Preliminary Assessment of Inhaled Nitric Oxide for Acute Vaso-occlusive Crisis in Pediatric Patients With Sickle Cell Disease

• Published in: JAMA : the journal of the American Medical Association 2003-03, Vol.289 (9), p.1136-1142
• Main Authors: Weiner, Debra L, Hibberd, Patricia L, Betit, Peter, Cooper, Andrew B, Botelho, Christine A, Brugnara, Carlo
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adult; Anemia, Sickle Cell - drug therapy; Anemia, Sickle Cell - physiopathology; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Cardiovascular system; Child; Double-Blind Method; Female; Humans; Male; Medical sciences; Nitric Oxide - administration & dosage; Nitric Oxide - therapeutic use; Pain Measurement; Pediatrics; Pharmacology. Drug treatments; Pilot Projects; Prospective Studies; Sickle cell anemia; Treatment Outcome; Vasodilator Agents - administration & dosage; Vasodilator Agents - therapeutic use; Vasodilator agents. Cerebral vasodilators
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.289.9.1136

CONTEXT: Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide–dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease–based therapy for treatment of vaso-occlusion. OBJECTIVE: To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN: Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING: Urban, tertiary care children's hospital in the United States. PARTICIPANTS: Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION: Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES: Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS: Preinhalation VAS pain scores were similar in the INO and placebo groups (P = .80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P = .37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P = .02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P = .03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P = .21) or 24 hours (0.63 vs 0.91 mg/kg; P = .15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P = .19). No INO toxicity was observed. CONCLUSIONS: Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.