Glucagon-like Peptide 1 (GLP-1) Agonists in the Perioperative Period: Utility of Gastric Point-of-Care Ultrasonography (PoCUS)

Educational Objectives

The goal of this program is to improve management of patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the perioperative period. After hearing and assimilating this program, the clinician will be better able to:

1. Use ultrasonography (US) to assess gastric emptying in patients taking GLP-1RAs.
2. Advise patients taking GLP-1Ras on fasting times before surgery.
3. Recognize indications of gastric contents on US.

Summary

Case reports of regurgitation under anesthesia: multiple reports of particulate and liquid regurgitation (and sometimes pulmonary aspiration) under anesthesia in patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs) are available

Preda et al (2023): described gastroparesis with bezoar formation

Raven et al (2023): reported 2 patients assessed by esophagogastroduodenoscopy (EGD); one patient held semaglutide for 1 wk and had solid food in the stomach after a 13-hr fast, then held the drug for 3 wk and had an empty stomach after a 12-hr fast; a second patient held liraglutide for 1 day and had solid food present after a 10-hr fast

Wilson et al (2023): one patient held dulaglutide for 1 wk and had regurgitation of particulate matter under monitored anesthesia care after a 10-hr solid fast and a 4-hr liquid fast; a second patient held oral semaglutide for 1 day and experienced regurgitation of particulate matter shortly after extubation with a 16-hr solid fast and a 5-hr liquid fast

Avraham et al (2024): 2 patients held semaglutide for 4 or 6 days and had regurgitation of particulate matter during induction after a 12-hr fast or during laryngeal mask airway removal after an 8-hr fast

Gulak et al (2023): one patient held semaglutide and had regurgitation of clear liquid after induction with a 20-hr solid fast and an 8-hr liquid fast

Klein et al (2023): reported solids and liquids in the stomach during EGD after an 18-hr fast

Mechanism of GLP-1: GLP-1 is a natural hormone affecting several organ systems, and is involved in delayed gastric emptying and reduced peristalsis in the stomach and intestines; GLP-1RA is implicated in mechanisms of the liver, muscles, adipose tissues, and pancreas; plays a role in diabetes mellitus (DM) management and has cardioprotective properties

GLP-1 receptor agonists: approvals for DM — exenatide was approved in 2005, dulaglutide (Trulicity) in 2014, and semaglutide in 2017 (Ozempic) and 2019 (Rybelsus); tirzepatide (Mounjaro)is a GLP-1RA and gastric inhibitory peptide RA and was approved in 2022; approvals for weight loss — liraglutide (Victoza) was approved in 2014, semaglutide in 2021, and tirzepatide in 2023; studies have assessed the effect on gastric emptying with intravenous exenatide and semaglutide; Umapathysivam et al (2014) reported that intermittent infusions slow the stomach the most (168 min to 50% empty), acute infusions resulted in 143 min to 50% empty, and prolonged infusions resulted in 122 min to 50% empty; placebo took 79 min to 50% stomach emptying; Little et al (2006) reported 58% retention of food particles at 100 min after exogenous administration in the GLP-1RA group vs 29% retention in the placebo group; delayed gastric emptying was also reported with oral semaglutide (by 31% [Dahl et al {2021}] to 37%) and subcutaneous semaglutide (by ≤8% [Hjerpsted et al {2018}])

Delayed gastric emptying and anesthesia: a retrospective cohort study by Stark et al (2022) involving patients undergoing EGD to determine the rate of solid food retention found food retention in 6.8% of patients on GLP-1RA vs 1.7% in controls; the odds ratio was 4.22, but the result was not statistically significant; a prospective study by Sherwin et al (2023) used gastric ultrasonography (US) after an 8-hr fast and found solid food in 70% of the semaglutide group vs 10% of controls in the supine position and solid food in 90% of the semaglutide group vs 20% of controls in the right lateral decubitus (RLD) position; the results were statistically significant; Silveira et al (2023) studied patients having elective upper endoscopy; increased residual gastric contents (any solids seen on EGD or suction of 0.8 mL/kg) was more common in semaglutide users (24.2%) vs controls (6.7%), with a prevalence ratio (PR) of 5.15; the PR was 16.5 in semaglutide users with digestive symptoms; combining colonoscopy with EGD reduced the PR to 0.26

Perioperative gastric US: indications — uncertain prandial status (eg, cognitive dysfunction, language barriers, unclear history) and possible delayed gastric emptying because of, eg, chronic kidney disease, DM, acute pain, trauma, or in parturients; acquisition — US uses curved array and a low-frequency probe (1-5 MHz); a linear transducer may be used for pediatric patients or patients weighing <40 kg (good penetration is required to measure gastric contents); assessment should begin in the supine position to find the gastric antrum, proceed to the RLD for quantitative analysis; if solid food is identified in the supine position, RLD is not needed; the probe may be placed in the saggital plane below the xiphoid process to begin; the clinician sweeps along the right costal margins until visualizing (from deep to superficial), the vertebral bodies, long axis of the aorta (allows correct measurement of antral cross-sectional area [CSA]), head and neck of the pancreas (below the antrum), short axis of the gastric antrum, and left lobe of the liver

Qualitative analysis of gastric contents: the antrum is collapsed in an empty stomach; the layers of the antrum are the mucosa, muscularis propria (hypoechoic), and serosa (hypoechoic); all layers must be visualized and the muscularis must not be mistaken for the lumen; clear fluid and air bubbles are visible inside the antrum; the bubbles give a “starry night” appearance when the antrum is slightly more distended; early-stage solids give a frosted-glass appearance from air ingestion creating an acoustic shadow; late-stage solids are characterized by heterogeneous echogenicity (because no air remains)

Qualitative antrum grading: grade 0 indicates an empty, collapsed antrum in both supine and RLD position; grade 1 indicates an empty antrum in the supine position but a small amount of clear fluid in the RLD position (low risk for aspiration from sedation or anesthesia); grade 2 indicates clear liquid in the antrum in both the supine and RLD positions (high risk for aspiration); grade 2 is used if any solids are visualized

Quantitative interpretation: measure the CSA of the antrum in the RLD position; the most accepted upper limit of normal for gastric secretions is <1.5 mL/kg of actual body weight; CSA can be measured by 2 different methods depending on US capability; trace caliper function — involves tracing of the entire circumference of the outer serosal layer; calculating ellipse area — estimates CSA using the anteroposterior and craniocaudal diameters; the validated equation for gastric volume (mL) is 27+(14.6×CSA)-(1.28×age in yr); the muscles in the stomach have increased laxity with age, which causes the stomach to appear larger while containing the same amount of fluid; CSA is measured if clear fluid is present; the presence of any solids indicates a full stomach; low risk is <1.5 mL/kg in the average adult (≈70 kg); >1.5 mL/kg is considered a full stomach

American Society of Anesthesiologists consensus-based guidance for elective procedures in patients taking GLP-1RAs: the weekly dose of GLP-1RA should be held for 1 wk; patients on daily doses should hold the dose on the day of procedure; the recommendation is the same regardless of indication (DM or weight loss), dose, or the type of procedure or surgery; consider delaying elective procedures if patients have gastrointestinal (GI) symptoms, eg, severe nausea, vomiting, retching, abdominal bloating, abdominal pain, on the day of the procedure because of a higher risk for regurgitation or aspiration; if the patient has no GI symptoms but the GLP-1RA was not held as advised, proceed with full-stomach precautions, reschedule the procedure, or perform US to determine the risk for aspiration; fasting guidelines for patients on GLP-1RAs are the same as for other patients

Clinical pearls: a full stomach may be seen after medication was held for >1 mo; patients with gastric volume <1.5 mL/kg may regurgitate under anesthesia; the timing of holding GLP-1RAs prior to a procedure may not matter; however, patients undergoing colonoscopy typically have an empty stomach because they have had only clear liquids for ≥24 hr

Readings

Avraham SA, Hossein J, Somri F, et al. Pulmonary aspiration of gastric contents in two patients taking semaglutide for weight loss. Anaesth Rep. 2024;12(1):e12278. Published 2024 Jan 14. doi:10.1002/anr3.12278; Dahl K, Brooks A, Almazedi F, et al. Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes. Diabetes Obes Metab. 2021;23(7):1594-1603. doi:10.1111/dom.14373; Gulak MA, Murphy P. Regurgitation under anesthesia in a fasted patient prescribed semaglutide for weight loss: a case report. Can J Anaesth. 2023;70(8):1397-1400. doi:10.1007/s12630-023-02521-3; Hjerpsted JB, Flint A, Brooks A, et al. Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity. Diabetes Obes Metab. 2018;20(3):610-619. doi:10.1111/dom.13120; Klein SR, Hobai IA. Semaglutide, delayed gastric emptying, and intraoperative pulmonary aspiration: a case report. Can J Anaesth. 2023;70(8):1394-1396. doi:10.1007/s12630-023-02440-3; Miller AF, Levy JA, Krauss BS, et al. Does point-of-care gastric ultrasound correlate with reported fasting time? Pediatr Emerg Care. 2021;37(12):e1265-e1269. doi:10.1097/PEC.0000000000001997; Preda V, Khoo SS, Preda T, et al. Gastroparesis with bezoar formation in patients treated with glucagon-like peptide-1 receptor agonists: potential relevance for bariatric and other gastric surgery. BJS Open. 2023;7(1):zrac169. doi:10.1093/bjsopen/zrac169; Raven LM, Stoita A, Feller RB, et al. Delayed gastric emptying with perioperative use of glucagon-like peptide-1 receptor agonists. Am J Med. 2023;136(12):e233-e234. doi:10.1016/j.amjmed.2023.07.016; Sidhu NS, Robertson K. Atypical gastric ultrasound appearance immediately after food intake. Anaesth Rep. 2022;10(2):e12191. Published 2022 Nov 4. doi:10.1002/anr3.12191; Silveira SQ, da Silva LM, de Campos Vieira Abib A, et al. Relationship between perioperative semaglutide use and residual gastric content: A retrospective analysis of patients undergoing elective upper endoscopy. J Clin Anesth. 2023;87:111091. doi:10.1016/j.jclinane.2023.111091; Stark JE, Cole JL, Ghazarian RN, et al. Impact of glucagon-like peptide-1 receptor agonists (GLP-1RA) on food content during esophagogastroduodenoscopy (EGD). Ann Pharmacother. 2022;56(8):922-926. doi:10.1177/10600280211055804; Tan Y, Wang X, Yang H, et al. Ultrasonographic assessment of preoperative gastric volume in patients with dyspepsia: A prospective observational study. BMC Anesthesiol. 2022;22(1):21. Published 2022 Jan 12. doi:10.1186/s12871-021-01559-4; Umapathysivam MM, Lee MY, Jones KL, et al. Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia. Diabetes. 2014;63(2):785-790. doi:10.2337/db13-0893; Wilson PR, Bridges KH, Wilson SH. Particulate gastric contents in patients prescribed glucagon-like peptide 1 receptor agonists after appropriate perioperative fasting: A report of 2 cases. A A Pract. 2023;17(8):e01712. Published 2023 Aug 24. doi:10.1213/XAA.0000000000001712.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Wolla was recorded at American Osteopathic College of Anesthesiologists Mid-Year Seminar, held remotely March 16-17, 2024, and presented by the American Osteopathic College of Anesthesiologists. For information on future CME activities from this presenter, please visit https://www.aocaonline.org/. Audio Digest thanks the speakers and American Osteopathic College of Anesthesiologists for their cooperation in the production of this program.

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