title: A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes.
abstract: Painful episodes of vaso-occlusion are the leading cause of hospitalizations and emergency department visits in sickle cell disease, and are associated with increased mortality. Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease. Since arginine is the obligate substrate for nitric oxide production, and an acute deficiency is associated with pain, we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease. Thirty-eight children with sickle cell disease hospitalized for 56 episodes of pain were randomized into this double-blinded placebo-controlled trial. Patients received L-arginine (100 mg/kg tid) or placebo for 5 days or until discharge. A significant reduction in total parenteral opioid use by 54% (1.9 ± 2.0 mg/kg versus 4.1 ± 4.1 mg/kg, P=0.02) and lower pain scores at discharge (1.9 ± 2.4 versus 3.9 ± 2.9, P=0.01) were observed in the treatment arm compared to the placebo one. There was no significant difference in hospital length of stay (4.1 ± 01.8 versus 4.8 ± 2.5 days, P=0.34), although a trend favored the arginine arm, and total opioid use was strongly correlated with the duration of the admission (r=0.86, P<0.0001). No drug-related adverse events were observed. Arginine therapy represents a novel intervention for painful vaso-occlusive episodes. A reduction of narcotic use by >50% is remarkable. Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle cell-related pain in children. A large multi-center trial is warranted in order to confirm these observations.
authors: Department of Pediatrics, Division of Emergency Medicine, Emory-Children's Center for Developmental Lung Biology, Emory University School of Medicine, Atlanta, GA, USA. clauclaudia.r.morris@emory.edu
authors: Claudia R
authors: CR
authors: Morris
authors: Frans A
authors: FA
authors: Kuypers
authors: Lisa
authors: L
authors: Lavrisha
authors: Michael
authors: M
authors: Ansari
authors: Nancy
authors: N
authors: Sweeters
authors: Melinee
authors: M
authors: Stewart
authors: Ginny
authors: G
authors: Gildengorin
authors: Lynne
authors: L
authors: Neumayr
authors: Elliott P
authors: EP
authors: Vichinsky
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D001120:Arginine / Q000008:administration & dosage*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006760:Hospitalization / Q000639:trends; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D001120:Arginine
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