 |
|
Low-Dose Inhaled Nitric Oxide in Patients With Acute Lung Injury
A Randomized Controlled Trial
Robert W. Taylor, MD;
Janice L. Zimmerman, MD;
R. Phillip Dellinger, MD;
Richard C. Straube, MD;
Gerard J. Criner, MD;
Kenneth Davis, Jr, MD;
Kathleen M. Kelly, MD;
Thomas C. Smith, MD;
Robert J. Small, RN; for the Inhaled Nitric Oxide in ARDS Study Group
JAMA. 2004;291:1603-1609.
Context Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury.
Objective To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with acute lung injury.
Design and Setting Multicenter, randomized, placebo-controlled study, with blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and September 1999.
Patients Patients (n = 385) with moderately severe acute lung injury, a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio of PaO2 to FiO2 of  250, were enrolled if the onset was within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no significant nonpulmonary organ system dysfunction at randomization.
Interventions Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing, or death.
Main Outcome Measures The primary end point was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting oxygenation criteria for extubation, and days patients were alive following a successful unassisted ventilation test.
Results An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P = .97; difference, –0.1 day [95% confidence interval, –2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO2 that resolved by 48 hours. Mortality was similar between groups (20% placebo vs 23% nitric oxide; P = .54). Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P = .54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide (P = .89).
Conclusion Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality.
Author Affiliations: Critical Care Medicine, St Louis University/St John's Mercy Medical Center, St Louis, Mo (Dr Taylor); Department of Medicine, Baylor College of Medicine and Ben Taub General Hospital, Houston, Tex (Dr Zimmerman); Critical Care Medicine, Robert Wood Johnson Medical School–UMDNJ, Cooper University Hospital, Camden, NJ (Dr Dellinger); INO Therapeutics Inc, Clinton, NJ (Dr Straube and Mr Small); Pulmonary and Critical Care Medicine, Temple Lung Center, Temple University Hospital, Philadelphia, Pa (Dr Criner); Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio (Dr Davis); Department of Clinical Research, Ortho Biotech, Bridgewater, NJ (Dr Kelly); and Department of Pulmonary Medicine, Albany Medical College, Albany, NY (Dr Smith).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Patients with Pulmonary Arterial Hypertension in Clinical Trials: Who Are They?
Hill et al.
Proc Am Thorac Soc 2008;5:603-609.
ABSTRACT
| FULL TEXT
Point: Evidence-Based Medicine Has a Sound Scientific Base
Karanicolas et al.
Chest 2008;133:1067-1071.
FULL TEXT
Mortality Rates for Patients With Acute Lung Injury/ARDS Have Decreased Over Time
Zambon and Vincent
Chest 2008;133:1120-1127.
ABSTRACT
| FULL TEXT
Recent developments in the management of acute respiratory distress syndrome in adults
Bream-Rouwenhorst et al.
Am J Health Syst Pharm 2008;65:29-36.
ABSTRACT
| FULL TEXT
An Early PEEP/FIO2 Trial Identifies Different Degrees of Lung Injury in Patients with Acute Respiratory Distress Syndrome
Villar et al.
Am. J. Respir. Crit. Care Med. 2007;176:795-804.
ABSTRACT
| FULL TEXT
Nitric Oxide in the Pulmonary Vasculature
Coggins and Bloch
Arterioscler. Thromb. Vasc. Bio. 2007;27:1877-1885.
ABSTRACT
| FULL TEXT
Nonventilatory Treatments for Acute Lung Injury and ARDS
Calfee and Matthay
Chest 2007;131:913-920.
ABSTRACT
| FULL TEXT
Review article: Organ perfusion/permeability-related effects of norepinephrine and vasopressin in sepsis: [Expose de synthese : Les effets relies a la perfusion et a la permeabilite organique de la norepinephrine et de la vasopressine durant le "sepsis"].
Farand et al.
Canadian J. Anesthesia 2006;53:934-946.
ABSTRACT
| FULL TEXT
Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome.
Cepkova and Matthay
J Intensive Care Med 2006;21:119-143.
ABSTRACT
Immunoregulatory and antimicrobial effects of nitrogen oxides.
Mannick
Proc Am Thorac Soc 2006;3:161-165.
ABSTRACT
| FULL TEXT
Summary: systemic effects of inhaled nitric oxide.
Gaston
Proc Am Thorac Soc 2006;3:170-172.
ABSTRACT
| FULL TEXT
Inhaled Nitric Oxide Therapy in Adults
Griffiths and Evans
NEJM 2005;353:2683-2695.
FULL TEXT
Ventilatory Management of Acute Lung Injury and Acute Respiratory Distress Syndrome
Fan et al.
JAMA 2005;294:2889-2896.
ABSTRACT
| FULL TEXT
Tidal Volume Reduction in Patients with Acute Lung Injury When Plateau Pressures Are Not High
Hager et al.
Am. J. Respir. Crit. Care Med. 2005;172:1241-1245.
ABSTRACT
| FULL TEXT
"Stop Right There...I Gotta Know Right Now!" Do Steroids Really Help for CAP?
Meduri and Confalonieri
Am. J. Respir. Crit. Care Med. 2005;172:644-645.
FULL TEXT
"Stop Right There...I Gotta Know Right Now!" Do Steroids Really Help for CAP?
Scales et al.
Am. J. Respir. Crit. Care Med. 2005;172:643-644.
FULL TEXT
Effect of Prone Positioning on Clinical Outcomes in Children With Acute Lung Injury: A Randomized Controlled Trial
Curley et al.
JAMA 2005;294:229-237.
ABSTRACT
| FULL TEXT
Case 17-2005 - A 22-Year-Old Woman with Back and Leg Pain and Respiratory Failure
Medoff et al.
NEJM 2005;352:2425-2434.
FULL TEXT
Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil?
Ng et al.
Br J Anaesth 2005;94:774-777.
ABSTRACT
| FULL TEXT
Acute Respiratory Distress Syndrome
Burleson and Maki
Journal of Pharmacy Practice 2005;18:118-131.
ABSTRACT
Therapeutic Hypercapnia: Careful Science, Better Trials
Kavanagh
Am. J. Respir. Crit. Care Med. 2005;171:96-97.
FULL TEXT
Other articles noted
Evid. Based Med. 2004;9:e5-e5.
FULL TEXT
Inhaled Nitric Oxide in Acute Lung Injury
Kaisers et al.
JAMA 2004;292:327-327.
FULL TEXT
Inhaled Nitric Oxide: A Selective Pulmonary Vasodilator: Current Uses and Therapeutic Potential
Ichinose et al.
Circulation 2004;109:3106-3111.
FULL TEXT
Inhaled Nitric Oxide for Acute Lung Injury: No Place for NO?
Adhikari and Granton
JAMA 2004;291:1629-1631.
FULL TEXT
|
