Optimizing Pain Treatment in Children On Mechanical Ventilation

The OPTICOM (Optimizing Pain Treatment In Children On Mechanical Ventilation) study is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to improve pain management and reduce opioid exposure in critically ill children requiring invasive mechanical ventilation (MV) for acute respiratory failure (ARF). More than 24,000 children annually in the United States require MV for ARF, yet current analgesic management relies heavily on opioids, often resulting in suboptimal pain control and significant risks including physiological dependence, withdrawal, delirium, and prolonged hospitalization. Despite the high-dose opioid use, over 90% of these children experience inadequate pain relief. There are currently no evidence-based, pediatric-specific guidelines to optimize analgesia in this population. OPTICOM will evaluate whether the administration of intravenous acetaminophen (IV-A) and/or intravenous ketorolac (IV-K), as non-opioid adjuncts, can reduce pain and opioid exposure in this vulnerable population. A total of approximately 644 participants aged 2 months to 17 years 6 months, requiring MV and opioid infusions, will be randomized in a 1:1:1:1 ratio into one of four treatment arms: (1) IV-A + placebo, (2) IV-K + placebo, (3) IV-A + IV-K, or (4) placebo + placebo. Study drugs will be administered for a maximum of 5 days. Opioid and benzodiazepine use will continue as open-label per local standard of care. The study employs a factorial design with stratified randomization by site. The analysis plan includes multivariable Poisson regression models to evaluate the independent and combined effects of IV-A and IV-K on primary and secondary outcomes. Sample size calculations provide \>90% power to detect meaningful differences in pain control and opioid reduction.