Neostigmine‐induced weakness: what are the facts?

Abstract

This editorial accompanies an article by Kent et al., Anaesthesia 2018; 73: 1079-89.'There is nothing more deceptive than an obvious fact. ' -Sir Arthur Ignatius Conan Doyle (May 1859-July 1930)In this issue of Anaesthesia, Kent et al. [1] report that administration of neostigmine 2.5 mg (mean (SD) dose 35 (6) lg.kg À1 ) plus glycopyrrolate 450 lg to a small number of healthy volunteers, in the absence of a previously administered non-depolarising neuromuscular blocker (NMB), resulted in manifestations of a depolarising neuromuscular block: muscle weakness, fasciculations and multiple subjective symptoms such as diplopia and dysphagia. These data appear to stand in marked contrast to the observations of a recent investigation by Murphy et al. [2] whose findings could not have been more different. In the latter study, the authors administered neostigmine 40 lg.kg À1 once the train-of-four (TOF) ratio had spontaneously recovered to a value > 0.90 from an initial dose of rocuronium. Neostigmine was not associated with any objective evidence of anticholinesterase-induced muscle weakness, and was also associated with decreased incidence of postoperative diplopia [2]. Who should we believe, Kent or Murphy? The answer is that both sets of observations are credible, but the study of Kent probably has little or no clinical relevance. In the peri-operative setting, neostigmine is never administered in the absence of a preceding dose of a non-depolarising NMB. Kent's observations appear to be valid only when neostigmine administration is not preceded by a non-depolarising NMB. This difference in response to neostigmine probably is the result of continued receptor occupancy by the nondepolarising NMB. Even when the TOF ratio approaches unity following recovery from a non-depolarising block, there is still a substantial degree of receptor occupancy at the neuromuscular junction. Waud and Waud estimated that at full return of the TOF ratio, 70-75% of postsynaptic receptors are still occupied [3]. Kopman found that following recovery to a TOF ratio of 0.95 post mivacurium administration that the ED 50 (the dose the caused 50% reduction of twitch height) value for the relaxant was decreased by 56% [4]. Thus, partial receptor occupancy undoubtedly persists at a time when even objective evidence (e.g. the TOF ratio) is indicative of full recovery of neuromuscular function. It appears that this receptor occupancy provides a protective effect from the depolarising actions of excess acetylcholine. The notion that neostigmine administration at a time when spontaneous clinical recovery from non-depolarising block is almost complete may have adverse clinical consequences has been disputed [2, 5-7]. Murphy's observations are not unique. Choi [8] and Schaller [9] report successful reversal of residual neuromuscular block at a TOF ratio of 0.50 with neostigmine ≤ 40 lg.kg À1 and others [10, 11] found that even lower doses of neostigmine (10-30 lg.kg À1 ) are required at TOF ratios of 0.60. Furthermore, Harper et al. [12] administered a l...

Tracheal extubation in children: Planning, technique, and complications

“…Both approaches are inappropriate because the duration of action of muscle relaxants is highly variable among individuals (risk of residual neuromuscular blockade) and because unnecessary administration of neostigmine is potentially harmful. It has indeed been shown in adult volunteers that neostigmine administered when TOF ratio has recovered to 1.0 transiently increases upper airway collapsibility to the same extent as when muscular blockade had recovered to a TOF ratio of 0.5 and without altering the TOF ratio of the adductor pollicis muscle . Although the clinical relevance of this finding is a matter of controversy, any risk of decreasing the upper airway muscles activity should be avoided at a time when upper airway obstruction could occur, that is, when the tracheal tube is removed (see below): Neostigmine should therefore not be administered when no muscular blockade is still present.…”

Providence, patient or provider? Looking for truth in retrospective database studies

“…Was this in response to hypoventilation and desaturation? Or a second dose of reversal due to residual neuromuscular block ? The authors’ results indicated that ‘lung‐protective ventilation’ was found to be protective against early hypoxia in this study but the definition (a plateau threshold of 16 cmH 2 O) is not consistent with previous definitions .…”

Neostigmine‐induced weakness after sugammadex

“…We would like to challenge Naguib and Kopman's editorial assertion that Kent et al. 's study on neostigmine‐induced weakness in awake volunteers ‘probably has little or no clinical relevance’.…”