Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI)

<b>Rationale:</b> Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. <b>Objectives:</b> To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. <b>Methods:</b> In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. <b>Measurements and Main Results:</b> The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.79; <i>P</i> = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06-3.42; <i>P</i> = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01-2.28; <i>P</i> = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85-2.27; <i>P</i> = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. <b>Conclusions:</b> In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

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Journal
American Journal of Respiratory and Critical Care Medicine
Published
2024-09-17
DOI
https://doi.org/10.1164/rccm.202402-0375oc
Citations
33
Primary Topic
Respiratory Support and Mechanisms
Type
article
Field-Weighted Citation Impact
13.82
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article

Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI)

Claudia Filippini, Matteo Filippini, Paolo Pelosi, Frank Rasulo et al.
33 citations
American Journal of Respiratory and Critical Care Medicine
Respiratory Support and Mechanisms
13.82
article

Lung-Protective Mechanical Ventilation in Patients with Severe Acute Brain Injury: A Multicenter Randomized Clinical Trial (PROLABI)

Claudia Filippini, Matteo Filippini, Paolo Pelosi, Frank Rasulo, Francesco Alessandri, Marina Munari, Paola Rucci, Maurizio Berardino, Irene Cavalli, Tommaso Tonetti, Massimo M. Antonelli, Paolo Zanatta, Mario Mezzapesa, Anna Teresa Mazzeo, Mattia Zanin, Vito Fanelli, Massimiliano Caravello, Alice Mistretta, Luciana Mascia, Anselmo Caricato, Lucia Martina Silvestri, Marilena Casartelli Liviero, Francesca Grossi, Giuseppe Citerio, Francesco Della Corte
article en
33 citations

Abstract

<b>Rationale:</b> Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. <b>Objectives:</b> To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. <b>Methods:</b> In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency, and acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. <b>Measurements and Main Results:</b> The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.79; <i>P</i> = 0.025). Mortality was 28.9% and 15.1% (RR, 1.91; 95% CI, 1.06-3.42; <i>P</i> = 0.02), ventilator dependency was 42.3% and 27.9% (RR, 1.52; 95% CI, 1.01-2.28; <i>P</i> = 0.039), and incidence of ARDS was 30.8% and 22.1% (RR, 1.39; 95% CI, 0.85-2.27; <i>P</i> = 0.179), respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. <b>Conclusions:</b> In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

American Journal of Respiratory and Critical Care MedicineVol. 210(9)
Università Cattolica del Sacro Cuore (IT), University of Messina (IT), University of Verona (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Padua (IT), University of Salento (IT), Policlinico Umberto I (IT), Agostino Gemelli University Polyclinic (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Azienda Ospedaliera Universitaria Integrata Verona (IT), Fondazione Ricerca Molinette (IT), Ohkawara Neurosurgical Hospital (JP), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Azienda Ospedaliera San Gerardo (IT), Azienda USL di Bologna (IT), Azienda Ospedaliero Universitaria Maggiore della Carita (IT), Azienda Ospedaliera Ospedale Maggiore (IT), Ospedale Policlinico San Martino (IT), Azienda Ospedale - Università Padova (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Center Orthopedic & Neurosurgical Care & Research (US), University of Turin (IT), University of Milano-Bicocca (IT), University of Brescia (IT), University of Genoa (IT), Sapienza University of Rome (IT), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 1%
Respiratory Support and Mechanisms
13.82
DOIOpen Access PDFOpenAlex
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