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N Engl J Med. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
[Source: New England Journal of Medicine, full text: (LINK). Abstract, edited.]
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Original Article
High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
Niall D. Ferguson, M.D., Deborah J. Cook, M.D., Gordon H. Guyatt, M.D., Sangeeta Mehta, M.D., Lori Hand, R.R.T., Peggy Austin, C.C.R.A., Qi Zhou, Ph.D., Andrea Matte, R.R.T., Stephen D. Walter, Ph.D., Francois Lamontagne, M.D., John T. Granton, M.D., Yaseen M. Arabi, M.D., Alejandro C. Arroliga, M.D., Thomas E. Stewart, M.D., Arthur S. Slutsky, M.D., and Maureen O. Meade, M.D. for the OSCILLATE Trial Investigators and the Canadian Critical Care Trials Group
N Engl J Med 2013; 368:795-805 - February 28, 2013 - DOI: 10.1056/NEJMoa1215554
Background
Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes.
Methods
In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause.
Results
On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01).
Conclusions
In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.)
Supported by the Canadian Institutes of Health Research, Randomized Controlled Trial (RCT) Program (Ottawa) and the King Abdullah International Medical Research Center (Riyadh, Saudi Arabia). Dr. Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award; Dr. Cook holds a Canada Research Chair; Dr. Lamontagne is supported by a Fonds de Recherche de Qu?bec?Sant? Research Career Award; and Drs. Ferguson and Meade and Drs. Lamontagne and Meade were supported by Canadian Institutes of Health Research RCT Mentorship awards.
Dr. Ferguson reports receiving grant support through his institution from the Physicians Services Incorporated Foundation; Dr. Granton, receiving consulting fees from Ikaria, lecture fees from Actelion and Eli Lilly, grant support through his institution from Pfizer, Actelion, Eli Lilly, GlaxoSmithKline, and Bayer, payment through his institution from Telus for the sale of a software site license, and support from Actelion for his hospital foundation for pulmonary hypertension research and providing expert testimony for Pfizer regarding patent legal action; and Dr. Slutsky, receiving consulting fees from Maquet Medical, Novalung, Gambro, Ikaria, and Hemodec. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on January 22, 2013, at NEJM.org.
Source Information
From the Interdepartmental Division of Critical Care Medicine (N.D.F., S.M., J.T.G., T.E.S., A.S.S.), Departments of Medicine and Physiology (N.D.F.), the Department of Medicine, Division of Respirology (S.M., J.T.G., T.E.S.), and the Departments of Medicine, Surgery, and Biomedical Engineering (A.S.S.), University of Toronto, University Health Network and Mount Sinai Hospital (N.D.F., J.T.G.), Mount Sinai Hospital (S.M., T.E.S.), St. Michael's Hospital (A.S.S.), and the Critical Care Program, University Health Network (A.M.), Toronto; the Interdepartmental Division of Critical Care, Hamilton Health Sciences (D.J.C., M.O.M.), the Departments of Medicine and Clinical Epidemiology and Biostatistics (D.J.C., G.H.G., S.D.W., M.O.M.), and the CLARITY Research Centre (D.J.C., G.H.G., S.D.W., M.O.M., L.H., P.A., Q.Z.), McMaster University, Hamilton, ON; and the Centre de Recherche Clinique ?tienne-Le Bel, Universit? de Sherbrooke, Sherbrooke, QC (F.L.) ? all in Canada; the Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia (Y.M.A.); and the Department of Medicine, Scott and White Healthcare and Texas A&M Health Science Center College of Medicine, Temple (A.C.A.).
Address reprint requests to Dr. Meade at 1280 Main St. W., Hamilton, ON L8N 3Z5, Canada, or at meadema@hhsc.ca.
A complete list of the investigators in the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) trial is provided in the Supplementary Appendix, available at NEJM.org.
-High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
Niall D. Ferguson, M.D., Deborah J. Cook, M.D., Gordon H. Guyatt, M.D., Sangeeta Mehta, M.D., Lori Hand, R.R.T., Peggy Austin, C.C.R.A., Qi Zhou, Ph.D., Andrea Matte, R.R.T., Stephen D. Walter, Ph.D., Francois Lamontagne, M.D., John T. Granton, M.D., Yaseen M. Arabi, M.D., Alejandro C. Arroliga, M.D., Thomas E. Stewart, M.D., Arthur S. Slutsky, M.D., and Maureen O. Meade, M.D. for the OSCILLATE Trial Investigators and the Canadian Critical Care Trials Group
N Engl J Med 2013; 368:795-805 - February 28, 2013 - DOI: 10.1056/NEJMoa1215554
Background
Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes.
Methods
In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause.
Results
On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01).
Conclusions
In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.)
Supported by the Canadian Institutes of Health Research, Randomized Controlled Trial (RCT) Program (Ottawa) and the King Abdullah International Medical Research Center (Riyadh, Saudi Arabia). Dr. Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award; Dr. Cook holds a Canada Research Chair; Dr. Lamontagne is supported by a Fonds de Recherche de Qu?bec?Sant? Research Career Award; and Drs. Ferguson and Meade and Drs. Lamontagne and Meade were supported by Canadian Institutes of Health Research RCT Mentorship awards.
Dr. Ferguson reports receiving grant support through his institution from the Physicians Services Incorporated Foundation; Dr. Granton, receiving consulting fees from Ikaria, lecture fees from Actelion and Eli Lilly, grant support through his institution from Pfizer, Actelion, Eli Lilly, GlaxoSmithKline, and Bayer, payment through his institution from Telus for the sale of a software site license, and support from Actelion for his hospital foundation for pulmonary hypertension research and providing expert testimony for Pfizer regarding patent legal action; and Dr. Slutsky, receiving consulting fees from Maquet Medical, Novalung, Gambro, Ikaria, and Hemodec. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on January 22, 2013, at NEJM.org.
Source Information
From the Interdepartmental Division of Critical Care Medicine (N.D.F., S.M., J.T.G., T.E.S., A.S.S.), Departments of Medicine and Physiology (N.D.F.), the Department of Medicine, Division of Respirology (S.M., J.T.G., T.E.S.), and the Departments of Medicine, Surgery, and Biomedical Engineering (A.S.S.), University of Toronto, University Health Network and Mount Sinai Hospital (N.D.F., J.T.G.), Mount Sinai Hospital (S.M., T.E.S.), St. Michael's Hospital (A.S.S.), and the Critical Care Program, University Health Network (A.M.), Toronto; the Interdepartmental Division of Critical Care, Hamilton Health Sciences (D.J.C., M.O.M.), the Departments of Medicine and Clinical Epidemiology and Biostatistics (D.J.C., G.H.G., S.D.W., M.O.M.), and the CLARITY Research Centre (D.J.C., G.H.G., S.D.W., M.O.M., L.H., P.A., Q.Z.), McMaster University, Hamilton, ON; and the Centre de Recherche Clinique ?tienne-Le Bel, Universit? de Sherbrooke, Sherbrooke, QC (F.L.) ? all in Canada; the Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia (Y.M.A.); and the Department of Medicine, Scott and White Healthcare and Texas A&M Health Science Center College of Medicine, Temple (A.C.A.).
Address reprint requests to Dr. Meade at 1280 Main St. W., Hamilton, ON L8N 3Z5, Canada, or at meadema@hhsc.ca.
A complete list of the investigators in the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) trial is provided in the Supplementary Appendix, available at NEJM.org.
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