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GENERAL ARTICLES

Visual Estimation of Onset Time at the Orbicularis Oculi After Five Muscle Relaxants: Application to Clinical Monitoring of Tracheal Intubation

Frédérique Le Corre, MD^*, Benoît Plaud, MD^*, Ellen Benhamou, MD, PhD, and Bertrand Debaene, MD

*Département d’anesthésie-réanimation and Département de biostatistique et d’épidémiologie, Institut Gustave Roussy, Villejuif, France; and Département d’anesthésie-réanimation, Hôpital Jean Bernard, Poitiers, France

Address correspondence and reprint requests to Bertrand Debaene, MD, Département d’anesthésie-réanimation, Hôpital Jean Bernard, BP 577, 86021 Poitiers Cedex, France. Address e-mail to b.debaene{at}ecol.chu.univ-poitiers.fr

	Abstract

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The onset time of neuromuscular blockade at the adductor pollicis (AP) is different among neuromuscular blocking drugs, but these discrepancies had never been studied at the orbicularis oculi (OO). The purpose of this study was to verify if the differences in onset time observed at the AP still existed at the OO and to score the intubating conditions using monitoring at the OO after five muscle relaxants. The study included 172 adults aged 18–75 yr. Anesthesia was induced with fentanyl and propofol. Atracurium (0.5 mg/kg), mivacurium (0.20 mg/kg), rocuronium (0.6 mg/kg), succinylcholine (1.0 mg/kg), or vecuronium (0.08 mg/kg) was injected by random allocation. Time to complete disappearance of the response at the OO was assessed visually after train-of-four stimulation of the facial nerve. Laryngoscopy was then performed, and intubating conditions were determined on a scale of 1–4. Results were based on 150 patients. Onset time at the OO was (mean ± SD): succinylcholine (57 ± 17 s) < mivacurium (99 ± 19 s) = rocuronium (99 ± 47 s) < atracurium (129 ± 33 s) = vecuronium (135 ± 38 s) (P < 0.05). Overall intubating conditions were excellent (84%), good (14%), poor (1.3%), impossible (0.7%), and were similar among the five groups. We conclude that differences in onset time of muscle relaxants observed at the AP were also found at the OO. Visual estimation of the response at the OO correctly predicted good-to-excellent intubating conditions in more than 90% of cases for all the currently available muscle relaxants.

Implications: Onset time of neuromuscular blockade, as estimated visually at the orbicularis oculi, depends on the muscle relaxants given. Regardless of the relaxant used, intubating conditions at loss of orbicularis oculi are acceptable.

	Introduction

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In clinical practice, neuromuscular blockade is monitored by assessing the response of the adductor pollicis after ulnar nerve stimulation. The onset time of neuromuscular blockade, measured at the adductor pollicis, depends on the muscle relaxant used. Moreover, onset time differs from one muscle to another. Previous study has shown that the orbicularis oculi and the respiratory muscles have the same pharmacodynamic profile in terms of onset time and recovery profile after vecuronium administration (1). For instance, after a single dose of nondepolarizing muscle relaxant, the onset time was shorter at the respiratory muscles (i.e., the diaphragm and the laryngeal muscles) than at peripheral muscles, such as the adductor pollicis (2–6). Likewise, after atracurium, neuromuscular blockade appears earlier at the orbicularis oculi than at the adductor pollicis, but is close to the onset time in laryngeal muscles (7). Monitoring the onset time of muscle relaxants at the orbicularis oculi is associated with good intubating conditions earlier than monitoring at the adductor pollicis, at least with atracurium 0.5 mg/kg (8). No data concerning onset time of neuromuscular blockade and monitoring at the orbicularis oculi as a guide for tracheal intubation are available with other muscle relaxants in a large number of patients.

Therefore, the aim of the study was to verify if the differences in onset time observed among muscle relaxants at the adductor pollicis still exist when determined at the orbicularis oculi, and compare the intubating conditions when laryngoscopy is performed once the orbicularis oculi is completely blocked after five different muscle relaxants: atracurium, mivacurium, rocuronium, vecuronium, and succinylcholine.

	Methods

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One hundred seventy-two ASA physical status I or II patients, 18–75 yr old, were included in the study after obtaining written informed consent. The study was approved by the local ethics committee. Patients were scheduled for elective surgery (gynecological, abdominal, or breast surgery) requiring tracheal intubation. All patients were free of cardiovascular, hepatic, renal, or neuromuscular disease. They were not taking any drugs suspected to interfere with neuromuscular transmission. Exclusion criteria included anticipated abnormal airway (9), suspected allergy to muscle relaxants, and weight more than 30% of ideal body weight. All patients were premedicated with alprazolam 0.5 mg/kg per os 1 h before induction of anesthesia. Usual monitoring was used. Anesthesia was induced with fentanyl 3 µg/kg and propofol 2.5 mg/kg 30 s later. Ventilation with 100% oxygen was controlled manually, via a face mask, until tracheal intubation. Two cutaneous electrodes were placed on the temporal branch of the facial nerve, anterior to the earlobe as previously described (7). The facial nerve was stimulated supramaximally with train-of-four stimulation (four pulses 2 ms duration, at a frequency of 2 Hz, current intensity at 30 mA) every 10 s, and the muscular responses were estimated visually at the orbicularis oculi. Muscle relaxants were administered 60 s after propofol injection more than 10 s. The patients were allocated at random to one of the five muscle relaxants: atracurium 0.5 mg/kg (2 x ED₉₅), mivacurium 0.2 mg/kg (3 x ED₉₅), rocuronium 0.6 mg/kg (2 x ED₉5), vecuronium 0.08 mg/kg (2 x ED₉₅), and succinylcholine 1.0 mg/kg (3 x ED₉₅). The onset time of neuromuscular blockade, defined as the time elapsed between the end of the muscle relaxant injection and the suppression of the four responses at the orbicularis oculi, was estimated by a blinded physician who was not involved in the intubating procedure. When the orbicularis oculi was completely blocked, intubation was performed by another physician unaware of the muscle relaxant injected. The same physician estimated the quality of intubation by scoring the intubating conditions on a I–IV scale (Table 1)(10). Patients were excluded from the final analysis in two cases: 1) when the vocal cords were not completely visualized during the laryngoscopy and 2) when onset time was longer than 300 s. In patients not fully paralyzed after 300 s after the administration of the muscle relaxant, intubation was performed after giving a supplemental dose of muscle relaxant. Based on the estimated variability in onset time, it was calculated that a minimum of 30 patients per group would be necessary to demonstrate a 30-s difference in onset time with = 5% and ß = 20%. A test of normality was performed and statistical analysis used a one-way analysis of variance and Scheffé F-test to compare onset time and demographic data among the five different groups. A -test was used to compare intubating conditions. The differences were considered as significant when P < 0.05. The results are presented as means ± standard deviation with the ranges and coefficient of variation.

	Results

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Vocal cords were open in 93%, 83%, 93%, 97%, and 100% after atracurium, mivacurium, rocuronium, vecuronium, and succinylcholine, respectively. Laryngoscopy was easy in 93%, 76%, 90%, 83%, and 87%, respectively. Intubating conditions did not differ significantly in the five groups and were excellent (84%), good (14%), poor (1.3%), and impossible (0.7%) (Fig. 1). Laryngoscopy, vocal cords position, coughing, and intubating conditions were not significantly different among the five groups.

View larger version (40K): [in this window] [in a new window]   Figure 1. Intubating conditions after five muscle relaxants evaluated using a scale adapted from Krieg et al. (10) (Table 1): I = excellent, II = good, III = poor, and IV = bad. There is no significant difference between groups, and intubating conditions were excellent or good in 98% of cases.

	Discussion

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Factors such as hemodynamic effects of anesthetics (11) and the pattern of stimulation may induce variation in onset time of muscle relaxants (12). Therefore, we used the same anesthetic induction technique and the same pattern of stimulation to avoid this factor of variation.

Neuromuscular blockade was assessed visually because quantitative neuromuscular monitoring at the orbicularis oculi (i.e., electromyography, mechanomyography, accelerometry) cannot be used routinely.

We did not compare our results to a control group (i.e., without muscle relaxant). This is justified because the aim of the study was not to investigate the respective role of the anesthetics and muscle relaxants on intubating conditions, but to compare the intubating conditions when intubation was performed once the orbicularis oculi was completely blocked. It has been suggested that tracheal intubation can be performed without using a muscle relaxant (13). However, this technique requires a large dose of narcotic (alfentanil up to 40 µg/kg), and the incidence of good-to-excellent intubating conditions (<75%) is much less than in the present study (98%). The role of an anesthetic on intubating conditions may decline with the time spent to achieve complete neuromuscular blockade. If this is true, a difference in intubating conditions would be observed between the succinylcholine group (i.e., the shortest onset time) and the atracurium and vecuronium groups (i.e., the longest onset times) (Table 4). In fact, as our results clearly showed, the intubating conditions did not differ from one group to another. Thus, the role of the anesthetic on the intubating conditions is probably low when complete blockade is achieved at the orbicularis oculi. Likewise, the delay between propofol injection and intubating procedure is dependent on the muscle relaxant and cannot be controlled. Our results are in accordance with this because no difference was observed between groups even if the time between propofol injection and intubating procedure was different with respect to the onset time of neuromuscular blockade at the orbicularis oculi (Table 4).

Since the intubating conditions were good or excellent when complete blockade was achieved at the orbicularis oculi, one can assume that the onset time at this latter muscle was close to the onset time at the laryngeal adductor muscles. Only one study has confirmed this hypothesis after 0.5 mg/kg atracurium (7). In that study, onset time at the laryngeal adductor muscles was determined using a quantitative method, whereas the onset time at the orbicularis oculi was evaluated visually, as in our study. The onset time at the laryngeal muscles (132 ± 80 s, mean ± SD) was not significantly different from that at the orbicularis oculi (146 ± 58 s, mean ± SD) (7). This latter result was comparable with the onset time at the orbicularis oculi we found (129 ± 33 s) after the same dose of atracurium. Unfortunately, direct comparison between onset time at the orbicularis oculi and at the laryngeal muscle are not available, as most studies have compared adductor pollicis with laryngeal adductor muscles. After vecuronium 0.07 mg/kg, onset time was 3.3 ± 0.2 min (mean ± SEM) at the laryngeal muscle (2) and 3.4 ± 0.5 min (mean ± SEM) at the orbicularis oculi (1). Because the dose of vecuronium we used (0.08 mg/kg) was slightly larger, onset at the orbicularis oculi was shorter (135 ± 38 s), and the onset time at the laryngeal adductor muscles was probably shorter too. After rocuronium 0.5 mg/kg, onset time was 1.4 ± 0.1 min (mean ± SEM) at the laryngeal muscles (3), a value close to our data at the orbicularis oculi (99 ± 47 s) after 0.6 mg/kg of rocuronium. Thus, monitoring the onset time at the orbicularis oculi could be considered a good estimate of the onset time at the larynx after nondepolarizing neuromuscular blocking drugs and could be a useful guide for assessing the intubating conditions. Likewise, after succinylcholine, the onset time at the orbicularis oculi was close to that at the laryngeal muscles: 57 ± 17 s in our study vs 54 ± 6 s (mean ± SEM) at the orbicularis oculi and the laryngeal muscles, respectively, even if the dose was different (0.5 mg/kg vs 1 mg/kg in our study) (14). In clinical practice, during rapid sequence induction, it is expected that monitoring the onset time at the orbicularis oculi would also be a valuable guide to predict the quality of the intubating conditions.

After twice the ED₉₅ at the adductor pollicis, the onset time at the orbicularis oculi was significantly shorter after rocuronium (99 ± 47 s), compared with atracurium (129 ± 33 s) and vecuronium (135 ± 38 s). There was no difference between atracurium and vecuronium. This onset time classification at the orbicularis oculi was similar to that observed at the adductor pollicis (15). In our study, the onset time at the orbicularis oculi after mivacurium was similar to that at rocuronium (99 ± 19 s vs 99 ± 47 s, respectively). In fact, these data were not comparable because the doses were not equipotent. The dose of mivacurium was 0.2 mg/kg, which represented three times the ED₉₅. The choice was justified according to previous studies that showed inadequate intubating conditions after twice the ED₉₅ (0.14 mg/kg) (16). With this dose, we have already demonstrated that maximum blockade at the larynx was only 90%, and complete blockade was obtained in only 1 of the 11 studied patients (17). Despite lack of a statistical significant difference in intubating conditions (Fig. 1), it should be noted that the incidence of vocal cords opening and easiness of laryngoscopy were slightly lower after 0.2 mg/kg of mivacurium (83% and 76%, respectively).

After succinylcholine, the onset time at the orbicularis oculi was the shortest of all muscles relaxants we used. Likewise, the dose of succinylcholine we used was over three times the ED₉₅ (1.0 mg/kg) and was the dose usually administered in clinical practice. It has been shown that increasing the dose of succinylcholine did not shorten the onset time at the laryngeal muscles (14). The onset time of succinylcholine was close to the circulation time to muscles (an important factor governing onset) and thus did not influence by increasing the dose (18).

We observed a wide interindividual variability. For example, the onset time coefficient of variation at the orbicularis oculi ranged between 19% for mivacurium and 47% for rocuronium at equipotent doses (Table 4). Magorian et al. (19) observed a 37% and 34% onset time coefficient of variation at the adductor pollicis after 0.6 mg/kg rocuronium and 1.0 mg/kg succinylcholine, respectively. Moreover, when increasing the dose of rocuronium to three times the ED₉₅, the coefficient of variation of the onset time remained constant, and began to decrease only after a dose larger than four times the ED₉₅. Factors contributing to this interindividual variability remain unknown. Ten patients were excluded because the orbicularis oculi was not completely blocked 300 s after the administration of the different muscle relaxants. All of these patients received a supplemental dose of relaxants. In all these cases, the orbicularis oculi was fully blocked thereafter. Thus, the results confirmed that the interindividual variability was large even during the onset time of the neuromuscular blockade.

Twelve patients were excluded from the study because their vocal cords were not totally visualized during laryngoscopy. Of course, these exclusions may have impacted our results. If these patients were maintained in this final analysis, one option was to score their intubating conditions as impossible. With this pessimistic hypothesis, the incidence of clinically acceptable intubating conditions would decrease to 91% instead of 98%. In a more realistic point of view, one can assumed that intubating conditions would not be that poor in all the cases, and thus the rate of clinically acceptable conditions would be included between these two limits, with a theoretical average of 94.5%.

In summary, this study has clinical implications. Although it did not compare two muscles, the differences in onset time reported previously at the adductor pollicis among the five muscle relaxants were also observed at the orbicularis oculi. Furthermore, a wide interindividual variability of the onset time suggests that it is impossible to determine the moment in which the orbicularis oculi, and thus the laryngeal muscles, are fully paralyzed unless monitoring is used. This study demonstrated that excellent or good intubating conditions were obtained in 98% when the orbicularis oculi completely blocked whatever the muscle relaxants used with a dose at least twice the ED₉₅.

In conclusion, after an intubating dose of succinylcholine, atracurium, mivacurium, rocuronium or vecuronium, the onset time at the orbicularis oculi is different among the five muscle relaxants, but there is a great interindividual variability. The differences observed are consistent with those already known for the adductor pollicis. Likewise when the orbicularis oculi is completely blocked, intubating conditions were good or excellent in 98% of cases. According to these results, monitoring the onset time at the orbicularis oculi could be recommended for the clinical setting to assess individual sensitivity to muscle relaxants.

	Acknowledgments

 
The authors thank François Donati, MD, PhD, for carefully reviewing the manuscript.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999