What class of oral hypoglycemic agents, such as GLP-1 (Glucagon-Like Peptide-1) receptor agonists, should be withheld in the perioperative period due to risks of aspiration and gastroperesis according to the American Diabetes Association (ADA)?

GLP-1 Receptor Agonists Should Be Withheld Perioperatively Due to Aspiration Risk from Delayed Gastric Emptying

The American Diabetes Association and American Society of Anesthesiologists recommend withholding GLP-1 receptor agonists (such as semaglutide, liraglutide, dulaglutide) in the perioperative period due to their association with delayed gastric emptying, retained gastric contents, and increased risk of pulmonary aspiration and gastroparesis. 1

Mechanism of Risk

GLP-1 receptor agonists significantly delay gastric emptying as part of their therapeutic mechanism, creating a situation where patients retain gastric contents despite following standard fasting guidelines 1. Studies demonstrate that 56% of patients on GLP-1 receptor agonists had retained gastric contents compared to 19% of controls, even when complying with current fasting protocols 1. Multiple case reports document regurgitation and pulmonary aspiration during general anesthesia in patients taking these medications despite prolonged fasting periods 1.

Recommended Withholding Periods

For Weight Loss Patients (Non-Diabetic)

Hold GLP-1 receptor agonists for at least three half-lives before elective procedures 1:

• Semaglutide (weekly): 3 weeks before surgery 1
• Dulaglutide (weekly): approximately 2-3 weeks 1
• Liraglutide (daily): 3-4 days 1

The risks of continuing these medications until shortly before surgery outweigh the benefits in non-diabetic patients using them for weight management 1.

For Type 2 Diabetes Patients

The approach differs for diabetic patients because prolonged cessation may worsen perioperative glycemic control and potentially increase major adverse cardiac events 1. Consult with the treating endocrinologist regarding risks and benefits of holding the drug for at least three half-lives, and recommendations for bridging diabetic therapy if held longer than the next scheduled dosing time 1.

Critical Caveats and Pitfalls

The ASA One-Week Recommendation May Be Insufficient

The American Society of Anesthesiologists initially recommended holding weekly GLP-1 receptor agonists for only 1 week before elective surgery 1. However, emerging evidence demonstrates this may be inadequate, as discontinuation for 7 days did not decrease the prevalence of retained gastric contents 1. There was no association between duration of discontinuation and prevalence of retained gastric contents in studies examining short cessation periods 1.

High-Risk Situations Requiring Enhanced Precautions

Implement aspiration risk reduction strategies for patients who 1:

• Cannot hold the medication for three half-lives before the procedure
• Recently started the medication or increased their dose
• Experience nausea, vomiting, or abdominal distention
• Have only 8 days between last dose and surgery (considered high risk) 2

Risk Mitigation Strategies When Medication Cannot Be Held

When GLP-1 receptor agonists have not been stopped for adequate duration, treat these patients with "full stomach precautions" 1:

• Consider pre-operative gastric ultrasonography to evaluate gastric volume 1
• Use rapid sequence intubation with airway protection 1, 2
• Administer prokinetic drugs like metoclopramide pre-operatively 2
• Choose endotracheal intubation over supraglottic airways 2
• Proceed with general anesthesia in an appropriate environment if indicated 1

Pre-Procedure Documentation Requirements

Document the following for all patients 1:

• Indication and dose of GLP-1 receptor agonist
• Date drug commenced, dose variations, and last dose taken
• Symptoms of nausea, vomiting, or abdominal distention
• Co-prescribed drugs that delay gastric emptying (opioids, proton pump inhibitors, tricyclic antidepressants)
• Recent recreational drug use that delays gastric emptying (alcohol, cannabis)
• Previous gastro-esophageal surgery

Distinction Between Diabetes and Weight Loss Indications

A critical distinction exists in perioperative management based on indication 1. In patients with diabetes mellitus, the benefits of GLP-1 receptor agonists in the perioperative period (glycemic control, potential decrease in postoperative major adverse cardiac events) may outweigh the issues related to delayed gastric emptying 1. However, when higher doses are used for weight loss management, gastric stasis may be more prolonged and the risks clearly outweigh benefits 1.