Reasons for discontinuation of acute postoperative pain ketamine infusions: A retrospective case-control study

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

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, American Society of Anesthesiologists (ASA) classification, administration of specific perioperative anxiolytic, anesthetic, and analgesic medications, and use of regional anesthesia.

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, pre-operative gabapentinoid and antidepressant use, average ketamine infusion dose, or postoperative use of peripheral nerve catheters, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, muscle relaxants, and nonbenzodiazepine sleep aides. Study patients had higher rates of intra-operative volatile anesthetic use (78.7% vs. 57.7%, p = 0.03) and more postoperative opioid patient-controlled analgesia (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.

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