Because treatment options are limited, management of acute painful crises in sickle cell disease (SCD) patients is challenging. Pain control with opioids is the mainstay of treatment but is associated with adverse effects and carries a risk of dependency. The objective of this study is to determine if ketamine therapy is superior to opioid therapy alone in the management of acute sickle cell pain crisis. This is a prospective parallel groups randomized controlled trial in which patients were randomized in a 1:1 ratio to receive either a single dose low-dose ketamine (0.3 mg/kg in 0.9% sodium chloride, 100 ml bag) or a single dose morphine (0.1 mg/kg in 0.9% sodium chloride, 100 ml bag) infused over 30 minutes including subsequent pain management with opioids at the treating physician’s discretion. The primary outcome was the changes in the numerical pain rating score (NPRS) over time. Secondary outcomes included the cumulative dose of opioids, emergency department (ED) length of stay, hospital admission rate, and drug-related side effects. We conducted the analysis using the intention-to-treat principle and generalized estimation equations to model the average difference between groups across all time points (30, 60, 90, 120 minutes). Of the 278 patients randomized, 140 patients were allocated to ketamine arm and 138 patients to morphine. Ketamine use compared to morphine was associated with similar reduction in NPRS 5.6 versus 5.7 (mean difference 0.13; 95% confidence interval (CI) -0.34 to 0.60). The use of rescue opioid analgesia (MD 0.74 mg morphine equivalent; 95% CI -0.36 to 1.84), ED stay (MD -3.99 min; 95% CI -35.85 to 27.85), hospital admission (OR 0.71; 95% CI 0.44 to 1.39), and drug-related side effects were similar between groups. Sensitivity per-protocol analyses yielded similar results to the main analyses. The use of ketamine in patients with acute sickle cell pain crisis was not superior to morphine in reducing NPRS over the first 2 hours of treatment, nor in reducing rescue opioids, ED length of stay, or hospitalization with similar drug-related side effects.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)