New Weight-Loss Drugs Spark Debate About Safety During Surgery

Anesthesiologists are sharply divided over how to handle the growing number of surgical patients on GLP-1 receptor agonists, given that the drugs can raise the risk of aspiration during surgery.

While the leading U.S. anesthesiology society suggests that patients stop taking injectable versions of the medications for 7 days ahead of surgery, some anesthesiologists are turning to alternative strategies such as intubating all at-risk patients, even for minor procedures.

Other anesthesiologists are calling for patients to stay off the drugs for weeks, not days, or titrate down to lower doses.

"This topic is being heavily discussed in the anesthesia community right now, and it's very polarizing," Michael Gulak, MD, a resident anesthesiologist at the University of Toronto, told MedPage Today.

Last fall, Gulak hustled to save a patient on injectable semaglutide (Ozempic for type 2 diabetes, Wegovy for weight loss) who regurgitated stomach contents while under sedation for a lumpectomy.

Normally, clinicians reduce the risk of aspiration by requiring patients to fast prior to scheduled surgery in order to keep their stomachs clear.

"In theory, their stomachs are pretty empty," Daniel Cole, MD, an anesthesiologist at the University of California Los Angeles (UCLA) and president of the Anesthesia Patient Safety Foundation, said in an interview.

But GLP-1 agonists, including the blockbuster semaglutide, can dramatically disrupt the normal digestive process. The stomachs of users may not empty out within the usual 90 minutes to 2 hours after a meal.

Slower gastric emptying makes patients feel more full, leading them to eat less. But anesthesiologists say there's a risk that lingering food in the stomach -- say, the pizza the patient ate 2 days ago -- will be regurgitated while a patient is under anesthesia and cannot voluntarily cough to prevent the airway from being clogged.

This raises the risk that food will be inhaled into the lungs, "a rare but devastating event with a high incidence of death and severe injury," Cole said.

The worry among anesthesiologists is so high that "the anesthetic plan for any surgery could be affected by a patient taking these medications," Kathryn Cobb, MD, an anesthesiologist at the University of North Carolina at Chapel Hill, told MedPage Today. "Not only are some anesthesiologists choosing now to intubate patients on these meds for seemingly minor procedures, but they are also likely performing a technique we use in patients at high risk for aspiration."

Lumpectomy Patient Regurgitates in 'Dramatic' Fashion

Alarm has grown among anesthesiologists as the number of cases of regurgitation has risen among patients undergoing surgery while taking GLP-1 receptor agonists. In one harrowing case in October 2022, a 48-year-old woman undergoing a lumpectomy in Toronto began to regurgitate while under anesthesia. This happened even though she'd been fasting from solid foods for 20 hours and clear fluids for 8 hours.

"It was very dramatic," recalled Gulak, who reported the incident in a case report in the Canadian Journal of Anesthesia. The woman regurgitated clear fluid within 20 minutes of being put to sleep via a standard sequence induction of fentanyl, lidocaine, propofol, and rocuronium.

"We turned her onto her side to make sure no stomach contents got into her airway, and we suctioned them," Gulak told MedPage Today. "Then we laid her onto her back, intubated her, and inspected her lungs with a bronchoscope to make sure there were no stomach contents inside. Thankfully, none went into her airway."

The patient had taken a weekly injectable dose of semaglutide 2 days earlier. The woman recovered and was discharged the next day after the procedure.

It does not appear that anyone has died from aspirating during surgery after taking a GLP-1 agonist. However, another case report in the same journal, this one from Boston, depicted an even more disturbing incident. An endoscopy patient on weekly semaglutide injections aspirated food from the stomach into the trachea and bronchi despite 18 hours of fasting. The food was removed via bronchoscope prior to intubation.

Sulphur Burps, Weird Dreams, and Slowed Digestion

Several anesthesiologists told MedPage Today that they're seeing multiple patients who are taking GLP-1 agonists, including patients undergoing minor procedures that typically don't require intubation such as colonoscopies, upper endoscopies, and breast biopsies.

These drugs have skyrocketed in popularity this year amid reports in the medical literature and mainstream media about how users -- including celebrities -- have lost remarkable amounts of weight. For example, a 2022 retrospective study tracked 175 Mayo Clinic patients (mean baseline BMI 41, weight 260 lb) and found they lost an average of 5.9% of their weight at just 3 months on injectable semaglutide, and 10.9% at 6 months.

In addition to the injectable form of semaglutide (Ozempic and Wegovy), these agents include the oral version of semaglutide (Rybelsus), dulaglutide (Trulicity), exenatide (Byetta and Bydureon), and liraglutide (Saxenda and Victoza). Tirzepatide (Mounjaro), a glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonist, is similar.

The medications have been plagued by reports about side effects ranging from nausea and diarrhea to constipation, sulfurous burps, and even weird dreams about famous people. Still, their sales have ballooned this year. Wegovy, approved for weight loss, reportedly saw a 344% percent jump in U.S. sales during the first 6 months of this year.

Meanwhile, new research is revealing just how much the drugs slow the digestive system. In one recent study, researchers in Slovenia gave injectable semaglutide or a placebo for 12 weeks to 20 women with polycystic ovary syndrome and obesity. At the study's end, 37% of meals remained in the stomachs of women taking the drug at 4 hours versus none in the placebo group.

In another study, researchers from Brazil found that upper endoscopy patients taking semaglutide were several times more likely than other patients to retain an abnormal level of liquid or solid food in their stomachs despite fasting.

Strategies Range from Brief Drug Hiatus to Intubation

In a June 29 consensus statement, the American Society of Anesthesiologists (ASA) suggested that clinicians tell patients to stop taking weekly doses of GLP-1 agonists for 7 days before procedures. Daily doses of the agents -- such as oral semaglutide -- should be stopped for 1 day.

"If GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia," the society advises. As for fasting, the society suggests following its current guidelines since "there is no evidence to suggest the optimal duration of fasting for patients on GLP-1 agonists."

UCLA anesthesiologist Cole, a former president of ASA, supports the recommendations. But he cautioned that they're based on limited evidence. "It's essentially the ASA doing their best with what we have," he said, adding that there's a "wide lane" of possible strategies to protect patients.

At the McGovern Medical School at UTHealth Houston, anesthesiologist Omonele Nwokolo, MD, said she and several of her colleagues are bypassing the ASA's recommendations and intubating every patient who's taking the weight-loss drugs. The risk of a dangerous or even fatal case of pulmonary aspiration is "significant enough to take any extra caution you possibly can," she said.

Intubation is typically reserved for longer, more painful surgical procedures performed in the operating room or emergencies where clinicians don't know when patients last ate and must assume their stomachs are full.

Nwokolo said she and her colleagues are using a technique known as rapid sequence induction in these patients.

"Before these semaglutide medications, we would reserve this technique for specific situations such as emergent procedures where patients were not appropriately fasted, pregnant patients, and patients with bowel obstructions," said Cobb, the University of North Carolina anesthesiologist.

She cautioned that "intubation is not always an easy option," especially "at a procedural location where anesthesia machines are not utilized and intubation is only for emergencies."

According to Cole, intubation risks include "rare damage to the mouth, teeth, and the airway. In general, a greater anesthetic dose is required, which may impact heart and vascular function and cognitive recovery."

Intubation can also raise costs. More medication costs more money, and procedures and recoveries can take longer. This is especially true if clinicians have trouble inserting the tube into the airway. "Difficult" intubations, which are hard to predict, raised mean U.S. hospital costs for procedures by $14,468 and lengthened hospital stays by 3.8 days, according to a 2021 study.

Other Options Include 4 Weeks Off Drug or 'Bridging'

In a July report in the Canadian Journal of Anesthesia, a trio of anesthesiologists led by Mayo Clinic Florida's Philip Jones, MD, MSc, challenged the ASA's recommendation to keep patients off weekly doses of GLP-1 agonists prior to procedures. They suggested that the drugs should be held for at least three half-lives -- 3 weeks for injectable semaglutide. If the drug is being used for diabetes control, an endocrinologist should be consulted about whether this is a good idea.

If the drugs can't be held, clinicians should consider intubation via rapid sequence induction: "assume the patient has a full stomach." And they suggest the use of ultrasound to inspect stomach contents, "but keep in mind the potential for both false positives and negatives using this modality."

Gulak said ultrasound examinations of stomach contents are "a relatively newer technique. A lot of the younger anesthesiologists coming in are familiar with it, but not a lot of the older generation knows about it very much."

He supports holding the drugs for 3 to 4 weeks prior to surgery but acknowledges that "it's hard to identify [patients] early enough to tell them to stop the medication."

Another alternative is to "bridge" the patients prior to surgery by temporarily switching them to a lower dose, Gulak said. A patient on weekly injections of semaglutide, for example, could briefly switch to the semaglutide pill, which has a much shorter half-life.

"We do that with patients who are on blood thinners," Gulak said. "Obviously you don't want them to be on a blood thinner before they go into surgery, so we bridge them with a shorter-acting blood thinner that we can stop just before the procedure."

More data may be available soon to help clinicians make decisions about patients on these weight-loss drugs. "My team is currently finishing up a study to gather baseline data on the stomach content of these patients," Nwokolo said. "This will assist in coming up with more robust recommendations based on data."

Nwokolo said her team is also planning studies on the best strategies for fasting and discontinuation of these drugs.

As anesthesiologists wait for research to come in, UCLA's Cole said they "really need to come down on the side of patient safety and caution, particularly when the consequences of a wrong decision are potentially life-threatening."

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