Purpose: The purpose of the study was to investigate factors associated with early discontinuation of low-dose ketamine infusions due to adverse drug events (ADEs).

Methods: A retrospective, matched case-control study of surgical patients who received low-dose ketamine infusions for postoperative pain over 6 years was conducted. Forty-seven study patients, who required early discontinuation of their infusion due to ADEs, were included and matched 1:1 with 47 controls, who did not experience ADEs, for a total of 94 patients. The two groups were compared based on surgery type, ASA classification, administration of specific perioperative anxiolytic, anesthetic, and analgesic medications, and use of regional anesthesia.

Results: Of the study patients, 44.7% underwent spine procedures (vs 34% of controls), 27.6% underwent abdominal procedures (vs 8.5% of controls), 19.2% underwent orthopedic procedures (vs 46.8% of controls), and 8.5% underwent thoracic procedures (vs 6.4% of controls). There were no statistically significant differences in ASA classification, preoperative gabapentinoid and antidepressant use, average ketamine infusion dose, or postoperative use of peripheral nerve catheters, NSAIDs, acetaminophen, muscle relaxants and non-benzodiazepine sleep aides. Study patients had higher rates of intraoperative volatile anesthetic use (78.7% vs 57.7%, p=0.03) and more postoperative opioid PCA use (53.2% vs 29.8%, p=0.02) than controls. Control patients had higher rates of preoperative opioid use (76.7% vs 53.2%, p=0.02) and premedication with midazolam (89.4% vs 70.2%, p=0.02) than study patients.

Conclusion: Patients who required discontinuation of their low-dose ketamine infusion due to ADEs were more likely to be opioid naïve, received less preoperative benzodiazepines, and had greater postoperative opioid PCA requirements. Control patients, on the other hand, had higher rates of preoperative opioid use and experienced fewer ADEs despite greater total ketamine doses.

Keywords: acute pain; adverse drug-event; ketamine; postoperative pain.