Continuous ketamine infusion for surgical patients in the intensive care unit: a systematic review and meta-analysis...

Optimal pain and sedation management in intensive care unit (ICU) remains challenging. While opioids and benzodiazepines are widely used, their adverse effects highlight the need for alternative or adjunctive strategies. Ketamine, with its analgesic and opioid-sparing has been proposed as an adjuvant. However, current evidence regarding its efficacy in ICU patients, particularly within the surgical population, remains inconclusive. We evaluated whether continuous low-dose ketamine infusion in postoperative surgical ICU patients reduces opioid consumption and improves pain intensity, and whether it affects opioid-related adverse events and key ICU recovery outcomes.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing continuous postoperative ketamine infusion versus non-ketamine based infusion for analgesia & sedation in patients admitted to the surgical ICU. Literature searches were performed in PubMed, Cochrane Central, and ClinicalTrials.gov from inception until July 2025. The primary endpoints were cumulative opioid consumption in the first 24-48 h (standardized to IV morphine equivalents where applicable) and rest pain intensity at prespecified early postoperative timepoints. Secondary endpoints included PONV, psychotomimetic events (e.g., hallucinations), and ICU recovery outcomes (e.g., ICU length of stay and duration of mechanical ventilation) when reported. We performed random-effects meta-analyses and assessed certainty using GRADE.

Nine RCTs comprising 666 patients were included. Ketamine significantly reduced opioid consumption at 24 h in adults (mean difference [MD] - 5.77 mg morphine equivalents; 95% CI - 6.32 to - 5.23; p < 0.0001), although the reduction at 48 h and in pediatric subgroups was not statistically significant. Pain scores at 12, 24, and 48 h were comparable between the groups. Ketamine did not significantly shorten the mechanical ventilation time (MD - 0.84 h; 95% CI - 1.93 to 0.24) or ICU length of stay (MD - 0.97 h; 95% CI - 1.95 to 0.02). However, ketamine use was associated with a lower incidence of PONV (RR 0.59; 95% CI 0.36-0.98; p = 0.0399). Psychotomimetic adverse events were infrequent and not significantly increased. GRADE evidence was moderate for opioids in adults at 24 h and low to very low for the remaining outcomes.

In postoperative surgical ICU patients, continuous low-dose ketamine infusion provides modest opioid sparing and is associated with lower PONV, without clear improvements in pain scores or ICU recovery outcomes. Large-scale trials with different dosing protocols are needed to explore the optimal role of ketamine beyond analgesia and PONV reduction.