Brain tissue oxygenation guided therapy and outcome in non-traumatic subarachnoid hemorrhage

Brain hypoxia can occur after non-traumatic subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO2) can be measured as a part of a neurological multimodal neuromonitoring. Low PbtO2 has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO2 guided-therapy on patients’ outcome. This single-center cohort study (June 2014–March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO2-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO2 and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO2-guided therapy (OR 0.33 [CI 95% 0.12–0.89]) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. In this cohort of SAH patients, PbtO2-guided therapy might be associated with improved long-term neurological outcome, only when compared to ICP-guided therapy.

Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post-Cardiac Arrest

Rationale: Secondary brain hypoxia portends significant mortality in ischemic brain diseases, yet our understanding of hypoxic ischemic brain injury (HIBI) pathophysiology in humans remains rudimentary. Objective: To quantify the impact of secondary brain hypoxia on injury to the neurovascular unit in patients with HIBI. Methods and Results: We conducted a prospective interventional study of invasive neuromonitoring in 18 post-cardiac arrest patients with HIBI. The partial pressures of brain tissue O 2 (PbtO 2 ) and intracranial pressure were directly measured via intra-parenchymal micro-catheters. To isolate the cerebrovascular bed, we conducted paired sampling of arterial and jugular venous bulb blood and calculated the trans-cerebral release of biomarkers of neurovascular injury and inflammation in the HIBI patients and 14 healthy volunteers for control comparisons. Ten HIBI patients exhibited secondary brain hypoxia (PbtO 2 <20mmHg), while eight exhibited brain normoxia (PbtO 2 ≥20mmHg). In the patients with secondary brain hypoxia, we observed active cerebral release of glial fibrillary acidic protein (-161[ -3695 - -75] pg/mL; P=0.0078), neurofilament light chain (-231[-370 - -11] pg/mL; P=0.010), total tau (-32[-310 - -3] pg/mL; P=0.0039), neuron specific enolase (-14890[-148813 - -3311] pg/mL; P=0.0039), and ubiquitin carboxy-terminal hydrolase L1 (-14.7[-37.7 - -4.1] pg/mL; P=0.0059) indicating de novo neuroglial injury. This injury was unrelated to the systemic global ischemic burden or cerebral endothelial injury but rather was associated with cerebral release of interleukin-6 (-10.3[-43.0 - -4.2] pg/mL; P=0.0039). No cerebral release of the aforementioned biomarkers was observed in HIBI patients with brain normoxia or the healthy volunteers. Hyperosmolar therapy in the patients with secondary brain hypoxia reduced the partial pressure of jugular venous O 2 -to-PbtO 2 gradient (39.6[34.1-51.1] vs. 32.0[24.5-39.2] mmHg; P=0.0078) and increased PbtO2 (17.0[9.1-19.7] vs. 20.2[11.9-22.7] mmHg; P=0.039) suggesting improved cerebrovascular-to-parenchymal O 2 transport. Conclusions: Secondary brain hypoxia is associated with de novo neuroglial injury and cerebral release of interleukin-6. Mitigating cerebrovascular-to-parenchymal limitations to O 2 transport is a promising therapeutic strategy for HIBI patients with secondary brain hypoxia.

Efferocytosis Mediated Modulation of Injury after Neonatal Brain Hypoxia-Ischemia

Neonatal brain hypoxia-ischemia (HI) is a leading cause of morbidity and long-term disabilities in children. While we have made significant progress in describing HI mechanisms, the limited therapies currently offered for HI treatment in the clinical setting stress the importance of discovering new targetable pathways. Efferocytosis is an immunoregulatory and homeostatic process of clearance of apoptotic cells (AC) and cellular debris, best described in the brain during neurodevelopment. The therapeutic potential of stimulating defective efferocytosis has been recognized in neurodegenerative diseases. In this review, we will explore the involvement of efferocytosis after a stroke and HI as a promising target for new HI therapies.

Brain Tissue Oxygenation Guided Therapy and Outcome in Non-Traumatic Subarachnoid Hemorrhage

Background Brain hypoxia can occur after spontaneous subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO2) can be measured as a part of a neurological multimodal neuromonitoring Low PbtO2 has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO2 guided-therapy on patients’ outcome. Methods This single-center cohort study (June 2014-March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO2-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Results Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO2 and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO2-guided therapy (OR 0.33 [CI 95% 0.12–0.90]) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. Brain hypoxia was associated with unfavorable neurological (OR 4.51 [95% CI 1.17–17.45]). Conclusions In this cohort of SAH patients, PbtO2-guided therapy when compared to ICP guided therapy may be associated with improved long-term neurological outcome.