The POOR Get POORer: A Hypothesis for the Pathogenesis of Ventilator-induced Lung Injury

Am J Respir Crit Care Med. 2020 Oct 15;202(8):1081-1087. doi: 10.1164/rccm.202002-0453CP.

Abstract

Protective ventilation strategies for the injured lung currently revolve around the use of low Vt, ostensibly to avoid volutrauma, together with positive end-expiratory pressure to increase the fraction of open lung and reduce atelectrauma. Protective ventilation is currently applied in a one-size-fits-all manner, and although this practical approach has reduced acute respiratory distress syndrome deaths, mortality is still high and improvements are at a standstill. Furthermore, how to minimize ventilator-induced lung injury (VILI) for any given lung remains controversial and poorly understood. Here we present a hypothesis of VILI pathogenesis that potentially serves as a basis upon which minimally injurious ventilation strategies might be developed. This hypothesis is based on evidence demonstrating that VILI begins in isolated lung regions manifesting a Permeability-Originated Obstruction Response (POOR) in which alveolar leak leads to surfactant dysfunction and increases local tissue stresses. VILI progresses topographically outward from these regions in a POOR-get-POORer fashion unless steps are taken to interrupt it. We propose that interrupting the POOR-get-POORer progression of lung injury relies on two principles: 1) open the lung to minimize the presence of heterogeneity-induced stress concentrators that are focused around the regions of atelectasis, and 2) ventilate in a patient-dependent manner that minimizes the number of lung units that close during each expiration so that they are not forced to rerecruit during the subsequent inspiration. These principles appear to be borne out in both patient and animal studies in which expiration is terminated before derecruitment of lung units has enough time to occur.

Keywords: acute respiratory distress syndrome; atelectrauma; mechanical ventilation; surfactant; volutrauma.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Disease
  • Biomechanical Phenomena
  • Chronic Disease
  • Female
  • Humans
  • Male
  • Monitoring, Physiologic
  • Primary Prevention / methods*
  • Prognosis
  • Pulmonary Atelectasis / etiology
  • Pulmonary Atelectasis / prevention & control*
  • Pulmonary Edema / etiology
  • Pulmonary Edema / prevention & control*
  • Respiratory Distress Syndrome / physiopathology*
  • Respiratory Distress Syndrome / therapy
  • Respiratory Function Tests
  • Ventilator-Induced Lung Injury / physiopathology*
  • Ventilator-Induced Lung Injury / prevention & control*