We thank Dr. Caruso for his comments related to our observational study reporting a substantially increased risk of postoperative residual paralysis in patients having qualitative train-of-four (TOF) monitoring of eye muscles compared with those monitored at the adductor pollicis.1  Reversal of neuromuscular blockade before extubation was assessed clinically as per routine care. Due to the observational nature of the study, we did not standardize what clinical tests that may have been used. We agree with Dr. Caruso that subjective assessment of the response to nerve stimulation, and of clinical tests, is inadequate to confirm successful reversal.

Although the presumed mechanism behind the association of monitoring site and residual paralysis would be a more generous administration of neuromuscular-blocking drugs to patients with monitoring of eye muscles, we did not observe differences in neuromuscular-blocking drugs dosing. It is conceivable that patients in the eye muscle monitored group would have had lower adductor pollicis TOF-counts at the time of neostigmine administration, had such assessments been made. The degree of spontaneous recovery at the time of reversal has repeatedly been shown to be a major determinant of successful timely reversal. Studies such as those by Kim et al.2  and Kirkegaard et al.3  clearly demonstrate the critical importance of spontaneous recovery and form the basis for current recommendations to administer reversal only after a TOF count of 4 has been achieved.4  These studies, and current recommendations for clinical practice, are based on monitoring of the adductor pollicis. As there were no simultaneous assessments of the TOF response at both sites, this explanation remains speculative in our data.

Dr. Caruso mentions that depending on intensity of the block, reversal may take up to 50min. Such a delayed reversal is rare if TOF-monitoring is used at the adductor pollicis to guide the appropriate administration of neostigmine. We believe that the administration of neostigmine earlier than approximately 10min before anticipated extubation is not optimal. This is because peak effect of neostigmine’s inhibition of anticholinesterase is achieved by 10min.5  We agree with Dr. Caruso that before extubation, optimal management would include the objective assessment of neuromuscular function, and extubation should be deferred until residual paralysis is not detected. If the TOF-ratio has not reached 0.90, 10min after neostigmine administration, it is unlikely that this is the result of delayed administration of neostigmine. Rather, the explanation is more likely to be that the sufficient spontaneous recovery was not achieved before administration of neostigmine. When discussing about earlier administration of reversal, at deep levels of block and using qualitative monitoring, Kopman et al.6  stated that this practice “places the patient at risk and the anesthetist in the dark”. Early administration of neostigmine will prolong the postreversal amount of time with a TOF-ratio in the range 0.4–0.9 and a TOF-count of 4 without fade (referred to as the “zone of blind paralysis” by Plaud et al.4 ) and will not shorten the time to full reversal.7  An additional disadvantage of too early administration of neostigmine is that the patient will not have the benefit of maximal effect (i.e., maximal acetylcholinesterase inhibition) at time of extubation.5,8 

Accomplishing full reversal of paralysis is often challenging but more likely to be successful if guided by published data on administration of neostigmine after assessment of TOF-monitoring at the adductor pollicis. We therefore completely agree with Dr. Donati who wrote the editorial accompanying our report: “In practice, reversal and recovery should be guided by adductor pollicis response, and if needed, a switch from facial to ulnar nerve stimulation should be accomplished at the end of the surgical procedure.”9 

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