GIs clash with GLP-1 restrictions for endoscopy, but ‘anesthesiologists have final say’
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The explosive popularity of glucagon-like peptide-1 receptor agonists for diabetes and weight loss may have revolutionized obesity management, but their widespread use has also sparked concerns — and ignited a turf war — in the endoscopy suite.
Symptoms of abdominal pain, constipation, diarrhea, nausea and vomiting are well-known adverse events for glucagon-like peptide-1 receptor agonists (GLP-1s), often related to delayed gastric emptying. However, when anecdotal reports began to link these medications to increased risk for regurgitation and pulmonary aspiration of gastric contents in patients under anesthesia, anesthesiologists quickly sounded the alarm.
At the insistence of its members, the American Society of Anesthesiologists recommended halting GLP-1s at least 1 week prior to any elective surgery that requires sedation. However, this decision has placed anesthesiologists at odds with gastroenterologists performing endoscopic procedures, who maintain that there is sparse available evidence to back claims of potential complications and that this overly conservative measure will only disrupt patient care.
“The overarching concern for all gastroenterologists is delaying care and canceling procedures unnecessarily because of these recommendations,” Jennifer Phan, MD, medical director at Hoag Advanced Endoscopy Center in Irvine, California, and director of bariatric endoscopy at Hoag Digestive Health Institute, told Healio Gastroenterology. “We know time to endoscopy is important, even though they are elective procedures. Patients take time off work, and they prep for certain procedures. Any delay because of an unvalidated recommendation is a concern for all parties — patients and physicians included.”
According to Allison R. Schulman, MD, MPH, FASGE, an interventional and bariatric endoscopist and chief of endoscopy at Michigan Medicine, the ASA’s guidance has led to cancellations and postponements of “innumerable endoscopic procedures.”
“We have required many patients to undergo general anesthesia who may otherwise have had their procedures performed under moderate sedation, which adds cost and clinical risk. Many institutions have also been forced to revise their preprocedural protocols, despite a lack of high-level evidence to suggest that these adjustments are necessary,” Schulman told Healio Gastroenterology. “This has changed the landscape of endoscopy.”
Dueling Guidance
In June 2023, after reviewing available literature on the risk for delayed gastric emptying with GLP-1 use, the ASA Taskforce on Perioperative Fasting suggested the following guidance for preoperative management of GLP-1s:
- Hold GLP-1s on the day of the procedure in patients who use GLP-1s daily; discontinue the week before surgery with weekly GLP-1 use.
- On the day of surgery, delay the procedure if GI symptoms, including severe nausea/vomiting/retching, abdominal bloating or abdominal pain, are present.
- Proceed as usual if the patient has no GI symptoms and they discontinued GLP-1s.
- Surgeons should proceed with “full-stomach” precautions in patients with no GI symptoms that did not hold GLP-1s. Surgeons also should consider using ultrasound to assess gastric volume and, if full or inconclusive, they should delay the procedure or treat patients as “full-stomach.”
- Treat and manage patients who require urgent or emergent procedures as “full-stomach.”
In opposition to the ASA’s statement, the AGA, AASLD, ACG, ASGE and NASPGHAN released a combined consensus statement encouraging gastroenterologists to follow “best practices” for endoscopy procedures.
Despite anecdotal evidence suggesting a possible risk for delayed gastric emptying, the multisociety statement indicated there was “little or no data” related to the relative risk for complications from aspiration. The GI societies also noted the impact of stopping this medication prior to upper gastrointestinal endoscopy or other moderate to deep sedated procedures is “unknown at this time.”
“As clinical gastroenterologists and hepatologists, we are very familiar with safety issues regarding the performance of endoscopy in our patients suffering from gastroparesis, as well as unexplained nausea, vomiting and epigastric pain, particularly in emergency situations,” the GI societies wrote. “As patient safety will always be paramount, and in the absence of actionable data, we encourage our members to exercise best practices when performing endoscopy on these patients on GLP-1 receptor agonists.”
Data ‘Somewhat Contradictory’
Studies have yielded mixed results as to whether patients on GLP-1s are at increased risk for aspiration while undergoing endoscopic procedures, Schulman said.
“Randomized controlled trials are needed to guide us forward. While these medications may pose a theoretical risk, the limited data available are inconsistent,” she added.
A study in Gastroenterology showed GLP-1 use was associated with a higher incidence of aspiration pneumonia (0.83% vs. 0.63%), as well as a significantly higher risk for aspiration pneumonia (HR = 1.33; 95% CI, 1.02-1.74), within a month of an endoscopic procedure vs. the nonuser group. The risk also was higher among GLP-1 users who underwent upper endoscopy or combined upper and lower procedures.
However, researchers reported contrasting results in a study published in Clinical Gastroenterology and Hepatology, in which a nationwide commercial administrative claims database showed that compared with dipeptidyl peptidase 4 inhibitors or chronic opioids, GLP-1 use did not correlate with an increased risk for aspiration pneumonia in patients with type 2 diabetes. Researchers also reported that pulmonary complications were rare and ranged from six to 25 events per 10,000 procedures and included 6.8 aspirations, 7.61 aspiration pneumonias and 25.56 cases of respiratory failure.
Another study in Clinical Gastroenterology and Hepatology showed more than 9% of patients on GLP-1s who underwent esophagogastroduodenoscopy had retained gastric contents, with 78.9% being solid residue. Still, risk for aspiration remained low.
According to Phan, a multicenter study is currently in submission that poses the theory that GLP-1s may not be a risk factor in procedures, but rather a patient’s underlying diabetes.
“That tends to lend more credence to what the pathophysiology shows, which is that tachyphylaxis can happen after a certain time point,” she said. “If patients are on GLP-1s long enough that delayed emptying doesn’t continue to that degree, it’s mostly the hyperglycemia control and/or insulin use.”
Schulman also said, “More research is needed to determine whether length of usage or dosing frequency alters an individual’s procedural risk. Additionally, point-of-care ultrasound may help to determine the presence of food in the stomach.”
Preoperative Liquid Diet ‘Totally Reasonable’
In an effort to ease concerns and confusion among gastroenterologists, the AGA published a rapid clinical practice update for GLP-1 use prior to elective endoscopy.
This guidance “was necessary to provide clinical perspective” for the consensus-based perioperative guidance from the ASA, Andrew Y. Wang, MD, AGAF, FACG, FJGES, FASGE, one of the authors and professor of medicine in the division of gastroenterology and hepatology at the University of Virginia, previously told Healio Gastroenterology.
“[The ASA guidance] was being used by anesthesia providers to cancel or postpone endoscopic procedures in patients taking GLP-1 agonists who did not stop this medication prior to their procedures,” Wang said. “Anesthesia providers were not advised to consider the indication for GLP-1RA or the potential harm of holding the medication, in particular for patients taking this class of medications to treat diabetes.”
He added, “The ASA’s suggestions were having a real impact on patient care, and many gastroenterologists and endoscopists were reaching out with questions regarding how to care for patients taking GLP-1 agonists who require endoscopic procedures.”
Wang and colleagues suggested that patients prescribed GLP-1s who follow the standard perioperative procedures, including an 8-hour solid food fast and a 2-hour liquid diet fast without symptoms of nausea, vomiting, dyspepsia or abdominal distention, could proceed with endoscopy. If patients exhibit symptoms demonstrating potential retained gastric contents, clinicians could examine the stomach with a transabdominal ultrasound if available; however, the evidence to “support this modality in standard practice is lacking,” the researchers noted.
Rather than stopping GLP-1s, Wang and colleagues suggested patients be placed on a liquid diet the day before procedures requiring sedation.
According to Phan, a recent systematic review and meta-analysis of 15 randomized controlled trials on gastric emptying measures with GLP-1s, published in the American Journal of Gastroenterology, “is the first paper to strongly state a consideration for a liquid diet.”
The results showed “a very limited increase in delayed time to emptying,” Phan said, with a delay of around 36 minutes in patients prescribed GLP-1s. There was no delay with a liquid diet.
Based on the results, the researchers suggested that patients prescribed GLP-1s continue the medication prior to a procedure but also follow the standard fasting period and go on a liquid diet the day before, until more research is available.
“Some endoscopy units have gone toward [following] that but that’s not a universal standard,” Phan added.
A 24-hour liquid diet is “totally reasonable,” Schulman said. “I think this will help decrease the concern and the alarm in patients on GLP-1s undergoing these procedures.”
Schulman noted, however, that “the bigger question is what happens with urgent or emergent cases. In these situa-tions, care should not be delayed.”
Anesthesiologists ‘Have the Final Say’
Following the AGA clinical update, Ali Rezaie, MD, director of the GI motility program at Cedars Sinai in Los Angeles, recalled there being tension among all those involved in managing preoperative care for GLP-1 users.
But, he said, the reality is that anesthesiologists make the final decision on procedure-related airway protection measures.
“It was becoming a little bit of a struggle between proceduralists and the anesthesiologists but, at the end of the day, anesthesiologists have the final say on this. ASA wants to hold [GLP-1s] prior to elective procedures and I agreed with them,” Rezaie said in an interview with Healio Gastroenterology.
As anesthesiologists play such a vital role during these procedures, Phan also said surgeons and endoscopists are “beholden to their comfort level, and currently their comfort level lies with the ASA’s recommendations.”
As a result, most endoscopy units are holding GLP-1s before procedures, she said, depending on daily or weekly dosing.
Similarly, Rezaie holds GLP-1s prior to elective endoscopic procedures, including colorectal cancer screening, since their use may affect gastric motility and colonoscopy prep.
This was observed in a study published in The American Journal of Gastroenterology, in which researchers compared colonoscopy bowel prep among 265 GLP-1 users and 181 nonuser controls. Results showed GLP-1 use correlated with poorer bowel prep and greater need for repeat colonoscopy. The nonuser group had a significantly higher mean Boston Bowel Preparation Scale score compared with the GLP-1 group (7.5 vs. 7), which remained significant after controlling for diabetes. In addition, the percentage of patients with a score lower than 5 also was higher in the GLP-1 group vs. controls (15.5% vs. 6.6%).
The best prevention for aspiration risk in patients prescribed GLP-1s is to hold these medications prior to the procedure, according to Rezaie. However, more research needs to be done to determine how long to hold, especially with longer acting GLP-1s being developed.
“This is not to demonize GLP-1s, which are one of the wonders of modern medicine with a lot of positive effects, but we need to know the adverse events to act accordingly,” Rezaie said. “They are here to stay, so I think the prudent thing right now is to stop for the risk of aspiration. We need to hold them, depending on their half-life for elective cases. For urgent cases, a preprocedural discussion between the anesthesiologist and the proceduralist is essential to determine the necessary precautions”
While Rezaie has halted elective procedures, Schulman noted her institution has developed policies with anesthesia to provide safe and timely care to patients on these medications and prevent cancelations.
“The care teams review the risks and benefits on a case-by-case basis and include shared decision-making with the patients,” she said. “Furthermore, if a patient exhibits symptoms of delayed gastric emptying, we consider general anesthesia over moderate sedation.”
In the end, Phan said, “No one wants to cancel procedures unnecessarily.”
She added, “I think what we can forecast in the future is that there are going to be quite a few more studies coming out from the GI perspective that will hopefully shed a bit of light. That’s going to be most important — bringing all disciplines to the table to discuss what to do with these medications and with future GLP-1s and combination GLP-1 medications that are going to be commercially available in the upcoming years.”
New Guidance to Come
At this year’s Digestive Disease Week, Schulman told attendees that ASGE recruited a panel of experts to develop a Delphi position statement with “expert panel consensus guidance.” The team included seven gastroenterologists (including three bariatric endoscopists, one motility expert and three experts in guideline development/methodology), two endocrinologists and two anesthesiologists.
“We quickly recognized the need to risk-stratify patients undergoing endoscopy,” Schulman, who co-chaired the panel, said.
The document is currently under review. Highlights presented at DDW include:
- All patients using GLP-1s should undergo immediate preprocedural evaluation of GI symptoms, including severe nausea, vomiting, regurgitation when lying supine, abdominal bloating, distention and pain, which may suggest delayed gastric emptying.
- Physicians should have detailed discussions with patients about the risk for aspiration.
- A liquid diet 24 hours prior to endoscopic procedure is suggested.
- For hospitalized GLP-1 users who need emergent or urgent diagnostic or therapeutic endoscopy, the procedure should not be delayed. Full-stomach precautions should be considered if patients have symptoms suggestive of delayed emptying. If they do not, consider point-of-care ultrasound “when available but otherwise proceed based on a shared decision-making process.”
“This is a changing landscape,” Schulman told attendees. “I fully expect that as more data become available, these recommendations will likely change.”
According to Schulman, more research is needed to create scientifically based guidelines for the interdisciplinary teams that manage these patients.
“The main goal right now is to recognize that even though we do not have robust data and we do not truly know the impact of these medications in the setting of endoscopy, we should be triaging cases based on the urgency of the procedure and individualizing patient care,” she said.
- References:
- AGA opposes holding GLP-1 agonists for endoscopy without ‘high-level published evidence’. https://www.healio.com/news/gastroenterology/20231218/aga-opposes-holding-glp1-agonists-for-endoscopy-without-highlevel-published-evidence. Published Dec. 20, 2023. Accessed July 11, 2024.
- American Society of Anesthesiologists consensus-based guidance on preoperative management of patients (adults and children) on glucagon-like peptide-1 (GLP-1) receptor agonists. https://www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative. Published June 29, 2023. Accessed July 11, 2024.
- Barlowe, TS, et al. Clin Gastroenterol Hepatol. 2024;doi:10.1016/j.cgh.2024.04.038.
- Firkins SA, et al. Clin Gastroenterol Hepatol. 2024;doi:10.1016/j.cgh.2024.03.013.
- Hashash JG, et al. Clin Gastroenterol Hepatol. 2023;doi:10.1016/j.cgh.2023.11.002.
- Hiramoto B, et al. Am J Gastroenterol. 2024;doi:10.14309/ajg.0000000000002820.
- No data to support stopping GLP-1 agonists prior to elective endoscopy. https://gastro.org/news/gi-multi-society-statement-regarding-glp-1-agonists-and-endoscopy/. Published Aug. 11, 2023. Accessed July 11, 2024.
- Schulman AR. The skinny of GLP-1 agonists and endoscopy. Presented at Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
- Yao R, et al. Am J Gastroenterol. 2024;doi:10.14309/ajg.0000000000002564.
- Yeo YH, et al. Gastroenterology. 2024;doi:10.1053/j.gastro.2024.03.015.
- For more information:
- Jennifer Phan, MD, is medical director at Hoag Advanced Endoscopy Center in Irvine, California, and director of bariatric endoscopy at Hoag Digestive Health Institute; she can be reached at jennifer.c.phan@gmail.com.
- Ali Rezaie, MD, is director of the GI motility program at Cedars Sinai in Los Angeles; he can be reached at ali.rezaie@cshs.org.
- Allison R. Schulman, MD, MPH, FASGE, is an interventional and bariatric endoscopist and chief of endoscopy at Michigan Medicine; she can be reached at arschulm@med.umich.edu.
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