–90 s, whereas the onset at the orbicularis oculi and the corrugator supercilii muscle is more than 150 s and at the adductor pollicis muscle is more than 3 min. Time for T1/T0 to reach 25% was 10–12 min at the larynx and the diaphragm, more than 15 min at the orbicularis oculi and corrugator supercilii muscle and more than 20 min at the adductor pollicis muscle.

The onset times determined in this study correspond well with times determined by judging the intubating conditions at the larynx and the diaphragm, but the responses are in contrast to visual observation of the orbicularis oculi response to stimulation.

Le Corre and colleagues7 estimated the onset of several neuromuscular blocking drugs at the orbicularis oculi muscle and found that visual estimation was a good predictor of excellent or good intubation conditions. They concluded that loss of orbicularis oculi responses are acceptable predictors of good intubation conditions. They estimated an onset time of 99 s at the orbicularis oculi muscle after mivacurium 0.2 mg kg–1 and performed tracheal intubation with good to excellent intubation conditions. This would be in concordance with the diaphragmatic and laryngeal onset times measured in this study (78 and 89 s) but not with another study which compared the effects of mivacurium 0.2 mg kg–1 at the diaphragm and the geniohyoid muscles. D’Honneur and colleagues8 determined the onset time at the diaphragm, using surface EMG at 158 s longer than it was in our study. The major difference between their study and this one is the different calibration time: whereas D’Honneur and colleagues only waited 3 min before measurements were started, the current study set-up used a 10-min calibration time of supramaximal stimulation. McCoy and colleagues9 found that the longer the duration of control stimulation the shorter the onset measured.

Rimaniol and colleagues6 studied the effect of mivacurium 0.15 and 0.25 mg kg–1 at the orbicularis oculi muscle using AMG. They found that for mivacurium 0.15 mg kg–1 the onset of neuromuscular block was not different between the orbicularis oculi and the adductor pollicis muscle (235 (SD 76) versus 232 (67) s), but the offset was significantly shorter at the orbicularis oculi muscle. For mivacurium 0.25 mg kg–1, the onset was significantly shorter at the orbicularis oculi muscle than at the adductor pollicis muscle (90 (25) versus 160 (30) s). In the current study, the onset of block after mivacurium 0.2 mg kg–1 was shorter at the orbicularis oculi muscle than at the adductor pollicis muscle (194 (40) versus 202 (45) s) but failed to reach statistical significance.

We stimulated the phrenic and the recurrent laryngeal nerve transcutaneously without difficulty. It could be that in patients with large necks or an enlargened thyroid gland, transcutaneous stimulation of the phrenic nerve using a surface probe might be difficult; in those patients, we prefer percutaneous stimulation via needle electrodes. Concomitant stimulation of the brachial plexus was absent or minimal and did not affect the monitoring of the diaphragmatic response; monitoring the diaphragm on the patient’s back is certainly advantageous to rule out artefacts from concomitant stimulation of the brachial plexus.

Donati and colleagues2 introduced surface EMG of the diaphragm to monitor neuromuscular block into research practice; it was an easy and objective way to measure onset and offset of block at this muscle. Skin electrodes attached at the 7th or 8th intercostal space between the mid-clavicular and the anterior axillary line, however, cannot be used during open and laparoscopic abdominal surgery as they are within the surgical fields.

Because the muscular crura of the lumbar diaphragm are inserted into the first two to three lumbar vertebrae, it seemed possible to monitor the response to phrenic stimulation on the patient’s back, lateral to vertebrae T12/L1 or L1/L2 (Fig. 2). Future studies will show whether this location can be used for routine intra-operative monitoring of the diaphragm.

The corrugator supercilii muscle, a small muscle of the superciliary arch, located medially under the eyebrow, is inserted into the forehead skin and responsible for vertical frowning of the forehead. It can be monitored using an AMG probe attached to the medial part of the superciliary arch at a 90° angle to the muscle contraction direction, in a similar way to the AMG measurement of the orbicularis oculi muscle.6 10

The only study of neuromuscular block at the corrugator supercilii muscle was recently presented as an abstract by Plaud and Donati.11 They measured maximum block and recovery to T1/T0=25% after rocuronium 0.6 mg kg –1 at the corrugator supercilii muscle and the larynx. They concluded that the neuromuscular response measured at the corrugator supercilii muscle was a good reflection of the laryngeal muscle response. We found significant differences in onset time and clinical duration between the larynx and the corrugator supercilii muscle but the maximum block was not significantly different.

The morphological difference between the orbicularis oculi muscle and the corrugator supercilii muscle has been the focus of a recent anatomical study. Goodmurphy and colleagues12 have found that the orbicularis oculi muscle fibres are small, rounded and 89% fast-twitch type-II-muscle fibres, whereas the corrugator supercilii muscle fibres were larger, polygonal, and 49% of fast-twitch type II. The capillary index (capillary area per unit of contractile area) of the corrugator supercilii muscle, however, was 2.4 times the capillary index of the orbicularis oculi muscle. The difference in capillary index and the larger size of the muscle fibres13 might explain the faster onset of neuromuscular blocking drugs at the corrugator supercilii muscle. Further studies of the action of other neuromuscular blocking drugs at the corrugator supercilii muscle are needed to define the role of this muscle as a predictor of the laryngeal muscle response.

In conclusion, we present the first simultaneous determination of neuromuscular block at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscle. Surface electrodes were used to record evoked responses at all sites. The monitoring of the diaphragmatic response at the back of the patient allows intra-operative monitoring during abdominal surgery. In contrast to previous findings with rocuronium,11 onset and clinical duration of neuromuscular block after mivacurium at the corrugator supercilii muscle did not accurately reflect onset and clinical duration of neuromuscular block at the larynx or the diaphragm. More studies are needed to define the role of this muscle for neuromuscular monitoring in clinical practice.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 Donati F, Plaud B, Meistelman C. A method to measure elicited contraction of laryngeal adductor muscles during anesthesia. Anesthesiology 1991; 74: 827–32[ISI][Medline]

2 Donati F, Antzaka C, Bevan DR. Potency pancuronium at the diaphragm and the adductor pollicis muscle in humans. Anesthesiology 1986; 65: 1–5[ISI][Medline]

3 Goldberg ME, Larijani GE, Azad SS et al. Comparison of tracheal intubating conditions and neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical outpatients. Anesth Analg 1989; 69: 93–9[Abstract]

4 Hemmerling TM, Schmidt J, Wolf T, Klein P, Jacobi K. Comparison of onset of succinylcholine vs. two doses of rocuronium with a new method of monitoring neuromuscular block at the laryngeal muscles using surface laryngeal electromyography. Br J Anaesth 2000; 85: 251–5[Abstract/Free Full Text]

5 Moore KL, Dalley, AF. Clinically Oriented Anatomy. Baltimore: Lippincott Williams & Wilkins, 1999: 291

6 Rimaniol JM, D’Honneur G, Sperry L, Duvaldestin P. A comparison of the neuromuscular blocking effects of atracurium, mivacurium, and vecuronium on the adductor pollicis and the orbicularis oculi muscle in humans. Anesth Analg 1996; 83: 808–13[Abstract]

7 Le Corre F, Plaud B, Benhamou E, Debaene B. Visual estimation of onset time at the orbicularis oculi after five muscle relaxants; application to clinical monitoring of tracheal intubation. Anesth Analg 1999; 89: 1305–10[Abstract/Free Full Text]

8 D’Honneur G, Slavov V, Merle JC et al. Comparison of the effects of mivacurium on the diaphragm and geniohyoid muscles. Br J Anaesth 1996; 77: 716–9[Abstract/Free Full Text]

9 McCoy EP, Mirakhur RK, Connolly FM, Loan PB. The influence of the duration of control stimulation on the onset and recovery of neuromuscular block. Anesth Analg 1995; 80: 364–7[Abstract]

10 De Rossi L, Fritz H, Kroeber L, Klein U. Cisatracurium am M. orbicularis oculi. Anaesthesist 1999; 48: 602–6[ISI][Medline]

11 Plaud B, Donati F. The corrugator supercilii, not the orbicularis oculi, reflects rocuronium neuromuscular blockade of the adducting laryngeal muscles. Anesthesiology 1999; 91 (Suppl. 3A): A1032

12 Goodmurphy CW, Ovalle WK. Morphological study of two human facial muscles: orbicularis oculi and corrugator supercilii. Clin Anat 1999; 12: 1–11[ISI][Medline]

13 Ibebunjo C, Hall LW. Muscle fibre diameter and sensitivity to neuromuscular blocking drugs. Br J Anaesth 1993; 71: 732–3[Abstract]