In the present study, we investigated the predictors of poor neurologic outcomes and optimal MAP target for patients who underwent ECPR. The major findings were as follows: First, significant variables of the risk prediction model for poor neurological outcomes by ensemble algorithms for machine learning and multiple logistic regression included the old age, GCS on ICU admission, CPR duration, and average MAPs. Second, six models were composed by ensemble algorithms and logistic regression according to specific times. There were no significant differences in the predictive performances of poor neurological outcomes between each model. Therefore, it is proposed that observing a patient’s MAP during the first 6 hrs after ECPR might not be substandard to predict the ECPR patient’s neurologic outcomes than observing it during 96 hrs. Third, the patients with average MAP around 75 mmHg demonstrated the least probability of poor neurologic outcomes in all the models. However, those with average MAPs below 60 mmHg had a high probability of poor neurological outcomes. Based on an increase in average MAP, the risk of poor neurological outcomes tended to increase in patients with average MAP greater than 75 mmHg.
The current guideline only recommends circumvention and immediate correction of hypotension, such as systolic blood pressure less than 90 mmHg or MAP less than 65 mmHg, during post-cardiac arrest care [6, 7]. However, it is not clear whether only avoiding hypotension is the best treatment for a favorable neurological prognosis. Usually, the cerebral autoregulation curve can shift to the right in survivors with preserved autoregulation after cardiac arrest . Therefore, MAP should be maintained at a higher level than generally accepted to ensure cerebral perfusion to adapt to altered cerebral autoregulation after cardiac arrest . In deed, several studies on survivors after conventional CPR reported favorable neurologic outcomes with higher blood pressure than that of recommended current guidelines [4, 9, 18–20]. In addition, MAP higher than 65 mmHg was also identified to be associated with favorable neurologic outcomes in the studies that employed neuro-monitoring devices [5, 21]. A recent publication identified the optimal MAP as 89 mmHg in post-cardiac arrest survivors using near-infrared spectroscopy . Another pilot study using brain tissue regional saturation of oxygen revealed the mean optimal MAP to be 76 mmHg . In the present study, the ECPR survivors with an average MAP of 75 mmHg demonstrated the least probability of poor neurologic outcomes.
However, the association between extremely high MAP and favorable neurological outcomes in survivors after ECPR remains unclear. In this study, some patients with extremely high MAPs over 100 mmHg had poor neurological outcomes. We hypothesized two reasons for the poor outcomes in survivors with high MAPs. First, high MAPs may be associated with significant bleeding complications such as intracerebral hemorrhage in survivors with anticoagulation or coagulation abnormality due to the use of ECMO. Second, when cerebral autoregulation is impaired, high MAPs may increase CBF and ICP. Therefore, high MAPs may exacerbate cerebral edema in survivors after ECPR . However, in this study, routine brain imaging or brain perfusion scans could not be performed in all the survivors with MAPs over 100 mmHg due to the risk of complications from intra-hospital transport during ECMO support.
The results showed that according to an increase in the average MAP, the risk of poor neurological outcomes tended to increase in patients with an average MAP over 75 mmHg. During the early short duration of MAP measurements, the risk of poor neurological outcomes tended to increase when the average MAP was greater than 75 mmHg. However, this tendency was not obvious in the long duration of MAP measurement. Since a small number of the patients had high average MAP after ECPR, the spline curve could respond sensitively to a few events. The patterns of covariate-adjusted curves were also similar to those of spline curves. Although the risk of poor neurological outcomes tended to increase in patients with average MAPs over 75 mmHg, it was not obvious whether average MAP over 75 mmHg was statistically associated with poor neurological outcomes in this study.
To prevent secondary cerebral injury, which is the additive cerebral injury characterized by an imbalance between post-resuscitation cerebral oxygen delivery and use, proper oxygen delivery with optimal CBF is important in survivors after ECPR . At an early stage, maintenance of proper blood pressure is important to secure CBF and to prevent secondary cerebral injury in the patients. Previous publications revealed the association between neurologic outcomes and MAP during the first 6 hrs from CPR [4, 9, 20, 23]. In this study, average MAP during the initial 6 hrs was also identified to be associated with neurological outcomes in patients after ECPR. In addition, it is hypothesized that the predicted value of average MAP during the initial 6 hrs might not be substandard to those of 12, 24, 48, 72, and 96 hrs. Therefore, secondary brain injury at an early stage may be significantly associated with neurological outcomes in survivors after ECPR.
This study has several limitations. First, this was a retrospective review; thus, the CPC score was determined based on medical records. Second, this study was conducted over a long time at a single institution. During that time, post-cardiac arrest care might have been more advanced than in the past, which might have affected patient’s outcomes during the study period. Third, the effects of continuous ECMO flow on cerebral autoregulation were unknown in this study. Lastly, this study lacks a tool on an external validation cohort to overcome the possible limitations of the external validation of our model.