K-PASS: Ketamine for Postoperative Avoidance of Depressive Symptoms

Bradley Fritz, MD, MSCI, Instructor, Anesthesiology

Surgical patients with a history of depression are at elevated risk for experiencing postoperative depressive symptoms, which have been linked to other complications such as cognitive dysfunction, hospital readmission, and death. The NMDA antagonist ketamine, which has proven to be a potential therapy for treatment-resistant depression, has shown promise for preventing depressive symptoms after surgery. However, ketamine’s antidepressant effects are transient, waning quickly after a few days. In treatment-resistant depression, a sustained sub-anesthetic ketamine infusion has produced longer-lasting effects, with symptom resolution for up to 8 weeks. Based on this knowledge, the investigators hypothesize that a postoperative sustained, low-dose ketamine infusion can enhance slow wave activity during sleep and prevent postoperative depressive symptoms when administered to a targeted population of surgical patients with a history of depression.

This pilot study will evaluate the feasibility of conducting a double-blind, placebo-controlled randomized clinical trial to test this hypothesis. The aims of the feasibility study are (1) to evaluate the feasibility of recruiting participants, (2) to evaluate the feasibility of delivering the study medication, and (3) to evaluate the feasibility of collecting participant outcomes. Patients with a history of depression scheduled for neurosurgery with planned intensive care unit admission will be recruited. After surgery, they will receive a 0.5 mg/kg bolus of ketamine over 40 minutes followed by 0.3 mg/kg/h for an additional 7 hours 20 minutes, or an equal volume of saline. Depressive symptoms will be measured at baseline and at several post-infusion timepoints using the Montgomery-Asberg Depression Rating Scale, and nocturnal electroencephalograms will be captured before and after surgery. This feasibility study will provide preliminary data to support an R01 application to the NIMH.