Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

Michael Coffin; Muhammad Zain Azhar; Walker Shepherd; Kyle McGrath; Rebecca Garner; Christiana Cornea; Joseph Cheng; Justin Virojanapa

doi:10.1016/j.jocn.2026.112239

PubMed · 42566840

Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

Michael Coffin·Muhammad Zain Azhar·Walker Shepherd·Kyle McGrath·Rebecca Garner·Christiana Cornea·Joseph Cheng·Justin Virojanapa

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Abstract

BACKGROUND CONTEXT: Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion. METHODS: Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool. RESULTS: Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control. CONCLUSIONS: Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.

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Humans Analgesics Analgesics, Opioid Ketamine Pain Management Postoperative Pain Pregabalin Randomized Controlled Trials as Topic Spinal Fusion Network Meta-analysis Randomized Controlled Trials Systematic Review Journal Article Network Meta-Analysis Comparative Study Review

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Michael Coffin, Muhammad Zain Azhar, Walker Shepherd, Kyle McGrath, Rebecca Garner, Christiana Cornea, Joseph Cheng, Justin Virojanapa. 2026-08-07. Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.. https://doi.org/10.1016/j.jocn.2026.112239

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Analgesics subject Analgesics, Opioid subject Comparative Study subject Humans subject Journal Article subject Ketamine subject Network Meta-Analysis subject Pain Management subject Systematic reviews study

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