The immune system can cause greater damage to the brain after cardiac arrest

Around 3,000 people are affected by sudden and unexpected cardiac arrest in Norway every year. One in four survives after resuscitation and CPR (cardiopulmonary resuscitation).

However, about half of the patients for whom resuscitation was successful, lose their lives days, weeks or months later during hospitalisation mainly because of severe brain injury.

In Norway, of the 3,000 yearly cases, only around 450 people recover.

Cardiac arrest causes great damage to the body’s cells, since the oxygen supply to all cells is dramatically reduced. Immediately after resuscitation, the innate immune system responds and tries to save as many cells as possible.

The innate immune system is the oldest part of the immune system in our body. It responds quickly, broadly and non-specifically when it detects that the body is in danger.

More damage with strong immune response

However, a new study from the University of Oslo and Oslo University Hospital shows that the innate immune system's reaction is associated with whether, and how well, cardiac arrest patients recover.

– We found that the way the innate immune system responds in patients immediately after resuscitation, is associated with how well patients are doing six months later, researcher and intensive care physician Søren Erik Pischke, who is one of the authors behind the new study, says.

A strong immune response is associated with greater damage

The new study showed a greater risk of severe brain damage, coma or death in patients who had a strong immune response in the time immediately after resuscitation.

– We have learned that the immune system reacts more strongly in some patients than in others, and that the strong reaction is associated with poorer outcomes, in the worst case death, Pischke says.

Explains why some people get serious injuries despite rapid resuscitation

The innate immune system’s response immediately after resuscitation, only affected outcomes in patients where the resuscitation was relatively rapid, i.e. between 5 and 25 minutes. If the resuscitation takes longer than this, the damage to the brain is already so dominant that the immune system's response does not play a decisive role.

– After resuscitation, brain damage is the most important factor affecting patient outcomes, since the heart itself will, in most cases, regain a stable function. We knew that if the resuscitation took a long time, the risk of brain damage was greater since the brain cannot tolerate a long time without oxygen supply from the blood, the researcher says.

What researchers and medical doctors did not know, however, is why some patients suffer major brain damage even though resuscitation was rapid.

– What we found indicates that it was the innate immune system's response that caused the brain damage in patients for whom resuscitation was rapid but who nevertheless suffered serious brain damage, Pischke explains.

Medications can prevent the immune system from doing more harm

The researchers believe that it may be possible to prevent the immune system from its devastating impact immediately after resuscitation. Inhibition of the part of the innate immune system after cardiac arrest may reduce the risk of serious injury.

– The findings mean that we should control how strongly the innate immune system responds in patients who receive treatment at the emergency and intensive care wards immediately after successful resuscitation. We can do this with the help of already approved medications, he says.

Pischke explains that he finds it important that the basic research he conducts, where he studies different phenomena at the molecular level, ultimately benefits patients. He believes that connecting his research to already existing medications, to discover new ways or areas of applying them, has great potential and value.

– The most important thing for us is that more patients survive. To achieve this, we must first demonstrate that there is a connection between different phenomena. We therefore need basic research and studies like this one, he explains, and adds:

– A clinical study should look into whether inhibition of parts of the immune system immediately after resuscitation has an effect on the patient's brain function six months later.

Pischke points out that future studies should focus on cardiac arrest patients for whom resuscitation was rapid, since it is in these patients that the innate immune system's response is associated with patients’ outcomes.

Reference:

Publication Chaban, V., Nakstad, E. R., Stær-Jensen, H., Schjalm, C., Seljeflot, I., Vaage, J., ... & Pischke, S. E. (2021). Complement activation is associated with poor outcome after out-of-hospital cardiac arrest. Resuscitation. DOI: https://doi.org/10.1016/j.resuscitation.2021.05.038

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