Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial

Abstract

Background: Postoperative depressive symptoms are associated with pain, readmissions, death, and other undesirable outcomes. Ketamine produces rapid but transient antidepressant effects in the perioperative setting. Longer infusions confer lasting antidepressant activity in patients with treatment-resistant depression, but it is unknown whether a similar approach may produce a lasting antidepressant effect after surgery. This protocol describes a pilot study that will assess the feasibility of conducting a larger scale randomized clinical trial addressing this knowledge gap. Methods: This single-center, double-blind, placebo-controlled pilot trial involves the enrollment of 32 patients aged 18 years or older with a history of depression scheduled for surgery with planned intensive care unit admission. On the first day following surgery and extubation, participants will be randomized to an intravenous eight-hour infusion of either ketamine (0.5 mg kg-1 over 10 minutes followed by a continuous rate of 0.3 mg kg-1 h-1) or an equal volume of normal saline. Depressive symptoms will be quantified using the Montgomery-Asberg Depression Rating Scale preoperatively and serially up to 14 days after the infusion. To detect ketamine-induced changes on overnight sleep architecture, a wireless headband will be used to record electroencephalograms preoperatively, during the study infusion, and after infusion. The primary feasibility endpoints will include the fraction of patients approached who enroll, the fraction of randomized patients who complete the study infusion, and the fraction of randomized patients who complete outcome data collection. Conclusions: This pilot study will evaluate the feasibility of a future large comparative effectiveness trial of ketamine to reduce depressive symptoms in postsurgical patients. Registration: K-PASS is registered on ClinicalTrials.gov: NCT05233566; registered February 10, 2022.

Ketamine for postoperative avoidance of depressive symptoms: the K-PASS feasibility randomised trial

“…The trial protocol was revised in August 2022 to increase eligibility and enrolment. In the original published protocol, 32 patients with a history of depression undergoing surgery with planned intensive care unit (ICU) admission were randomly allocated to receive 8 h of ketamine or placebo. This design was chosen because local hospital policy permits ketamine administration in ICUs but not on postoperative wards.…”

“…The pre-specified primary measure of depressive symptoms was the change in MADRS from baseline to post-infusion day 4. 32 …”

Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care

“…89 Given the potential confounders of studying the effects of intraoperative administration of ketamine, some investigators have begun investigating postoperative ketamine infusions instead. 163 It will be important to understand the effects of routine anesthetic care on patients with psychiatric illnesses and, similarly, the interactions of the anesthetic drugs with other substances that may have novel psychotropic effects.…”