Therapy High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
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Summary
Posted By:	Elizabeth Sweetman & Gordon Doig
E-Mail:	esweetman@med.usyd.edu.au
Posted Date:	27.02.2013
Title:	High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
Authors:	Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD, Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; the OSCILLATE Trial Investigators and the Canadian Critical Care Trials Group.
Reference:	N Engl J Med. 2013 Jan 22.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	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(HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes.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 .).
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Yes. Allocation concealment was maintained with a central web based randomisation system. Eligible patients were randomly assigned to one of two study groups; the HFOV (high frequency oscillation ventilation)Group OR the Conventional Ventilation Group.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	Yes all 548 patients(randomised up to the point of this trial's early termination) were followed up, analysed and appeared in the Patient flow diagram, Figure 1, page 6.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes patients were analysed in the groups to which they were randomised.
3. Were patients, health workers, and study personnel blind to treatment?
	There was no documented blinding in this trial.
4. Were the groups similar at the start of the trial?
	Yes the baseline characteristics were similar in both study groups at the start of the trial.
5. Aside from the experimental intervention, were the groups treated equally?
	Use of glucocorticoids, RRT, prone positioning similar in HFOV Group and Control Group. Larger proportion of patients in the HFOV Group received vasoactive drugs compared with Control Group (91% vs 84%, P = 0.01) and also neuromuscular blocking agents compared with Control Group(83% vs 68%, P = <0.001). Median doses of Midazolam in the first week significantly higher in HFOV Group compared to the Control Group (199 mg per day [Interquartile range 100-382 ug] vs 141 mg per day [Interquartile range 68-240 ug] , P = <0.001) A trend towards higher doses of Fentanyl in the first week in the HFOV Group compared to the Control Group (2980 ug per day [Interquartile range 1258-4800 ug] vs 2400 per day [Interquartile range 1140-4430 ug], P = 0.06. *Midazolam and Fentanyl administered for same duration in HFOV and Control Groups (median 10 days [Interquartile range 6-18 days] vs median 10 days [Interquartile range 6-17 days], P = 0.99). HFOV Group had vasoactive drugs administered for an average of 2 days longer compared to Control Group (Suppl Appendix Table S5). HFOV Group had neuromuscular blocking agents admistered for an average of 1 day longer than the Control Group (Suppl Appendix Table S5).
What are the Results?
1. How large was the treatment effect?
	Primary Outcome: Lower in hospital mortality attributable to continued strict adherence to the ARDs NET Low Tidal Volume protocol compared to early HFOV Group (35% vs 47%, P = 0.005), table 4, page 8.
2. How precise was the estimate of the treatment effect?
	Relative risk of Death with HFOV 1.33 95% Confidence Interval for In hospital mortality 1.09 to 1.64, P = 0.005
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	Yes. These results suggest that continued ventilation using strict adherence to the ARDs NET Low Tidal Volume protocol may be more beneficial than an earlyswitch to HFOV.
2. Were all clinically important outcomes considered?
	Yes, in the context of improved mortality attributable to continued strict adherence to the ARDs NET Low Tidal Volume protocol.
3. Are the likely treatment benefits worth the potential harms and costs?
	Yes, in the context of improved mortality attributable to continued strict adherence to the ARDs NET Low Tidal Volume protocol.
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