Pathophysiology of Cerebral Microbleeds in Patients with Severe Respiratory Failure and Acute Respiratory Distress Syndrome: A Scoping Review

Abstract: Cerebral microbleeds (CMBs) are increasingly identified in critically ill patients with severe respiratory failure and acute respiratory distress syndrome (ARDS). This scoping review aims to systematically examine the existing literature to explore the mechanisms contributing to the development of CMBs in ARDS and to summarize current evidence on CMBs associated with severe respiratory failure. We conducted a comprehensive search across two databases, PubMed and CENTRAL, and relevant study registries (PROSPERO and Clinicaltrials.gov), between February 1 and March 3, 2025. Eligible studies included those reporting on the presence of CMBs in adult patients with severe respiratory failure or ARDS, regardless of whether mechanical ventilation (MV) was used. Eighteen observational studies involving critically ill patients with respiratory failure or ARDS were included, with sample sizes ranging from 9 to 214 patients. The proposed pathophysiological mechanisms for the development of CMBs include hypoxaemia and inflammation leading to endothelial injury and blood–brain barrier (BBB) dysfunction, cerebral hypoperfusion facilitating interaction between coronavirus disease 2019 (COVID-19) and angiotensin-converting enzyme 2 (ACE2) receptors, microangiopathy with the formation of diffuse microthrombi, and renal failure contributing to uraemia-associated BBB disruption. CMBs were predominantly localized in the corpus callosum and juxtacortical white matter. The majority of patients with CMBs were mechanically ventilated and experienced a prolonged duration of ventilation. Identified risk factors for CMBs development included greater disease severity, coagulation abnormalities, and renal dysfunction. In conclusion, CMBs are increasingly recognized in critically ill patients with ARDS, particularly in the corpus callosum and juxtacortical white matter, but current evidence is associative rather than causal. Their pathophysiology likely involves compromised small vessel integrity due to hypoxia-induced endothelial injury, inflammation, and possible direct viral effects on cerebral microvasculature. These mechanisms are further exacerbated by coagulation abnormalities and disruption of the BBB. Keywords: acute respiratory distress syndrome, cerebral microbleeds, coagulation abnormalities, hypoxaemia, inflammation, lung injury, mechanical ventilation