OBJECTIVE:Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity. DESIGN: A randomized, prospective interventional study. SETTING:A university hospital's general intensive care unit. PATIENTS: Thirty-two patients with acute lung injury. INTERVENTIONS:Patients who responded to test doses ofnitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%. MEASUREMENTS AND MAIN RESULTS: Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receivinginhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter. CONCLUSIONS: The decrease in activity of nitric oxide synthase in patients receivingnitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.
RCT Entities:
OBJECTIVE: Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity. DESIGN: A randomized, prospective interventional study. SETTING: A university hospital's general intensive care unit. PATIENTS: Thirty-two patients with acute lung injury. INTERVENTIONS:Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%. MEASUREMENTS AND MAIN RESULTS:Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter. CONCLUSIONS: The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.
Authors: Florence Ader; Rozenn Le Berre; Steve Lancel; Karine Faure; Nathalie B Viget; Emmanuel Nowak; Rémi Nevière; Benoit P Guery Journal: Intensive Care Med Date: 2007-01-12 Impact factor: 17.440
Authors: Amarjit S Naura; Mourad Zerfaoui; Hogyoung Kim; Zakaria Y Abd Elmageed; Paulo C Rodriguez; Chetan P Hans; Jihang Ju; Youssef Errami; Jiwon Park; Augusto C Ochoa; A Hamid Boulares Journal: J Immunol Date: 2010-07-28 Impact factor: 5.422