title: Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome (ARDS).
  
  
  METHODS
  Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of iNO (20 ppm) or nebulized epoprostenol (10 μg/mL) was done in all patients. Thereafter, inhaled milrinone (1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide (iNO) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen (PaO2) were recorded before and after each inhaled therapy administration.
  
  
  RESULTS
  The majority of ARDS were of pulmonary cause (n= 13) and pneumonia (n= 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass (n= 2), smoke inhalation injury (n= 1), thoracic trauma and pulmonary contusions (n= 2) and aspiration (n= 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and iNO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO2from baseline was 8.8 mmHg [interquartile range (IQR) = 16.3], 6.0 mmHg (IQR = 18.4), 6 mmHg (IQR = 15.8) and 9.2 mmHg (IQR = 20.2) respectively with iNO, epoprostenol, inhaled milrinone, and iNO added to milrinone. Only iNO and the combination of inhaled milrinone and iNO had a statistically significant effect on PaO2.
  
  
  CONCLUSIONS
  When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Albert
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Corsilli
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Williamson
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Brosseau
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bellemare
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Delisle
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: Anne Qn
authors.initials: AQ
authors.lastname: Nguyen
authors.affiliation: Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Varin
keywords: Acute respiratory distress syndrome; Hypoxemia; Inhaled milrinone; Nitric oxide; Prostacyclin; Pulmonary hypertension