Atracurium is associated with postoperative residual curarization

C. McCaul, É. Tobin, J. F. Boylan and A. J. McShane*

Department of Anaesthesia, Intensive Care and Pain Medicine, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland*Corresponding author

Accepted for publication: July 3, 2002


    Abstract
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Background. Residual paralysis following the use of neuromuscular blocking drugs remains a clinical problem. As part of departmental quality assurance, we examined the degree of postoperative residual curarization (PORC) following atracurium.

Methods. Forty patients undergoing general anaesthesia involving atracurium were studied. Quantitative neuromuscular monitoring (mechanomyography, Myograph 2000, Biometer, Denmark) was performed by assessing the response to supramaximal train-of-four (TOF) stimulation of the ulnar nerve. Anaesthesia was provided by non-participating clinicians who were blinded to the study data. A TOF ratio <=0.7 at extubation was classified as PORC.

Results. At antagonism of neuromuscular block, 70% (28/40) of patients had a TOF ratio <=0.7, and 65% (26/40) of patients had a TOF ratio <=0.7 at extubation. Peripheral nerve stimulator use was associated with a longer interval from antagonism of block to extubation (P=0.01), but was not associated with differences in atracurium dosage or a reduction in PORC at extubation. Patients with TOF ratio <=0.7 at extubation had surgery of shorter duration [59 (SEM 6) vs 103 (9) min, P<0.001], greater doses of atracurium relative to the duration of surgery [6 (1) vs 11 (1) µg kg–1 min–1, P<0.005], and shorter intervals from administration of last dose of atracurium to antagonism of neuromuscular block [29 (2) vs 53 (9) min, P<0.005] and from antagonism to extubation [6 (1) vs 15 (4) min, P<0.01]. Duration of surgical procedure was the sole multivariate predictor of PORC [odds ratio 0.94 (95% confidence intervals 0.91–0.98), P<0.01].

Conclusions. PORC remains a clinical problem despite use of intermediate-duration neuromuscular blocking drugs and peripheral nerve stimulators. Patients undergoing procedures of short duration may be at risk of inappropriately early tracheal extubation, possibly due to work pressures. The association between suboptimal antagonism of neuromuscular blockade and short procedures needs reinforcement during postgraduate training and departmental quality assurance.

Br J Anaesth 2002; 89: 766–9

Keywords: anaesthesia; complications, morbidity; complications, postoperative; neuromuscular block, atracurium


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Residual postoperative paralysis following use of neuromuscular blocking drugs may result in morbidity and mortality.1 2 Residual paralysis resulting from absent or incomplete antagonism of competitive neuromuscular blockade is known as postoperative residual curarization (PORC). Recent literature suggests that PORC remains a problem.3

As part of departmental quality assurance, we examined the incidence and degree of PORC associated with the use of the intermediate-duration neuromuscular blocking agent, atracurium at: (i) antagonism of block, (ii) extubation, and (iii) in the recovery area. The study also examined factors contributing to PORC, such as drug dosage, timing of drug administration, duration of surgery, experience of anaesthetists and use of peripheral nerve stimulators.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Following approval by the hospital research ethics committee, informed consent was obtained from 40 ASA I elective surgical patients [age 38 (19–63) yr] who were scheduled to undergo general anaesthesia with tracheal intubation, muscle relaxation and mechanical ventilation. The surgical procedures involved were abdominal (20), breast (6), varicose veins (6), and miscellaneous (8).

Premedication, induction technique, neuromuscular blocking drug dosage and antagonism, maintenance agents, neuromuscular monitoring and timing of extubation were chosen by the anaesthetist controlling the case. Only patients who were to receive atracurium were included in the study.

Train-of-four (TOF) ratio (TOFR) monitoring was continuous and was recorded from induction of anaesthesia to extubation, which took place in the operating theatre. The mechanical response of adductor pollicis was measured using a force displacement transducer (Myograph 2000, Biometer, Denmark). After induction, but before administration of the neuromuscular blocking drug, a stable baseline was established. TOF stimulation was then assessed at 10-s intervals by stimulation of the ulnar nerve with four impulses at 0.5-s intervals, duration 0.2 ms and current 60 mA. PORC was judged to be present when the ratio of the twitch height of the fourth impulse to the height of the first (TOFR) was <=0.7. Myographic data recordings were not available to the responsible clinical anaesthetists, but peripheral nerve stimulators were. After tracheal extubation, patients were observed continuously in the operating theatre and the recovery room for clinical signs and symptoms of PORC.

Data are presented as frequencies or means (SEM) as appropriate. A Student’s t-test was used to analyse patient characteristics and to compare the patients with and without PORC. The chi-squared test was used to analyse the incidence of peripheral nerve stimulator use and clinical problems. Logistic regression was used for multivariate analysis.

Twenty-six (65%) patients had a TOFR <=0.7 at extubation (Table 1). Compared with patients with a TOFR >0.7, patients with a TOFR <=0.7 at extubation had had shorter procedures (P<0.001), and more profound neuromuscular block at the time of neostigmine administration. Patients with residual paralysis (TOFR <=0.7 at extubation) had significantly shorter time intervals from administration of last dose of atracurium to administration of antagonist [29 (2) vs 53 (9) min, P<0.001] and from administration of antagonist to extubation [6 (1) vs 15 (4) min, P=0.01]. TOFR at the time of antagonism was positively correlated with time elapsed since last dose of atracurium (r2=0.57, F=50.4, P=0.0001).


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Table 1 Patient characteristics, neuromuscular block, antagonism, and clinical signs of postoperative residual curarization, characterized by train-of-four ratio (TOFR) at extubation. Values are absolute (n) or mean (SEM). ****P<0.0001; ***P<0.001; **P<0.005; *P<0.05
 
After extubation, 19 patients had clinical evidence of impaired neuromuscular function as evidenced by a total of 40 clinical events. These comprised uncoordinated movements, oxygen desaturation, upper airway obstruction, ptosis and diplopia/blurring of vision. Of these patients, 18/19 had a TOFR <0.7 at extubation. The episodes of desaturation and obstruction were treated successfully with increased concentrations of inspired oxygen and airway manipulation. A further dose of neostigmine was administered to one patient in the recovery room after the anaesthetist observed uncoordinated movements.

A peripheral nerve stimulator was used in 50% (20/40) of patients. Trainees who did not use nerve stimulators were more experienced than those who did [6.3 (0.8) vs 4.5 (0.4) yr, P=0.04]. Use of nerve stimulators was not associated with altered atracurium dosage, depth of blockade before antagonism, time interval from antagonism of neuromuscular block to tracheal extubation, or incidence of PORC.

The sole multivariate predictor of residual neuromuscular block was duration of surgical procedure, which correlated inversely with PORC [odds ratio 0.94 (95% confidence interval 0.91–0.98), P<0.01].


    Comment
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
In patients emerging from general anaesthesia, we found a high incidence of curarization at the time of tracheal extubation, with many patients having significant residual neuromuscular block on clinical testing in the recovery room. This occurred despite the use of an intermediate-duration neuromuscular blocking drug, frequent (though not universal) use of peripheral nerve stimulator monitoring, and routine use of pharmacological antagonism. The incidence of PORC at the time of extubation observed in this study is higher than that reported in other studies.35 In our study, we assessed the TOFR at the time of extubation whilst in the majority of other studies, neuromuscular assessment was done in the postoperative care unit,35 at time intervals exceeding the recovery index of atracurium,6 thus allowing greater recovery of neuromuscular function.

PORC remains a problem even in carefully conducted clinical trials when the short-acting agent mivacurium is used and routinely antagonized.7 In many patients in our study, the degree of neuromuscular block was profound at the time of antagonism, with many patients having a TOFR of zero, demonstrating low levels of spontaneous recovery from neuromuscular block.

The attempted antagonism of deep levels of neuromuscular blockade may reflect the pressure on anaesthesia providers to turn over cases rapidly, and increased reliance on the skills and services of recovery personnel in order to meet these time demands.8 In support of this hypothesis, PORC was associated with shorter procedures and shorter intervals from administration of an antagonist to extubation. TOFR at antagonism was directly related to time elapsed since the last dose of atracurium.

We speculate that a level of complacency exists with regard to usage of intermediate-duration neuromuscular blocking agents. Contemporary audit data from France,3 Belgium,4 and Northern Ireland5 report incidences of PORC in the recovery room of 30–64%, although many instances occurred in patients who did not receive an anticholinesterase. The data from our series suggest that there is an assumption that routine use of an anticholinesterase guarantees adequate antagonism of neuromuscular block, and may explain the relatively low use of peripheral nerve stimulators. Complacency may also exist because, although strong outcome data have established that PORC after the use of pancuronium is associated with postoperative pulmonary complications,1 substantial evidence has yet to be accrued for atracurium or vecuronium. Despite the availability of peripheral nerve stimulators, they are frequently not employed and even in experienced hands may not detect PORC.

Our study has obvious limitations. While atracurium was used in all patients, its mode of use and the conduct of the anaesthesia, including temperature measurement and regulation, was entirely at the discretion of the responsible anaesthetist. Since our study was carried out it has been demonstrated that pharyngeal constrictor function is not normalized until recovery of an adductor pollicis TOF>0.9.9 Thus the previously accepted parameter of 0.7 may be inappropriate.

In conclusion, we have found that PORC is still a clinical problem despite the use of intermediate-duration neuromuscular blocking drugs and their routine antagonism. The association between suboptimal antagonism and both relatively short procedures and a short interval between antagonism of neuromuscular block and extubation needs to be reinforced during postgraduate training and departmental quality assurance.


    Acknowledgement
 
É. Tobin and A. McShane were supported by the Health Research Board (Ireland).


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
1 Berg H, Roed J, Viby-Mogensen J, et al. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomized, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand 1997; 41: 1095–103[ISI][Medline]

2 Lunn JN, Hunter AR, Scott DB. Anaesthesia-related surgical mortality. Anaesthesia 1983; 38: 1090–6[ISI][Medline]

3 Baillard C, Gehan G, Reboul-Marty J, Larmignat S, Samana CM, Cupa M. Residual curarization in the recovery room after vecuronium. Br J Anaesth 2000; 84: 394–5[Abstract]

4 Fezing AK, d’Hollander A, Boogaerts JG. Assessment of the postoperative residual curarisation using the train of four stimulation with acceleromyography. Acta Anaesthesiol Belg 1999; 50: 83–6[Medline]

5 Hayes AH, Mirakhur RK, Breslin DS, Reid JE, McCourt KC. Postoperative residual block after intermediate-acting neuromuscular blocking drugs. Anaesthesia 2000; 56: 312–18[ISI]

6 Basta SJ, Ali HH, Savarese JJ, et al. Clinical pharmacology of atracurium besylate (BW 33A): A new non depolarizing muscle relaxant. Anesth Analg 1982; 68: 723–32

7 Bevan DR, Kahwaji R, Ansermino JM, et al. Residual block after mivacurium with or without edrophonium reversal in adults and children. Anesthesiology 1996; 84: 362–7[ISI][Medline]

8 Gaba DM, Howard SK, Jump B. Production pressures in the work environment: California anesthesiologists’ attitudes and experiences. Anesthesiology 1994; 81: 488–500[ISI][Medline]

9 Eriksson LI, Sundman E, Olsson R, et al. Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology 1997; 87: 1035–43[ISI][Medline]