Sugammadex: A Costly Simple Solution That Is Not Really Solving the Problem

To the Editor

The study by Krause et al¹ is one more in a series of studies that show improved outcomes when the only change in care is use of sugammadex instead of neostigmine for reversal. What are we supposed to take away from these studies? The authors seem to suggest that we may want to follow their example: “A systematic transition to sugammadex is therefore feasible and could likely be reproduced elsewhere.” The problem with this is 2-fold, high cost and missing an accurate assessment of return of strength.

Sugammadex is expensive. If we reverse 30 million patients per year with sugammadex, the additional annual drug acquisition cost to institutions is likely to be ≥3 billion dollars; however, the cost to the health care system, which includes actual cost to patients and insurers, is likely at least twice this amount. This estimate is based on the following 3 assumptions. First, we administer well over 60 million anesthetics in the United States each year. It is estimated that 50% of these patients receive nondepolarizing muscle relaxants. Second, sugammadex currently costs approximately $90–$100 for the smaller vial of 200 mg, and many patients receive >1 vial. The cost of neostigmine varies but generally is now about 10% of the cost of sugammadex. Third, beyond comparing the cost of vials, we compared the actual cost of reversal (cost of all vials for total dose of sugammadex versus cost of all vials for total doses of neostigmine plus glycopyrrolate) and found sugammadex reversal cost was over 5 times greater for sugammadex ($117 vs $21).

Transitioning from neostigmine to sugammadex ignores the several clear recommendations for management of perioperative paralysis that are based on good evidence and that have been published repeatedly. It is now 20 years since experts first recommended routine use of quantitative monitoring.² In the intervening years, an increasing number of anesthesia societies have promulgated recommendations and standards to include quantitative monitoring,³ and in 2018, a consensus statement was published in support of routine quantitative monitoring.⁴ Quantitative monitoring has several advantages. One is that it allows us to identify which patients actually have residual paralysis. Sugammadex has only one indication, to prevent residual paralysis, and is not needed for the majority of patients in a mixed surgical population who do not have residual paralysis either before or after routine reversal with neostigmine. Contrary to the often presented narrative that sugammadex has less severe side effects than neostigmine, there is no convincing evidence that sugammadex is safer than neostigmine, as long as residual paralysis is prevented.⁵ Although serious side effects from sugammadex or neostigmine are rare, potential side effect is one more reason why patients who do not have an indication for a drug should not be exposed to it. When quantitative monitoring is used routinely in our practice, we find that up to 20% of patients in a mixed surgical population recover spontaneously to train-of-four (TOF) ratio ≥90%. In the report by Krause et al,¹ quantitative monitoring was not used and undoubtedly sugammadex was administered to some patients who had no need for pharmacological reversal.

Quantitative monitoring is not the only recommendation that is being ignored. In many cases, not even use of a peripheral nerve stimulator was recorded (Table 1 in the report by Krause et al¹). Moreover, it has been clearly established since 2002 that attempts at reversal with neostigmine from low TOF counts are not meaningful. In the report by Krause et al,¹ many patients were apparently reversed with neostigmine when they still had low TOF counts (Table 1 in the report by Krause et al¹), although it is unclear what is meant by “Final TOF count/ST” in this table. Are all these data obtained before or after reversal? Was it 100 or 50 Hz sustained tetanus? If they are prereversal assessments, then the majority of patients with sustained tetanus for 5 seconds without fade would almost certainly have been excellent candidates for either inexpensive neostigmine reversal or no reversal in cases where full recovery could be confirmed by quantitative monitoring.

The article is silent with regard to addressing other risk factors for residual paralysis, including but not limited to avoiding overdosing of muscle relaxants by appropriate dose adjustment for age, sex, and body mass index, avoiding neuromuscular monitoring at the eye muscles and dose adjustment of neostigmine to avoid the so-called paradoxical paralysis.

In 2007, one of the greatest experts on perioperative muscle relaxant management, Dr Francois Donati, cautioned against simply relying on sugammadex to solve the important clinical problem of residual paralysis: “The introduction of sugammadex has the potential to change radically our approach to reversal, but will it spare us from the need to understand neuromuscular blockade? Is the era of cookbook blockade management at our doorstep or will our patients be better off if we try to understand what we are doing?”⁶

Importantly, this article eliminates all patients who receive a benzylisoquinoline or who have a contraindication to sugammadex (renal failure, allergic reaction). Caution is required when relying solely on a drug that cannot serve all our patients.

There is no doubt that sugammadex is a very important addition to our armamentarium. It allows us to prevent residual paralysis in patients who are not candidates for efficacious neostigmine reversal. However, there are obvious opportunities to prevent residual paralysis in a more cost-effective manner than system-wide transitions to universal administration of sugammadex to all patients having received rocuronium or vecuronium.

Stephan R. Thilen, MD, MS
Department of Anesthesiology & Pain Medicine
University of Washington
Seattle, Washington
Wade A. Weigel, MD
Department of Anesthesiology
Virginia Mason Medical Center
Seattle, Washington
[email protected]