Potential Anaesthesia Risk with GLP-1 Agonists

The tirzepatide (Mounjaro®) product information has been updated to include a warning of pulmonary aspiration in patients undergoing general anaesthesia or deep sedation.

Tirzepatide is indicated for the treatment of type 2 diabetes. It is a long-acting agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Its action on the GLP-1 receptor stimulates insulin secretion in hyperglycaemic states, suppresses glucagon secretion, delays gastric emptying, and decreases appetite. Activation of GIP receptors enhances some of the effects of GLP-1 stimulation, particularly in regard to appetite. This dual mechanism significantly improves glycaemic control, insulin sensitivity, and lipid metabolism while reducing body weight.

Delayed gastric emptying

The effect of tirzepatide and other GLP-1 agonists on gastric emptying may increase the risk of aspiration during anaesthesia. Aspiration of regurgitated gastric contents into the lungs is a serious event that can lead to pneumonitis, aspiration pneumonia, or other lung injury. Patients taking a GLP-1 agonist may have high gastric volumes despite appropriate fasting before the procedure. During anaesthesia, the presence of food or fluid contents in the stomach is a major risk factor for aspiration.

Other GLP-1 agonists available in Australia are shown in Table 1. Dulaglutide and semaglutide are considered long-acting agents, and liraglutide is short-acting. While GLP-1 agonists were originally used in the management of type 2 diabetes, the expansion of indications and off-label use for weight loss has led to a significant increase in their use.

Table 1. GLP-1 agonists registered in Australia

A recently published study investigated the potential for semaglutide to increase residual gastric content (RGC) despite adequate preoperative fasting. Patients undergoing upper gastrointestinal endoscopy who had taken semaglutide within 30 days had their RGC compared to patients who had not taken semaglutide. The findings suggest that semaglutide increased the risk of elevated RGC almost five-fold.

The effect of GLP-1 agonists on gastric emptying is thought to be most pronounced at the beginning of therapy. Tachyphylaxis occurs with ongoing use, particularly in the case of long-acting agents. Evidence suggests that the dosing regimen may affect this, with intermittent dosing (as may occur when used for weight loss) showing a similar effect on gastric emptying to acute dosing.

It should be noted that delayed gastric emptying is often associated with diabetes, regardless of GLP-1 agonist use. In addition, many commonly prescribed medications can also slow gastric emptying. This includes opioids, proton pump inhibitors, anticholinergics, calcium channel blockers, and levodopa. Concomitant use of a GLP-1 agonist with another drug that slows gastric emptying may further increase the risk of aspiration during anaesthesia.

Managing therapy during the perioperative period

Holding medications that delay gastric emptying can help to reduce the risk of pulmonary aspiration. However, three to five half-lives are normally required to clear a drug from the body. This may not be practical for surgery scheduling, particularly when considering the long half-lives of many GLP-1 agonists. For example, semaglutide has a half-life of around one week. In addition, it may not be desirable to hold the medication for so long, given their clinical benefits on glucose control and cardiovascular health.

Further evidence is required to guide recommendations in this area. In patients with type 2 diabetes, the glycaemic benefits of continuing GLP-1 agonist therapy throughout the perioperative period may outweigh the potential issues related to delayed gastric emptying. They offer effective glycaemic control with a low risk of fasting hypoglycaemia. Therefore, continuing their use before surgery could potentially deliver cardiovascular benefits, improve wound healing, and avoid wound infections. However, the risk-benefit profile may not be the same when these agents are used for weight loss. Higher doses are used in the management of obesity, which may have a more pronounced effect on gastric emptying. In addition, patients may be more likely to use these agents intermittently, which could mitigate the development of tachyphylaxis.

The American Society of Anesthesiologists recommends that prescribers consider withholding the GLP-1 agonist for one dose before an elective procedure (i.e., hold on the day of surgery for daily dosing, hold for one week before surgery for weekly dosing). This advice remains the same regardless of the indication for the GLP-1 agonist. If holding the dose is not possible, they advise that ‘full stomach’ precautions should be implemented. The Australian and New Zealand College of Anaesthetists (ANZCA) highlights GLP-1 agonists as a risk factor and advises that gastric ultrasound can be used to mitigate risk and guide perioperative management. Other possible strategies to reduce the risk of aspiration include using a longer fasting duration and consideration of a prokinetic (e.g. metoclopramide or erythromycin).

Summary

Tirzepatide and GLP-1 agonists slow gastric emptying. A potential adverse event related to this effect is aspiration during anaesthesia or deep sedation, even in patients who have fasted according to standard recommendations.

The risk of aspiration is potentially higher in patients who have recently started a GLP-1 agonist, use intermittent dosing, or take another medication that delays gastric emptying. It is currently unclear when gastric emptying returns to normal after cessation of a GLP-1 agonist, and more evidence is needed to understand the potential role of withholding these agents during the perioperative period. ANZCA has recommended the use of gastric ultrasound as a means of assessing the aspiration risk of individual patients.