Ketamine for Sickle Cell Vaso-Occlusive Crises: A Systematic Review

Introduction: Vaso-occlusive crisis (VOC) is one of the main causes of hospital admission in patients with sickle cell disease (SCD). Ketamine is often used as an adjuvant to opioids to control sickle cell crisis; however, there is a lack of evidence about its safety and efficacy for VOC in SCD patients. Objective: To synthesize evidence from published reports about the efficacy and safety of ketamine in the management of acute painful VOC in both pediatric and adult SCD patients. Methods: A systematic literature search of PubMed, Scopus, Web of Science, EBSCO and Cochrane Library was conducted, up to March 2019. Studies reporting the analgesic effects and side effects of ketamine in the management of acute painful VOC in pediatric and adult SCD patients were included. The primary outcome measure was improvement in pain scale, and the secondary outcomes were reduction in opioid utilization and side effects. Studies were narratively summarized in this review. Results: Fourteen studies (with a total of 604 patients) were included in the final analysis. Several case reports and case series showed that ketamine significantly reduced pain scales and opioid utilization in both populations. The only randomized controlled trial available showed that ketamine was noninferior to morphine in reducing pain scores, but had a higher incidence of nonlife-threatening, reversible adverse effects. However, a retrospective study of 33 patients showed a higher pain score in the ketamine group with an acceptable short-term adverse effect. Conclusion: Ketamine has a potentially comparable efficacy with other opioids in reducing the pain during VOC in SCD patients. However, it also likely has a higher rate of transient adverse events. Owing to the lack of published randomized controlled trials, current evidence is not sufficient to confirm the safety and efficacy of ketamine. Future well-designed randomized controlled trials are strongly recommended.