How long should Zepbound (generic name) be held prior to anesthesia in a patient with severe cardiovascular disease?

Zepbound (Tirzepatide) Perioperative Management

There is no specific guideline evidence for holding Zepbound (tirzepatide) before anesthesia, but based on the GLP-1 receptor agonist class mechanism and delayed gastric emptying risk, a conservative approach of holding the medication for at least one week (approximately 5 half-lives) before elective surgery requiring general anesthesia is recommended to minimize aspiration risk.

Rationale for Holding Period

The primary concern with GLP-1 receptor agonists like tirzepatide is delayed gastric emptying, which increases aspiration risk during anesthesia induction. While no direct evidence exists in the provided guidelines for tirzepatide specifically, the pharmacokinetic profile suggests:

• Tirzepatide has a half-life of approximately 5 days, requiring roughly 25 days for complete elimination but significant reduction in effect occurs after 1-2 weeks
• Delayed gastric emptying is a class effect that persists as long as therapeutic drug levels remain
• The risk is particularly relevant for patients requiring endotracheal intubation under general anesthesia

Risk Stratification Approach

For Patients with Severe Cardiovascular Disease

Cardiovascular optimization takes precedence over routine medication holds. The provided guidelines emphasize that patients with severe cardiovascular disease require:

• ACE inhibitors should be continued perioperatively in patients with LV systolic dysfunction undergoing non-cardiac surgery under close monitoring 1
• Beta-blockers must be continued and should be administered for at least 24 hours before surgery in all patients without contraindications 1
• Statins should never be discontinued perioperatively as they reduce cardiovascular events 1, 2

Balancing Aspiration Risk vs. Surgical Delay

For patients with severe cardiovascular disease requiring urgent surgery:

• If surgery cannot be delayed 1 week: Proceed with enhanced aspiration precautions including rapid sequence induction, cricoid pressure consideration, and experienced anesthesia team
• If surgery is elective: Hold tirzepatide for 1 week minimum to allow gastric emptying normalization
• Hemodynamic monitoring is critical in cardiovascular disease patients regardless of tirzepatide status 1

Perioperative Hemodynamic Management

Given the cardiovascular disease context, specific attention must be paid to:

• Maintain adequate preload and avoid hypotension, as cardiovascular patients are particularly sensitive to anesthetic-induced hemodynamic changes 1
• Continuous optimization of loading conditions with invasive monitoring (arterial line, possible PA catheter or TEE) should be considered 1
• Avoid tachycardia and maintain sinus rhythm, as these patients have limited cardiac reserve 1

Common Pitfalls to Avoid

• Do not assume gastric emptying is normal even if the patient reports fasting appropriately—GLP-1 agonists can cause retained gastric contents despite NPO status
• Do not discontinue cardiovascular medications (ACE inhibitors, beta-blockers, statins) in an attempt to "clear" all medications before surgery—these provide mortality benefit that outweighs theoretical risks 1, 2
• Do not use standard aspiration risk assessment tools without considering the pharmacologic gastric paresis from tirzepatide
• Avoid rapid sequence induction without adequate preparation for potential difficult airway management in the setting of full stomach

Resumption After Surgery

• Tirzepatide can be resumed once oral intake is established and the patient is hemodynamically stable
• Ensure adequate volume status before resumption as GLP-1 agonists can affect fluid balance
• Coordinate with cardiology regarding timing of resumption in patients with severe cardiovascular disease to ensure other cardiovascular medications are optimized first 1