Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease

JAMA. 2003 Mar 5;289(9):1136-42. 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Anemia, Sickle Cell / drug therapy*
  • Anemia, Sickle Cell / physiopathology*
  • Child
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / therapeutic use*
  • Pain Measurement
  • Pilot Projects
  • Prospective Studies
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / therapeutic use*


  • Vasodilator Agents
  • Nitric Oxide