Prospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Feb 4, 2017; 6(1): 74-78
Published online Feb 4, 2017. doi: 10.5492/wjccm.v6.i1.74
Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome
Martin Albert, Daniel Corsilli, David R Williamson, Marc Brosseau, Patrick Bellemare, Stéphane Delisle, Anne QN Nguyen, France Varin
Martin Albert, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada
Daniel Corsilli, Marc Brosseau, Patrick Bellemare, Department of Intensive Care, Centre Hospitalier Universitaire de Montréal, Université de Montréal, Montréal H2W 1T8, Canada
David R Williamson, Anne QN Nguyen, France Varin, Department of Pharmacy, Université de Montréal, Hôpital du Sacré-Coeur de Montréal Research Center, Montréal H4J 1C5, Canada
Patrick Bellemare, Department of Respiratory Care, Hôpital du Sacré-Coeur de, Montréal H4J 1C5, Canada
Stéphane Delisle, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, Montréal H4J 1C5, Canada
Author contributions: All the authors contributed to the manuscript.
Institutional review board statement: The protocol was approved by the Hôpital du Sacré-Coeur de Montréal ethics committee and consent was obtained from patients or their next of kin. The protocol was submitted to and approved by Health Canada.
Informed consent statement: Consent for data sharing was not obtained but the presented data are anonymized and risk of identification is insignificant.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Martin Albert, MD, Departments of Intensive Care and Medicine, Hôpital du Sacré-Coeur, de Montréal Research Center, Université de Montréal, 5400 boul, Gouin Ouest, Montréal H4J 1C5, Canada. m.albert@umontreal.ca
Telephone: +1-514-3382050 Fax: +1-514-3383557
Received: September 1, 2016
Peer-review started: September 5, 2016
First decision: September 29, 2016
Revised: November 26, 2016
Accepted: December 16, 2016
Article in press: December 19, 2016
Published online: February 4, 2017
Abstract
AIM

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 PaO2 from 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.

CONCLUSION

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.

Keywords: Inhaled milrinone, Nitric oxide, Pulmonary hypertension, Hypoxemia, Acute respiratory distress syndrome, Prostacyclin

Core tip: To our knowledge, this is the first study testing inhaled milrinone as a therapy in acute respiratory distress syndrome and comparing it to more frequently used inhaled therapies. It shows that inhaled milrinone is safe but is not efficacious.