title: Technical considerations for inhaled nitric oxide therapy: time response to nitric oxide dosing changes and formation of nitrogen dioxide.
abstract: The aim of the present study was to analyse the time response to nitric oxide (NO) dosing changes as well as the formation of nitrogen dioxide (NO2) with different ventilation systems, respirator settings and application sites during NO inhalation. The inspired NO and NO2 concentrations were continuously measured using chemiluminiscence within a dummy ventilatory system equipped with two different respirator systems (Siemens Servo 900c and Bear BP 2001). NO was either introduced into the afferent limb of the ventilatory circuit close to the endotracheal tube (site A) or into the so-called low pressure port of the Servo 900c respirator, far away from the endotracheal tube (site B). In addition, the decay of the inspired NO concentration after cessation of the NO gas flow was studied. This decay was considerably prolonged when NO was introduced at site B (time constants: tau = 7.19 min versus tau = 0.29 min). Within the concentration range studied (0-25 ppm NO) a linear correlation between the NO and NO2 concentration was found. At site A and an inspired oxygen concentration of > 0.95 NO2 formation amounts to 1.14% +/- 0.11% of the NO concentration. Using this value one can calculate the NO2 formation for a given NO dose. For example, when 40 ppm NO are applied, a concentration of 0.45 ppm NO2 can be expected, which is well below the relevant toxic concentrations. However, when NO was introduced at site B, NO2 formation was significantly increased to 1.61% +/- 0.16%. Passage of the ventilated gas through soda lime led only to a slight and insignificant reduction in NO2 concentration. The continuous flow respirator BP 2001 showed a significantly lower NO2 concentration when compared to the non-continuous flow respirator Servo 900c (0.64 +/- 0.11% vs.1.14 +/- 0.11%).
  
  
  CONCLUSIONS
  The application of NO close to the endotracheal tube is associated with a much faster response of the actual inspired NO concentration to dosing changes and shows the lowest NO2 formation. In order to avoid toxic NO2 concentrations, an upper limit of 40 ppm NO is recommended for continuous NO inhalation.
authors.affiliation: Department of Paediatrics, University of Tübingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Breuer
authors.forename: F
authors.initials: F
authors.lastname: Waidelich
authors.forename: C
authors.initials: C
authors.lastname: Irtel von Brenndorff
authors.forename: L
authors.initials: L
authors.lastname: Sieverding
authors.forename: W
authors.initials: W
authors.lastname: Rosendahl
authors.forename: W
authors.initials: W
authors.lastname: Baden
authors.forename: M
authors.initials: M
authors.lastname: Gass
authors.forename: J
authors.initials: J
authors.lastname: Apitz
mesh_terms: D000704:Analysis of Variance; D002648:Child; D006801:Humans; D007223:Infant; D007362:Intensive Care Units; D008163:Luminescent Measurements; D008171:Lung Diseases / Q000517:prevention & control; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000737:chemistry; D009585:Nitrogen Dioxide / Q000032:analysis; D012044:Regression Analysis; D012138:Respiratory Therapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D012122:Ventilators, Mechanical
chemical_list: D009569:Nitric Oxide; D009585:Nitrogen Dioxide