Drug Interactions between desflurane and insulin degludec / liraglutide

ADJUST DOSING INTERVAL: Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist or a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist may increase the risk of regurgitation and pulmonary aspiration of gastric contents in patients undergoing general anesthesia due to delayed gastric emptying caused by stimulation of central nervous system GLP-1 receptors and vagal nerve activation. Pulmonary aspiration of regurgitated gastric contents during anesthesia may result in pneumonitis, aspiration pneumonia, other lung injury, and even death. Cases associated with the use of GLP-1 agonists, particularly for the treatment of weight loss, have been documented in the medical literature. There have also been reports of aborted procedures in patients treated with these agents due to the presence of significant residual gastric contents despite adherence to preoperative fasting protocols prior to anesthesia. The effects on gastric emptying may be reduced with long-term use, most likely through rapid tachyphylaxis at the level of vagal nerve activation. Therefore, patients who have recently started treatment with these agents may be at greater risk of delayed gastric emptying and pulmonary aspiration than those who have been taking them for a longer period. Additionally, patients experiencing gastrointestinal (GI) symptoms from these agents, including nausea, vomiting or abdominal distension, have a greater risk of increased residual gastric contents regardless of fasting.

MANAGEMENT: Although data are limited, caution and close monitoring are advisable when general anesthesia or deep sedation is required in patients receiving GLP-1 agonists or dual GIP/GLP-1 agonists. Consideration should be given to withholding these medications prior to the scheduled procedure whenever possible, although the optimal duration of treatment interruption has not been established. The benefits of these medications on glycemic control should also be weighed against the risk of regurgitation and pulmonary aspiration in determining if and for how long these medications should be withheld. For elective procedures, the American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting suggests pausing the GLP-1 agonist or dual GIP/GLP-1 agonist on the day of the procedure for patients on daily dosing and a week prior to the procedure for patients on weekly dosing. This recommendation is irrespective of the indication (type 2 diabetes mellitus or weight loss) or the type of procedure or surgery. If treatment is suspended for longer than the dosing schedule in patients with diabetes, consult with an endocrinologist on bridging the antidiabetic therapy to avoid hyperglycemia. On the day of the procedure, if GI symptoms such as severe nausea/vomiting/retching, abdominal bloating, or abdominal pain are present, consider delaying elective procedure; otherwise, proceed as usual if the GLP-1 agonist or dual GIP/GLP-1 agonist has been held as advised. If no GI symptoms are present, but the GLP-1 agonist or dual GIP/GLP-1 agonist was not held as advised, proceed with "full stomach" precautions or consider evaluating gastric volume by ultrasound. Patients whose stomach is empty can proceed as usual. For patients whose stomach is full or gastric ultrasound is inconclusive or not possible, consider delaying the procedure or treat the patient as "full stomach" and manage accordingly. Likewise, patients requiring urgent or emergent procedures should be treated as "full stomach" and managed accordingly. Similar guidelines have been provided by the Canadian Anesthesiologists' Society, the main difference being its recommendation that GLP-1 agonists and dual GIP/GLP-1 agonists be held for 3 half-lives (approximately 88% clearance of the drug) in patients receiving these agents for weight management.

ADJUST DOSE: Coadministration of a glucagon-like peptide-1 (GLP-1) receptor agonist or dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist with insulin may potentiate the risk of hypoglycemia. GLP-1 receptor agonists and dual GLP-1 and GIP receptor agonists lower blood glucose by stimulating insulin secretion and lowering glucagon secretion. An increased incidence of hypoglycemia has been observed in patients treated with a combination of basal insulin and GLP-1 or dual GLP-1 and GIP receptor agonists. Additionally, patients with diabetic retinopathy who received treatment with basal insulin and subcutaneous semaglutide in one clinical trial had an increased risk of developing diabetic retinopathy complications. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, but other mechanisms cannot be excluded. The safety and efficacy of GLP-1 or dual GLP-1 and GIP receptor agonists in combination with non-basal insulin have not been established.

MANAGEMENT: When a GLP-1 receptor agonist or dual GLP-1 and GIP receptor agonist is used as add-on therapy to basal insulin, a lower dosage of insulin may be required. Some clinical trials have reduced the basal insulin dose by 20% in patients with a baseline hemoglobin A1c <= 8% when a GLP-1 or dual GLP-1 and GIP receptor agonist was initiated. Because diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin, a stepwise approach to insulin dose reduction is recommended and blood glucose levels should be closely monitored. Patients should receive guidance on the recognition and management of hypoglycemia as well as precautions to take to avoid hypoglycemia, particularly while driving or operating hazardous machinery. Those with diabetic retinopathy should also be monitored for progression of the condition or complications. A rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy.