Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents. Response to Br J Anaesth 2024; 132: 461–5

Editor—We read with interest the recent editorial by Hunter and Blobner¹ regarding risks related to under-dosing and over-dosing neuromuscular blocking drugs and reversal agents, an issue of ongoing importance in anaesthesiology. We agree with the authors that more research on recurrent paralysis after rocuronium and sugammadex reversal is necessary as the mechanism of recurrent paralysis is not understood. We are unaware of any evidence to date that recurrent paralysis is caused by neuromuscular blocking drug redistribution from the extravascular space to the plasma, as suggested by Hunter and Blobner,¹ although this is a possible explanation. Confirmation of this hypothesis would require pharmacokinetic evidence, such as demonstration of an increase in unbound rocuronium plasma concentration after reversal with sugammadex, that corresponds to recurrent paralysis.

Hunter and Blobner¹ stated ‘Further studies are indicated on the efficacy and dose requirements of sugammadex when reversing deep neuromuscular block … ’ In regards to such studies, we recently published a dose-finding study of sugammadex for reversal of rocuronium in cardiac surgery patients that was not cited in the editorial.² The study was also accompanied by an editorial comment.³ In our study, 97 cardiac surgery patients received incremental doses of sugammadex during sternal closure and were then monitored in the intensive care unit for up to 7 h in a systematic search for residual paralysis. The effective dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.42 to 5.6 mg kg⁻¹. Patients with deep block (post-tetanic count 0–4) required a mean sugammadex dose of 2.35 (0.98) mg kg⁻¹; 87% of patients required less than the manufacturer's recommended dose whereas 13% required more. Two patients developed recurrent paralysis; one having been reversed from a post-tetanic count of 0, the other from a train-of-four ratio of 0.47. In the latter case, the recurrence occurred 5 min after reversal to a train-of-four ratio >0.9, which is inconsistent with the editorialists' statement¹ that there is a ‘ … time delay of at least 30 mins after tracheal extubation until neuromuscular block recurs ….’ We also reviewed the available literature concerning recurrent paralysis after sugammadex, as summarised in the Supplemental Digital Content that accompanied the article.

We agree with the authors that quantitative monitoring is necessary to ensure complete recovery from neuromuscular block, including when sugammadex is used at the manufacturer's recommended dose, as shown by the fact that 13% of patients in our study required a dose greater than the recommended dose. Many anaesthesia providers discontinue monitoring immediately after administering sugammadex or immediately after reaching a train-of-four ratio of >0.9. We recommend that after successful reversal, quantitative twitch monitoring should be continued until the time the patient's trachea is extubated and the patient is awake. Monitoring for as long as the patient remains anaesthetised provides an opportunity to detect recurrent paralysis, should it occur soon after reversal. Our recommendation is similar to that of Todd and Kopman³: ‘Until we better understand this phenomenon [recurrent paralysis], we believe the best recommendation is careful quantitative monitoring and verification that the train-of-four ratio reaches a value of 0.9 and persists at this level for at least a few monitor cycles or continues to increase.’

Declaration of interest

The authors declare that they have no conflict of interest.

Funding

The Washington Research Foundation to KM (Seattle, WA, USA). The Laura Cheney Professorship in Anesthesia Patient Safety to AB (Seattle, WA, USA).