The publication of guidelines regarding the use, monitoring and antagonism of neuromuscular blocking agents by the ASA in 20231 has sparked many-a-hallway-conversation. “Am I going to be forced to use sugammadex now, considering the high-cost of this medication?” “Can I use this information to advocate for the use of sugammadex in my institution, considering the high-cost of this medication and its efficacy compared to neostigmine?” “Will I be forced to buy quantitative monitors or be at risk of practicing below standards if I don’t?” “If I am using sugammadex, is monitoring even necessary anyway?”
We are sure you can think of, or even have more questions of your own.
Let’s start with the assumption that you are going to antagonize rocuronium neuromuscular blockade using an electromyography-based quantitative neuromuscular blockade monitor. Which reversal agent, neostigmine or sugammadex, are you going to use? Today’s PAAD by Thilen et al.2 is an adult study that provides insight into how to make this decision…and yes…quantitative monitoring is necessary!
Original article
Thilen SR, Sherpa JR, James AM, Cain KC, Treggiari MM, Bhananker SM. Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring. Anesth Analg. 2024 Sep 1;139(3):536-544. doi: 10.1213/ANE.0000000000006511. Epub 2023 May 12. PMID: 37171989.
The use of quantitative neuromuscular monitoring has been recommended by the ASA1 and several international anesthesiology societies3,4 to prevent postoperative residual neuromuscular blockade (PRNB).5 Thilen et al.2 “designed a cohort study aimed to evaluate a protocol for management of rocuronium blockade and reversal with neostigmine or sugammadex, guided by quantitative neuromuscular monitoring. The primary goal of this descriptive study was to estimate the incidence of PRNB when this protocolized approach is implemented. They also computed the acquisition costs for all pharmacologic reversal drugs used to treat our cohort of patients and compared this to the potential cost with routine use of sugammadex for all patients, not as a formal cost-benefit analysis but merely a descriptive analysis including only the acquisition costs of reversal agents.”2
Thilen et al. used a protocol in which adult patients were paralyzed with rocuronium and at the end of the procedure: “a pre-reversal assessment was made using quantitative train of four (TOF) measurements to determine the appropriate method of reversal. No pharmacologic reversal was recommended if the train of four ratio (TOFR) was ≥0.9. Neostigmine 15–30 mcg/kg (rounded up to next 0.5 mg) was recommended when the TOFR was ≥0.4 but <0.9. Glycopyrrolate was administered immediately before neostigmine in a 1:5 weight relationship (eg, glycopyrrolate 0.2 mg before neostigmine 1 mg). Sugammadex 2 mg/kg was recommended when the TOF count was at least 1 and TOFR <0.4, while sugammadex 4 mg/kg was recommended for TOF count = 0 and PTC ≥1. The protocol called for providers not to extubate before confirming recovery to a TOFR of at least 0.9. The protocol suggested to consider a rescue reversal with sugammadex no earlier than 10 minutes following administration of neostigmine and 3 minutes following administration of sugammadex.”2
What did they find? “A total of 189 patients completed the study: 66 patients (35%) were reversed with neostigmine, 90 patients (48%) with sugammadex, and 33 (17%) patients recovered spontaneously without pharmacological reversal. The overall incidence of residual paralysis was 0% (95% CI, 0–1.9). The total acquisition cost for all reversal drugs was United States dollar (USD) 11,358 (USD 60 per patient) while the cost would have been USD 19,312 (USD 103 per patient, 70% higher) if sugammadex had been used in all patients. Three patients (4.5%) were administered rescue reversal after initially having been administered neostigmine per protocol, and 3 patients (3.3%) were administered additional sugammadex after an initial sugammadex dose. One of these cases was a dosing error in which the patient had received an inadequate dose of sugammadex (2 mg/kg instead of 4 mg/kg when the pre-reversal level of block was PTC = 3).”2
OK, you may be wondering why did we pick this adult article for the PAAD? We find it fascinating for several reasons, and the bottom line is the over-whelming support for quantitative monitoring to do this stuff right.
The argument supporting the superiority of sugammadex over neostigmine to prevent (eliminate?) the ongoing problem of residual neuromuscular blockade touts its ability to effectively and efficiently antagonize all levels of block, unlike it’s historical predecessor, neostigmine. While it is true that neostigmine is limited in its efficacy at deeper than minimal levels of blockade, Thilen et al. demonstrate that it is as effective and efficient as sugammadex when utilized in this specific recovery range. This mandates quantitative monitoring! At minimal depths of block where the TOFR is 0.4 to <0.9, the human senses are unable to detect subtle weakness or fade in the train-of-four response!
Proponents for sugammadex may argue that even at a minimal level of block, sugammadex is more efficient. Is this true? The time from procedure end to extubation or PACU arrival was 4 and 2 minutes longer, respectively, if neostigmine vs sugammadex was used. But interestingly, these time points were the same between the neostigmine group and those patients who spontaneously recovered from their blockade (i.e.-no need to wait for recovery to occur before extubation and OR exit), suggesting that these time differences may not have been solely based on the efficiency of antagonism by these respective agents.
6 patients in this study required sugammadex rescue, 3 following neostigmine antagonism, but also 3 following the administration of sugammadex. This highlights what has been shown in other studies, which is that even with sugammadex, patients may experience residual neuromuscular blockade with recommended dosing. Kotake et al.6 reported residual blockade with a TOFR <0.9 present in 4.3% of their study patients when sugammadex dosing and adequate recovery was based on qualitative assessments. Bowdle et al.7 performed a dose finding study and found that many patients needed less than the recommended sugammadex dosing, but found 13% of their study population required more!
Faulk et al. found that pediatric anesthesiologists prefer sugammadex and believe its use makes monitoring unnecessary.8 This is simply untrue.9 And, it should be remembered that the recommended doses of sugammadex are based on quantitative monitoring!
Today’s PAAD underscores the value of quantitative neuromuscular blockade monitoring in preventing postoperative residual neuromuscular blockade and why you should be using these monitors ROUTINELY in ALL of your paralyzed patients. Simply put, we can eliminate PRNB. And a final thought. I (MY) am always a bit leery of cost-benefit analysis studies because how much a drug costs. The cost of neostigmine, glycopyrrolate, and sugammadex are very institution specific and these costs are usually proprietary and very difficult to obtain. It is often based on bundling of multiple drugs to the hospital pharmacy and the costs of stocking, dispensing, and labor. Is neostigmine really cheaper than sugammadex in your hospital? Will using neostigmine really result in cost savings?
Sugammadex has transformed our practice allowing us to keep patients at deep levels of blockade through surgery and effectively and efficiently antagonize this block at the end of surgery. It is far easier to use than neostigmine, but I (DF) believe this has made us a bit cavalier in our approach to using neuromuscular blocking agents. A point that may be lost in Thilen et al’s report is that the use of quantitative monitoring was not just at the end of surgery, but throughout the course of blockade administration, using a defined protocol for repeat rocuronium administration to target a certain depth of block. In my opinion (DF), to win the battle against residual neuromuscular block, more crucial than which antagonist we chose to facilitate recovery is how we are using these agents from block onset to recovery, and appropriately monitoring to ensure the goal of adequate recovery has been achieved.
Send your thoughts and comments to Myron who will post in a Friday 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 2023;138(1):13-41. (In eng). DOI: 10.1097/aln.0000000000004379.
2. Thilen SR, Sherpa JR, James AM, Cain KC, Treggiari MM, Bhananker SM. Management of Muscle Relaxation With Rocuronium and Reversal With Neostigmine or Sugammadex Guided by Quantitative Neuromuscular Monitoring. Anesthesia and analgesia 2024;139(3):536-544. (In eng). DOI: 10.1213/ane.0000000000006511.
3. Fuchs-Buder T, Romero CS, Lewald H, et al. Peri-operative management of neuromuscular blockade: A guideline from the European Society of Anaesthesiology and Intensive Care. European journal of anaesthesiology 2023;40(2):82-94. (In eng). DOI: 10.1097/eja.0000000000001769.
4. Klein AA, Meek T, Allcock E, et al. Recommendations for standards of monitoring during anaesthesia and recovery 2021: Guideline from the Association of Anaesthetists. Anaesthesia 2021;76(9):1212-1223. (In eng). DOI: 10.1111/anae.15501.
5. Murphy GS, Brull SJ. Quantitative Neuromuscular Monitoring and Postoperative Outcomes: A Narrative Review. Anesthesiology 2022;136(2):345-361. (In eng). DOI: 10.1097/aln.0000000000004044.
6. Kotake Y, Ochiai R, Suzuki T, et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesthesia and analgesia 2013;117(2):345-51. (In eng). DOI: 10.1213/ANE.0b013e3182999672.
7. Bowdle TA, Haththotuwegama KJ, Jelacic S, Nguyen ST, Togashi K, Michaelsen KE. A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis. Anesthesiology 2023;139(1):6-15. (In eng). DOI: 10.1097/aln.0000000000004578.
8. Faulk DJ, Austin TM, Thomas JJ, Strupp K, Macrae AW, Yaster M. A Survey of the Society for Pediatric Anesthesia on the Use, Monitoring, and Antagonism of Neuromuscular Blockade. Anesthesia and analgesia 2021;132(6):1518-1526. (In eng). DOI: 10.1213/ane.0000000000005386.
9. Faulk DJ, Karlik JB, Strupp KM, et al. The Incidence of Residual Neuromuscular Block in Pediatrics: A Prospective, Pragmatic, Multi-institutional Cohort Study. Cureus 2024;16(3):e56408. (In eng). DOI: 10.7759/cureus.56408.
I do believe in cost analysis cause so many things are possibly in short supply and cost may dictate which one to choose and some may push a cheaper less useful option also. Institutional cost do matter as some products go up in cost and others lower and this MAY allow for a choice if necessary.
So Suggammedax is more expensive up front by some 70%. Well if that was used across the board many small hospitals would go out.
However, my real reason to object to Suggameddiax is two fold. I have seen more than a 3% occurrence of PRND after suggameddax with what to do next , I think from poor anesthesia planning and a lack of medical attention and knowledge. Just give Suggameddax is the running statement. We are either physicians or not. I say with sadness that I see younger physicians clearly just pushing meds without forethought of cost or events.
My other real concern not discussed, is the real risk of post medication blockage of OCPs. As we ALL know and see , most of the patient population rarely follows our post op orders. And here we again are expose ourselves to a pregnancy and complications there of that will be reviews back to our anesthestic. Unfortunately, there is a state of litigation, and a post procedural pregnancy that might lead to complications of mother or fetus or both may be way fodder for the lawyers among us . I know many will say that if we warn the patients we are in the clear, but I doubt that.
I do believe in cost analysis cause so many things are possibly in short supply and cost may dictate which one to choose and some may push a cheaper less useful option also. Institutional cost do matter as some products go up in cost and others lower and this MAY allow for a choice if necessary.
So Suggammedax is more expensive up front by some 70%. Well if that was used across the board many small hospitals would go out.
However, my real reason to object to Suggameddiax is two fold. I have seen more than a 3% occurrence of PRND after suggameddax with what to do next , I think from poor anesthesia planning and a lack of medical attention and knowledge. Just give Suggameddax is the running statement. We are either physicians or not. I say with sadness that I see younger physicians clearly just pushing meds without forethought of cost or events.
My other real concern not discussed, is the real risk of post medication blockage of OCPs. As we ALL know and see , most of the patient population rarely follows our post op orders. And here we again are expose ourselves to a pregnancy and complications there of that will be reviews back to our anesthestic. Unfortunately, there is a state of litigation, and a post procedural pregnancy that might lead to complications of mother or fetus or both may be way fodder for the lawyers among us . I know many will say that if we warn the patients we are in the clear, but I doubt that.