Oral Ketamine for Acute Postoperative Analgesia (OKAPA) Trial

Summary by Loai Alghifees, MD 4.28.25
https://www.sciencedirect.com/science/article/pii/S0952818024003192

Clinical Hypothesis: 
Low-dose oral ketamine after major spine surgery improves recovery and reduces opioid use compared to placebo. 

Take Home Message:

  • Oral ketamine reduced opioid consumption after spine surgery. 

  • No significant improvement in recovery quality (QoR-15 scores) or pain scores. 

  • Safe and well-tolerated with no major side effects. 

  • Supports oral ketamine as an opioid-sparing strategy postoperatively.  

Summary: 
This pilot randomized controlled trial studied 35 patients undergoing multilevel lumbar spine surgery. Patients received either oral ketamine (30 mg TID) or placebo for 3 days after surgery. The primary goal was to improve the Quality of Recovery (QoR-15); secondary goals included reducing opioid use, pain, and side effects. 

 

Background: 
Opioids are effective but risky for surgical pain. Ketamine might offer pain relief and opioid reduction with fewer side effects, especially when given orally. 

 

Study Design: 

  • Single-center, double-blind, randomized, placebo-controlled pilot trial. 

  • Conducted at Toronto Western Hospital. 

 

Methods: 

  • Intervention: Oral ketamine 30 mg TID x 3 days vs. placebo. 

  • Outcomes: QoR-15 score, opioid use, pain scores, mood (PHQ-9), side effects. 

 

Inclusion criteria: 

  • Age 18–75, scheduled for multilevel lumbar spine fusion, inpatient stay. 

Exclusion criteria: 

  • Chronic high-dose opioid use, substance abuse, severe organ dysfunction, psychiatric illness, pregnancy. 

 

Primary outcome: 

  • Quality of Recovery-15 (QoR-15) score at postoperative days 1, 3, 7, and 30. 

Secondary outcome: 

  • Opioid use, pain scores, mood (PHQ-9), pain interference (PROMIS), side effects. 

 

Results: 

  • No significant difference in QoR-15 scores or pain scores. 

  • Significantly less opioid use in the ketamine group by postoperative days 3 and 7. 

  • Patients on ketamine used opioids for fewer days (median 4 vs 6 days). 

  • No increase in side effects with ketamine. 

 

Discussion/Conclusion: 
Oral ketamine is safe and effective for reducing opioid use after spine surgery but did not improve patient-reported recovery. It shows promise as an opioid-sparing agent and warrants larger studies to confirm these findings.