Volume 75 Number 4

One Institution’s Response to the Perioperative Risk of GLP-1 Receptor Agonists

Since approval of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus, these drugs have become widely prescribed for the specific purpose of weight loss.1 A recent study estimated that 2% of all adult residents in the area surrounding Mount Sinai Hospital were prescribed one of these agents.2 Our practice at Mount Sinai Hospital has seen an increase in patients taking them. GLP-1 receptor agonists cause delayed gastric emptying, and our faculty had an acute concern that many of our surgical patients were at high risk of aspiration. Reconsideration of long-standing preoperative fasting guidelines was in order.

In response to this challenge, Mount Sinai Health System’s Department of Anesthesiology formed an emergency task force to determine if we needed to change our routine preoperative NPO policy. We reviewed the relevant available literature,3-5 including an internally performed gastric residual ultrasound study,6 and relied extensively on faculty expert opinion.

The task force decided to write very conservative guidelines emphasizing risk mitigation, even at the inconvenience of patients and their proceduralists. While we considered the ASA’s recommendations,⁷ significant emphasis was given to the pharmacokinetics and pharmacodynamics of this class of drugs as well as the literature, scant as it was. Notably, GLP-1 receptor agonists have very long half-lives, and their effects would likely remain within one half-life of time. We decided that our guidelines would exceed those times published by the ASA.

Our internal study was of particular help in reaching this consensus, so we offer the following brief summary. Gastric ultrasound evaluation of volunteers was undertaken to determine the incidence of significant gastric residual content attributed to semaglutide after the usual recommended NPO guidelines. We compared volunteers who were taking semaglutide for weight loss to those who were not. For reference sake, previous studies have shown that a small proportion (6.2%) of elective surgical patients may present with a full stomach despite the recommended duration of fasting.8 Ninety percent of semaglutide participants, compared with 10% of control participants, had solids in their stomachs (RR, 7.36; 95% CI, 1.13 to 47.7; P = 0.005).

Mount Sinai Health System (MSHS) Guidelines for the Management of Patients Taking GLP-1 Receptor Agonists Presenting for Procedures Requiring an Anesthetic

Situation

GLP-1 receptor agonists are widely prescribed to treat diabetes and to promote weight loss. These medications delay gastric emptying and pose an increased risk of a “full stomach,” regurgitation and pulmonary aspiration.

Background

The increased risk to patients receiving these medications has only recently been recognized, and the American Society of Anesthesiologists has published “Consensus-Based Guidance.” Anecdotally, in the MSHS we have seen several patients on these medications who followed their NPO instructions and had solid food in their stomachs.

Assessment

The Mount Sinai Health System needs guidelines for peri-procedural management of patients taking these medications in order to reduce the risk of serious and life-threatening pulmonary aspiration.

Guidelines

1. Discuss concerns regarding the potential risk of regurgitation and pulmonary aspiration of gastric contents with the proceduralist/surgeon and the patient as part of the routine consent
2. These medications should not be taken for a minimum of two dosing intervals (e.g., semaglutide and tirzepatide should be held for a minimum of 15 days). While there is no evidence to guide the optimal duration of these medications’ cessation, this approach is cautious and practical.
   • Elective cases failing to follow this guidance should be postponed.
   • Diabetic patients should consult their prescribing physician to manage their care without these medications during this time.
3. If the patient has other significant risk factors for aspiration, including obesity, GERD, pregnancy, prior aspiration, partial bowel obstruction, or current GI symptoms (e.g., bloating, sensation of fullness, abdominal distention, retching, nausea, vomiting), consider scheduling the procedure in a hospital setting, especially if potential tracheal intubation and gastric ultrasound is desired.
4. NPO guidelines (regardless of medication cessation compliance)
   
   Day prior to the procedure, starting at 8 a.m.:
   i. NPO for all solids and non-clear liquids (normal breakfast consumed before 8:00 a.m. is OK).
   ii. Clear liquids should be consumed for the duration of that day
   
   Day of the procedure, starting at midnight:
   iii. Strict NPO: No food including clear liquids should be consumed, except for critical medications with a small quantity of water, or a prescribed bowel preparation.
5. Consider the risks and benefits of alternative anesthetic plans (e.g., “light sedation” with intact airway reflexes vs. deep sedation with blunted airway reflexes vs. GA with ETT/RSI).
6. Consider the use of adjuncts to mitigate the chance and risk of aspiration, including:
   • Metoclopramide 10 mg intravenous over 1-3 minutes
   • Sodium citrate 30 mL orally immediately before the procedure
   • Famotidine 20 mg intravenous > 30 minutes before the procedure, or Pantoprazole 40 mg intravenous > 30 minutes before the procedure

These guidelines were disseminated to more than 3,500 providers in the Mount Sinai Health System using e-mail announcements, a system procedural policy committee, and our preoperative application that is accessible on mobile devices and the intranet. After the policy roll-out, the FAQ page (see below) was immediately created. While time will determine the optimal approach, our policy creation process, stated concerns, and implementation strategy should prove useful to individual anesthesiologists and departments tackling this subject.

Frequently Asked Questions About the GLP-1 Receptor Agonist Guidelines

1. Do the guidelines apply to patients taking these medications for weight loss or diabetes?
   The guidelines apply regardless of indication but suggest that patients taking GLP-1 agonists for diabetes should consult their provider in case special management of their diabetes in absence of these agents will be required, although we do not anticipate that diabetics who discontinue these agents for a relatively short time will require significant interim management.
2. Do the guidelines apply to patients scheduled to receive mild to moderate sedation by non-anesthesiologists?
   No, the guidelines do not apply to these types of procedures usually performed in non-operating room settings and managed without an anesthesiologist. The main risk for regurgitation and aspiration is loss of airway reflexes. Mild and moderate sedation guidelines are written to avoid the loss of airway reflexes, and providers administering mild to moderate sedation should be extra cognizant of this goal.
3. If a patient stopped taking their GLP-1 agonist a long time ago, do the guidelines apply?
   It is unclear for how long after discontinuation of these medications gastric emptying remains abnormal, with rare patients appearing to have lifelong issues. Given the known half-life of these medications, the current recommendations are as follows, with routine/customary NPO guidelines noted in the last column for patients who have ceased taking these medications for a particularly long time. The two medications most prescribed for weight loss, semaglutide and tirzepatide (highlighted in yellow), likely have the greatest impact on gastric emptying and the longest half-life; thus, they are the greatest concern.

Brand Name(s)	Generic Name	Recommended time since last dose	Follow routine NPO guidelines if the last dose was
Byetta, Bydureon	Exenatide	>1 day	>2 days
Adlyxin	Lixisenatide	>1 day	>2 days
Ozempic, Wegovy, Rybelsus	Semaglutide	>14 days	>35 days
Saxenda, Victoza	Liraglutide	>2 days	>3 days
Trulicity	Dulaglutide	>14 days	>21 days
Mounjaro	Tirzepatide	>14 days	>35 days

4. Do these guidelines apply to patients scheduled for MAC anesthesia or procedures scheduled to be performed under a spinal anesthetic or a nerve block?
   Yes. Patients scheduled for MAC anesthetics as well as regional techniques are often sedated to the point of loss of airway reflexes; in a small percentage of cases, these patients are converted to general anesthetics.
5. Will these guidelines affect many patients?
   With type 2 diabetes, metformin is the first line therapy and a GLP-1 agonist is usually added if the HbA1c goal is not met, there is underlying CAD, or when weight loss is desirable. Increasingly we have seen many patients without diabetes who take these medications for weight loss. Asking patients if they take any of these medications prior to a procedure should be as routine as double-checking that they do not take anticoagulants or aspirin.

Marc Sherwin, M.D., is an assistant professor of anesthesiology, perioperative and pain medicine, an assistant professor of medical education, associate program director of the Anesthesiology Residency Training Program, and director of the Introduction to Internship course in the Department of Anesthesiology, Perioperative and Pain Medicine at the Icahn School of Medicine at Mount Sinai. Samuel DeMaria Jr., M.D., is a professor of anesthesiology and otolaryngology and vice chairman for research in the Department of Anesthesiology, Perioperative and Pain Medicine at the Mount Sinai Health System. Andrew Leibowitz, M.D., is a professor of anesthesiology, perioperative and pain medicine and system chair for the Department of Anesthesiology, Perioperative and Pain Medicine at the Mount Sinai Health System.