Antagonising neuromuscular block at the end of surgery

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6666 (Published 16 October 2012) Cite this as: BMJ 2012;345:e6666
  1. Jennifer M Hunter, emeritus professor of anaesthesia
  1. 1Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L69 3GA, UK
  1. bja{at}liverpool.ac.uk

To reverse or not to reverse? That is the question

The introduction of neuromuscular blocking drugs (muscle relaxants) into anaesthetic practice 70 years ago revolutionised acute clinical care. It led to the development of major cardiac surgery, paediatric surgery, and neurosurgery, as well as the specialty of critical care. In the presence of muscle relaxants, anaesthesia could be lightened and postoperative recovery was faster. This allowed patients to protect their airway more rapidly on recovery, thereby preventing pulmonary aspiration of stomach contents. In a linked study (doi:10.1136/bmj.e6329), Grosse-Sundrup and colleagues used a prospective propensity score matched cohort analysis to compare outcomes in 18 579 patients who received intermediate acting muscle relaxants and 18 579 who did not.1

In the United Kingdom, the development of anaesthesia using neuromuscular blockade was led by T Cecil Gray in Liverpool. In 1946, he described a series of more than 1000 cases of what became known as the Liverpool anaesthetic technique, which consisted of sleep induced with a barbiturate and maintained with nitrous oxide in oxygen, analgesia with morphine, and profound muscle relaxation with D-tubocurarine.2 He insisted on the need for good oxygenation throughout anaesthesia—in itself a new concept at the time—and diligent clinical monitoring of the patient throughout surgery.

This approach soon became recognised throughout the world, but within a decade it almost fell into disrepute. In 1954, two surgeons in Massachusetts, United States, Beecher and Todd, retrospectively analysed mortality after 599 548 anaesthetic procedures.3 They found that survival was better in patients anaesthetised only with potent inhalational agents rather than when muscle relaxants were also used.

Gray soon realised the problem: the first descriptions of the Liverpool anaesthetic technique had not stressed the need to use an anticholinesterase to antagonise residual block from the long acting tubocurarine at the end of surgery. By the mid-1950s, the Liverpool technique included, at all times, reversal of residual block with neostigmine, and this improved survival after anaesthesia.4 It is still routine practice in the UK to reverse residual neuromuscular blockade in this way, although in some European countries, including France and Germany, not all anaesthetists routinely do so.5 6

The likelihood of postoperative respiratory complications in the presence of persistent paralysis from the long acting muscle relaxant, pancuronium, was highlighted in 1997,7 when Danish researchers found a significantly lower incidence of pneumonia after reversal if muscle relaxants of intermediate duration, such as atracurium or vecuronium, were used rather than the long acting agent. Intermediate acting agents produce a clinical effect for about 40 minutes and long acting agents for 60 minutes or more. This contribution also changed anaesthetic practice, but the findings have never been substantiated.

During the interim, many studies have determined the incidence of postoperative residual paralysis, but fewer have examined its consequences,8 9 so it is timely for such a prospective study to be repeated. It is now recommended that intermediate acting agents are used for neuromuscular blockade, that neuromuscular block is monitored and measured quantitatively throughout surgery, and that residual block is antagonised unless full recovery has been demonstrated using appropriate equipment.10

The current prospective study used data routinely collected from the hospital’s electronic records (with all their potential inaccuracies). The authors found that only 64% of patients who received a muscle relaxant also received neostigmine at the end of surgery, and only half of patients who were paralysed during surgery had intraoperative neuromuscular monitoring.1 Surprisingly, postoperative complications in the form of transient oxygen desaturations (an outcome of questionable clinical relevance) or the need for reintubation of the trachea were more common if a muscle relaxant had been given and if residual block had been reversed by neostigmine.

Outcomes after intraoperative neuromuscular monitoring and reversal were somewhat better than if no monitoring was used, although this was not well highlighted by the authors. This is not the first study to suggest that the use of qualitative unmeasured monitoring intraoperatively may not decrease the incidence of postoperative residual block or respiratory complications,11 or that residual block is more common after shorter procedures (because the interval between administration of relaxant and reversal agent is shorter).5 12 However, it is surprising that a higher incidence of postoperative desaturation and the need for reintubation was found when neostigmine had been given.

It would be a mistake to conclude that current recommended clinical practice should change on the basis of the findings of this one study, however large and well executed. It is difficult to accurately define the incidence of rare but serious complications associated with widely practised techniques. To set up an adequately powered prospective randomised controlled and blinded study would need not only very large numbers to determine statistically significant differences, but also comparable groups. It is unlikely that it would be possible to randomise patients who have the same physical characteristics and medical condition, and are having the same operations of the same duration, preferably performed by the same anaesthetist and surgeon. All the confounding factors of acute care, including the multiplicity of drugs administered perioperatively and the reasons for giving them, would preclude it. Such confounding factors are likely to have influenced the current study.

For instance, the decision by clinicians on whether to use neostigmine may have been based on the individual doctor’s clinical assessment of the patient’s condition. Variability in technical skill and clinical acumen among anaesthetists may also have affected outcomes. In light of currently available evidence it would seem wise to continue to use quantitative neuromuscular monitoring, intermediate acting neuromuscular blocking agents, and a reversal agent unless full recovery of neuromuscular function has been adequately demonstrated.


Cite this as: BMJ 2012;345:e6666


  • Research, doi:10.1136/bmj.e6329
  • Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; not externally peer reviewed.