NDLI: First do no harm: surrogate endpoints and the lesson of β-agonists in acute lung injury

Content Provider	Springer Nature : BioMed Central
Author	Lakshminarayana, Pradeep H Kahn, Jeremy M
Abstract	Citation Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, Kallet RH, Liu KD, MacIntyre N, Moss M, Schoenfeld D, Steingrub J, Thompson BT: Randomized, placebo-controlled clinical trial of an aerosolized β-agonist for treatment of acute lung injury. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Am J Respir Crit Care Med 2011, 184: 561-568. Background β2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies of acute lung injury (ALI). Methods Objective: To determine whether an aerosolized β2-agonist would improve clinical outcomes in patients with ALI. Design: Multi-center, phase III randomized, placebo-controlled clinical trial. Setting: 33 hospitals participating National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Subjects: Patients who were intubated and receiving mechanical ventilation, had bilateral infiltrates consistent with edema on frontal chest radiograph, had a ratio of PaO2 to FIO2 (fraction of inspired oxygen) of 300 or less, and not had clinical evidence of left atrial hypertension. A maximum enrolment of 1,000 patients was planned. Intervention: Patients were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. Outcomes: The primary outcome variable was ventilator-free days (VFD). Secondary outcome measures included mortality before hospital discharge on day 60 and day 90, the number of intensive care unit (ICU)-free days and the number of organ failure-free days. Results There were 282 patients enrolled before the trial was stopped for futility after the second interim analysis. The VFDs difference with albuterol treatment was unfavourable by -2.2 days, well past the futility boundary of -0.4 VFDs. VFDs were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 days, respectively; 95% confidence interval for the difference, -4.7 to 0.3 days; P = 0.087). Rates of death before hospital discharge and the number of organ failure-free days were also not significantly different between the two groups. The number of ICU-free days was lower in the albuterol group in comparison with the placebo group (means of 13.5 and 16.2 days respectively; 95% confidence intervals for the mean difference, -4.9 to -0.4 days; P = 0.023). Overall, heart rates were significantly higher in the albuterol group by approximately 5 beats/minute in the first 2 days after randomization (P < 0.05), but rates of new onset atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. Conclusions These results suggest that aerosolized albuterol does not improve clinical outcomes in ALI patients. Routine use of β2 agonist therapy in mechanically ventilated ALI patients cannot be recommended.
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/CC11392.pdf
Ending Page	3
Page Count	3
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/CC11392
Journal	Critical Care
Issue Number	3
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2012-06-26
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine
Content Type	Text
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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