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.
RCT Entities:
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.
Authors: Peter Germann; Antonio Braschi; Giorgio Della Rocca; Anh Tuan Dinh-Xuan; Konrad Falke; Claes Frostell; Lars E Gustafsson; Philippe Hervé; Philippe Jolliet; Udo Kaisers; Hector Litvan; Duncan J Macrae; Marco Maggiorini; Nandor Marczin; Bernd Mueller; Didier Payen; Marco Ranucci; Dietmar Schranz; Rainer Zimmermann; Roman Ullrich Journal: Intensive Care Med Date: 2005-06-23 Impact factor: 17.440
Authors: Michael Hawkes; Robert Opika Opoka; Sophie Namasopo; Christopher Miller; Andrea L Conroy; Lena Serghides; Hani Kim; Nisha Thampi; W Conrad Liles; Chandy C John; Kevin C Kain Journal: Med Hypotheses Date: 2011-07-13 Impact factor: 1.538