Effects sites of NMBA and the monitoring of clinical muscular relaxation

 

Claude Meistelman, Department of Anaesthesiology, School of medicine, Nancy, France

 

Several studies have demonstrated that the time course of neuromuscular block in various skeletal muscles is different from that in the adductor pollicis and discrepancies could exist both in onset time, duration of action and intensity of paralysis. Therefore the understanding and knowledge of the relationship between neuromuscular function at the monitored muscle and the other muscles are important in the interpretation of monitoring.

The diaphragm and the laryngeal adductor muscles are more resistant to non depolarising muscle relaxants (NDMR) than the adductor pollicis, complete paralysis of these muscles is not expected with a dose that barely blocks the adductor pollicis. The resistance of the respiratory muscles explain why the diaphragm and the laryngeal adductor muscles recover from paralysis induced by muscle relaxants more rapidly than does the adductor pollicis; Although respiratory muscles are more resistant to NDMR, paralysis may occur before complete paralysis at the adductor pollicis. This apparent discrepancy can be explained by considering the factors which influence neuromuscular effect, particularly the rate of equilibration between plasma and the effect compartment. After a bolus dose of NDMR, equilibrium between plasma and the neuromuscular junction will be reached sooner at the muscle group with a more rapid equilibration.. Even if the muscle group with a more rapid equilibration is resistant, the greater peak concentration will offset this to produce a more intense peak effect; Using a pharmacodynamic modelling approach, it was shown that that the rate of equilibration between plasma and effect was faster for the diaphragm and the laryngeal adductor muscles than for the adductor pollicis 1. Another study has shown, following rocuronium administration, that the rate constant of transport between plasma and the effect compartment (ke0) was significantly greater at the laryngeal adductor muscles (0.260 minutes) than at the adductor pollicis (0.168 minutes) The EC50 was significantly greater at the laryngeal muscles (1424 g/L) than at the adductor pollicis (823 g/l) 2. Although the respiratory muscles are resistant they are blocked before the adductor pollicis because concentration at the neuromuscular junction increase more rapidly at the respiratory muscles than at the adductor pollicis. The Ke0 of NDMR is mainly dependant of circulatory factors (muscle blood flow) and the partitioning of the relaxant between blood and muscle 3. Therefore, it is likely that the more rapid equilibration of laryngeal muscles when compared with the adductor pollicis is the result of the greater perfusion of the respiratory muscles. During recovery, both rapid equilibration and lesser sensitivity of the respiratory muscles contribute to earlier recovery when compared with the adductor pollicis.

Surprisingly, ventilatory weakness may still be detected until the adductor pollicis has recovered almost completely. Small doses of pancuronium (0.02 mg/kg) depress the swallowing reflex to a greater extent than the strength of peripheral muscles. This indicates that muscles involved with maintenance of airway patency are more sensitive to relaxants than other respiratory muscles and possibly peripheral muscles. Thus following administration of small doses of non depolarising muscle relaxants such as used during the priming technique, there is a risk of aspirating gastric content by paralysis of upper airway muscles. Recent studies have demonstrated that impaired swallowing and pharyngeal dysfunction could be observed for TOF ratio less than 90% at the adductor pollicis. Pharyngeal function is not normalised until an TOF ratio above 90% at the adductor pollicis is reached 4.

As suggested by Donati, although the effect of NMBA is different on the thumb, the airway and respiratory muscles, we persist in using the adductor pollicis to monitor neuromuscular block because it is convenient. However neuromuscular monitoring can be improved by using different types and sites of stimulation.

During onset, the use of the adductor pollicis to determine good intubating conditions can be misleading because paralysis of the adductor pollicis lags behind onset of neuromuscular block at the vocal cords and the diaphragm. Furthermore, the adductor pollicis may be blocked with a dose insufficient to block these respiratory muscles. Several studies have demonstrated that the sensitivity of the orbicularis oculi to NDMR and the time course of onset was close to that of respiratory and laryngeal muscles. It has been shown that when a NDMR was given at a dose sufficient to block respiratory muscles (2xED95), disappearance of the TOF at the orbicularis oculi could predict good intubating conditions. Detection of good intubating conditions could be provided in all the patients approximately 1 min before complete paralysis at the adductor pollicis.

During surgery, the choice of the site and the type of stimulation will depend of the degree of muscular relaxation sought. When an intense neuromuscular blockade is required, disappearance of the TOF at the adductor pollicis does not eliminate the possibility of hiccups, cough or extrusion of abdominal contents. During that phase of so called period of no response, two different techniques may allow the evaluation of very intense blockade when complete paralysis of the diaphragm is sought and predict the time to reappearance of the TOF at the adductor pollicis. Post-tetanic-count (PTC) at the adductor pollicis was the first technique of assessment of very intense neuromuscular blockade. Less than 5 responses indicate a deep neuromuscular block. For a given muscle relaxant, time until spontaneous return of the first response of the TOF is related to the PTC at a given time. Monitoring of the orbicularis oculi, using TOF stimulus has also a role during surgery because it is a good reflection of diaphragmatic paralysis. When profound blockade is not required, monitoring of the adductor pollicis using TOF is sufficient and allows easier antagonism of relaxation at the end of the case. No tetanic stimulation must be applied when TOF monitoring is used in order to avoid post-tetanic facilitation and artificial increase of the response to the TOF.

As previously discussed, although orbicularis oculi may be valuable for monitoring onset of relaxation or maintenance of profound blockade, the adductor pollicis is preferable for the management of recovery because it represents one of the most sensitive muscles. When the adductor pollicis has almost completely recovered, it can be assumes that no residual paralysis exists at both the diaphragm and the laryngeal adductor muscles. When the fourth response at the TOF reappears, neuromuscular blockade is usually less than 75% and the TOF ratio may be estimated. It has been demonstrated that a TOF ration of 90% was needed to avoid any respiratory problems secondary to residual neuromuscular blockade 4. Unfortunately, visual or tactile assessment of fade of the TOF when it is above 40% is very difficult, even for experienced anaesthetists. The double-burst stimulation (DBS) has been introduced to improve the clinicians ability to detect residual blockade by visual or tactile means. Fade can be detected more easily and can be observed at degrees of block corresponding to a TOF ratio under 60%. However postoperative ventilatory weakness must be anticipated if the adductor pollicis activity has not returned fully at the end of anaesthesia. It is therefore important that monitoring can be used in association with clinical tests for recovery such as the patient ability to swallow to stick out his tongue or to strongly appose the incisor teeth 5

In conclusion the type and the site of monitoring should be adapted to the requirement of paralysis.

 

1. Bragg P, Fisher DM, Shi J, Donati F, Meistelman C, Lau M, Sheiner LB. Anesthesiology 1994; 80: 310-9

2. Plaud B, Proost JH, Wierda JM, Barre J, Debaene B, Meistelman C. Clinical Pharmacology and Therapeutics 1995; 58: 185-91

3. Stanski DR, Ham J, Miller RD, Sheiner LB. Anesthesiology 1979; 51: 235-41

4. Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, Kuylenstierna R. Anesthesiology 1997; 87: 1035-43

5. Kopman AF, Yee PS, Neuman GG. Anesthesiology 1997; 86: 765-71