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Continued use of a glucagon-like peptide 1 (GLP-1) receptor agonist leading up to surgery may not increase the risk for regurgitation and pulmonary aspiration during operations after all, an analysis of insurance claims data suggested.
In patients with diabetes undergoing surgery the same day as an emergency department visit -- a scenario where the recommended withholding of a GLP-1 drug would be unlikely -- the incidence of postoperative respiratory complications was similar for patients on GLP-1 agents and those on other types of antidiabetic medications, reported researchers led by Anjali Dixit, MD, MPH, of Stanford University School of Medicine in California.
In adjusted analyses, the composite outcome of aspiration pneumonitis, postoperative respiratory failure, and/or admission to the intensive care unit through 7 postoperative days occurred in 4% of GLP-1 agonist users and 3.9% of non-users (adjusted OR 1.03, 95% CI 0.82-1.29, P=0.80), the team detailed in a research letter.
The findings provide reassurance but also call into question recent preoperative guidelines from the American Society of Anesthesiologists (ASA) that recommend patients pause GLP-1 agents such as semaglutide (Ozempic, Rybelsus, Wegovy) prior to surgery to reduce the risk of regurgitation and aspiration of food during general anesthesia and deep sedation.
"We were surprised by our findings given the case reports of large-volume emesis, as well as other studies showing increased gastric volumes, in appropriately fasted patients who had used GLP-1 receptor agonists," Dixit told ľֱ. "These studies had raised concerns that patients who had recently taken a GLP-1 receptor agonist would have a much higher risk of pulmonary aspiration under anesthesia, which is a serious and potentially fatal complication."
Based on the new findings, it may in fact be safe to carry on with surgery even if a patient using a GLP-1 agonist did not follow the medication withholding guidelines, she said.
Because GLP-1 agonists work by delaying gastric emptying, the ASA's 2023 guidelines recommended that patients undergoing an operation pause their GLP-1 drug a week before in the case of once-weekly injectables or the day of surgery for once-daily medications.
"The current recommendation to withhold most GLP-1 receptor agonists for a week before surgery is logistically burdensome, requiring patients to be contacted over a week ahead of time," Dixit pointed out. "If they don't follow the guidelines, their surgery may be canceled -- and canceled surgeries are sometimes never rescheduled. This can lead to patient harm."
In addition, she said that for patients using these agents for diabetes, a week-long hiatus may lead to suboptimal glycemic control on the day of surgery, which carries its own flurry of risks for adverse events in the post-surgery period.
"The ASA should weigh these potential risks of GLP-1 receptor agonist withholding against the low risks of severe postoperative complications estimated in our study," said Dixit. "Further work in other patient populations, including those taking GLP-1 receptor agonists specifically for management of obesity, would also bolster a decision to liberalize the ASA's preoperative guidelines."
In the meantime, she recommended anesthesiologists consider using pulmonary aspiration risk mitigation strategies that are commonly used for patients undergoing emergency surgery or who have known delayed gastric emptying.
For their analysis, administrative claims data from 2015 to 2021 were pulled from the Merative MarketScan Commercial Database, representing people under 65 with employer-sponsored health insurance. The sample included patients with type 2 diabetes either with a GLP-1 receptor agonist fill (n=3,502) or with at least one fill for a non-GLP-1 antidiabetic agent (n=20,177).
The average patient age for the GLP-1 users and non-users was 54 years, and both groups had the same average Diabetes Complications Severity Index score (1.3). Patients in the GLP-1 group were more likely to be male (51% vs 46%), to be on insulin (32.3% vs 28%) or a greater number of antidiabetic agents (2.4 vs 1.5), and to have obesity (52% vs 42%).
Patients who underwent any of 13 emergency surgeries were included. The most common of these was transurethral intervention (35-36%), laparoscopic cholecystectomy (33-34%), laparoscopic appendectomy (11-13%), and incarcerated or strangulated hernia (11%).
Other surgeries included colectomy for diverticulitis, traumatic hip fracture, adhesive small bowel obstruction, ovarian torsion, testicular torsion, ectopic pregnancy, laparoscopic or open repair of perforated ulcer, upper endoscopy for bleeding peptic or duodenal ulcer, and upper endoscopy for foreign body removal.
Sensitivity analyses, including one that only included an aspiration and/or postoperative respiratory failure diagnosis, showed results similar to the primary outcome.
While several GLP-1 agonists are also approved for weight management, the sample only included patients prescribed an agent in this class approved for diabetes. Dixit also noted these findings don't apply to patients using GLP-1 agonists undergoing procedures under light or moderate sedation without an anesthesiologist or other advanced airway practitioner.
Other limitations to the study included a lack of data on patient adherence to medication prior to surgery, as well as a lack of data on preoperative duration of GLP-1 use.
Disclosures
The study was supported by grants from the National Institute of General ľֱ Sciences and from the National Institute of Drug Abuse.
Dixit and co-authors reported no disclosures.
Primary Source
JAMA
Dixit AA, et al "Preoperative GLP-1 receptor agonist use and risk of postoperative respiratory complications" JAMA 2024; DOI: 10.1001/jama.2024.5003.