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N Engl J Med. 2013 Feb 28;368(9):795-805. doi: 10.1056/NEJMoa1215554. Epub 2013 Jan 22.

High-frequency oscillation in early acute respiratory distress syndrome.

Collaborators (165)

Ferguson ND, Meade MO, Cook DJ, Ferguson ND, Guyatt GH, Meade MO, Mehta S, Stewart TE, Slutsky AS, Walter SD, Granton JT, Matte A, Ferguson ND, Matte A, Farias P, Mehta S, Brown M, Campbell V, Friedrich JO, Smith O, Poretta K, Lee Y, Lee J, Adhikari NK, Sinuff T, Marinoff N, Moncrieffe M, Meyer J, Dionne J, Ng S, Davies K, Meade MO, Freitag A, Karachi T, Hand L, Cook DJ, Clarke F, McDonald E, Bosma K, Sen M, Taneja R, Bentall T, Campbell E, Steinmann M, Didiodato G, Austgarden D, Salway R, Jones S, Milletin M, Raso T, Klages R, Patel R, MacIntyre L, Watpool I, Porteous R, Boulianne J, Hodder R, McArdle T, Laufer B, Skrobik Y, Harvey J, Bardier L, Aslanian P, Parent S, Ferland L, Bellemare P, Albert M, Simard H, Delisle S, Lesur O, Lamontagne F, Proulx S, Grodin K, Turgeon A, Lessard M, Gagné C, Thibodeau M, Langis N, Chalifour JF, Laflamme S, Battisti-Charbonney E, Bergeron M, Henzler D, Julien L, Moriarty T, Wood G, Auld F, Atkins L, Ronco J, Foster D, Logie S, Gardner M, Sima D, Dorscheid D, Lazosky L, Novakowski K, Reynolds S, Keenan S, Rohrs L, Svetik M, Reynolds S, McCormack G, Rohrs L, Dhaliwal D, Jacka M, Bagshaw SM, Foster S, Littlewood K, Taylor S, Drummond J, Berthiaume L, Shaheen A, Winston B, Skinner C, Funk D, Janz W, Arroliga AC, Sanchez J, Guerra D, Cormier S, Cernosek C, Goldwater M, Almoosa K, Mullaly A, Graham R, Morin K, Girod C, Lange B, Ziegler D, Burch V, Baumann P, Jimenez E, Danesh V, Tate J, Park P, Brierly K, Haas C, Douglas I, Overdier K, Wolken B, Goettler C, Watkins F, Arabi YM, Tlayjeh H, Trinidad O, Abahussein O, Mandourah Y, Abu Daya A, Hood G, Weber Q, Cruz A, Romero I, Bugedo G, Tomicic V, Jog S, Phalke A, Dominguez G, Cárdenas C, Weiss M, Haskins N, Thompson B, Arnold JH, Beale R, Gajic O, Wells GH.

Author information

Interdepartmental Division of Critical Care Medicine, Department of Medicine, University of Toronto, University Health Network and Mount Sinai Hospital, Toronto, ON, Canada.



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(HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes.


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.


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).


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 numbers, NCT00474656 and NCT01506401.).

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