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Tirzepatide, marketed as Mounjaro and Zepbound, is a dual GIP/GLP-1 receptor agonist FDA-approved for type 2 diabetes and weight management. As use of tirzepatide and general anesthesia increasingly intersect in surgical settings, understanding perioperative risks is essential. The medication's effect on gastric emptying raises concerns about aspiration during anesthesia, prompting updated guidance on perioperative management. This article reviews tirzepatide's mechanism, anesthesia-related risks, evidence-based perioperative protocols, and postoperative considerations to help clinicians safely manage patients on this medication undergoing surgical procedures.
Summary: Tirzepatide delays gastric emptying, increasing aspiration risk during general anesthesia, but most patients can continue the medication perioperatively with appropriate risk stratification per 2024 multi-society guidance.
We offer compounded medications and Zepbound®. Compounded medications are prepared by licensed pharmacies and are not FDA-approved. References to Wegovy®, Ozempic®, Rybelsus®, Mounjaro®, or Saxenda®, or other GLP-1 brands, are informational only. Compounded and FDA-approved medications are not interchangeable.
Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved by the FDA for the treatment of type 2 diabetes mellitus and chronic weight management. Marketed under the brand names Mounjaro (for diabetes) and Zepbound (for weight management), tirzepatide represents a dual incretin mimetic that offers enhanced glycemic control and significant weight reduction compared to single-receptor agonists.
The mechanism of action involves binding to both GIP and GLP-1 receptors, which are expressed in pancreatic beta cells and various other tissues. By activating these receptors, tirzepatide stimulates glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The delayed gastric emptying effect is most pronounced during medication initiation and dose escalation, and typically attenuates with chronic therapy. This effect is particularly relevant in the perioperative setting as it may increase the risk of aspiration during anesthesia induction.
Tirzepatide is administered as a once-weekly subcutaneous injection, with doses ranging from 2.5 mg to 15 mg depending on the indication and titration schedule. The medication has a half-life of approximately five days. Common adverse effects include gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation, which typically diminish over time but may be exacerbated in the perioperative period. Importantly, hypoglycemia risk with tirzepatide monotherapy is low; this risk increases when combined with insulin or sulfonylureas. The FDA labeling notes that tirzepatide has not been studied in patients with severe gastroparesis and is not recommended for this population.
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The primary anesthesia-related concern with tirzepatide and other GLP-1 receptor agonists is the risk of pulmonary aspiration due to delayed gastric emptying. This pharmacologic effect can result in retained gastric contents even after appropriate fasting periods, potentially leading to aspiration of gastric material during anesthesia induction or emergence. Aspiration pneumonitis represents a serious complication that can cause significant morbidity and mortality, making this risk a critical consideration in perioperative planning.
In 2024, a multi-society clinical practice guidance (including the American Society of Anesthesiologists, American Gastroenterological Association, and American Society for Metabolic and Bariatric Surgery) updated previous recommendations, indicating that most patients can continue GLP-1 receptor agonists perioperatively with appropriate risk stratification. Higher-risk patients—those on dose escalation, at maximum doses, experiencing active gastrointestinal symptoms, or with known gastroparesis—may benefit from a 24-hour clear liquid diet, gastric ultrasound assessment if available, or withholding the medication.
Standard preoperative fasting guidelines from the ASA recommend 2 hours for clear liquids, 6 hours for a light meal, and 8 hours for fatty/fried foods or meat. However, patients taking tirzepatide may have residual gastric contents despite adhering to these guidelines.
Additional considerations include perioperative glycemic management—noting that hypoglycemia risk is low with tirzepatide monotherapy but increases when combined with insulin or sulfonylureas. Conversely, withholding tirzepatide may lead to hyperglycemia. The medication's impact on gastric motility may also complicate postoperative nausea and vomiting (PONV) management and delay return to normal oral intake. Anesthesiologists should consider that patients on tirzepatide may have obesity-related comorbidities such as obstructive sleep apnea, cardiovascular disease, and difficult airway anatomy, which independently increase anesthetic risk. A thorough preoperative assessment should include evaluation of glycemic control, weight loss trajectory, gastrointestinal symptoms, and any history of gastroparesis or reflux disease.
Current evidence-based recommendations for managing tirzepatide in the perioperative period emphasize individualized risk assessment and shared decision-making between patients, surgeons, and anesthesiologists. The 2024 multi-society guidance suggests that most patients can continue GLP-1 receptor agonists perioperatively with appropriate risk stratification. For higher-risk patients—those on dose escalation, at maximum doses, experiencing active gastrointestinal symptoms, or with known gastroparesis—a 24-hour clear liquid diet, gastric ultrasound assessment (where available), or withholding the medication may be appropriate.
For patients undergoing elective procedures, the surgical team should assess the urgency of surgery against the risks of continuing tirzepatide. If a decision is made to withhold tirzepatide, this should be guided by institutional protocols and specialist input, recognizing that evidence for specific hold intervals remains limited. Some institutions have adopted protocols requiring point-of-care gastric ultrasound assessment in patients who have recently taken GLP-1 receptor agonists, though this requires trained operators and may not be universally available.
For urgent or emergency procedures where tirzepatide cannot be withheld, anesthesiologists should implement aspiration risk mitigation strategies according to institutional protocols. These may include treating the patient as having a full stomach regardless of fasting duration, considering modified rapid sequence induction techniques, administering aspiration prophylaxis medications (such as sodium citrate, H2-receptor antagonists, or proton pump inhibitors), and ensuring availability of appropriate airway equipment. Preoperative administration of prokinetic agents such as metoclopramide may be considered, though evidence for their efficacy in the context of GLP-1-induced delayed emptying is limited.
If tirzepatide is withheld, perioperative glucose management should be addressed, particularly in patients with diabetes. Hyperglycemia may occur when therapy is interrupted, and patients on insulin or sulfonylureas may require adjustment of these medications. Endocrinology consultation may be beneficial for complex cases. Clear documentation of tirzepatide use, timing of last dose, and the anesthetic plan should be included in the medical record.
Postoperative management of patients on tirzepatide requires attention to glycemic control, nutritional status, and timing of medication resumption. In the immediate postoperative period, patients with diabetes should have blood glucose monitoring protocols in place, with target ranges typically between 80-180 mg/dL per American Diabetes Association guidelines. The combination of surgical stress, altered oral intake, and tirzepatide's glucose-lowering effects can lead to glycemic variability. Remember that hypoglycemia risk is low with tirzepatide monotherapy but increases when combined with insulin or sulfonylureas.
The decision to resume tirzepatide after surgery should be individualized based on the type and extent of surgery, the patient's recovery trajectory, and return of normal gastrointestinal function. For minor procedures with rapid recovery and minimal impact on oral intake, tirzepatide can typically be resumed at the next scheduled dose once the patient tolerates oral nutrition without significant nausea or vomiting. For major abdominal or gastrointestinal surgeries, a more conservative approach is warranted, with resumption delayed until bowel function has normalized, evidenced by return of bowel sounds, passage of flatus, and tolerance of solid foods without emesis.
According to FDA labeling, if a dose is missed and the next scheduled dose is more than 4 days away, the missed dose should be administered as soon as possible. If less than 4 days remain, the missed dose should be skipped and the next dose administered on the regularly scheduled day.
Based on expert opinion (though not specified in FDA labeling), patients may experience more pronounced gastrointestinal side effects when restarting tirzepatide after a significant interruption, particularly if they had previously titrated to higher doses. Some clinicians recommend restarting at a lower dose and re-titrating gradually, especially if the medication was held for more than two weeks. Close follow-up is essential to monitor for adverse effects, assess glycemic control in diabetic patients, and ensure appropriate wound healing and nutritional recovery. Patients should be advised to contact their healthcare provider if they experience persistent nausea, vomiting, inability to maintain adequate oral intake, signs of hypoglycemia, or any surgical complications.
Most patients can continue tirzepatide perioperatively with appropriate risk stratification per 2024 multi-society guidance. Higher-risk patients—those on dose escalation, maximum doses, with active GI symptoms, or known gastroparesis—may benefit from withholding the medication or additional precautions such as gastric ultrasound assessment.
Tirzepatide delays gastric emptying, which can result in retained gastric contents even after appropriate fasting periods, increasing the risk of pulmonary aspiration during anesthesia induction or emergence.
For minor procedures, tirzepatide can typically be resumed at the next scheduled dose once the patient tolerates oral nutrition. For major abdominal or gastrointestinal surgeries, resumption should be delayed until bowel function normalizes and the patient tolerates solid foods without emesis.
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