Sugammadex and Postoperative Pulmonary Complications: Is Stronger Evidence Required?

Residual neuromuscular blockade is common and associated with increased risk of airway obstruction, hypoxemia, and postoperative pulmonary complications. Sugammadex reverses moderately deep rocuronium-induced blockade 7 times faster and deep blockade 17 times faster than neostigmine, and only 13 patients need to be treated with sugammadex rather than neostigmine to avoid residual neuromuscular blockade. However, despite this strong biologic rationale for a reduction in postoperative pulmonary complications with sugammadex, evidence from large well-conducted multicenter studies is lacking. In this issue of Anesthesiology, Kheterpal et al. report the results of the largest observational study to date investigating the association between choice of reversal agent and postoperative pulmonary complications (the sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications [STRONGER] study). They included 45,712 adults admitted to 12 academic and community hospitals in the United States for elective noncardiac surgery. Of these, 22,856 patients received sugammadex and 22,856 patients received neostigmine for reversal of rocuronium or vecuronium. The incidence of a composite of pneumonia, respiratory failure, pneumothorax, and other major pulmonary complications was 3.5% in the sugammadex group and 4.8% in the neostigmine group (adjusted odds ratio, 0.70; 95% CI, 0.63–0.77; number needed to treat 77 to avoid a major pulmonary complication in one patient in this population). Given the millions of people at risk, the suffering of patients who experience postoperative pulmonary complications, and the financial implications for the healthcare system, this 30% reduction could be practice-changing if it is true. Kheterpal et al. took several steps to reduce the pitfalls associated with observational studies. Because of the cost, services and providers often restrict the use of sugammadex to patients with risk factors for postoperative pulmonary complications (i.e., obesity, pulmonary disease, deep neuromuscular blockade). To mitigate this bias, the neostigmine patients underwent surgery between 2014 and 2015, before sugammadex was approved for use in the United States. To make the two groups as similar as possible, patients were matched on the basis of age, sex, obesity, and comorbidities and surgeries associated with postoperative pulmonary complications. Statistical adjustments were made for preoperative and intraoperative factors showing significant imbalance between the sugammadexand neostigmine-treated groups. Sensitivity analyses were conducted to determine whether changes to the types of patients included or the coding of postoperative pulmonary complications made a difference to the results, and to determine how susceptible the results were to confounding by unmeasured or unknown factors. The investigators achieved balance between the two groups in many important known confounding factors; their results were stable in a wide range of sensitivity analyses, and the results had low susceptibility to residual confounding. Nevertheless, Kheterpal et al. acknowledge that their observational study lacks the power of a large randomized, controlled trial to produce a definitive result. If a large randomized, controlled trial were to be conducted, what would it look like? A traditional randomized, controlled trial would compare sugammadex and neostigmine under ideal conditions. The patients would be carefully selected to reduce variability. Perioperative drug “. choosing sugammadex in combination with quantitative neuromuscular monitoring with the intent of reducing the risk of postoperative pulmonary complication is justifiable. ”