BACKGROUND: Sickle cell disease (SCD) is a common disorder among African-Americans and other minority populations that is characterized by chronic anemia and episodic vaso-occlusive crises. The most common of these crises is the painful crisis. The treatment of painful crisis is supportive, including rest, hydration, and analgesia, and therapy is guided by evidence from only a few rigorous clinical trials. Morphine is the cornerstone of analgesia for moderate to severe painful episodes, but it has significant toxicities, such as somnolence, respiratory depression, constipation, dysphoria, and pruritus. Adjuvant analgesics, including non-steroidal antiinflammatory drugs (NSAIDs), may improve pain control and decrease the requirement for opioids; however, most have not been studied rigorously in patients with SCD, including the elucidation of disease-specific toxicities.

DESIGN NARRATIVE: The study is a prospective, randomized, double-blind, placebo-controlled clinical trial within a sickle cell center. In subproject 3, an estimated 70 subjects will receive standard opioid and supportive therapy, and will be randomly assigned to receive either (1) intravenous ketorolac and oral placebo or (2) intravenous placebo and oral ibuprofen. Efficacy will be assessed by three measures: the duration of hospitalization for parenteral opioid therapy; the degree of pain intensity and relief determined by validated pain scales; and the utilization of parenteral opioids during hospitalization. All subjects will be monitored for potential adverse effects of the study medications by laboratory measurements and clinical assessments. The primary endpoint is the length of hospital stay. This serves as a surrogate for adequate pain control. Additionally, subjects pain control will be self-reported using the Oucher pain scale. Patients will be monitored for the development of adverse events including gastrointestinal symptoms and deterioration of renal function as evidenced by daily renal function tests including BUN, creatinine and hematuria.