diffuse alveolar damage
Last edited 11/2021 and last reviewed 09/2022
Adult respiratory distress syndrome/acute respiratory distress syndrome (ARDS) is characterised by fulminant interstitial and alveolar oedema which usually develops 12 to 48 hours after an initial trauma. It results from increased alveolar capillary permeability and is not cardiogenic in origin. Injury may occur directly or as part of a generalised systemic acute inflammatory process.
Progressive pulmonary insufficiency ensues which may be self-limiting if the patient is adequately supported without exacerbating injury to the lung. Approximately a third of patients have a residual pulmonary disability due to pulmonary fibrosis.
Some advocate that ARDS, as opposed to acute lung injury, occurs only when there is severe abnormalities in pulmonary gas exchange - defined by a PaO2:FiO2 ratio < 20 KPa.
ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma and is present in about 10% of all patients in intensive care units worldwide. Despite some improvements, mortality remains high at 30-40% in most studies (1).
Definitions of ARDS in adults
2012 Berlin definition (2)
Timing: respiratory failure within 1 week of a known insult or new and/or worsening respiratory symptoms
Origin: respiratory failure not fully explained by cardiac function or volume overload (need objective criterion such as echocardiography to exclude hydrostatic oedema if no risk factor is present)
Imaging: bilateral opacities on chest radiograph or CT not fully explained by effusion, collapse or nodules
Oxygenation: acute onset of hypoxaemia defined as PaO2/FiO2 <300 mmHg on at least PEEP 5 cmH2O*
PaO2/FiO2 of 201-300 mmHg is mild ARDS
PaO2/FiO2 of 101-200 mmHg is moderate ARDS
PaO2/FiO2 <= 100 mmHg is severe ARDS
2016 Kigali modification (3)
Timing and origin: as in the Berlin definition
Imaging: bilateral opacities on chest radiography or ultrasonography scan not fully explained by effusion, collapse or nodules
Oxygenation: SpO2/FiO2 <315; no PEEP requirement
* positive end-expiratory pressure (PEEP) may be delivered non-invasively if the criteria are in the mild category.
ARDS, acute respiratory distress syndrome; FiO2, fraction of inspired oxygen; PaO2, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure; SpO2, peripheral capillary oxygen saturation.
ARDS occurs as a consequence of an alveolar injury due to various causes producing diffuse alveolar damage
- causes the release of pro-inflammatory cytokines [tumor necrosis factor, interleukin (IL)-1, IL-6, IL-8], which recruit neutrophils to the lungs, where they get activated and release toxic mediators (reactive oxygen species and proteases) that damage the capillary endothelium and alveolar epithelium leading to alveolar edema
- leads to impairment of gas exchange, decreased lung compliance, and increased pulmonary arterial pressure.
Pathological stages (4):
- initial stage is the exudative stage, characterized by diffuse alveolar damage
- second stage of proliferation develops after approximately 10-14 days
- characterized by resolution of pulmonary edema, proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of collagen
- third stage
- some patients progress to the third stage of fibrosis, characterized by obliteration of normal lung architecture, diffuse fibrosis, and cyst formation.
- recommended therapies to decrease mortality in ARDS remain limited and include low-tidal volume mechanical ventilation, prone ventilation and recently, the ECMO (extracorporeal membrane oxygenation) rescue therapy in extreme cases (4)
- Matthay MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5(1):18. Published 2019 Mar 14. doi:10.1038/s41572-019-0069-0.
- Ranieri VM, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526-2533.
- Riviello ED, et al. Hospital incidence and outcomes of the acute respiratory distress syndrome using the Kigali Modification of the Berlin Definition. Am. J. Respir. Crit. Care Med. 2016;193:52-59. doi: 10.1164/rccm.201503-0584OC
- Rawal G, Yadav S, Kumar R. Acute Respiratory Distress Syndrome: An Update and Review. J Transl Int Med. 2018;6(2):74-77. Published 2018 Jun 26. doi:10.1515/jtim-2016-0012