Drug Interactions between bupivacaine / ketamine / ketorolac and exenatide

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.

MONITOR: The risk of neurotoxicity may be increased when local anesthetics are used together with intraspinal ketamine. Animal and cell studies have shown that the combined neurotoxicity of lidocaine and ketamine are additive.

MANAGEMENT: Caution is advised during concomitant use of local anesthetics with intraspinal ketamine.

MONITOR: Drugs that affect renal function and/or hydration status may potentiate the adverse renal effects of exenatide. The mechanism of interaction is unknown. Exenatide has not been found to be directly nephrotoxic in preclinical or clinical studies. However, there have been reports of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure during postmarketing use. In some cases, hemodialysis or kidney transplantation was required. Some of these events occurred in patients receiving one or more pharmacologic agents known to affect renal function or hydration status (e.g., ACE inhibitors, nonsteroidal anti-inflammatory drugs, diuretics), and some occurred in patients who had been experiencing nausea, vomiting or diarrhea, with or without dehydration. Most cases were reversible with supportive treatment and discontinuation of potentially causative agents, including exenatide.

MANAGEMENT: Clinicians should be aware of the potential for increased adverse renal effects of exenatide during coadministration with drugs that are known to affect renal function or hydration status.