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Debra L. Weiner, MD, PhD; Patricia L. Hibberd, MD, PhD; Peter Betit, RRT; Andrew B. Cooper, PhD; Christine A. Botelho, MPH; Carlo Brugnara, MD

JAMA. 2003;289:1136-1142.

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.

Author Affiliations: Pediatric Emergency (Dr Weiner), Clinical Research Program (Drs Hibberd and Cooper and Ms Botelho), Respiratory Care (Mr Betit), and Department of Laboratory Medicine (Dr Brugnara), Children's Hospital Boston, and Harvard Medical School (Drs Weiner, Hibberd, and Brugnara and Mr Betit), Boston, Mass.

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