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Can arginine supplements improve the hemodynamics of children with severe pain or acute chest syndrome (ACS) related to sickle cell anemia? Although mortality rates in children with sickle cell disease (SCD) have improved over the past decade, ACS and vasoocclusive episodes (VOE) remain relatively common diagnoses in pediatric ICUs. This Concise Critical Appraisal explores an article in which Onalo et al completed the second phase of their work determining the role that L-arginine treatment may play in the cardiopulmonary status of children with SCD and VOE, with or without ACS. In the first phase of their work, the authors demonstrated decreased hospitalization time, decreased opioid use, and the absence of serious adverse events in children with SCD after receiving L-arginine therapy.