Arginine Therapy for Sickle Cell Disease Pain

Inclusion Criteria: * Established diagnosis of sickle cell disease (SCD); all genotypes * Pain requiring medical care in an acute care setting (such as the emergency department or ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, that is moderate-to-severe requiring parenteral opioids Exclusion Criteria: * Decision to discharge home from the acute care setting * Hemoglobin less than 5 gm/dL or immediate need for red cell transfusion anticipated within next 12 hours * Hepatic dysfunction of SGPT greater than 3 times the upper value * Renal dysfunction of creatinine greater than 1.0 * Mental status or neurological changes * Acute stroke or clinical concern for stroke * Pregnancy * Allergy to arginine * Two (2) or more ED visits for VOE within the last 7 days prior to CURRENT ED visit * Hospitalization within 14 days * Previous randomization in this arginine RCT (patient consented and screen failed before receiving study drug or placebo remains eligible for future participation). * Use of inhaled nitric oxide, sildenafil or arginine within the last month * PICU admission from the emergency department * Hypotension requiring treatment with clinical intervention * Acidosis with Co2≤ 16 * Newly started on HU for \<3 months * Not an appropriate candidate in the investigator's judgment * Patient refusal