Revising Thoughts on Neuromuscular Blocking Reversal Agents

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 >4 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.

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