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Anesth Analg 2004;98:1729-1733
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000112305.87873.61

TECHNOLOGY, COMPUTING, AND SIMULATION

Steven J. Barker Section Editor

Simultaneous Determination of Neuromuscular Blockade at the Adducting and Abducting Laryngeal Muscles Using Phonomyography

Thomas M. Hemmerling, MD, DEAA, Guillaume Michaud, Guillaume Trager, DESS, and François Donati, PhD, MD, FRCPC

Neuromuscular Research Group (NRG), Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal (CHUM) Hôtel-Dieu, Université de Montréal, Canada

Address correspondence and reprint requests to T.M. Hemmerling, MD, DEAA, Department of Anesthesiology, Université de Montréal, Hôtel-Dieu, 3580 Rue St. Urbain, Montréal (Québec) H2W 1T8, Canada. Address e-mail to thomashemmerling{at}hotmail.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Phonomyography (PMG) is a new method for measuring neuromuscular blockade (NMB) at the larynx. In this study, we used PMG to compare NMB at the posterior cricoarytenoid (PCA) and the lateral cricoarytenoid muscle (LCA) in humans. Twelve patients were included in this study. Endotracheal intubation was performed without aid of neuromuscular blocking drugs. One small condenser microphone was inserted beside the vocal cords into the muscular process at the base of the arytenoid cartilage to record acoustic responses of the LCA (vocal cord adduction), and a second microphone was placed behind the larynx to measure NMB of the PCA (vocal cord abduction). Stimulation of the recurrent laryngeal nerve was performed using superficial electrodes placed at the neck (midline between jugular notch and cricoid cartilage) using train-of-four (TOF) stimulation every 12 s. After supramaximal stimulation, mivacurium 0.1 mg/kg was injected and onset, peak effect, and offset of NMB measured and compared using t-test (P < 0.05). The data are presented as mean (SD). Peak effect, onset time, and early recovery to 25% of control twitch height were not significantly different between PCA and LCA at 86% (13) versus 78% (16), 2.3 min (0.45) versus 2.3 min (1.0), and 9.55 min (3.05) versus 8.5 min (4.7), respectively. However, recovery to 75%, 90% of control twitch height, and recovery to a TOF ratio of 0.8 were significantly longer at the PCA than at the LCA at 14 min (4) versus 11 min (5), 17 min (5) versus 11.8 min (5.6), and 17.5 min (5.6) versus 12.3 min (5.5), respectively. The authors conclude that recovery of NMB at the PCA takes longer than at the LCA in humans after mivacurium.

IMPLICATIONS: After neuromuscular blockade in humans, the recovery of the ability to open the vocal cords takes longer than the ability to close the vocal cords.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Phonomyography (PMG) is based on the fact that contracting muscles emit low frequency sounds (1,2). Those acoustic signals can be recorded by special microphones (3). Recently, PMG was presented as a novel, sensitive, and noninvasive method to measure neuromuscular blockade (NMB) at the larynx, which can be used interchangeably with the standard cuff pressure method (4). Thereby, a small microphone was placed lateral to the vocal cords, next to the lateral cricoarytenoid muscle (LCA) to record NMB at the adducting laryngeal muscles. However, measuring NMB at the adducting laryngeal muscles might not reflect the complete profile of NMB at the larynx because several animal studies have shown that the pharmacodynamic behavior of adducting and abducting laryngeal muscles is different (5–7). A more detailed look at the differential laryngeal muscle block in humans requires a sensitive method able to differentiate between adduction and abduction of the vocal cords, should ideally be noninvasive, and should present the complete profile of NMB. The most interesting muscles seem to be the posterior cricoarytenoid muscle (PCA) as the sole abductor of the vocal cords and the LCA as the principal adductor of the vocal cords. We used PMG to simultaneously measure onset and offset of NMB at the PCA and LCA in humans.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After approval of the local ethics committee and obtaining informed consent, 12 patients undergoing general surgery were included in the study. Patients with coexisting neuromuscular disease or patients on medication known to interact with neuromuscular transmission were excluded.

After arrival in the operating room, routine monitoring was started. Anesthesia was induced with remifentanil 0.25–0.5 µg · kg–1 · min–1; 2 min later, propofol 2–3 mg/kg was injected. After loss of consciousness and ventilation via face mask for 2 min with 100% oxygen, an endotracheal tube was inserted without the aid of NMB drugs, and ventilation was controlled to maintain an end-tidal PETCO2 of 3.5–4.5 kPa. Anesthesia was maintained with 1–1.5 mean alveolar anesthetic concentration (MAC) of sevoflurane in a breathing gas mixture of 30% oxygen in air to maintain a target bispectral index of 50 (A 2000 monitoring system, Aspect Medical Company, Newton, MA). Analgesia was provided by remifentanil 0.05–0.25 µg · kg–1 · min–1 throughout surgery.

One small condenser microphone was inserted using a Magill forceps beside the vocal cords into the muscular process at the base of the arytenoid cartilage to record acoustic signals from the contraction of the LCA (Fig. 1 and 2). A second microphone was inserted directly posterior of the larynx to record the contraction of the posterior cricothyroid (CT) muscle, the sole abducting laryngeal muscle (8). Correct positioning of the microphones before and immediately after the observation period was controlled in all patients. The microphone signals were amplified and band pass filtered between 0.5 Hz and 1000 Hz using an AC/DC amplifier (Model 7P122, Grass Instruments, Astra-Med, Inc, West Warwick, RI). The signals were continuously sampled at 100 Hz using the Polyview® software package, digitized and stored on a portable microcomputer. The single twitch PMG signals were measured peak-to-peak (Fig. 3). NMB was measured simultaneously at both sites.



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  		Figure 1. Illustration of location of the lateral (1) and posterior (2) microphones. PCA = posterior cricoarytenoid muscle; LCA = lateral cricoarytenoid muscle.

 


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  		Figure 2. Illustration of location of the lateral (1) and posterior (2) microphones. PCA = posterior cricoarytenoid muscle; LCA = lateral cricoarytenoid muscle. Modified after Gray (24).

 


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  		Figure 3. Typical phonomyographic train-of-four signal. First twitch amplitudes were calculated from M1-M2.

 
Stimulation of the recurrent laryngeal nerve was performed by using two superficial electrodes placed medially at a vertical line between the sternal notch and the cricoid cartilage (9). Supramaximal stimulation was determined using single-twitch stimulation at 0.1 Hz. Stimulation was performed using a constant current stimulator (Innervator®, Fisher and Paykel Healthcare, Auckland, New Zealand), which generated single-twitch square pulses of 0.2 ms with a current intensity between 0 and 70 mA (train-of-four [TOF] stimulation every 12 s). After at least 5 min of supramaximal stimulation and stable baselines for all signals, mivacurium 0.1 mg/kg was injected within 5 s into fast-flowing Ringer’s lactate solution. Onset, maximum effect, and offset of NMB were determined.

The first twitch response was used to analyze onset time (time to reach maximum decrease in twitch amplitude), time to reach 25%, 75%, and 90% of control twitch response (T 25%, T 75%, and T 90%), and the time to reach T 75% from T 25% (recovery index). The maximum effect was determined as the maximum decrease of the twitch response and recorded. Time to reach a TOF ratio of 0.8 was also calculated for all signals. Fast Fourier transformation was used to determine peak frequency of the first twitch response at control stimulation for both muscles in all patients.

Sample size was calculated to detect an estimated difference of 20% of mean TOF 0.8 between the 2 sites with a type I error rate of 5% and a power of 90%. Data of NMB at both sites were compared using a paired t-test. P < 0.05 was considered as showing a significant difference. Bias and precision of all measured times (onset time, T 25%, T 75%, T 90%, recovery index, and TOF 0.8) and maximum frequency between the 2 recording sites were calculated using the Bland Altman method (10). Data are presented as mean (SD; range where indicated).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
NMB was determined in eight men and four women with a mean age of 45 yr (11) and weight of 77 kg (11). Correct positioning of the microphones at their respective monitoring sites was confirmed in all patients before the stimulation and after the observation period by direct laryngoscopy. Microphones were all in place and in correct position with the recording surface towards the respective muscles. The peak frequencies were in the ranges of 5–8 Hz for PCA and 1–6 Hz for LCA, with means of 5.63 (0.92) Hz and 5.10 (1.62) Hz (no significant difference). A typical PMG signal is shown in Figure 3. Pharmacodynamic data are presented in Table 1. There was no significant difference of onset time and T 25% between both recording sites. Peak effect was also not different between PCA at 86% (13%) and the LCA at 78% (16%). Recovery index, T 75%, T 90%, and TOF 0.8 were significantly longer at the PCA than at the LCA (Fig. 4). The bias and precision of pharmacodynamic data between the two muscle groups are presented in Table 2.


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  		Table 1. Neuromuscular Blockade for Posterior Cricoarytenoid Muscle (PCA) and Lateral Cricoarytenoid Muscle (LCA)
 


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  		Figure 4. Recovery curves for LCA and PCA muscles. Mean times (first twitch responses) and SD of time-response curves for n = 12 patients. (T 25% calculated for n = 10 patients) (ajouté selon les reviewers). PCA = posterior cricoarytenoid muscle; LCA = lateral cricoarytenoid muscle.

 

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  		Table 2. Bias and Precision for Both Muscles (Posterior Cricoarytenoid Minus Lateral Cricoarytenoid Muscle)
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
We were able to measure onset time, peak effect, and offset of NMB at both adductor and abductor laryngeal muscles using PMG. We found that offset of NMB is longer at the PCA than at the LCA. On average, recovery index is twice as long at the PCA than at the LCA, and time to reach TOF 0.8 is almost 50% longer for PCA than for LCA. However, onset, peak effect, and start of recovery of NMB (as documented in T 25%) are similar between the two muscles. The peak frequencies measured for the PCA and LCA were similar and comparable to the ones found for other small muscles at around 5 Hz (11).

There are only four published studies comparing the NMB profile between different intrinsic muscles of the larynx (5,6,7,12). These studies indicate that offset at the PCA (abducting laryngeal muscles) is different from muscles responsible for adduction or tension of the vocal cords and that the difference is species specific. Igarashi and Iwasaki (7) found, in an in vitro study using rat larynxes, that the PCA is more sensitive to tubocurarine than the LCA and explained this by different sensitivities at the pre- and postsynaptic sites of the neuromuscular junction and not by different blood supply. Another finding was that the LCA contained significantly more slow-twitch muscle fibers than the PCA muscle. Michalek-Sauberer et al. (6) determined onset and recovery of NMB after vecuronium for PCA and the LCA in cats. They found a shorter onset time at the PCA than the LCA but a longer recovery time at the PCA in comparison to the LCA.

In the only study performed in humans, Iwasaki et al. (12) found a more intense NMB at the CT muscle (a tensor of the vocal cords) than at the PCA, with faster recovery at the PCA than in the CT. They found that vecuronium created a more intense block at the CT than at the PCA. Although the peak effect at the PCA was 8.3% higher than at the LCA (± 13.6% SD), this difference did not reach statistical significance. The problem with Iwasaki et al.’s (12) study is that it was not performed in a conventional manner by giving a bolus injection of a muscle relaxant and observing onset, offset, and peak effect of the NMB. They determined the onset of NMB and the maximum effect after a vecuronium infusion and did not measure recovery of NMB.

Multiple factors might explain the neuromuscular differences between different laryngeal muscles. First, human PCA muscle contains more of type I muscle fibers (slow contraction) than LCA and human LCA muscle has the most frequent proportion of type II fibers (high contraction speed) from all intrinsic laryngeal muscles (13). There is a different sensitivity in fast and slow muscles to nondepolarizing blocking drugs (14–16). Pharmacokinetics can also be modified by the size of muscle fibers (17), blood perfusion (18,19), and density of acetylcholine receptors.

Measuring simultaneously NMB at the adducting and abducting laryngeal muscles in humans is difficult. The most common method to measure NMB at the larynx, the cuff pressure method (9), consists of inserting the endotracheal tube into the trachea with the cuff placed between the vocal cords; this method can only measure the adduction of the vocal cords. Similarly, electromyography using a surface electrode glued around the tube can only record electromyographic signals of vocal cord adduction (20). Iwasaki et al. (12) used electromyography via needle electrodes to measure NMB at different laryngeal muscles in one study. However, the needles were inserted in patients where subsequently the larynxes were removed because of tumor growth. This method obviously bears the risk of laryngeal hematoma, especially when more than one muscle is monitored and several needles have to be inserted.

PMG has been validated as a method that can be used interchangeably with the cuff pressure method to determine NMB at the adducting laryngeal muscles (4).

Small muscles can be identified with minimal signal power (11). Perhaps a microphone placed posterior to the larynx should mainly record acoustic signals caused by the contraction of the posteriously located laryngeal muscle. Anatomically, this is the PCA muscle, the only laryngeal muscle responsible for vocal cord abduction. It is unlikely that the posteriorly placed microphone also recorded signals of the vocal cord adduction because it was placed in such a position that it was distant enough from the adducting laryngeal muscles. It is also unlikely that the posterior microphone recorded signals from muscles of the pharynx. Anatomically, the inferior constrictor of the pharynx is located at the upper entrance of the esophagus and is innervated by the pharyngeal nerve plexus, which receives its nerve supply from branches of the vagus. Our stimulation setup was chosen to avoid concomitant stimulation of the vagus nerve while stimulating the recurrent laryngeal nerve; in no patient did we observe a change in heart rate as an indication of concomitant vagal stimulation. During the study period, great care was taken to confirm the microphone position immediately before and immediately after the end of the measurement period.

In earlier studies of NMB of the larynx, only recovery of NMB at the adducting laryngeal muscles is presented. This has led to the opinion that laryngeal recovery is much faster than recovery of peripheral muscles, such as the adductor pollicis muscle (21–23). However, our study shows that some muscles of the larynx take longer. This suggests that complete recovery of the larynx (required for unimpaired breathing and complete protection of the airway) actually takes longer than previously thought. Complete recovery of all laryngeal functions might be closer to peripheral muscles than previously thought.

Our findings indicate that NMB at various intrinsic laryngeal muscles is variable and that recovery of laryngeal block determined using methods measuring response of adducting laryngeal muscles cannot be taken as representative for other intrinsic muscles. In humans, the ability to open the vocal cords after NMB returns later than the ability to close the vocal cords.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Barry DT. Muscle sounds from evoked twitches in the hand. Arch Phys Med Rehabil 1991; 72: 573–5.[Web of Science][Medline]
  2. Barry DT, Cole NM. Muscle sounds are emitted at the resonant frequencies of skeletal muscle. IEEE Trans Biomed Engl 1990; 37: 525–31.
  3. Hemmerling TM, Babin D. Phonomyography-acoustic myography using condenser microphones: a promising new method of monitoring neuromuscular transmission. Anaesth Intensive Care 2002; 30: 532–3.
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  7. Igarashi M, Iwasaki H. Mechanism of the differential sensitivity in the rat adductor and abductor laryngeal muscles to a non-depolarizing neuromuscular blocker. Br J Anaesth 1995; 75: 339–43.[Abstract/Free Full Text]
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Accepted for publication November 26, 2003.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2004 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press