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人工呼吸器の設定

著者: 加藤之紀 医療法人EMS 植田救急クリニック

監修: 林寛之 福井大学医学部附属病院

著者校正/監修レビュー済:2020/06/05
参考ガイドライン:
患者向け説明資料

概要・推奨   

  1. 人工呼吸器管理は人体にとっては非生理的なものであり、陽圧換気による肺損傷等を最小限にするように設定を行い、可能な限り早期の離脱を図ることが重要である。
  1. 気管内挿管・人工呼吸器管理の適応は、①誤嚥や窒息を防ぐための気道確保、②酸素化、換気の障害、③呼吸仕事量と呼吸筋力の不均衡であり、SpO₂の値のみではその適応可否は判断できない。
  1. 酸素化の指標である動脈酸素分圧(PaO₂)は平均気道内圧と吸入酸素濃度(FiO₂)に比例し、換気の指標である動脈二酸化炭素分圧(PaCO₂)は分時換気量(一回換気量×呼吸回数/分)に反比例する。そのため呼吸器の設定変更ではどちらを改善するために行っているのか常に意識をすることで混乱を防ぐことができる。
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  1. 人工呼吸器管理において、プラトー圧は30㎝H2O以下に制限することが推奨される(推奨度1)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
加藤之紀 : 特に申告事項無し[2021年]
監修:林寛之 : 講演料(メディカ出版),原稿料(羊土社)[2021年]

改訂のポイント:
●定期レビューを行い、FiO₂、PEEP、換気量の設定等について加筆修正を行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 気管内挿管・人工呼吸器管理の適応は、①誤嚥や窒息を防ぐための気道確保、②酸素化、換気の障害、③呼吸仕事量と呼吸筋力の不均衡、――である。
  1. 呼吸仕事量と呼吸筋力のバランス:図<図表>
  1. 一般的に動脈酸素分圧(PaO₂)は平均気道内圧と吸入酸素濃度(FiO2)に比例し、動脈二酸化炭素分圧(PaCO₂)は分時換気量に反比例する。
  1. 換気の方式には大きく分けると、①換気量を設定して決められた量を換気する従量式換気(Volume-Control Ventilation:VCV)、②呼吸器からかける圧を設定してその圧力の分肺を換気する従圧式換気(Pressure-Control Ventilation:PCV)、――の2種類がある。VCVでは換気量は設定できるが吸気圧は設定できず、PCVでは吸気圧は設定できるが換気量は設定できない。いずれの換気方式にしても、設定した換気を行った結果のパラメータ(VCVであれば吸気圧、PCVであれば換気量)に注意する。
  1. 人工呼吸器の基本的なモードには、①呼吸努力がないときにも換気を行い、呼吸努力があったときには設定された換気を毎回行うA/C(Assist/Control Ventilation)、②自発呼吸があればそれに合わせて患者の吸気の間サポート圧をかけるCPAP+PS、③設定された回数までは設定された換気を行うが、それ以上に自発呼吸があればその分はCPAP+PSと同様の換気を行うSIMV(Synchronized intermittent mandatory ventilation)、――の3つがある。
  1. 各呼吸モードの違い:表<図表>
  1. 人工呼吸とはあくまで患者の呼吸の補助であり、常に患者自身の観察を行い、その呼吸状態に合わせて設定を行う。
  1. 人工呼吸器での換気はチューブを通してガスを押し込む陽圧換気であり、それ自体が肺への損傷を伴う。様々な機序が報告されているが総称してVALI(Ventilator Associated Lung Injury)と呼ばれ、VALIを防ぐための肺保護換気が重要となる。現時点で有効とされる肺保護換気には、以下の2点が挙げられる。
  1. ① 6~8mL/kg(予測体重計算)の小さい一回換気量での換気(Low Tidal Volume Ventilation)
  1. 身長と予測体重の換算表:表<図表>
  1. ② プラトー圧の30㎝H₂O以下への制限
 
  1. 人工呼吸とはあくまで患者の呼吸の補助であり、常に患者自身の観察を行いその呼吸状態に合わせて設定を行う。 
  1. トラブルシューティングとしては、auto-PEEPやリーク、患者との非同調性などに注意するが、緊急時には人工呼吸器から外してバッグバルブマスクなどで用手的に換気することも重要である。

各論

気管内挿管と人工呼吸の適応  
  1. 気管内挿管と人工呼吸は必ずしも同一の概念ではないが、同時に行われることも多く、その適応は大きく分けると以下のように挙げられる。
  1. 気道の確保と保護:上気道の狭窄の恐れがある場合の気道確保や意識レベル低下患者の誤嚥防止を目的とする(例:窒息、喉頭蓋炎、薬物中毒や脳卒中などでの意識レベル低下)。
  1. 酸素化や換気の障害:次項( >詳細情報 )にて詳述する。
  1. 呼吸仕事量と呼吸筋力の不均衡:酸素化や換気に異常がなくても、呼吸努力が強く呼吸仕事量が増加している場合(敗血症など)、呼吸筋力が追いつかず疲労するため補助が必要になる。また呼吸仕事量が増えなくても呼吸筋力が弱くなる病態(ALSなど)では、相対的に呼吸仕事量の方が大きくなり呼吸器での補助が必要になる。
 
呼吸仕事量と呼吸筋力のバランス

出典

img1:  著者提供
 
 
酸素化、換気とその障害  
  1. 一般に我々が呼吸障害と呼ぶものには酸素化の障害と換気障害によるものがある。酸素化の障害では動脈酸素分圧(PaO₂)の低下を来し、換気障害では動脈二酸化炭素分圧(PaCO₂)の上昇を来す。
  1. 酸素化とその障害:体循環から戻ってきた静脈血は、肺での血液と肺胞のガス交換によって酸素化が行われる。肺自体の障害や肺への血流障害などで肺胞でのガス交換は障害され酸素化は悪化する(例:肺炎、肺塞栓、ARDSなど)。
  1. 換気とその障害:二酸化炭素は静脈血から拡散によって肺胞内に移動する。換気障害にて肺胞が十分換気されず肺胞内の二酸化炭素濃度が高いままであれば、静脈血との二酸化炭素濃度差が少なくなり拡散の効率が落ちるためPaCO₂は上昇する(例:窒息、COPD急性増悪、薬物中毒での呼吸努力低下など)。
  1. 酸素化の改善は、吸入酸素濃度(FiO₂)を上げ肺胞内の酸素分圧を上げる方法と、気道内圧を上げガス交換の効率を上げる方法がある。つまりPaO₂はFiO₂と平均気道内圧に比例する。
  1. 二酸化炭素排出は、換気量を上げ肺胞内の二酸化炭素濃度を下げることにより促進される。PaCO₂は換気量(分時換気量)に反比例する。
  1. つまりPaO₂を上昇させるためには、平均気道内圧の上昇や吸入酸素濃度の上昇が必要となり、上昇したPaCO₂を下げるためには一回換気量の増加や呼吸数の上昇で分時換気量を上げることが必要となる。

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文献 

著者: C G Elliott, B Y Rasmusson, R O Crapo, A H Morris, R L Jensen
雑誌名: Am Rev Respir Dis. 1987 Mar;135(3):634-8. doi: 10.1164/arrd.1987.135.3.634.
Abstract/Text To determine if measures of ARDS severity during the acute illness correlate with lung function after recovery from ARDS, we regressed lowest total thoracic compliance (CTH), initial intrapulmonary shunt fraction (Qsp/Qt), initial mean pulmonary artery pressure (PAP), maximal level of positive end-expiratory pressure (PEEP), time ventilated (Tvent), and time with FlO2 greater than 0.6 (TO2) against the percent of predicted FVC, TLC, and DLCO of 16 previously healthy, nonsmoking ARDS survivors. Pulmonary function tests were performed more than 1 yr after ARDS. Percent of predicted FVC correlated with CTH (r = 0.66, p less than 0.01) and PAP (r = 0.53, p less than 0.05), and percent of predicted TLC correlated with CTH (r = 0.71, p less than 0.01), PEEP (r = -0.55, p less than 0.05), and Qsp/Qt (r = -0.53, p less than 0.05). Only TO2 correlated with percent of predicted DLCO (r = -0.53, p less than 0.05). Five of 7 ARDS survivors with an abnormal DLCO were supported at FlO2 greater than 0.6 for more than 24 h, whereas all of 9 survivors with a normal DLCO received FlO2 greater than 0.6 for less than 24 h. We conclude that physiologic markers of ARDS severity during the acute illness correlate with residual pulmonary dysfunction after recovery from ARDS. Support with FlO2 greater than 0.6 for more than 24 h appears to be a sensitive and specific predictor of an abnormally reduced DLCO more than 1 yr after ARDS.

PMID 3548507  Am Rev Respir Dis. 1987 Mar;135(3):634-8. doi: 10.1164/・・・
著者: P D Wagner, R B Laravuso, R R Uhl, J B West
雑誌名: J Clin Invest. 1974 Jul;54(1):54-68. doi: 10.1172/JCI107750.
Abstract/Text A new method has been developed for measuring virtually continuous distributions of ventilation-perfusion ratios (V(A)/Q) based on the steadystate elimination of six gases of different solubilities. The method is applied here to 12 normal subjects, aged 21-60. In nine, the distributions were compared breathing air and 100% oxygen, while in the remaining three, effects of changes in posture were examined. In four young semirecumbent subjects (ages 21-24) the distributions of blood flow and ventilation with respect to V(A)/Q were virtually log-normal with little dispersion (mean log standard deviations 0.43 and 0.35, respectively). The 95.5% range of both blood flow and ventilation was from V(A)/Q ratios of 0.3-2.1, and there was no intrapulmonary shunt (V(A)/Q of 0). On breathing oxygen, a shunt developed in three of these subjects, the mean value being 0.5% of the cardiac output. The five older subjects (ages 39-60) had broader distributions (mean log standard deviations, 0.76 and 0.44) containing areas with V(A)/Q ratios in the range 0.01-0.1 in three subjects. As for the young subjects, there was no shunt breathing air, but all five developed a shunt breathing oxygen (mean value 3.2%), and in one the value was 10.7%. Postural changes were generally those expected from the known effects of gravity, with more ventilation to high V(A)/Q areas when the subjects were erect than supine. Measurements of the shunt while breathing oxygen, the Bohr CO(2) dead space, and the alveolar-arterial oxygen difference were all consistent with the observed distributions. Since the method involves only a short infusion of dissolved inert gases, sampling of arterial blood and expired gas, and measurement of cardiac output and minute ventilation, we conclude that it is well suited to the investigation of pulmonary gas exchange in man.

PMID 4601004  J Clin Invest. 1974 Jul;54(1):54-68. doi: 10.1172/JCI10・・・
著者: Jonathan Elmer, Michael Scutella, Raghevesh Pullalarevu, Bo Wang, Nishit Vaghasia, Stephen Trzeciak, Bedda L Rosario-Rivera, Francis X Guyette, Jon C Rittenberger, Cameron Dezfulian, Pittsburgh Post-Cardiac Arrest Service (PCAS)
雑誌名: Intensive Care Med. 2015 Jan;41(1):49-57. doi: 10.1007/s00134-014-3555-6. Epub 2014 Dec 4.
Abstract/Text PURPOSE: Previous observational studies have inconsistently associated early hyperoxia with worse outcomes after cardiac arrest, and have methodological limitations. We tested this association using a high-resolution database controlling for multiple disease-specific markers of severity of illness and care processes.
METHODS: This was a retrospective analysis of a single-center, prospective registry of consecutive cardiac arrest patients. We included patients who survived and were mechanically ventilated ≥24 h after arrest. Our main exposure was arterial oxygen tension (PaO2), which we categorized hourly for 24 h as severe hyperoxia (>300 mmHg), moderate or probable hyperoxia (101-299 mmHg), normoxia (60-100 mmHg) or hypoxia (<60 mmHg). We controlled for Utstein-style covariates, markers of disease severity and markers of care responsiveness. We performed unadjusted and multiple logistic regression to test the association between oxygen exposure and survival to discharge, and used ordered logistic regression to test the association of oxygen exposure with neurological outcome and Sequential Organ Failure Assessment (SOFA) score at 24 h.
RESULTS: Of 184 patients, 36 % were exposed to severe hyperoxia and overall mortality was 54 %. Severe hyperoxia, but not moderate or probable hyperoxia, was associated with decreased survival in both unadjusted and adjusted analysis [adjusted odds ratio (OR) for survival 0.83 per hour exposure, P = 0.04]. Moderate or probable hyperoxia was not associated with survival but was associated with improved SOFA score 24 h (OR 0.92, P < 0.01).
CONCLUSION: Severe hyperoxia was independently associated with decreased survival to hospital discharge. Moderate or probable hyperoxia was not associated with decreased survival and was associated with improved organ function at 24 h.

PMID 25472570  Intensive Care Med. 2015 Jan;41(1):49-57. doi: 10.1007/・・・
著者: Derek K Chu, Lisa H-Y Kim, Paul J Young, Nima Zamiri, Saleh A Almenawer, Roman Jaeschke, Wojciech Szczeklik, Holger J Schünemann, John D Neary, Waleed Alhazzani
雑誌名: Lancet. 2018 Apr 28;391(10131):1693-1705. doi: 10.1016/S0140-6736(18)30479-3. Epub 2018 Apr 26.
Abstract/Text BACKGROUND: Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults.
METHODS: In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697.
FINDINGS: 25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94-99%, IQR 96-98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03-1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01-1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00-1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses.
INTERPRETATION: In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94-96%. These results support the conservative administration of oxygen therapy.
FUNDING: None.

Copyright © 2018 Elsevier Ltd. All rights reserved.
PMID 29726345  Lancet. 2018 Apr 28;391(10131):1693-1705. doi: 10.1016/・・・
著者: Marija Barbateskovic, Olav L Schjørring, Sara Russo Krauss, Janus C Jakobsen, Christian S Meyhoff, Rikke M Dahl, Bodil S Rasmussen, Anders Perner, Jørn Wetterslev
雑誌名: Cochrane Database Syst Rev. 2019 Nov 27;2019(11). doi: 10.1002/14651858.CD012631.pub2. Epub 2019 Nov 27.
Abstract/Text BACKGROUND: The mainstay treatment for hypoxaemia is oxygen therapy, which is given to the vast majority of adults admitted to the intensive care unit (ICU). The practice of oxygen administration has been liberal, which may result in hyperoxaemia. Some studies have indicated an association between hyperoxaemia and mortality, whilst other studies have not. The ideal target for supplemental oxygen for adults admitted to the ICU is uncertain. Despite a lack of robust evidence of effectiveness, oxygen administration is widely recommended in international clinical practice guidelines. The potential benefit of supplemental oxygen must be weighed against the potentially harmful effects of hyperoxaemia.
OBJECTIVES: To assess the benefits and harms of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU.
SEARCH METHODS: We identified trials through electronic searches of CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, CINAHL, and LILACS. We searched for ongoing or unpublished trials in clinical trials registers. We also scanned the reference lists of included studies. We ran the searches in December 2018.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language. We included trials with a difference between the intervention and control groups of a minimum 1 kPa in partial pressure of arterial oxygen (PaO2), minimum 10% in fraction of inspired oxygen (FiO2), or minimum 2% in arterial oxygen saturation of haemoglobin/non-invasive peripheral oxygen saturation (SaO2/SpO2). We excluded trials randomizing participants to hypoxaemia (FiO2 below 0.21, SaO2/SpO2 below 80%, and PaO2 below 6 kPa) and to hyperbaric oxygen.
DATA COLLECTION AND ANALYSIS: Three review authors independently, and in pairs, screened the references retrieved in the literature searches and extracted data. Our primary outcomes were all-cause mortality, the proportion of participants with one or more serious adverse events, and quality of life. None of the trials reported the proportion of participants with one or more serious adverse events according to the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) criteria. Nonetheless, most trials reported several serious adverse events. We therefore included an analysis of the effect of higher versus lower fraction of inspired oxygen, or targets using the highest reported proportion of participants with a serious adverse event in each trial. Our secondary outcomes were lung injury, acute myocardial infarction, stroke, and sepsis. None of the trials reported on lung injury as a composite outcome, however some trials reported on acute respiratory distress syndrome (ARDS) and pneumonia. We included an analysis of the effect of higher versus lower fraction of inspired oxygen or targets using the highest reported proportion of participants with ARDS or pneumonia in each trial. To assess the risk of systematic errors, we evaluated the risk of bias of the included trials. We used GRADE to assess the overall certainty of the evidence.
MAIN RESULTS: We included 10 RCTs (1458 participants), seven of which reported relevant outcomes for this review (1285 participants). All included trials had an overall high risk of bias, whilst two trials had a low risk of bias for all domains except blinding of participants and personnel. Meta-analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding mortality at the time point closest to three months (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.01 to 1.37; I2 = 0%; 4 trials; 1135 participants; very low-certainty evidence). Meta-analysis indicated harm from higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation regarding serious adverse events at the time point closest to three months (estimated highest proportion of specific serious adverse events in each trial RR 1.13, 95% CI 1.04 to 1.23; I2 = 0%; 1234 participants; 6 trials; very low-certainty evidence). These findings should be interpreted with caution given that they are based on very low-certainty evidence. None of the included trials reported any data on quality of life at any time point. Meta-analysis indicated no evidence of a difference between higher fraction of inspired oxygen or targets as compared with lower fraction or targets of arterial oxygenation on lung injury at the time point closest to three months (estimated highest reported proportion of lung injury RR 1.03, 95% CI 0.78 to 1.36; I2 = 0%; 1167 participants; 5 trials; very low-certainty evidence). None of the included trials reported any data on acute myocardial infarction or stroke, and only one trial reported data on the effects on sepsis.
AUTHORS' CONCLUSIONS: We are very uncertain about the effects of higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the ICU on all-cause mortality, serious adverse events, and lung injuries at the time point closest to three months due to very low-certainty evidence. Our results indicate that oxygen supplementation with higher versus lower fractions or oxygenation targets may increase mortality. None of the trials reported the proportion of participants with one or more serious adverse events according to the ICH-GCP criteria, however we found that the trials reported an increase in the number of serious adverse events with higher fractions or oxygenation targets. The effects on quality of life, acute myocardial infarction, stroke, and sepsis are unknown due to insufficient data.

Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PMID 31773728  Cochrane Database Syst Rev. 2019 Nov 27;2019(11). doi: ・・・
著者: Francisco Manzano, Enrique Fernández-Mondéjar, Manuel Colmenero, María Eugenia Poyatos, Ricardo Rivera, Juan Machado, Iñaki Catalán, Antonio Artigas
雑誌名: Crit Care Med. 2008 Aug;36(8):2225-31. doi: 10.1097/CCM.0b013e31817b8a92.
Abstract/Text OBJECTIVE: To analyze the effect on clinical outcomes of prophylactic positive end expiratory pressure in nonhypoxemic ventilated patients.
DESIGN: Multicenter randomized controlled clinical trial.
SETTING: One trauma and two general intensive care units in two university hospitals.
PATIENTS: One hundred thirty-one mechanically ventilated patients with normal chest radiograph and PaO2/FiO2 above 250.
INTERVENTIONS: Patients were randomly allocated to receive mechanical ventilation with 5-8 cm H2O of positive end-expiratory pressure (PEEP) (PEEP group, n = 66) or no-PEEP (control group, n = 65).
MEASUREMENTS AND MAIN RESULTS: Primary end-point variable was hospital mortality. Secondary outcomes included microbiologically confirmed ventilator-associated pneumonia, acute respiratory distress syndrome, barotrauma, atelectasis, and hypoxemia (PaO2/FiO2 <175). Both groups were similar at randomization in demographic characteristics, intensive care unit admission diagnoses, severity of illness, and risk factors for ventilator-associated pneumonia. Hospital mortality rate was similar (p = 0.58) between PEEP (29.7%) and control (25.4%) groups. Ventilator-associated pneumonia was detected in 16 (25.4%) patients in the control group and 6 (9.4%) in the PEEP group (relative risk, 0.37; 95% confidence interval = 0.15-0.84; p = 0.017). The number of patients who developed hypoxemia was significantly higher in the control group (34 of 63 patients, 54%) than in the PEEP group (12 of 64, 19%) (p < 0.001), and the hypoxemia developed after a shorter period (median [interquartile range]) in the control group than in the PEEP group (38 [20-70] hrs vs. 77 [32-164] hrs, p < 0.001). Groups did not significantly differ in incidence of acute respiratory distress syndrome (14% in controls vs. 5% in the PEEP group, p = 0.08), barotrauma (8% vs. 2%, respectively, p = 0.12), or atelectasis (27% vs. 19%, respectively, p = 0.26).
CONCLUSIONS: These findings indicate that application of prophylactic PEEP in nonhypoxemic ventilated patients reduces the number of hypoxemia episodes and the incidence of ventilator-associated pneumonia.

PMID 18664777  Crit Care Med. 2008 Aug;36(8):2225-31. doi: 10.1097/CCM・・・
著者: Umberto Lucangelo, Walter A Zin, Vittorio Antonaglia, Lara Petrucci, Marino Viviani, Giovanni Buscema, Massimo Borelli, Giorgio Berlot
雑誌名: Crit Care Med. 2008 Feb;36(2):409-13. doi: 10.1097/01.CCM.0000297888.82492.31.
Abstract/Text OBJECTIVE: To test the effects of positive expiratory pressure on the leakage of fluid around cuffs of different tracheal tubes, in mechanically ventilated patients and in a benchtop model.
DESIGN: Randomized clinical trial and experimental in vitro study.
SETTING: Intensive care unit of a university hospital.
PATIENTS: Forty patients recovering in the intensive care unit were ventilated in volume-controlled mode. Twenty patients were randomly intubated with Hi-Lo tubes (HL group), whereas the remaining 20 subjects were intubated with SealGuard tubes (SG group).
INTERVENTIONS: Immediately after intubation and cuff inflation with 30 cm H2O, Evans blue was applied onto the cephalic surface of the tracheal tube cuff. A 5-cm H2O positive expiratory pressure was used during the first 5 hrs of stay, and thereafter it was removed. Bronchoscopy verified whether the dye leaked around the cuff. The experiment lasted 12 hrs. Leakage was also tested in vitro with the same tracheal tubes with incremental level of positive expiratory pressure.
MEASUREMENTS AND MAIN RESULTS: At 1 hr, 5 hrs, and thereafter hourly until 12 hrs, bronchoscopy was used to test the presence of dye on the trachea caudal to the cuff. At the fifth hour, two patients of the HL group failed the test. One hour after positive expiratory pressure removal, all subjects in group HL exhibited a dyed lower trachea. On the other hand, one patient in group SG presented a leak at the eighth hour, and at the 12th hour three of them were still sealed. In vitro, the same level of positive expiratory pressure delayed the passage of dye around the cuff; after 30 mins positive expiratory pressure was removed, and in 10 mins all dye leaked only in the Hi-Lo tube.
CONCLUSIONS: We found that 5 cm H2O positive expiratory pressure was effective in delaying the passage of fluid around the cuffs of tracheal tubes both in vivo and in vitro. The SealGuard tube proved to be more resistant to leakage than Hi-Lo.

PMID 18007268  Crit Care Med. 2008 Feb;36(2):409-13. doi: 10.1097/01.C・・・
著者: Matthias Briel, Maureen Meade, Alain Mercat, Roy G Brower, Daniel Talmor, Stephen D Walter, Arthur S Slutsky, Eleanor Pullenayegum, Qi Zhou, Deborah Cook, Laurent Brochard, Jean-Christophe M Richard, Francois Lamontagne, Neera Bhatnagar, Thomas E Stewart, Gordon Guyatt
雑誌名: JAMA. 2010 Mar 3;303(9):865-73. doi: 10.1001/jama.2010.218.
Abstract/Text CONTEXT: Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences.
OBJECTIVES: To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups.
DATA SOURCES: Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010).
STUDY SELECTION: Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality.
DATA EXTRACTION: Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects.
RESULTS: There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar.
CONCLUSIONS: Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS.

PMID 20197533  JAMA. 2010 Mar 3;303(9):865-73. doi: 10.1001/jama.2010.・・・
著者: Roberto Santa Cruz, Juan Ignacio Rojas, Rolando Nervi, Roberto Heredia, Agustín Ciapponi
雑誌名: Cochrane Database Syst Rev. 2013 Jun 6;(6):CD009098. doi: 10.1002/14651858.CD009098.pub2. Epub 2013 Jun 6.
Abstract/Text BACKGROUND: Mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains high. These patients require mechanical ventilation, but this modality has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival.
OBJECTIVES: To assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 4), MEDLINE (1950 to May 2013), EMBASE (1982 to May 2013), LILACS (1982 to May 2013) and SCI (Science Citation Index). We used the Science Citation Index to find references that have cited the identified trials. We did not specifically conduct manual searches of abstracts of conference proceedings for this review. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov and www.controlled-trials.com).    
SELECTION CRITERIA: We included randomized controlled trials that compared the effects of two levels of PEEP in ALI and ARDS participants who were intubated and mechanically ventilated in intensive care for at least 24 hours.
DATA COLLECTION AND ANALYSIS: Two review authors assessed the trial quality and extracted data independently. We contacted investigators to identify additional published and unpublished studies. 
MAIN RESULTS: We included seven studies that compared high versus low levels of PEEP (2565 participants). In five of the studies (2417 participants), a comparison was made between high and low levels of PEEP with the same tidal volume in both groups, but in the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. We saw evidence of risk of bias in three studies, and the remaining studies fulfilled all criteria for adequate trial quality.In the main analysis, we assessed mortality occurring before hospital discharge only in those studies that compared high versus low PEEP with the same tidal volume in both groups. With the three studies that were included, the meta-analysis revealed no statistically significant differences between the two groups (relative risk (RR) 0.90, 95% confidence interval (CI) 0.81 to 1.01), nor was any statistically significant difference seen in the risk of barotrauma (RR 0.97, 95% CI 0.66 to 1.42). Oxygenation was improved in the high-PEEP group, although data derived from the studies showed a considerable degree of statistical heterogeneity. The number of ventilator-free days showed no significant difference between the two groups. Available data were insufficient to allow pooling of length of stay in the intensive care unit (ICU). The subgroup of participants with ARDS showed decreased mortality in the ICU, although it must be noted that in two of the three included studies, the authors used a protective ventilatory strategy involving a low tidal volume and high levels of PEEP.
AUTHORS' CONCLUSIONS: Available evidence indicates that high levels of PEEP, as compared with low levels, did not reduce mortality before hospital discharge. The data also show that high levels of PEEP produced no significant difference in the risk of barotrauma, but rather improved participants' oxygenation to the first, third, and seventh days. This review indicates that the included studies were characterized by clinical heterogeneity.  

PMID 23740697  Cochrane Database Syst Rev. 2013 Jun 6;(6):CD009098. do・・・
著者: F M Hasan, T A Beller, R E Sobonya, N Heller, G W Brown
雑誌名: J Appl Physiol Respir Environ Exerc Physiol. 1982 Jan;52(1):147-54.
Abstract/Text Positive end-expiratory pressure (PEEP), by increasing lung volume in acute lung injury, may recruit terminal air spaces in the involved regions, but may also distend noninvolved regions increasing extravascular lung water and worsening gas exchange. We investigated the effect of increasing levels of PEEP on arterial oxygenation in 26 anesthesized dogs with unilateral acid pneumonitis and studied the influences of gravity and distribution of the injury on this effect. Arterial PO2 was consistently higher when the noninjured lung was dependent than in the supine or injured lung-dependent positions. Low levels of PEEP (5, 10 cmH2O) improved arterial oxygenation and reduced intrapulmonary physiological shunt. However, 15 cmH2O PEEP resulted in worsening of gas exchange, increased dead space ventilation, and diminished static compliance. The adverse effects of high levels of PEEP on arterial oxygenation were similar whether the injured lung was dependent or not and were evident a lower levels of PEEP in one group of dogs in which the unilateral injury was more diffuse and in which the upper and middle lobes were also involved. Thus, the compressive effects of high levels of PEEP on alveolar capillaries in the noninjured lung are influenced by the extent and distribution of injury in the injured lung, but not by local forces governing regional blood flow distribution.

PMID 7037709  J Appl Physiol Respir Environ Exerc Physiol. 1982 Jan;5・・・
著者: Alejandro Bruhn, Glenn Hernandez, Guillermo Bugedo, Luis Castillo
雑誌名: Crit Care. 2004 Oct;8(5):R306-11. doi: 10.1186/cc2905. Epub 2004 Jul 15.
Abstract/Text INTRODUCTION: Positive end-expiratory pressure (PEEP) improves oxygenation and can prevent ventilator-induced lung injury in patients with acute respiratory distress syndrome (ARDS). Nevertheless, PEEP can also induce detrimental effects by its influence on the cardiovascular system. The purpose of this study was to assess the effects of PEEP on gastric mucosal perfusion while applying a protective ventilatory strategy in patients with ARDS.
METHODS: Eight patients were included. A pressure-volume curve was traced and ideal PEEP, defined as lower inflection point + 2 cmH2O, was determined. Gastric tonometry was measured continuously (Tonocap). After baseline measurements, 10, 15 and 20 cmH2O PEEP and ideal PEEP were applied for 30 min each. By the end of each period, hemodynamic, CO2 gap (gastric minus arterial partial pressures), and ventilatory measurements were performed.
RESULTS: PEEP had no effect on CO2 gap (median [range], baseline: 19 [2-30] mmHg; PEEP 10: 19 [0-40] mmHg; PEEP 15: 18 [0-39] mmHg; PEEP 20: 17 [4-39] mmHg; ideal PEEP: 19 [9-39] mmHg; P = 0.18). Cardiac index also remained unchanged (baseline: 4.6 [2.5-6.3] l min(-1) m(-2); PEEP 10: 4.5 [2.5-6.9] l min(-1) m(-2); PEEP 15: 4.3 [2-6.8] l min(-1) m(-2); PEEP 20: 4.7 [2.4-6.2] l min(-1) m(-2); ideal PEEP: 5.1 [2.1-6.3] l min(-1) m(-2); P = 0.08). One patient did not complete the protocol because of hypotension.
CONCLUSION: PEEP of 10-20 cmH2O does not affect gastric mucosal perfusion and is hemodynamically well tolerated in most patients with ARDS, including those receiving adrenergic drugs.

PMID 15469573  Crit Care. 2004 Oct;8(5):R306-11. doi: 10.1186/cc2905. ・・・
著者: S H Rappaport, R Shpiner, G Yoshihara, J Wright, P Chang, E Abraham
雑誌名: Crit Care Med. 1994 Jan;22(1):22-32.
Abstract/Text OBJECTIVE: Volume-controlled ventilation is frequently chosen as the initial mode of ventilatory support in patients with hypoxic respiratory failure. Recent data, however, suggest that pressure-limited ventilation, using a rapidly decelerating flow delivery pattern, may produce a more desirable clinical effect through reduced peak airway pressures and increased static compliance, tissue oxygen delivery, and consumption. This study was performed to assess the feasibility and utility of early and sustained use of pressure-limited ventilation in patients with this clinical syndrome.
DESIGN: Randomized, prospective trial.
SETTING: Medical intensive care unit (ICU) of a university hospital.
PATIENTS: The study encompassed all patients (n = 27) receiving care in a medical ICU for acute, severe hypoxic respiratory failure (PaO2/FIO2 ratio of < 150) during a 6-month period.
INTERVENTIONS: Ventilatory support via either pressure-limited or volume-controlled ventilation, initiated within 24 hrs of endotracheal intubation.
MEASUREMENTS: On-line monitoring of the following ten ventilatory variables at 1-min intervals for 72 hrs or until extubation or death (maximum of 43,200 data points per patient): peak airway pressure, mean airway pressure, end-tidal CO2 concentration, CO2 minute excretion, inspiratory tidal volume, expiratory tidal volume, pause pressure, end-expiratory pressure, static thoracic compliance, and inspiratory resistance. Additionally, PaO2/FIO2 values and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on a daily basis, as were significant clinical events and changes in ventilator settings.
RESULTS: Although the severity of illness at study entry as determined by APACHE II score and PaO2/FIO2 was similar in patients treated with pressure-limited or volume-controlled ventilation, peak airway pressure was consistently lower in patients randomized to pressure-limited ventilation (p = .05 at 12 hrs postintubation). The use of pressure-limited ventilation also was associated with a more rapid increase in static compliance (p = .05) than that found with volume-controlled ventilation. There was a trend toward more rapid normalization of CO2 minute excretion in patients treated with pressure-limited ventilation. Pressure-limited treated patients who survived their illness and were extubated, required fewer days of mechanical ventilation than did patients randomized to volume-controlled treated ventilation (p = .05). No pneumothoraces occurred in any study patients. One volume-controlled patient developed subcutaneous emphysema. Pressure-limited ventilation was well tolerated, and sedation requirements were equivalent in the two groups.
CONCLUSIONS: Pressure-limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure. Because the early initiation of pressure-limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume-controlled ventilation, pressure-limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition.

PMID 8124968  Crit Care Med. 1994 Jan;22(1):22-32.
著者: Maura Prella, François Feihl, Guido Domenighetti
雑誌名: Chest. 2002 Oct;122(4):1382-8.
Abstract/Text STUDY OBJECTIVES: The potential clinical benefits of pressure-controlled ventilation (PCV) over volume-controlled ventilation (VCV) in patients with acute lung injury (ALI) or ARDS still remain debated. We compared PCV with VCV in patients with ALI/ARDS with respect to the following physiologic end points: (1) gas exchange and airway pressures, and (2) CT scan intrapulmonary gas distribution at end-expiration.
DESIGN: Prospective, observational study.
SETTING: A multidisciplinary ICU in a nonuniversity, acute-care hospital.
PATIENTS: Ten patients with ALI or ARDS (9 men and 1 woman; age range, 17 to 80 years).
INTERVENTIONS: Sequential ventilation in PCV and VCV with a constant inspiratory/expiratory ratio, tidal volume, respiratory rate, and total positive end-expiratory pressure; measurement of gas exchange and airway pressures; and achievement of CT sections at lung base, hilum, and apex for the quantitative analysis of lung densities and of aerated vs nonaerated zones.
RESULTS: PaO(2), PaCO(2), and PaO(2)/fraction of inspired oxygen ratio levels did not differ between PCV and VCV. Peak airway pressure (Ppeak) was significantly lower in PCV compared with VCV (26 +/- 2 cm H(2)O vs 31 +/- 2 cm H(2)O; p < 0.001; mean +/- SEM). The surface areas of the nonaerated zones as well as the total areas at each section level were unchanged in PCV compared with VCV, except at the apex level, where there was a significantly greater nonaerated area in VCV (11 +/- 2 cm(2) vs 9 +/- 2 cm(2); p < 0.05). The total mean CT number of each lung (20 lungs from 10 patients) was similar in the two modes, as were the density values at the basal and apical levels; the hilum mean CT number was - 442 +/- 28 Hounsfield units (HU) in VCV and - 430 +/- 26 HU in PCV (p < 0.005).
CONCLUSIONS: These data show that PCV allows the generation of lower Ppeaks through the precise titration of the lung distending pressure, and might be applied to avoid regional overdistension by means of a more homogeneous gas distribution.

PMID 12377869  Chest. 2002 Oct;122(4):1382-8.
著者: C Imsand, F Feihl, C Perret, J W Fitting
雑誌名: Anesthesiology. 1994 Jan;80(1):13-22.
Abstract/Text BACKGROUND: In synchronized intermittent mandatory ventilation, it is generally accepted that the work of the inspiratory muscles is decreased by the ventilator so that their activity can be modulated by the frequency of assisted breaths. We examined the validity of this concept, which recently has been questioned.
METHODS: We studied five patients receiving synchronized intermittent mandatory ventilation because of an acute exacerbation of chronic obstructive pulmonary disease. The level of machine assistance, defined as the percentage of total ventilation delivered by the ventilator, was varied from a high (> 60%) to a medium (20-50%) and to the lowest tolerated value (0% in four patients). Esophageal pressure, air flow, and the electromyograms of the diaphragm and sternocleidomastoid muscles were recorded. At each level of machine assistance, distinguishing assisted from spontaneous breaths, the duration of electrical activation, the integrated electromyograms, and the work of breathing were computed.
RESULTS: The durations of electrical activation and the integrated electromyograms of the diaphragm and sternocleidomastoid were similar in successive spontaneous and assisted breaths. At > 60% of machine assistance, the cumulative values per minute of the integrated electromyograms of the diaphragm and sternocleidomastoid and the work of breathing were reduced only by 38, 32, and 44%, respectively, compared with the lowest tolerated level of machine assistance. The durations of electrical activation did not change with increasing level of machine assistance.
CONCLUSIONS: The degree of inspiratory muscle rest achieved by synchronized intermittent mandatory ventilation is not proportional to the level of machine assistance; furthermore, the inspiratory motor output is not regulated breath by breath but rather is constant for a given level of machine assistance.

PMID 8291702  Anesthesiology. 1994 Jan;80(1):13-22.
著者: L Brochard, A Rauss, S Benito, G Conti, J Mancebo, N Rekik, A Gasparetto, F Lemaire
雑誌名: Am J Respir Crit Care Med. 1994 Oct;150(4):896-903. doi: 10.1164/ajrccm.150.4.7921460.
Abstract/Text Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients who met standard weaning criteria. Those who could not sustain 2 h of spontaneous breathing were randomly assigned to be weaned with T-piece trials, with synchronized intermittent mandatory ventilation (SIMV), or with pressure support ventilation (PSV). Specific criteria for performing tracheal extubation were defined for each modality. The number of patients who could not be separated from the ventilator at 21 d (i.e., who failed to wean) was compared between the groups. Patients in whom tracheal intubation was required in a 48-h period following extubation were also classified as failures. Among 456 mechanically ventilated patients who met weaning criteria, 109 entered into the study (35 with T piece, 43 with SIMV, and 31 with PSV). The three groups were comparable in terms of etiology of disease or characteristics at entry in the study. When all causes for weaning failure were considered, a lower number of failures was found with PSV than with the other two modes, with the difference just reaching the level of significance (23% for PSV, 43% for T piece, 42% for SIMV; p = 0.05). After excluding patients whose weaning was terminated for complications unrelated to the weaning process, the difference became highly significant (8% for PSV versus 33% and 39%, p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 7921460  Am J Respir Crit Care Med. 1994 Oct;150(4):896-903. doi・・・
著者:
雑誌名: N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
Abstract/Text BACKGROUND: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients.
METHODS: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28.
RESULTS: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively.
CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.

PMID 10793162  N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/N・・・
著者: Christian Putensen, Nils Theuerkauf, Jörg Zinserling, Hermann Wrigge, Paolo Pelosi
雑誌名: Ann Intern Med. 2009 Oct 20;151(8):566-76.
Abstract/Text BACKGROUND: Trials have provided conflicting results regarding the effect of different ventilatory strategies on the outcomes of patients with the acute respiratory distress syndrome (ARDS) and acute lung injury.
PURPOSE: To determine whether ventilation with low tidal volume (Vt) and limited airway pressure or higher positive end-expiratory pressure (PEEP) improves outcomes for patients with ARDS or acute lung injury.
DATA SOURCES: Multiple computerized databases (through March 2009), reference lists of identified articles, and queries of principal investigators. No language restrictions were applied.
STUDY SELECTION: Randomized, controlled trials (RCTs) reporting mortality and comparing lower versus higher Vt ventilation, lower versus higher PEEP, or a combination of both in adults with ARDS or acute lung injury.
DATA EXTRACTION: Using a standard protocol, 2 reviewer teams assessed trial eligibility and abstracted data on quality of study design and conduct, population characteristics, intervention, co-interventions, and confounding variables.
DATA SYNTHESIS: 4 RCTs tested lower versus higher Vt ventilation at similar PEEP in 1149 patients, 3 RCTs compared lower versus higher PEEP at low Vt ventilation in 2299 patients, and 2 RCTs compared a combination of higher Vt and lower PEEP ventilation versus lower Vt and higher PEEP ventilation in 148 patients. Lower Vt ventilation reduced hospital mortality (odds ratio, 0.75 [95% CI, 0.58 to 0.96]; P = 0.02) compared with higher Vt ventilation at similar PEEP. Higher PEEP did not reduce hospital mortality (odds ratio, 0.86 [CI, 0.72 to 1.02]; P = 0.08) compared with lower PEEP using low Vt ventilation. Higher PEEP reduced the need for rescue therapy to prevent life-threatening hypoxemia (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) and death (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) in patients receiving rescue therapies.
LIMITATIONS: Pooling according to similar ventilatory strategies resulted in few RCTs analyzed in each group. The benefit of low Vt is derived from only 1 study.
CONCLUSION: Available evidence from a limited number of RCTs shows better outcomes with routine use of low Vt but not high PEEP ventilation in unselected patients with ARDS or acute lung injury. High PEEP may help to prevent life-threatening hypoxemia in selected patients.

PMID 19841457  Ann Intern Med. 2009 Oct 20;151(8):566-76.
著者: Nicola Petrucci, Carlo De Feo
雑誌名: Cochrane Database Syst Rev. 2013 Feb 28;(2):CD003844. doi: 10.1002/14651858.CD003844.pub4. Epub 2013 Feb 28.
Abstract/Text 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. This systematic review is an update of a Cochrane review originally published in 2003 and updated in 2007.
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 METHODS: In our previous 2007 updated review, we searched databases from inception until 2006. In this third updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and the Web of Science from 2006 to September 2012. We also updated our search of databases of ongoing research and of reference lists from 2006 to September 2012.
SELECTION CRITERIA: We included randomized controlled trials comparing ventilation using either a lower tidal volume (Vt) or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in a tidal volume of 7 ml/kg or less, versus ventilation that used Vt in the range of 10 to 15 ml/kg in adults (16 years old or older) with acute respiratory distress syndrome and acute lung injury.
DATA COLLECTION AND ANALYSIS: We independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. We applied fixed-effect and random-effects models.
MAIN RESULTS: We did not find any new study which were eligible for inclusion in this update. The total number of studies remained unchanged, six trials involving 1297 patients. Five trials had a low risk of bias. One trial had an unclear risk of bias. Mortality at day 28 was significantly reduced by lung-protective ventilation with a relative risk (RR) of 0.74 (95% confidence interval (CI) 0.61 to 0.88); hospital mortality was reduced with a RR of 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 the control group was used (RR 1.13, 95% CI 0.88 to 1.45). There was insufficient evidence for 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, makes the interpretation of the combined results difficult. Mortality was significantly reduced at day 28 and at the end of the hospital stay. The effects on long-term mortality are unknown, although the possibility of a clinically relevant benefit cannot be excluded. Ventilation with lower tidal volumes is becoming a routine strategy of treatment of acute respiratory distress syndrome and acute lung injury, stopping investigators from carrying out additional trials.

PMID 23450544  Cochrane Database Syst Rev. 2013 Feb 28;(2):CD003844. d・・・
著者: D Dreyfuss, P Soler, G Basset, G Saumon
雑誌名: Am Rev Respir Dis. 1988 May;137(5):1159-64. doi: 10.1164/ajrccm/137.5.1159.
Abstract/Text The respective roles of high pressure and high tidal volume to promote high airway pressure pulmonary edema are unclear. Positive end-expiratory pressure (PEEP) was shown to reduce lung water content in this type of edema, but its possible effects on cellular lesions were not documented. We compared the consequences of normal tidal volume ventilation in mechanically ventilated rats at a high airway pressure (HiP-LoV) with those of high tidal volume ventilation at a high (HiP-HiV) or low (LoP-HiV) airway pressure and the effects of PEEP (10 cm H2O) on both edema and lung ultrastructure. Pulmonary edema was assessed by extravascular lung water content and microvascular permeability by the drug lung weight and the distribution space of 125I-labeled albumin. HiP-LoV rat lungs were not different from those of controls (7 cm H2O peak pressure ventilation). By contrast, the lungs from the groups submitted to high volume ventilation had significant permeability type edema. This edema was more pronounced in LoP-HiV rats. It was markedly reduced by PEEP, which, in addition, preserved the normal ultrastructural aspect of the alveolar epithelium. This was in striking contrast to the diffuse alveolar damage usually encountered in this type of edema. To our knowledge, this constitutes the first example of a protective effect of PEEP during permeability edema.

PMID 3057957  Am Rev Respir Dis. 1988 May;137(5):1159-64. doi: 10.116・・・
著者: Elke Muench, Christian Bauhuf, Harry Roth, Peter Horn, Marc Phillips, Natali Marquetant, Michael Quintel, Peter Vajkoczy
雑誌名: Crit Care Med. 2005 Oct;33(10):2367-72.
Abstract/Text OBJECTIVE: Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables.
DESIGN: Animal research and clinical intervention study.
SETTING: Surgical intensive care unit of a university hospital.
SUBJECTS AND PATIENTS: Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage.
INTERVENTIONS: Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part.
MEASUREMENTS AND MAIN RESULTS: In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values.
CONCLUSIONS: Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.

PMID 16215394  Crit Care Med. 2005 Oct;33(10):2367-72.
著者: D Georgiadis, S Schwarz, R W Baumgartner, R Veltkamp, S Schwab
雑誌名: Stroke. 2001 Sep;32(9):2088-92.
Abstract/Text BACKGROUND AND PURPOSE: We undertook this study to evaluate the influence of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with acute stroke.
METHODS: A total of 20 ventilated patients of a neurological intensive care unit were examined under a protocol entailing variation of PEEP to 4, 8, 12, and 4 mm Hg; mean arterial blood pressure (MAP), ICP, heart rate, and mean velocity of the middle cerebral arteries (V(m) MCA) were recorded.
RESULTS: CPP significantly changed depending on the various PEEP levels. No significant differences in remaining parameters were evident. Three distinct reaction patterns of the parameters monitored were observed: (1) All parameters remained stable through the various PEEP levels (15 patients, 40 examinations). (2) Increase in PEEP resulted in a significant decrease of MAP, while V(m) MCA remained unchanged, indicating an intact cerebral autoregulation. A slight (statistically insignificant) increase in ICP, which was significantly related to the MAP changes, was evident (7 patients, 16 examinations). (3) Increase in PEEP resulted in a decrease of MAP and V(m) MCA; ICP remained unchanged or demonstrated a slight decline (3 patients, 6 examinations).
CONCLUSIONS: PEEP increase up to 12 mm Hg does not significantly influence ICP. The observed marked changes in CPP are mediated through the MAP. Thus, PEEP application should be safe, provided that MAP is maintained.

PMID 11546901  Stroke. 2001 Sep;32(9):2088-92.
著者: Toan Huynh, Marcia Messer, Ronald F Sing, William Miles, David G Jacobs, Michael H Thomason
雑誌名: J Trauma. 2002 Sep;53(3):488-92; discussion 492-3. doi: 10.1097/01.TA.0000025657.37314.2F.
Abstract/Text BACKGROUND: Optimizing intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is important in the management of severe traumatic brain injury (TBI). In trauma patients with TBI and respiratory dysfunction, positive end-expiratory pressure (PEEP) is often required to support oxygenation. Increases in PEEP may lead to reduced CPP. We hypothesized that increases in PEEP are associated with compromised hemodynamics and altered cerebral perfusion.
METHODS: Twenty patients (mean Injury Severity Score of 28) with TBI (Glasgow Coma Scale score < 8) were examined. All required simultaneous ICP and hemodynamic monitoring. Data were categorized on the basis of PEEP levels. Variables included central venous pressure, pulmonary artery occlusion pressure, cardiac index, oxygen delivery, and oxygen consumption indices. Differences were assessed using Kruskal-Wallis analysis of variance.
RESULTS: Data were expressed as mean +/- SE. As PEEP increased from 0 to 5, to 6 to 10 and 11 to 15 cm H O, ICP decreased from 14.7 +/- 0.2 to 13.6 +/- 0.2 and 13.1 +/- 0.3 mm Hg, respectively. Concurrently, CPP improved from 77.5 +/- 0.3 to 80.1 +/- 0.5 and 78.9 +/- 0.7 mm Hg. As central venous pressure (5.9 +/- 0.1, 8.3 +/- 0.2, and 12.0 +/- 0.3 mm Hg) and pulmonary artery occlusion pressure (8.3 +/- 0.2, 11.6 +/- 0.4, and 15.6 +/- 0.4 mm Hg) increased with rising levels of PEEP, cardiac index, oxygen delivery, and oxygen consumption indices remained unaffected. Overall mortality was 30%.
CONCLUSION: In trauma patients with severe TBI, the strategy of increasing PEEP to optimize oxygenation is not associated with reduced cerebral perfusion or compromised oxygen transport.

PMID 12352486  J Trauma. 2002 Sep;53(3):488-92; discussion 492-3. doi:・・・
著者: Daniel Talmor, Todd Sarge, Atul Malhotra, Carl R O'Donnell, Ray Ritz, Alan Lisbon, Victor Novack, Stephen H Loring
雑誌名: N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.1056/NEJMoa0708638. Epub 2008 Nov 11.
Abstract/Text BACKGROUND: Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention.
METHODS: We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes.
RESULTS: The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance).
CONCLUSIONS: As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

2008 Massachusetts Medical Society
PMID 19001507  N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.105・・・
著者: Jeremy R Beitler, Todd Sarge, Valerie M Banner-Goodspeed, Michelle N Gong, Deborah Cook, Victor Novack, Stephen H Loring, Daniel Talmor, EPVent-2 Study Group
雑誌名: JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555.
Abstract/Text Importance: Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS).
Objective: To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS.
Design, Setting, and Participants: Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018.
Interventions: Participants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes.
Main Outcomes and Measures: The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy.
Results: Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2.
Conclusions and Relevance: Among patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS.
Trial Registration: ClinicalTrials.gov Identifier NCT01681225.

PMID 30776290  JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019・・・
著者: Laurent Papazian, Jean-Marie Forel, Arnaud Gacouin, Christine Penot-Ragon, Gilles Perrin, Anderson Loundou, Samir Jaber, Jean-Michel Arnal, Didier Perez, Jean-Marie Seghboyan, Jean-Michel Constantin, Pierre Courant, Jean-Yves Lefrant, Claude Guérin, Gwenaël Prat, Sophie Morange, Antoine Roch, ACURASYS Study Investigators
雑誌名: N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.
Abstract/Text BACKGROUND: In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS.
METHODS: In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model.
RESULTS: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups.
CONCLUSIONS: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

PMID 20843245  N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056・・・

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