Improving post-CA neurological outcomes

A recent study correlates cerebral blood flow regulation and prognosis after cardiac arrest. The finding could improve patient management and post-resuscitation care.

Self-regulation of cerebral blood flow and prognosis after cardiac arrest

Out-of-hospital cardiac arrest (OHCA) occurs in approximately 80-100 patients per 100,000 people/year worldwide. Although standardisation of the treatment of out-of-hospital cardiopulmonary arrest has progressed and efforts are being made to improve outcomes, many patients continue to suffer neurological sequelae (HIBI, Hypoxic-Ischemic Brain Injury) even after returning to spontaneous circulation.

Improving neurological outcomes is an important research topic. Hypoxic-ischemic brain injury (HIBI) begins with cardiac arrest, which causes interruption of cerebral blood flow, neuronal ischaemia and cell death. Subsequently, reperfusion injury, microcirculatory disturbances and neuronal death may occur as secondary brain damage within hours or days after the return of spontaneous circulation (ROSC).

In a recent study, a research team analysed 100 patients who suffered out-of-hospital cardiac arrest. This prospective, observational, cohort study was conducted in Japan, in northern Osaka, at a single centre affiliated with the Osaka University Graduate School of Medicine. Patient data were collected from June 2017 to May 2020. The study enrolled adult patients (age ≥18 years) who were brought to the centre with CA and subsequently reached ROSC.

Is there a relationship between post-CA CVAR and neurological outcomes?

It is well known that if brain function is maintained normally, there is a mechanism (CVAR, or cerebrovascular autoregulation) that attempts to maintain cerebral blood flow at a constant level even if systemic blood pressure changes, but until now it was unclear whether this reaction occurs in the brain after resuscitation.

The researchers sought a method to assess the presence or absence of CVAR in the brain post-resuscitation using the correlation between brain region oxygen saturation (crSO2), a measure of the balance between oxygen supply and demand in the brain, and blood pressure. They then assessed the presence or absence of CVAR in the post-resuscitation brain and its relationship with life expectancy.

According to the authors, the analysis of crSO2 changes based on the consideration of haemodynamic variables - rather than the conventional interpretation of crSO2 alone - provides a clinical index for the assessment of appropriate CVAR and blood pressure. In addition, this assessment can lead to a reliable determination of treatment effects, prognosis, and personalised treatments, establishing a new target population. Several studies have reported altered CVAR post-CA, and some studies have evaluated the association between CVAR and neurological outcome in HIBI.

CVAR was determined by calculating the Pearson's correlation coefficient (r) and continuously monitoring crSO2 and mean arterial pressure for 96 hours after return to spontaneous circulation. Assuming undetected CVAR as a bad condition for the organism, the association with life prognosis was assessed by means of a Cox Proportional-Hazards model.

A long non-CVAR period may be associated with a significant increase in mortality

CVAR was detected in all 24 patients with good neuroprognosis and in 65 (88%) of the 76 patients with poor neuroprognosis. The analysis showed that mortality increased with an also increasing non-CVAR time after ROSC. Furthermore, the neurological outcome at 6 months could worsen with increasing non-CVAR time within 96 hours after ROSC.

In this study, the effect of TTM (target temperature management) decreased with increasing non-CVAR time, as demonstrated by non-linear analysis. A significant difference in neurological outcome was observed between the non-TTM and TTM groups when non-CVAR time was between 18% and 37%.

In contrast, there might not be a significant difference in the impact on hospital mortality between the TTM and non-TTM groups for those cases where the percentage of non-CVAR time was more than 37% after ROSC. These results can be incorporated into the early management of post-CA patients to help predict outcomes. Furthermore, these results may be useful in creating a new index for post-CA management based on cerebral perfusion.

This study suggests that with increasing non-CVAR time, mortality may increase, and the effect of TTM may decrease. Future studies should test the clinical efficacy of aggressive management within ideal pressure ranges to reduce secondary disability and improve outcomes after CA.

Time-dependent changes in cerebrovascular autoregulation after CA may be crucial for neurological outcomes

The study results have two main implications. First, the ability to identify high mortality subgroups from post-resuscitation clinical data may help identify populations that should receive enhanced therapeutic intervention. In addition, it may help avoid early withdrawal of treatment in those who are likely to recover.

Second, we believe that a intensive therapeutic management that maintains adequate cerebral perfusion suggests improved life outcomes, and that the development of a systemic management approach based on cerebral perfusion may represent a breakthrough in reducing post-resuscitation neurological sequelae.

  1. Tachino J, Nonomiya Y, Taniuchi S, Shintani A, Nakao S, Takegawa R, Hirose T, Sakai T, Ohnishi M, Shimazu T, Shiozaki T. Association between time-dependent changes in cerebrovascular autoregulation after cardiac arrest and outcomes: A prospective cohort study. J Cereb Blood Flow Metab. 2023 Jun 28:271678X231185658. doi: 10.1177/0271678X231185658. Epub ahead of print. PMID: 37377095.