INNOVATION FUND The Future of Academic Medicine Maternal, Child & Mental Health SHOWCASE 2023

The Ketamine for Acute Postoperative Analgesia (KAPA) Trial

Maternal, Child & Mental Health

Hance Clarke

416-340-4800 ext. 2927


MSU – Mount Sinai Hospital – University Health Network Academic Medical Organization, Toronto General Hospital

Karim Ladha


Michael Dinsmore



Toronto Western Hospital, University Health Network, University of Toronto


Pain after surgery remains an important challenge for both patients and clinicians. Poor surgical pain control is associated with increased post-operative complications and higher health care costs. Although opioids represent the mainstay of treating surgical pain, their use is associated with significant side effects. Therefore, there is an urgent need to find new pain relievers with safer side effect profiles. One such drug that has been receiving increasing attention is ketamine. However, previous studies have focused on using intravenous ketamine after surgery which has limited availability for patients as it requires a monitored setting. However, by using the oral route of administration, ketamine could potentially be used by patients in a less resource-intensive manner with similar efficacy. In this preliminary study, we have demonstrated that low dose oral ketamine can be safely used as an adjunct in postoperative pain treatment to help reduce opioid consumption after major surgical procedures.



This study aims to examine the role of oral ketamine in improving recovery after major spine surgery.


This is a single center, blinded (participant, caregiver, investigator, outcome assessor), parallel arm, randomized controlled feasibility trial of 40 patients aged between 18 and 75 years. The study was approved by Health Canada (control number 239065) and institutional research ethics board (REB#20-5064.0) and written informed consents were obtained from all patients.

Patients who underwent multi-level lumbar spine decompression and fusion were randomized 1:1 and received either the study treatment (oral ketamine 30 mg) or matching placebo. Patients received the study medication for three days or nine doses total or until hospital discharge.


Preliminary statistics show no significant differences between groups in age (ketamine group: median 62 [IQR 47-69], placebo group: median 63 [IQR 45-68]) or ASA class (ketamine group: median 3 [IQR 2-3], placebo group: median 3 [IQR 3-3]). However, we found significant differences between groups with regards to sex (ketamine group: 31.6% females, placebo group: 64.7% females).

There were no significant differences identified between groups in preoperative pain intensity scale scores, as well as postoperative pain intensity scale scores at postoperative days 1, 3, 7, and 30. Also, no significant differences were identified between groups in preoperative pain interference and PHQ-9 scores or with postoperative pain interference and PHQ-9 scores at postoperative days 7 and 30.

A significant difference was identified between groups for QoR-15 Part A scores at postoperative day 30 (ketamine group: median 70 [IQR 54.5-78], placebo group: median 79 [IQR 75-84.5]). In addition, a trend-level decrease in postoperative opioid consumption was also identified in the ketamine group compared to placebo (ketamine group: median 156 mg MED [IQR 60.0-330.5], placebo group: 292.5 mg MED [IQR 184.5-405.5]).

In conclusion, we have successfully demonstrated that oral ketamine may be used as an adjunct to manage postoperative surgical pain with the potential to reduce opioid consumption and enhance quality of recovery.


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