title: Bench test assessment of dosage accuracy and measurement inaccuracy in nitric oxide inhalational therapy during high frequency oscillatory ventilation.
abstract: OBJECTIVE
  The objective of this study is to determine the accuracy and precision of chemiluminescence and electrochemical nitric oxide (NO) measurements and accuracy of NO dosage with electronic mass flow controllers (MFC) versus rotameters during NO inhalational therapy.
  
  
  METHODS
  NO flow was delivered to a high frequency oscillator and mixed with ventilator flow. NO and NO2 concentrations were measured simultaneously with a standard chemiluminescence analyzer and a modified electrochemical analyzer. Dosage accuracy was assessed with gas flows adjusted with either MFC's or rotameters. Accuracy of both analyzers was validated with both NO and ventilator flow regulated with a MFC.
  
  
  RESULTS
  In dry air, without pulsatile pressure, MFC controlled NO and ventilator flow resulted in an accuracy expressed as the ratio of calculated concentration to measured concentration (RCM) of 0.995 (CI: 0.983-0.988) when measured with chemiluminescence. When the ventilator rotameter was used instead of a MFC, RCM was 0.856 (CI: 0.835-0.877). With a rotameter for both NO and ventilator flow, RCM increased to 1.175 (CI: 0.793-1.740) with an increase of confidence interval limits. Chemiluminescence was sensitive to humidification of the ventilatory gases (p < 0.05), slightly sensitive to the addition of oxygen and to pulsatile pressure (not significant). RCM obtained with the modified electrochemical analyzer was in close agreement with chemiluminescence RCM, although 95% CI were wider with electrochemical analysis.
  
  
  CONCLUSIONS
  During high frequency oscillatory ventilation (HFOV), standard rotameter flow control of both NO and ventilator flow results in unpredictable NO concentrations that would be clinically unacceptable. When one MFC was used for NO flow control, with ventilator flow controlled with a rotameter, this resulted in moderate dosage accuracy. To achieve a still higher accuracy, MFC flow control for both NO and ventilator flow is indicated. During HFOV, standard chemiluminescence analyzers cannot be considered to be the gold standard for determination of the NO concentration delivered. Measurement of NO concentration may not be mandatory for determination of inhaled NO dose during HFOV, but may be used to monitor for unsafe or unwanted events.
authors.affiliation: Department of Pediatrics, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: D G
authors.initials: DG
authors.lastname: Markhorst
authors.forename: T
authors.initials: T
authors.lastname: Leenhoven
authors.forename: H R
authors.initials: HR
authors.lastname: van Genderingen
authors.forename: J W
authors.initials: JW
authors.lastname: Uiterwijk
authors.forename: A J
authors.initials: AJ
authors.lastname: van Vught
mesh_terms: D000280:Administration, Inhalation; D004563:Electrochemistry; D006612:High-Frequency Ventilation / Q000295:instrumentation; D008163:Luminescent Measurements; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000032:analysis
chemical_list: D009569:Nitric Oxide