AB-201

INTRODUCTION Glucagon-like peptide-1 (GLP-1) is a hormone that belongs to the incretin family secreted by the intestinal tract during feeding, which enhances insulin secretion, inhibits glucagon secretion in a glucose concentration-dependent manner and delays gastric emptying.[1] GLP-1 receptor agonists (RAs) exert their glucose-lowering effect by stimulating GLP-1 receptors, which have significant glucose-lowering efficacy and the advantage of low incidence of hypoglycaemia. Exenatide (Byetta) and lixisenatide (Lyxumia) are classified as short-acting GLP-1 RAs since the drug's plasma concentration reaches near zero between the doses. Even though liraglutide (Victoza) is dosed once daily, it is classified as a long-acting GLP-1 RA, along with semaglutide (Ozempic, Wegovy) and dulaglutide (Trulicity) due to the constant elevated drug concentrations in between the drug dosages. Multiple studies have shown better glycated haemoglobin (HbA1c) reduction with long-acting GLP-1 RAs than basal insulin injection. They also consistently lead to weight loss as an added benefit.[2,3] Direct comparison of short- versus long-acting GLP-1 RAs showed that long-acting GLP-1 RAs were better at reducing HbA1c, fasting plasma glucose and body weight and had better gastrointestinal tolerability.[4] GLP-1 RAs have also been shown to significantly reduce major adverse cardiovascular events, which include myocardial infarction, cardiovascular mortality, stroke, all-cause mortality and hospitalisation for heart failure in patients with type 2 diabetes mellitus and preexisting heart disease.[5,6] Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in developed countries, which increases the risk of cirrhosis and hepatocellular carcinoma.[7,8] Both semaglutide and liraglutide significantly reduce and reverse biopsy-proven nonalcoholic steatohepatitis (NASH), which is the most severe form of NAFLD.[9,10] This is significant since, currently, there is no United States Food and Drug Administration-approved pharmacological treatment for NASH/NAFLD.[11] In addition to the above indications, GLP-1 RAs are being evaluated for their therapeutic effects on obstructive sleep apnoea, hypertension and polycystic ovarian syndrome.[12-14] Based on the ever-growing on- and off-label indications for GLP-1 RAs, we expect many patients undergoing anaesthesia to be on these medications. PERIOPERATIVE CONCERNS GLP-1 RAs can cause significant gastrointestinal side effects such as nausea, vomiting and diarrhoea, in addition to significant gastroparesis. Nausea and vomiting are more prominent at the initiation of therapy or during dose escalation and tend to subside over time. The mechanism of action is thought to be secondary to centrally mediated action by GLP-1 receptors in the area of postrema.[1] The most significant concern in the perioperative period for anaesthesiologists is the delayed gastric emptying secondary to decreased gastric motility by GLP-1 RAs. In March 2023, Klein and Hobai[15] reported a case of intraoperative pulmonary aspiration in a patient who was on GLP-1 RA (semaglutide). Gulak and Murphy[16] reported another case of regurgitation in a patient who was taking semaglutide. In a small prospective observational study, 90% of healthy volunteers taking semaglutide were found to have solid content in the stomach despite appropriate fasting.[17] Another retrospective observational study showed that fasting patients on semaglutide had a five times higher risk for residual gastric content (RGC) compared to controls.[18] Other retrospective observational studies have shown a 4- to 10-fold increase in RGC in patients taking GLP-1 RAs.[19,20] Most recently, a prospective, cross-sectional study utilising gastric ultrasound found increased RGC at risk for aspiration in 35 of 62 patients on GLP-1 RAs, despite following the standard American Society of Anesthesiologists (ASA) fasting guidelines.[21] The prevalence of increased RGC was greater than 40% even when the GLP-1 RAs were held for 1 week as currently recommended by the ASA expert consensus guidelines.[6] Evidence suggests that continuous stimulation of GLP-1 receptors in healthy volunteers leads to rapid tachyphylaxis of the gastric emptying effect.[22] Short-acting GLP-1 RAs primarily reduce postprandial hyperglycaemia by reducing gastric emptying due to intermittent receptor stimulation. In contrast, long-acting GLP-1 RAs cause a significant effect on gastric emptying at the time of initiation and dose escalation, which might subside over time due to tachyphylaxis.[23-27] So, it is important to consider the type of GLP-1 RA (short versus long acting), dose, indication, duration of treatment, presenting symptoms like abdominal bloating, nausea and vomiting, and recent dose escalation while assessing the risk for delayed gastric emptying in patients on GLP-1 RA medication. GASTRIC ULTRASOUND Gastric ultrasound to determine the patients' stomach contents and fasting status has been one of the most useful point-of-care ultrasound (POCUS) applications in perioperative medicine. Until we have large prospective randomised trials with strong evidence, gastric ultrasound could be an excellent bedside diagnostic tool to assess the risk of aspiration by objectively measuring the patient's gastric contents on GLP-1 RAs. Aspiration is the leading cause of death due to airway-related complications after anaesthesia.[28] ASA closed claims analysis report on pulmonary aspiration found that death was directly associated with pulmonary aspiration in 57% (66/115) of the claims and permanent injury in an additional 14% (16/115) of the claims, and suggests using gastric ultrasound to assess gastric contents for risk assessment.[29] BASICS POCUS for assessing RGCs relies on obtaining a satisfactory image of the gastric antrum. This superficial structure underlies the left lobe of the liver, providing a favourable sonographic window. Gastric antrum is a circular structure that distends uniformly in the presence of liquids and/or digested food particles, allowing for a fair estimate of the volume based on previously validated mathematical formulas. Image acquisition is easy to learn and involves placing a low-frequency probe in the parasagittal orientation in the epigastric region in the supine and right lateral decubitus positions.[30-32] ADVANTAGES Equipment: Basic ultrasound equipped with a low-frequency probe is universally available in most anaesthesia departments to perform ultrasound-guided nerve blocks. Image acquisition: Easy to learn with identifiable landmarks such as the liver, aorta and superior mesenteric artery. One study determined that anaesthesiologists need about 33 examinations to achieve a 95% success rate in qualitative bedside gastric ultrasound examinations.[33] Evidence: There is no robust evidence to support the current ASA expert consensus guidelines for patients on GLP-1 RAs, as more than half of the patients had RGC despite following this guideline in a recent study.[6,21] Gastric ultrasound is the only bedside tool currently available to provide objective evidence of the gastric contents. Reproducibility (interrater reliability): Ultrasound assessment of antral cross-sectional area is shown to have near-perfect intra- and interrater reliability (correlation coefficient >0.8).[34] CAUTION Image acquisition: Inconclusive imaging acquisition can happen in up to 5% of the scans, especially in morbidly obese patients.[35] False-negative scans: The pyloric sphincter can be mistaken for an empty gastric antrum, leading to the wrong conclusion of an empty stomach. Novice learners need to understand the relationship between the inferior vena cava, aorta, gastric antrum and pyloric sphincter since the consequences of a false-negative report can be catastrophic. False-positive scans and overdiagnosis: Based on the currently described interpretation of gastric ultrasound images, the presence of air in the stomach leads to the conclusion of a full stomach, even without visualisation of any food particles. This can lead to unnecessary cancellations and invasive airway instrumentations. A few tricks can help minimise the air interference, including placing the patient in the right lateral decubitus position for a few minutes while setting up the machine and interviewing the patient to allow the air to move to the non-dependent part of the stomach (fundus), applying gentle pressure with the probe and tilting the probe to scan towards the body of the stomach to try to look for further evidence of the presence of gastric contents in the presence of air shadow. In a recent study of gastric volume estimation with gastric ultrasound, 19% of control subjects (type 2 diabetes mellitus without GLP-1 RAs) had evidence of RGCs, which is a surprisingly high incidence of a full stomach.[21] Another recent gastric ultrasound study found that the baseline gastric content in fasting diabetics is not higher than that in nondiabetic patients.[36] Interestingly, more than 10% of both populations (11.5% of non-diabetics and 15% of diabetics) had more than 1.5 ml/kg of gastric volume, considered a full stomach under current interpretation guidelines. Most recently, an antral area of 10 cm2 and a volume threshold of 2.3 ml/kg were identified as the 95th percentile cut-off for fasting individuals.[37] Hundreds of thousands of patients following the standard fasting guidelines undergo general anaesthesia every day without clinically significant aspiration. These findings rekindle the age-old question of 'How much is too much?', especially in the era of encouraging liberal fluid intake, and beg the question, 'Is it time to consider placing less emphasis on a specific volume threshold for clear liquids and more emphasis on the presence of solid materials?'[38] Inconclusive image: Excessive bowel gas in the colon (air interference), the presence of a gastric tube and prior abdominal surgeries can alter the anatomy, leading to the inability to visualise the stomach with the ultrasound. CONCLUSION With sufficient training and expertise, point-of-care gastric ultrasound can quickly assess residual gastric content in the perioperative period in patients on Glucagon-like peptide-1 receptor antagonists.