臨床研究 P/F比 150 mmHgレベルの低酸素症に対するHigh Flow Oxygenの有効性：通常の酸素投与に変わる

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure.
FLORALI Study Group and the REVA Network.
Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Béduneau G, Delétage-Métreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group and the REVA Network.
N Engl J Med. 2015 Jun 4;372(23):2185-2196.

Background Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia.
Methods We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28.
Results A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006).
Conclusions In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384 .).

＜松田直之 コメント＞ MEIDAI救急・集中治療は2012年よりHFNCを導入し，全身性炎症の改善に末梢気道開放ブランチを設定してきました。我々のデータと同様に，本論文でもHFNCによるopen lungにより，生命予後が有意に改善しています。気管挿管リスクをNPPVは低下させていないのですが，P/F比≦200 mmHgがHFNCでは少ないです。本論文は，2011年２月から2013年4月までにフランスとベルギーの23のICUにおける酸素化の臨床研究ですが，このREVA（Reseau Europeen de Recherche en Ventilation Artificielle）Networkの治療成績も良くなってきています。
※ FLORALI trial：Non- invasive Ventilation and High Flow Nasal Oxygen Therapy in Resuscitation of Pa- tients with Acute Lung Injury trial


母体数を維持する上で，40.4%（212/525）脱落率は高いように思います。










参考文献
1. Blodgett AN. The continuous inhalation of oxygen in cases of pneumonia otherwise fatal, and in other diseases. Boston Med J 1890;123:481-5.
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3. Keenan SP, Sinuff T, Cook DJ, Hill NS. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A sys- tematic review of the literature. Ann Intern Med 2003;138:861- 70.
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8. Frat J-P, Thille AW, Mercat A, et al. High-flow versus Venturi mask oxygen therapy after extubation: effects on oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372:2185-96.
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文献紹介 Lung Protective Ventilation BMJ 2012 April

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study
Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, Sevransky JE, Dennison Himmelfarb CR, Desai SV, Shanholtz C, Brower RG, Pronovost PJ.
BMJ. 2012 Apr 5;344:e2124.

Abstract
OBJECTIVE:
To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury.
DESIGN:
Prospective cohort study.
SETTING:
13 intensive care units at four hospitals in Baltimore, Maryland, USA.
PARTICIPANTS:
485 consecutive mechanically ventilated patients with acute lung injury.
MAIN OUTCOME MEASURE:
Two year survival after onset of acute lung injury.
RESULTS:
485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011).
CONCLUSIONS:
Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury.

1回換気量が6.5 mL/kg vs 6.5-8.8 mL/kg ハザード比 1.59（1.19-2.14）


参考1　JAMA 2005 Dec 14;294(22):2889-96.
Ventilatory management of acute lung injury and acute respiratory distress syndrome.
Fan E, Needham DM, Stewart TE.
Interdepartmental Division of Critical Care Medicine and Department of Medicine, University of Toronto and University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada.

CONTEXT:
The acute lung injury and acute respiratory distress syndrome are critical illnesses associated with significant morbidity and mortality. Mechanical ventilation is the cornerstone of supportive therapy. However, despite several important advances, the optimal strategy for ventilation and adjunctive therapies for patients with acute lung injury and acute respiratory distress syndrome is still evolving.
EVIDENCE ACQUISITION:
To identify reports of invasive ventilatory and adjunctive therapies in adult patients with acute lung injury and acute respiratory distress syndrome, we performed a systematic English-language literature search of MEDLINE (1966-2005) using the Medical Subject Heading respiratory distress syndrome, adult, and related text words, with emphasis on randomized controlled trials and meta-analyses. EMBASE and the Cochrane Central Register of Controlled Trials were similarly searched. The search yielded 1357 potential articles of which 53 were relevant to the study objectives and considered in this review.
EVIDENCE SYNTHESIS:
There is strong evidence to support the use of volume- and pressure-limited lung-protective ventilation in adult patients with acute lung injury and acute respiratory distress syndrome. The benefit of increased levels of positive end-expiratory pressure and recruitment maneuvers is uncertain and is being further evaluated in ongoing trials. Existing randomized controlled trials of alternative ventilation modes, such as high-frequency oscillation and adjunctive therapies, including inhaled nitric oxide and prone positioning demonstrate no significant survival advantage. However, they may have a role as rescue therapy for patients with acute respiratory distress syndrome with refractory life-threatening hypoxemia.
CONCLUSIONS:
Volume- and pressure-limited ventilation strategies should be used in managing adult acute lung injury and acute respiratory distress syndrome patients. Further research is needed to identify barriers to widespread adoption of this strategy, as well as the role of alternative ventilation modes and adjunctive therapies.

参考2 Cochrane Database Syst Rev 2007 Jul 18;(3):CD003844.
Lung protective ventilation strategy for the acute respiratory distress syndrome.
Petrucci N, Iacovelli W.

BACKGROUND:
Patients with acute respiratory distress syndrome and acute lung injury require mechanical ventilatory support. Acute respiratory distress syndrome and acute lung injury are further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival.
OBJECTIVES:
To assess the effects of ventilation with lower tidal volume on morbidity and mortality in patients aged 16 years or older affected by acute respiratory distress syndrome and acute lung injury. A secondary objective was to determine whether the comparison between low and conventional tidal volume was different if a plateau airway pressure of greater than 30 to 35 cm H20 was used.
SEARCH STRATEGY:
In our original review, we searched databases from inception until 2003. In this updated review, we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2006, Issue 3). We updated our search of MEDLINE, EMBASE, CINAHL and the Web of Science from 2003 to 2006. We also updated our search of intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature' from 2003 to 2006.
SELECTION CRITERIA:
We included randomized controlled trials comparing ventilation using either lower tidal volume (Vt) or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in tidal volume of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (16 years old or older).
DATA COLLECTION AND ANALYSIS:
We independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. We applied fixed- and random-effects models.
MAIN RESULTS:
We found one new study in this update for a total of six trials, involving 1297 patients, which were eligible for inclusion. Mortality at day 28 was significantly reduced by lung-protective ventilation: relative risk (RR) 0.74 (95% confidence interval (CI) 0.61 to 0.88); hospital mortality was reduced: RR 0.80 (95% CI 0.69 to 0.92); overall mortality was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: RR 1.13 (95% CI 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes.
AUTHORS' CONCLUSIONS:
Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials, make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and at the end of hospital stay. The effects on long-term mortality are unknown, although the possibility of a clinically relevant benefit cannot be excluded.