Neuromuscular blockade Part 2

Myron Yaster MD and Debra Faulk MD

In today’s PAAD we’ll continue our review of the new ASA practice guidelines for monitoring and antagonism of neuromuscular blockade.   Because I was one of the authors of these guidelines, several of you have already sent me some questions about them so I will pre-emptively incorporate those questions into today’s review.  Myron Yaster MD

Original article

Stephan R Thilen, Wade A Weigel, Michael M Todd, Richard P Dutton, Cynthia A Lien, Stuart A Grant, Joseph W Szokol, Lars I Eriksson, Myron Yaster, Mark D Grant, Madhulika Agarkar, Anne M Marbella , Jaime F Blanck, Karen B Domino. 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on Neuromuscular Blockade.  Anesthesiology. 2023 Jan 1;138(1):13-41  PMID: 36520073

Editorial

Sorin J Brull and Aaron Kopman.  Measuring Success of Patient Safety Initiatives: The 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade.  Anesthesiology. 2023 Jan 1;138(1):4-6. PMID: 36520074

The guidelines can be boiled down to this summary: “This practice guideline provides evidence-based recommendations on the management of neuromuscular monitoring and antagonism of neuromuscular blocking agents. The objective is to guide practice that will enhance patient safety by reducing residual neuromuscular blockade. It is recommended to use quantitative neuromuscular monitoring at the adductor pollicis and to confirm a recovery of train-of-four ratio greater than or equal to 0.9 before extubation. Sugammadex is recommended from deep, moderate, and shallow levels of neuromuscular blockade that is induced by rocuronium or vecuronium. Neostigmine is a reasonable alternative from minimal blockade (train-of-four ratio in the range of 0.4 to less than 0.9). Patients with adequate spontaneous recovery to train-of-four ratio greater than or equal to 0.9 can be identified with quantitative monitoring, and these patients do not require pharmacological antagonism”.1

Regardless of the antagonist used, quantitative monitoring can and should be used to guide dosing and timing of reversal.  Some of the most contentious discussions amongst the guideline members involved antagonism of neuromuscular blockade.  “The antagonist drugs currently available include anticholinesterases (the study group really only evaluated neostigmine) and sugammadex, a selective relaxant binding drug.1 The group strongly recommended “sugammadex over neostigmine at deep, moderate, and shallow depths of neuromuscular blockade induced by rocuronium or vecuronium.”1 Why? Cutting to the chase, the published studies showed sugammadex was much faster and more reliably effective than neostigmine. 

For neostigmine to work, the degree of neuromuscular blockade must be minimal (quantitative TOFr of 0.4-09 or if using qualitative sensors, 4 out 4 twitches without fade.2, 3  A recurrent theme in the group discussions: “the antagonist effect of neostigmine is maximal within approximately 10 min,  and therefore, there is no benefit in administering neostigmine much more than 10 min before emergence and extubation. If recovery time exceeds 10 min (i.e., a train-of-four ratio greater than or equal to 0.9 has not been reached within 10 min after neostigmine administration), it is unlikely to be the result of delayed activity of neostigmine. Rather, the explanation is more likely to be that sufficient spontaneous recovery was not achieved before administration of neostigmine. When neostigmine has peaked but the train-of-four ratio is less than 0.9, three options remain to accomplish adequate antagonism: (i) allow for continued spontaneous recovery; (ii) administer sugammadex if appropriate to the relaxant given; or (iii) if a low dose of neostigmine was initially used, administer additional neostigmine (but not exceeding a total of 50 μg/kg because higher doses have not been reported as more effective)”.1

When neostigmine is used at minimal blockade (quantitative TOFr greater than or equal to 0.4 and less than 0.9), the dose should not exceed 40 µg/kg. The shallower the blockade, the lower the neostigmine dose required—when the train-of-four ratio exceeds 0.6, 15 to 30 μg/kg is usually adequate.  Quantitative monitoring can also guide how much sugammadex to administer as well.  “The FDA-approved dose recommendations for antagonizing rocuronium or vecuronium with sugammadex are 2 mg/kg for train-of-four count 2 to train-of-four ratio less than 0.9, 4 mg/kg for posttetanic count 1 to train-of-four count 1, and 16 mg/kg immediate antagonism after administration of a single dose of rocuronium 1.2 mg/kg.”1

Several readers of the PAAD have already reached out to me saying that sugammadex was simply too expensive to use routinely (hundreds of dollars per ampule compared to just a few dollars for neostigmine even if one also adds the cost of glycopyrrolate).  As pointed out by many members of the guideline group “Factors beyond drug costs require consideration—e.g., time to recovery and operating room costs, residual neuromuscular blockade and reparalysis, as well as the costs associated with adverse events caused by residual neuromuscular blockade”. Finally, “in discussions regarding costs during guideline development, the patient representative noted to the panel the rather small proportion added by sugammadex to overall operative charges.”1  We would add that the use of quantitative monitors may help reducing the costs of sugammadex.  There is absolutely no reason that an entire vial must be opened and used for each individual patient encounter.  If the pharmacy breaks down the sugammadex vials to smaller units (just like many of us do when using dexmedetomidine) and reversal is guided by quantitative TOFr how much sugammadex is used can be greatly reduced.  Indeed, some patients my not require reversal at all.

We would love to hear from you.  Send your thoughts to Myron and we’ll publish in a Reader response. 

References

1.            Thilen SR, Weigel WA, Todd MM, et al. 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade: A Report by the American Society of Anesthesiologists Task Force on Neuromuscular Blockade. Anesthesiology. Jan 1 2023;138(1):13-41. doi:10.1097/aln.0000000000004379

2.            Schaller SJ, Fink H, Ulm K, Blobner M. Sugammadex and neostigmine dose-finding study for reversal of shallow residual neuromuscular block. Anesthesiology. Nov 2010;113(5):1054-60. doi:10.1097/ALN.0b013e3181f4182a

3.            Naguib M, Brull SJ, Kopman AF, et al. Consensus Statement on Perioperative Use of Neuromuscular Monitoring. Anesthesia and analgesia. Jul 2018;127(1):71-80. doi:10.1213/ane.0000000000002670