February 8, 2021

Revising Thoughts on Neuromuscular Blocking Reversal Agents

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Revising Thoughts on Neuromuscular Blocking Reversal Agents

Deborah Wagner, Pharm.D., FASHP

Clinical Professor of Pharmacy, University of Michigan College of Pharmacy, Clinical Professor of Anesthesiology, Michigan Medicine, Ann Arbor, Michigan

Deborah Wagner, Pharm.D., FASHP, is Clinical Professor at the University of Michigan College of Pharmacy and Clinical Professor of Anesthesiology at Michigan Medicine in Ann Arbor.

Dr. Wagner earned her Doctor of Pharmacy degree from the University of Michigan College of Pharmacy. She is a fellow of ASHP.

Dr. Wagner precepts Doctor of Pharmacy students and residents and also teaches for the College of Pharmacy, School of Medicine, and Graduate Nurse Practitioner program at the University. She provides pain management consultation for the pediatric acute pain service and has developed standardized pain management strategies for intravenous acetaminophen, elastomeric pain pumps, and low dose lidocaine and ketamine infusions to enhance multimodal analgesia. Currently she is part of the University of Michigan Injury Prevention network collaborating to address the opioid epidemic regarding misuse and abuse across the state. Dr. Wagner also participates in the medication safety taskforce within the Department of Anesthesiology to address standardization of medications throughout the perioperative area, and she chairs the Pediatric Medication Safety Committee.

Dr. Wagner is widely recognized for promoting medication safety. She and colleagues at the University of Michigan Hospitals and Health System were a finalist for the 2011 ASHP Foundation Award for Excellence in Medication Use Safety for their advancements in pain management therapy and safe practice. In 2015 she received the Medication Safety Cheers Award from the Institute for Safe Medication Practices, and she was the runner up for the Anesthesia Patient Safety Foundation’s Medication Safety Award in 2018.


What barriers have you found for managing the reversal of neuromuscular blocking agents at your institution? (Check all that apply)

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Historically, hospital and health systems have faced both economic and ethical decisions about formulary additions. This is now impacted by a strong focus on patient quality and safety that creates a new challenge of sustaining value while, at the same time, supporting best practices based on scientific evidence. Pharmacy and therapeutics (P&T) committees have the leadership necessary to create balance between the need and want perspectives and what is fiscally reasonable. The case of neuromuscular blocker reversal agents fits these criteria uniquely. This can be found particularly when looking to a more value-based process in the overall therapeutic use of a medication and the fact that inpatient hospital prescription drug spending has consistently increased by 15-20% over the past 7 years.1 As ASHP suggests, drug cost management strategies are highly variable, and the use of reversal agents falls into the category of more complex, requiring high level strategic planning, as well as collaboration within groups, which in this case is anesthesiology.2 

With sugammadex the value is driven by its ability to reverse deep block, predictable pharmacokinetics, ease of administration, lack of cardiovascular adverse effects, use in high risk populations, and recent data on reduced postoperative pulmonary complications. These need to be weighed against the tried-and-true combination of neostigmine and glycopyrrolate, the gold standard for many years for neuromuscular blockade reversal. But, when is a gold standard not the gold standard any longer despite is familiarity and inexpensive cost relative to the newer agent? One must bear in mind that at a minimum, even today, at least 40% of patients will have postoperative residual neuromuscular blockade often leading to pulmonary complications, either in the hospital or after discharge, resulting in readmission or death.3,4 Three large international studies primarily using neostigmine found consistent rates of residual neuromuscular blockade over 50%.5 This does not predict postoperative pulmonary complications, but it is a major contributing factor. What is the cost of one case of a post-operative pulmonary complication, and what is its frequency? The data tells us that 4-50% of patients will experience an average cost increase either in length of stay (LOS)intensive-care unit (ICU) admission, or readmission post-surgery of approximately $50,000.6 This accounts for over 500,000 ICU days and over $3 billion in additional costs in the United States alone.7

As these numbers often are not reflected in reimbursements to pharmacy departments, we often look for measurable outcomes such as decreased operating room (OR) time, decreased post anesthesia care unit (PACU) LOS, or earlier times to discharge. With sugammadex the dilemma arises that these distinct criteria have yet to support a clear clinical difference. The one fact we know is that spontaneous recovery is an independent risk factor for the development of postoperative pulmonary complications, as well as use of high-dose neostigmine.8,9 Additionally, accurate assessment of the degree of neuromuscular blockade with quantitative monitoring is sorely lacking in the United States relying solely on a train of four (TOF) monitoring to direct reversal. It would be much easier to choose one reversal product over another if this were not the case. In an article by Naguib and colleagues current recommendations are that all patients receiving a neuromuscular blocking agent receive objective monitoring with a goal of a train of four ratio (TOFR) > 0.9 and that subjective monitoring, such as sustained head lift or hand grip, is eliminated from practice.10 This can be equated to driving a car at night without headlights or flying a plane without radar. 

An economic impact of using sugammadex to improve patient safety in Spain showed an offset of postoperative respiratory events avoided 70.4 million in complications resulting in a net savings of 57.1 million after accounting for drug acquisition costs.11 In the United States a cost-effectiveness evaluation including literature from January 2013 through October 2016 evaluated actual time saved in the PACU, OR, or LOS.12 In patients with moderate neuromuscular blockade, sugammadex use was estimated to save up to $358/case allowing one additional surgical case to be performed. Recently, several other published abstracts noted a direct reduction in PACU LOS. Other opportunities for cost savings, such as dose rounding within an acceptable amount to the closest package size, are options. An example would be using a sugammadex 200-mg vial for a 110-kg patient.  This still provides a dose of 1.8 mg/kg within a normally accepted 10% difference in dose. Reducing recommended mg/kg doses to 1 mg/kg is not recommended because, despite predictable reversal time, it risks possible repeated paralysis. Not all economic modeling fits every situation. Pharmacy departments should reflect on their individual hospital practices relative to types of procedures performed, patient factors, depth of neuromuscular blockade used, type of neuromuscular monitoring available, reversal practices, and risk stratifying high-risk patients for postoperative pulmonary complications that could benefit from the use of a more expensive reversal agent. This then needs to be balanced with an educational model to direct best practices for neuromuscular blocker reversal with engagement of all parties from both pharmacy and anesthesiology. 

Sugammadex’s approval has changed and is still changing how anesthesia is practiced and how this enables the depth of neuromuscular blockade to be optimized while at the same time avoiding potential complications with conventional reversal. Results from the Multicenter Perioperative Outcomes Group (MPOG) found sugammadex was associated with an overall 30% reduction in the risk of postoperative pulmonary complications.13 Without quantitative monitoring, anesthesia societies are supporting reversal of all patients with a twitch <4 and even with twitches >in high-risk patients. Although many factors contribute to patient outcomes in the PACU, reversal of neuromuscular blockade is clearly a predominant factor in poorer outcomes.   

Based on the available and emerging evidence, I think the statement “Sugammadex—The Price is Right” can be useful in guiding P&T decisions and the development of guidelines for its use within institutions.

More Information


  1. McCoy S. How hospitals leverage pharmacy teams to reduce costs and improve clinical outcomes. Wolters Kluwer Health. November 3, 2020.
  2. American Society of Health-System Pharmacists. ASHP guidelines on medication cost management strategies for hospitals and health systems. Am J Health-Syst Pharm. 2008; 65:1368-84.
  3. Brueckmann B, Sasaki N, Grobara P et al. Effects of sugammadex on incidence of postoperative residual neuromuscular blockers: a randomized, controlled study. Br J Anaesth. 2015; 115:743-51.
  4. Murphy GS. Neuromuscular monitoring in the perioperative period. Anesth Analg. 2018; 126(2):464-68.
  5. Fortier L, McKeen D, Turner K et al. The RECITE study: a Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade. Anesth Analg. 2015; 121(2):366-72.
  6. Foster C, Charles EJ, Turrentine F. Development and validation of a procedure-specific risk score for predicting postoperative pulmonary complication: a NSQIP analysis. J Am Coll Surg. 2019; 229(4):355-65.
  7. Shander A, Fleisher L, Barie P. Clinical and economic burden of postoperative pulmonary complications: patient safety summit on definition, risk-reducing interventions, and preventive strategies. Crit Care Med. 2011; 39:2163-72.
  8. Bronsert MR, Henderson W, Monk T et al. Intermediate-acting nondepolarizing neuromuscular blocking agents and risk of 30-day morbidity and mortality, and long-term survival. Anesth Analg. 2017; 124:1476-83.
  9. McLean DJ, Diaz-Gil D, Farhan H et al. Dose-dependent association between intermediate-acting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology. 2015; 122(6):1201-13.
  10. Naguib M, Brull S, Kopman A et al. Consensus statement on perioperative use of neuromuscular monitoring. Anesth Analg. 2017; 1-10.
  11. Ramirez Boix P, Cedillo Gomez S, de Pedro JM et al. PSY52 - economic impact of improving patient safety using sugammadex for routine reversal of neuromuscular blockage in Spain. Value Health. 2018; 21:3, S444.
  12. Zaouter C, Mion S, Palomba A et al. A short update on sugammadex with a special focus on economic assessment of its use in North America. J Anesth Clin Res. 2017; 8(7):1-10.
  13. Kheterpal S, Vaughn MT, Dubovoy T et al. Sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications (STRONGER): a multicenter matched cohort analysis. Anesthesiology. 2020; 132:1371-81.