Residual Blockade Tested Following Reversal With Sugammadex, Neostigmine

Author: Michael Vlessides

Anesthesiology News

While reversing moderate blockade with sugammadex (Bridion) reduces residual neuromuscular blockade relative to neostigmine, it does so without reducing the incidence of postoperative pulmonary complications, a new study has found.

Nevertheless, the trial found that sugammadex was associated with fewer 30-day hospital readmissions.

“We know that residual neuromuscular blockade is associated with postoperative pulmonary complications,” said Michael Aziz, MD, a professor of anesthesiology and perioperative medicine at Oregon Health & Science University, in Portland. “We also know that reversal of neuromuscular blockade with sugammadex compared to neostigmine results in reduced residual neuromuscular blockade.

“But what we don’t know is if the practice of routine reversal with sugammadex versus neostigmine results in any difference in outcomes with respect to pulmonary complications,” Dr. Aziz added.

To answer this question, principal investigator Brandon Togioka, MD, an assistant professor of anesthesiology and perioperative medicine, also at Oregon Health & Science University, and his colleagues enrolled 200 patients at high risk for pulmonary complications into the open-label, assessor-blinded, randomized controlled trial. Each patient presented for elective surgery at the institution between January 2017 and March 2018.

Primary End Point Was Pulmonary Complications

Patients were deemed eligible for the study if they were at least 70 years of age, were undergoing surgery at least three hours in duration, and did not have a contraindication to neuromuscular blockade. “These patients were at high risk of postoperative pulmonary complications because of their age and the nature and duration of their surgery,” Dr. Aziz told Anesthesiology News.

The researchers monitored the patients for adverse events at various time points: in the PACU, on daily visits until discharge, and by phone call and review of medical records 30 days after discharge.

The study’s primary end point was the incidence of postoperative pulmonary complications, which included postoperative pneumonia, aspiration pneumonitis, atelectasis, pneumothorax, desaturation/hypoxemia, upper airway obstruction and acute respiratory insufficiency. Secondary end points included residual postoperative paralysis (TOF <0.9).

Presenting the study at the 2019 annual meeting of the International Anesthesia Research Society (abstract D175), Dr. Aziz noted that 98 of 100 patients assigned to the intervention group received sugammadex and 99 of 100 patients receiving usual care were given neostigmine.

Although patients who underwent reversal with sugammadex experienced lower rates of residual postoperative paralysis (10% vs. 49%; P<0.001), no statistically significant difference was seen between groups in postoperative pulmonary complications, which affected 33% of sugammadex patients and 40% of those who received neostigmine.

Cost Issues Remain

Although no differences in PACU time and hospital length of stay between groups were observed, there was a difference in hospital readmission rates, at 5% in the sugammadex group and 15% in the neostigmine group. “Now, we don’t know if the patients were readmitted at day 2 or day 20,” Dr. Aziz said. “We need to do some further exploratory analyses to sort out what these readmissions look like.”

Given the cost of sugammadex, Dr. Aziz said he only uses the agent under certain circumstances. “Personally, I use it quite a bit after procedures that require deep block,” he said.

“I think of surgical airway procedures such as suspension laryngoscopy, where you’re performing a laryngoscopy and then it’s all over very quickly,” he added. “So having something that will reverse rapidly is useful.

“I even find it helpful in open abdominal procedures, if the closure is quick and you’re not recovering twitches,” Dr. Aziz continued. “And many of our providers’ practice is that if they’re not getting four solid twitches, they reach for the sugammadex because they know they’re going to have residual block if they just use neostigmine.”

Nevertheless, Dr. Aziz recognized that at this point, the researchers could claim no differences between the two agents with respect to their effect on postoperative pulmonary complications. “I think this trial allows us to draw some conclusions regarding the reduced rate of residual neuromuscular blockade with sugammadex, which are consistent with other studies,” he noted.

“Those differences may ultimately be associated with reduced postoperative pulmonary complications, but we didn’t observe it here,” he said. “So we can’t recommend the routine use of sugammadex to reduce the rate of postoperative pulmonary complications. More work needs to be done.”

As Stephan Thilen, MD, MS, discussed with Anesthesiology News, one of the main issues with the trial was its TOF goal of two twitches. “At a TOF count of 2, we do not recommend reversal with neostigmine,” said Dr. Thilen, an associate professor of anesthesiology and pain medicine at the University of Washington School of Medicine, in Seattle. “I believe you have to wait for the fourth twitch to return before reversing with neostigmine.

“François Donati wrote a great review article in 2013, on the topic [Can J Anaesth 2013;60[7]:714-729], saying if you’re going to reverse with neostigmine, there’s no benefit to giving it before the fourth twitch returns,” Dr. Thilen said. “But most providers in the real world feel they can’t do that because of production pressures.”