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Editorial Views

Evidence-based Practice and Neuromuscular Monitoring: It's Time for Routine Quantitative Assessment

Eriksson, Lars I. M.D., Ph.D.

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OVER the last years, a growing body of information has accumulated in the anesthesia literature about the advantages and pitfalls of various techniques used for quantitatively monitoring neuromuscular function in routine anesthetic practice and the associated incidence (and consequences) of residual neuromuscular block in the postoperative period. Many methods are available, ranging from quantitative strain–gauge techniques, electromyography, acceleromyography, phonomyography, etc. However, quantitative techniques are not widely used, with most anesthesiologists relying on visual or tactile assessment of the train-of-four (TOF) ratio, or, in many cases, no neuromuscular monitoring at all. One argument for such qualitative approaches to monitoring is that with modern short and intermediate acting relaxants, residual paralysis is not a clinical problem or, even if patients are not completely reversed by the end of the case, the block will dissipate in a few minutes. Another approach is “reverse everyone,” which is viewed by some as uniformly easy, safe, and effective for patients given these agents.
There is now increasing evidence that this relaxed attitude to neuromuscular monitoring is unwise. The study by Debaene et al., published in this issue of Anesthesiology, 1 has a clear message to all of us. The authors examined the incidence and magnitude of a neuromuscular block on arrival in the PACU in a large group of relatively unselected patients who had received a single dose of intermediate-duration relaxant for intubation (rocuronium, vecuronium, or atracurium). Patients received no other relaxant during their surgery and did not receive reversal agents at any time. The message is that, while it may be presumed that the attending anesthesiologists felt that adequate neuromuscular function was present at the time of transfer, 45% of the patients arrived in the recovery room with a residual neuromuscular block, defined as an adductor pollicis TOF ratio of less than 0.90! Sixteen percent had a TOF ratio of less than 0.7. Interestingly, in sufficiently cooperative patients, even clinical tests were frequently abnormal; 15% of tested patients failed a test of head lift. Even in patients tested more than 2 h after drug administration, the incidences of residual paralysis were 10 and 37% (based on a TOF ratio of less than 0.7 or less than 0.9, respectively). The specific relaxant used did not influence these incidences.
The study was not a rigorous study of drug kinetics or twitch depression and recovery. Instead, the authors examined something close to routine clinical practice; that is, the anesthesiologist was free to select the neuromuscular blocking drug, the dose, and whether to use or not use neuromuscular monitoring. There are clearly experimental problems with this approach, and it is unfortunate that the authors did not provide further information about the actual anesthetic practice (in particular whether or not some form of monitoring was used). This limits the external validity of the study. Nevertheless, the results clearly demonstrate that a disturbingly high fraction of patients did not have adequate neuromuscular function on arrival in the recovery room.
Recently, several studies focusing on this kind of broad, unselected patient population have been published. 2–8 They all found an alarmingly high incidence of residual paralysis in the recovery room despite the use of intermediate acting neuromuscular blocking agents (vecuronium, rocuronium, atracurium, and cisatracurium). There are several possible explanations for this unexpectedly high incidence. One reason might be the change in definition of clinically significant residual paralysis from a TOF ratio of 0.70 to 0.90. However, since clinical measures are also commonly abnormal, this cannot be a complete explanation. Thus, it is clear that the widespread belief that intermediate-acting muscle relaxants have a very low tendency to cause residual paralysis (and therefore, that it is not necessary to monitor or even to reverse the neuromuscular block) is very wrong. Combining the results of the current study 1 with the results from several similar investigations, 2–8 there is now sufficient information to support a general change in the attitude towards monitoring and reversal of a neuromuscular block in routine anesthetic practice.
Though anesthesiologists probably have a relatively low threshold for carrying new monitoring equipment into the operating room (e.g., BIS, AEP, ST-analysis, end-tidal anesthetic gas concentrations, etc.), few techniques have been documented to affect patient outcome. In this respect, neuromuscular monitoring is no exception. However, recent studies of the use of objective (acceleration or EMG) rather than subjective (visual/tactile evaluation) monitoring techniques may help anesthesiologists find a better way to insure safe recovery from a neuromuscular block.
Visual or tactile evaluation of the TOF response is inadequate for evaluating neuromuscular function. Several studies have documented that visual or tactile evaluation of the TOF response correlates poorly with the true TOF fade. 9–11 In fact, even very experienced observers are unable to manually detect TOF or DBS fade at TOF ratio of 0.40–0.60 or more. 10 The failure of these subjective methods, including clinical bedside tests, to detect residual neuromuscular block is once again demonstrated in the current investigation. 1 Consequently, the only way we reliably can assess a neuromuscular block is by objective monitoring methods, such as acceleromyography or EMG. Based on the current literature, it is time to replace our old subjective methods with new objective measurements. Of course, this also means that there is a need for easily used and reliable equipment for this purpose.
Does the use of perioperative objective neuromuscular monitoring exclude residual neuromuscular block in the postoperative period? There are several publications on this theme, all of them pointing towards the same conclusion. 5,8,9,12 Patients being monitored using an objective method will usually arrive in the recovery room with the desired level of recovery, i.e., a TOF ratio of more than 0.70 or 0.80. 5,8,9,12 However, patients exposed to subjective neuromuscular monitoring have a high incidence of residual neuromuscular block, though their anesthesiologists judged them to have recovered adequately. 5,8,9,12 As a corollary, objective monitoring would permit anticholinesterases to be reserved for only those patients who actually need a reversal agent.
One crucial question is do residual effects of muscle relaxants actually affect patient outcome? Or in other words, it is one thing to say that patients are inadequately reversed, based on some form of neuromuscular monitoring, but it is another to conclude that this residual paralysis constitutes an increased risk for morbidity or mortality. In this respect, little data are available for intermediate acting drugs. However, one large outcome study from Scandinavia does shed light on this important topic. 13 Patients with a long-acting residual neuromuscular block due to pancuronium have a higher risk of postoperative pulmonary complications, the risk being further increased with increasing age. For instance, patients greater than 60 yr of age undergoing major abdominal operations have a 40–50% risk of a postoperative pulmonary complication if left with a prolonged residual neuromuscular block in the PACU. This important study should make us all aware of the risk involved when a patient is left with a residual neuromuscular block in the recovery room. It also illustrates that the duration (time length) during which the patient actually is residually paralyzed is of importance, hence the strong correlation to a long-acting neuromuscular block. In this context, it is important to remember that even medium-acting neuromuscular blocking agents may become long-acting during very modest body hypothermia. 14
Apart from the interference with pulmonary function, the consequences of a residual neuromuscular block involve other vital organ functions. First, the muscle function and coordination of protection reflexes of the pharynx and upper esophagus are impaired in individuals with a residual paralysis. 15–16 The time course of this pharyngeal dysfunction and dyscoordination is markedly longer than that of peripheral skeletal muscle groups, such as the diaphragm, larynx, hand, and face. 15–17 Since we lack methods for monitoring these vital muscle groups, we must rely on the functional relationship between these muscle groups and the TOF response in the adductor pollicis muscle. Several studies 15–16 clearly show that airway protection and control have not recovered until an adductor pollicis TOF ratio of 0.90 has been reached. Second, the ventilatory response to hypoxia is reduced during residual neuromuscular block due to a direct inhibition of the chemoreceptor activity in the carotid bodies. 18–20 Third, the ability to control the jaw and the tongue and hereby maintain the airway and speech may be impaired such that it can interfere with the protection of the airway, even in an individual without sedation or impaired consciousness. 21 Debaene et al.1 touch on these matters in their attempts to perform two clinical bedside tests, but they do not more specifically address such effects or discuss alternative explanations for their failure. Anesthetic vapors (e.g., isoflurane and sevoflurane) and propofol may markedly impair the pharynx and esophageal coordination resulting in failed airway protection, even at subanesthetic concentrations. 22 They also cause a dyscoordination of the pharynx. 22 Residual effects from isoflurane, not directly related to sedation, thus may partly explain the inability of some of the patients to cooperate during head lift and tongue protrusion tests.
The message is short and clear—it is time to move from discussion to action and introduce objective neuromuscular monitoring in all operating rooms, not just those occupied by researchers and aficionados of muscle relaxants. I believe that objective neuromuscular monitoring is an evidence-based practice and should consequently be used whenever a nondepolarizing neuromuscular blocking agent is administered. Such monitoring is noninvasive and has little risk, and there are strong reasons to believe that its use can improve patient outcome.
This Editorial View accompanies the following article: Debaene B, Plaud B, Dilly M.-P., Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology 2003; 98:1042–8.
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1. Debaene B, Plaud B, Dilly M-P, Donati F: Residual paralysis in the PACU after a single intubating does of non-depolarizing muscle relaxant with an intermediate duration of action. A nesthesiology 2003; 98: 1042–8

2. Baillard C, Gehan G, Reboul-Marty J, Larmignat P, Samana CM, Cupa M: Residual curarization in the recovery room after vecuronium. Br J Anaesth 2000; 84: 394–395

3. Hayes AH, Mirakhur RK, Breslin DS, Reid JE, McCourt KC: Postoperative residual block after intermediate-acting neuromuscular blocking drugs. Anaesthesia 2001; 56: 312–318

4. Cammu G, de Baerdemaeker L, den Blauwen N, de Mey JC, Struys M, Mortier E: Postoperative residual curarization with cisatracurium and rocuronium infusions. Eur J Anaesthesiol 2002; 19: 129–134

5. Gätke MR, Viby-Mogensen J, Rosenstock C, Jensen FS, Skovgaard LT: Postoperative muscle paralyis after rocuronium: Less residual block when acceleromyography is used. Acta Anaesthesiol Scand 2002; 46: 207–213

6. Kim KS, Lew SH, Cho HY, Cheong MA: Residual paralysis induced by either vecuronium or rocuronium after reversal with pyridostigmine. Anesth Analg 2002; 95: 1656–1660

7. McCaul C, Tobin E, Boylan JF, McShane AJ: Atracurium is associated with postoperative residual curarization. Br J Anaesth 2002; 89: 766–769

8. Mortensen CR, Berg H, El-Mahdy A, Viby Mogensen J: Perioperative monitoring of neuromuscular transmission using acceleromyography prevents residual neuromuscular block following pancuronium. Acta Anaesthesiol Scand 1995; 39: 797–801

9. Fruergaard K, Viby Mogensen J, Berg H, el-Mahdy AM: Tactile evaluation of the response to double burst stimulation decreases, but do not eliminate, the problem of postoperative residual paralysis. Acta Anaesthesiol Scand 1998; 42: 1168–1174

10. Viby-Mogensen J, Jensen NH, Engbaek J, Ording H, Skovgaard LT, Chraemmer-Jorgensen B: Tactile and visual evaluation of response to train-of-four nerve stimulation. A nesthesiology 1985; 1985: 440–443

11. Drenck NE, Ueda N, Olsen NV, Engbaek J, Jensen E, Skovgaard LT, Viby Mogensen J: Manual evaluation of residual curarization using double burst stimulation: A comparison with train-of-four. A nesthesiology 1989; 70: 578–581

12. Pedersen T, Viby Mogensen J, Bang U, Olsen NV, Jensen E, Engbaek J: Does perioperative tactile evaluation of the train-of-four responses influence the frequency of postoperative neuromuscular blockade. A nesthesiology 1990; 73: 835–839

13. Berg H, Viby-Mogensen J, Roed Mortensen CR, Engbaek J, Skovgaard LT: Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomized and blinded study of postoperative complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand 1997; 41: 1095–1103

14. Heier T, Caldwell JE, Eriksson LI, Sessler DI, Miller RD: The effect of hypothermia on adductor pollicis twitch tension during continuous infusion of vecuronium in isoflurane-anesthetized humans. Anesth Analg 1994; 78: 312–317

15. Eriksson LI, Sundman E, Olsson R, Nilsson L, Witt H, Ekberg O, Kuylenstierna R: Functional assessment of the pharynx at rest and during swallowing in partially paralysed humans. A nesthesiology 1997; 87: 1035–1043

16. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI: The incidence and mechanism of pharyngeal and upper esophageal dysfunction in partially paralyzed humans Anesthesiology 2000; 92: 977–984

17. Isono S, Koichi T, Ide T, Suigimori K, Mizuguchi T, Nishino T: Differential effects of vecuronium at the diaphragm and geniohyoid muscle in anesthetized dogs. Br J Anaesth 1992; 77: 1070–1073

18. Eriksson LI, Sato M, Severinghaus JW: Effects of vecuronium-induced partial neuromuscular block on hypoxic ventilatory responses. A nesthesiology 1993; 78: 693–699

19. Wyon N, Joensen H, Yamamoto Y, Lindahl SGE, Eriksson LI: Carotid body chemoreceptor function is impaired by vecuronium during hypoxia. A nesthesiology 1999; 89: 1471–1479

20. Jonsson M, Kim C, Yamamoto Y, Runold MK, Lindahl SGE, Eriksson LI: Atracurium and vecuronium block nicotine-induced carotid body responses. Acta Anaesthesiol Scand 2002; 94: 117–122

21. Kopman AF, Yee PS, Neumann GG: Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. A nesthesiology 1997; 86: 765–771

22. Sundman E, Witt H, Sandin R, Kuylenstierna R, Bodén K, Ekberg O, Eriksson LI: Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane and sevoflurane. A nesthesiology 2001; 95: 1125–1132

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