Limitations
death
SEPARATION, SECONDARY
Our study has several limitations. The assumption for the main study (BOX) 2 × 2 factorial design was that the effects of the MAP and Oxygen interventions were independent (no interaction) in relation to the primary outcome (death or CPC 3–4). However, central factors influencing cerebral metabolism are mainly, e.g., MAP, carbon dioxide and oxygen levels. These main regulators of cerebral metabolism have the potential of important interaction, which justified the exclusion of the “restrictive” oxygen group.
The study is mainly limited by the fact that, due to established clinical routines, it was impossible to start JBM until about 3–4 h after ROSC. The clinical impact of the JBM technique should be re-evaluated when the JBM catheter is positioned within 60 min after ROSC. The blinded MAP intervention was limited to a 20% separation, because the module manufacturer did not support a larger modification without changing the module software. Based on the main BOX trial, we expected significantly higher vasopressor-doses in the high MAP group [Given the known significant limitations of INVOS monitoring to estimate meaningful cerebrovascular physiology, we were not able to state that a higher MAP did not improve brain oxygenation.
Interpretation of the biochemical patterns is based on experiences from intracerebral microdialysis. Further investigations regarding the relationship between global brain 18-FDG-PET (cerebral metabolic rate of glucose) and levels of biochemical variables in cerebral tissue and the draining venous blood are necessary. We did not measure CBF during the study periods to demonstrate coherent findings in cerebral blood flow and JBM. However, our results reflect the complex pathophysiologic mechanisms underpinning secondary brain injury, and combined JBM, CBF measurements (e.g., brain 