From the Guidelines
Sepsis is the most common indirect or systemic cause of acute respiratory distress syndrome (ARDS), accounting for approximately 40% of cases, and other significant systemic causes include severe trauma, pancreatitis, massive blood transfusions, drug overdose, and systemic inflammatory response syndrome. These conditions can lead to ARDS by triggering a cascade of inflammatory responses that damage the alveolar-capillary membrane, causing increased permeability and pulmonary edema 1. The systemic inflammation results in neutrophil activation and release of inflammatory mediators like cytokines, which cause diffuse alveolar damage even when the initial insult is not directly to the lungs. Key factors that contribute to the development of ARDS in these contexts include:
- The release of inflammatory cytokines and other mediators that increase vascular permeability and attract neutrophils to the lung tissue 1
- The activation of neutrophils and other immune cells that release destructive enzymes and reactive oxygen species, further damaging lung tissue 1
- The disruption of the alveolar-capillary barrier, leading to the influx of fluid and proteins into the alveolar space, which impairs gas exchange and contributes to hypoxemia 1 Understanding these indirect pathways is crucial for early recognition and management of at-risk patients, as mortality from ARDS remains significant, with a high mortality rate of 35–45% despite advances in supportive care 1.
From the Research
Indirect or Systemic Causes of Acute Respiratory Distress Syndrome
The indirect or systemic causes of acute respiratory distress syndrome (ARDS) include:
Pathophysiology and Mechanisms
These indirect causes can lead to ARDS by initiating a systemic inflammatory response, which can cause pulmonary endothelial and epithelial damage, increased permeability, and subsequent non-cardiogenic pulmonary edema 5, 4. The underlying mechanisms involve canonical inflammatory pathways, including MAP kinases, CXCR2 chemokines, PAF, leukotrienes, adhesion molecules, and elastase 5.
Clinical Relevance
The clinical relevance of these indirect causes is significant, as they can lead to severe hypoxemia, respiratory failure, and high mortality 2, 3, 6, 4. Early identification and treatment of the underlying disorder, along with aggressive supportive care, are essential to improve outcomes in patients with ARDS 4.