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

Abstract

Weiner DL, Hibberd PL, Betit P, et al (Children's Hospital, Boston, MA) The treatment of acute vaso-occlusion is challenging in the management of patients with sickle cell disease. At present, there are no disease-specific therapeutic agents approved for acute vaso-occlusion. Abnormal nitric oxide–dependent regulation of vascular adhesion, platelet activation, and inflammation add to the pathophysiology of vaso-occlusion. Treatment with nitric oxide may be beneficial as a mechanism-of-disease–based therapy for treatment of vaso-occlusion. The safety and efficacy of inhaled nitric oxide for treatment of vaso-occlusion crisis in pediatric patients with sickle cell disease were examined in a prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. Twenty-one patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusion were randomly assigned to treatment with either inhaled nitric oxide (80 ppm with 21% final concentration of inspired oxygen) or placebo (21% inspired oxygen) for 4 hours. The primary outcome measure was change in pain at 4 hours of inhalation versus preinhalation pain, measured on a 10-cm visual analogue scale; secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. Preinhalation visual analogue scale pain scores were similar for the inhaled nitric oxide and control groups (P=.80). The reductions in visual analogue scale pain score at 4 hours were 2.0 cm and 1.2 cm for the inhaled nitric oxide and control groups, respectively (P=.37). Repeated-measures analysis of variance for hourly pain scores revealed a 1-cm/h greater decrease in the inhaled nitric oxide group versus the placebo group (P=.02). Morphine use over 6 hours was significantly lower in the inhaled nitric oxide group (mean cumulative use, 0.29 vs 44 mg/kg; P=.03) and 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). The duration of hospitalization was 78 hours for the inhaled nitric oxide group and 100 hours for the placebo group (P=.19). There was no inhaled nitric oxide toxicity. Inhaled nitric oxide may be beneficial in the treatment of acute vaso-occlusion in patients with sickle cell disease. These encouraging findings reported in this first clinical trial to assess inhaled nitric oxide for treatment of vaso-occlusion are worthy of further investigation.