Unlocking the brain-lung dialogue key to future treatments for critical care patients

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.May 29 2023

Previous research has highlighted the importance of brain-lung interaction in critically unwell individuals. However, further investigation is needed to understand the pathophysiological linkages between the lungs and brain to develop neuroprotective-type ventilatory treatments for individuals with acute brain injury (ABI), provide advice on conflicting therapies for individuals with concomitant lung and brain injury, and increase predictive modeling efforts to improve tracheostomy and extubation decisions.

In a recent editorial published in the journal BMC Pulmonary Medicine, researchers review evidence on the crosstalk between the lung and brain and identified potential areas for further research.

Study: Brain-lung crosstalk: how should we manage the breathing brain? Image Credit: Prapat Aowsakorn / Shutterstock.com

How do the lungs and brain interact?

ABI can precipitate lung injury and modulate pulmonary physiology through several mechanisms, including elevated intracranial pressure (ICP), systemic inflammatory response, hormonal dysregulation, catecholamine surges, and dysregulated central breathing control.

Additionally, arterial blood gas derangements and systemic inflammation can precipitate secondary brain injury. Long-standing cognitive deficits and mood disorders occur frequently after acute respiratory distress syndrome (ARDS).

One phase II randomized controlled trial (RCT) showed that a strategy based on continuous brain tissue oxygen (PbtO₂) and ICP led to less cerebral hypoxia and fewer deaths among individuals suffering from severe trauma to the brain. As a driver of blood flow to the brain, the partial pressure of carbon dioxide (PaCO₂) is essential in ABI. Researchers have also investigated different ventilator variables and their associations with ABI results.

ARDS is frequently reported among critically ill ABI patients and can result in adverse consequences. However, ARDS investigations have excluded individuals with neurological illnesses, notably those with increased ICP. The risk of ICP increases due to pulmonary protective ventilation, prone position (PP), or increased positive end-expiratory pressure (PEEP) levels among individuals with ARDS and ABI.

According to recent research, protective lung ventilation was used more frequently in ABI between 2004 and 2016. Nevertheless, only 53% of clinicians utilized 4.0-6.0 ml/kg of predicted body weight (PBW) for ABI patients with a partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio less than 150.

One recent RCT reported no significant impact of protective lung ventilation on brain self-regulation and ICP levels in most patients. However, 22% required protocol interruptions due to prolonged ICP rises.

Several studies assessing the impact of positive end-expiratory pressure on ICP have yielded conflicting results. For example, some studies have reported that cerebral perfusion pressure (CPP) and ICP are mediated by PEEP-based reductions in average arterial pressure and cardiac output. Comparatively, other studies reported that PEEP-mediated ICP increases tend to occur among individuals with poor pulmonary conformity.

In addition, the recently published SETPOINT-2 multicenter RCT among mixed stroke individuals reported no significant benefits of performing tracheostomy in the initial five days. Notably, 22 individuals who underwent tracheostomy in the later period could wean from mechanical ventilators and did not need tracheostomy placements.

Future perspectives on the brain-lung crosstalk

ABI patients comprise 25% of individuals requiring MV. However, there is scarce evidence to guide ventilatory targets in this population.

Cerebral and pulmonary pathophysiology are intimately connected through complex and often bi-directional pathways that remain unclear. Different arterial blood gas targets may be needed in some patients to minimize secondary ischemic brain injury, optimize ICP, or enhance cerebral perfusion.

A recent European Society of Intensive Care Medicine (ESICM) consensus statement acknowledges uncertainties and the paucity of evidence regarding ventilator targets and parameters for patients with ABI. Optimal PaO₂ and PaCO₂ ranges remain to be determined for ABI patients. The potential benefits of targeting therapeutic PaCO₂ ranges in specific ABI subpopulations must be studied.

Given their impaired airway defenses and decreased degree of consciousness, ABI patients frequently need to be mechanically ventilated. Thus, further prognostic clarification is required to inform tracheostomy and extubation decisions.

The recent prospective-design ENIO trial reported a 19% failure rate for extubation within five days; however, the low precision of the score indicates that correctly forecasting extubation success remains a challenge. The indications and optimal timing for tracheostomy placement continue to be debatable.

Conclusions

The editorial highlights lung-brain interactions and identifies important areas for further research. Additional studies are needed to emphasize novel findings on the pathophysiological lung-brain interplay, inform MV techniques in ABI, aid in assessing the lung-brain dispute, and enhance predictive models used to guide tracheostomy and extubation decisions.