Safely and efficiently reducing pain are primary functions of emergency department (ED) providers. used as a dissociative anesthetic.4 However subdissociative doses of ketamine (SDDK) effectively relieve acute perioperative5 and chronic pain.6 Ketamine’s effectiveness in treating acute pain in the ED is worth exploring. ARTICLE SUMMARY This systematic review of randomized controlled trials (RCTs) evaluated SDDK compared with opiate or placebo for acute pain control in pediatric and adult patients.7 Eligible trials used at least one dose of SDDK (defined as less than 1 mg/kg) and were identified through MEDLINE and EMBASE searches. Abstracts reviews unpublished reports and non-English studies were excluded. The primary outcome was the change in pain score from patient arrival to the predetermined reassessment time. Secondary outcomes were the occurrence of adverse events such as dissociative phenomena or nausea and vomiting and the reduction in consumption of opiates in patients who received SDDK. Four NK314 studies met eligibility criteria: three adult trials and one pediatric trial. In total all four studies enrolled 428 patients. Three of the studies used ketamine 0.2 to 0.3 mg/kg/dose while one used an infusion of 0.1 mg/kg/hour. Each study used a different comparison group. Using the Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria two reviewers evaluated study quality of which three were deemed low quality and one moderate quality. Potential sources of bias included small sample sizes lack of (or compromised) blinding and lack of true randomization. QUALITY ASSESSMENT Only two electronic databases were used to identify potential studies. Exclusion of non-English RCTs abstracts and observational CD28 studies further threaten the complete identification of relevant literature. Inclusion of observational studies would have been particularly beneficial given NK314 the paucity of high-quality RCTs identified. The quality of this systematic review is jeopardized by the failure to adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines (http://www.equator-network.org/). Furthermore the GRADE instrument used was designed to weigh strength of evidence-based recommendations for guidelines. The Cochrane Risk of Bias tool was designed for systematic reviews of RCTs and may have been more appropriate.8 More concrete recommendations for future investigators regarding key questions and methodologic pitfalls would have been valuable to further define the role of SDDK for acute pain in the ED. Future investigations should use consistent ketamine9 and comparator dosing use a NK314 single pain scale to assess efficacy stratify outcomes by pain etiology 10 and adhere to Consolidated Standards of Reporting Trials (CONSORT) guidelines for monitoring and reporting of adverse events across studies. KEY RESULTS Two of four trials reported significant reductions in pain. Another study reported “significantly lower pain scores ” but did not provide absolute pain scores.11 The sole pediatric study used the Observational Scale of Behavior Distress (OSBD) and reported scores of 1 1.08 (SD ± 1.12) versus 2.70 (SD ± 2.16) in ketamine and fentanyl groups respectively (p < 0.05).12 The pediatric study reported increased incidence of vomiting when using ketamine with a number needed to harm of 17 (95% CI = 10 to infinity) meaning that for every 17 patients treated with ketamine versus fentanyl there will be one additional episode of vomiting with precision for that estimate ranging from 10 to infinity. No increased vomiting was noted in adults. Another study reported significantly increased use of a rescue therapy when using morphine (18 of 20) as opposed to ketamine (0 of 20). Only one case of emergence phenomenon was observed across all four studies: a pediatric patient who recovered without intervention or hospitalization. Other cases of neuropsychological phenomena were reported but the original articles lacked further description to determine if this referred to dissociation or emergence phenomena. Two studies demonstrated a significant reduction in opiate use by patients who received SDDK although the clinical relevance of the reduced opiate use is unclear. AUTHOR COMMENTS The review article7 was intended to foster interest in the topic of SDDK for acute pain based on existing published RCTs. The GRADE instrument was thought to be more easily understood by a diverse reader base than the PRISMA guidelines. The search strategy was NK314 limited to English-only RCTs.