TY - JOUR
T1 - Effect of Titrating Positive End-Expiratory Pressure (PEEP) with an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-F io 2 Strategy on Death and Days Free from Mechanical Ventilation among Patients with Acute Respiratory Distress Syndrome
T2 - A Randomized Clinical Trial
AU - Beitler, Jeremy R.
AU - Sarge, Todd
AU - Banner-Goodspeed, Valerie M.
AU - Gong, Michelle N.
AU - Cook, Deborah
AU - Novack, Victor
AU - Loring, Stephen H.
AU - Talmor, Daniel
N1 - Funding Information:
reported receiving support from the National Heart, Lung, and Blood Institute to conduct this trial. Ms Banner-Goodspeed reported receiving grants from the Department of Defense. Dr Gong reported receiving grants from the Agency for Healthcare and Research Quality outside the submitted work. Dr Novack reported receiving personal fees from CardioMed Consultants outside the submitted work. Dr Talmor reported receiving speaking fees and grant funds from Hamilton Medical outside the submitted work.
Funding Information:
AE Adverse Event AKI Acute Kidney Injury ALI Acute Lung Injury APACHE Acute Physiology and Chronic Health Evaluation ARDS Acute Respiratory Distress Syndrome ARDSNet Acute Respiratory Distress Syndrome Network for clinical trials BIDMC Beth Israel Deaconess Medical Center CFR Code of Federal Regulations CONSORT Consolidated Standards of Reporting Trials CPAP Continuous positive airway pressure CRF Case Report Form CTCAE Common Terminology Criteria For Adverse Events CVP Central venous pressure DSMB Data & Safety Monitoring Board ECMO Extracorporeal membrane oxygenation EDTA Ethylenediaminetetraacetic acid FiO2 Fraction of inspired oxygen GCP Good Clinical Practice HCO3 Bicarbonate HR Heart rate HSPH Harvard School of Public Health ICF Informed Consent Form ICH International Conference on Harmonization ICU Intensive Care Unit IMV Invasive mechanical ventilation INR International normalized ratio IRB Institutional Review Board ISBER International Society for Biological and Environmental Repositories ITT Intent-to-treat [analysis] LAR Legally Authorized Representative LOS Length of stay MCC Medical Coordinating Center NaHCO3 Sodium bicarbonate NCI National Cancer Institute NG Naso-gastric NHLBI National Heart, Lung and Blood Institute NIH National Institutes of Health OG Oro-gastric PaCO2 Partial pressure of carbon dioxide in arterial blood PaO2 Partial pressure of oxygen in arterial blood Paw Airway pressure PBW Predicted body weight PCL Physiology Core Laboratory PCV Pressure control ventilation
Funding Information:
AE Adverse Event AKI Acute Kidney Injury ALI Acute Lung Injury APACHE Acute Physiology and Chronic Health Evaluation ARDS Acute Respiratory Distress Syndrome ARDSNet Acute Respiratory Distress Syndrome Network for clinical trials BIDMC Beth Israel Deaconess Medical Center CFR Code of Federal Regulations CONSORT Consolidated Standards of Reporting Trials CPAP Continuous positive airway pressure CRF Case Report Form CTCAE Common Terminology Criteria For Adverse Events CVP Central venous pressure DSMB Data & Safety Monitoring Board ECMO Extracorporeal membrane oxygenation EDTA Ethylenediaminetetraacetic acid FiO2 Fraction of inspired oxygen GCP Good Clinical Practice HCO3Bicarbonate HR Heart rate HSPH Harvard School of Public Health ICF Informed Consent Form ICH International Conference on Harmonization ICU Intensive Care Unit IMV Invasive mechanical ventilation INR International normalized ratio IRB Institutional Review Board ISBER International Society for Biological and Environmental Repositories ITT Intent-to-treat [analysis] LAR Legally Authorized Representative LOS Length of stay MCC Medical Coordinating Center NaHCO3 Sodium bicarbonate NCI National Cancer Institute NG Naso-gastric NHLBI National Heart, Lung and Blood Institute NIH National Institutes of Health OG Oro-gastric PaCO2 Partial pressure of carbon dioxide in arterial blood PaO2 Partial pressure of oxygen in arterial blood Paw Airway pressure PBW Predicted body weight PCL Physiology Core Laboratory PCV Pressure control ventilation ___________________________________________________________________________________________________________ 7
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2019/3/5
Y1 - 2019/3/5
N2 - 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 (P ES ), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio 2 ) 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 (Pao 2 :Fio 2 ≤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 P ES -guided PEEP (n = 102) or empirical high PEEP-Fio 2 (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 P ES -guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P =.92). At 28 days, 33 of 102 patients (32.4%) assigned to P ES -guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio 2 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 P ES -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 P ES -guided PEEP and 5 patients with empirical PEEP-Fio 2 . Conclusions and Relevance: Among patients with moderate to severe ARDS, P ES -guided PEEP, compared with empirical high PEEP-Fio 2 , resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support P ES -guided PEEP titration in ARDS. Trial Registration: ClinicalTrials.gov Identifier NCT01681225.
AB - 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 (P ES ), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio 2 ) 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 (Pao 2 :Fio 2 ≤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 P ES -guided PEEP (n = 102) or empirical high PEEP-Fio 2 (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 P ES -guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P =.92). At 28 days, 33 of 102 patients (32.4%) assigned to P ES -guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio 2 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 P ES -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 P ES -guided PEEP and 5 patients with empirical PEEP-Fio 2 . Conclusions and Relevance: Among patients with moderate to severe ARDS, P ES -guided PEEP, compared with empirical high PEEP-Fio 2 , resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support P ES -guided PEEP titration in ARDS. Trial Registration: ClinicalTrials.gov Identifier NCT01681225.
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U2 - 10.1001/jama.2019.0555
DO - 10.1001/jama.2019.0555
M3 - Article
C2 - 30776290
AN - SCOPUS:85061571610
SN - 0098-7484
VL - 321
SP - 846
EP - 857
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 9
ER -