Neurocritical Care最新文献

Background: Delayed cerebral injury (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is a preventable injury that would improve patient outcomes if an effective treatment can be developed. The most common long-term disability in patients with SAH is cognitive dysfunction. Contrary to the common theory that damage from DCI originates solely from ischemia caused by cerebral vasospasm, inflammation has been shown to be an important independent mediator of DCI.

Methods: Neutrophil infiltration of the meninges is a critical step in developing late spatial memory deficits in a murine model of SAH and may serve as a surrogate marker for disease progression. Importantly, myeloperoxidase (MPO) null mice do not develop meningeal neutrophilia and are protected from spatial memory deficits.

Results: In this study, wildtype mice administered a single dose of the MPO inhibitor (MPOi) AZD5904 at peak neutrophil entry day have a higher percentage of neutrophils that remain in the meningeal blood vessel 6 days after the hemorrhage suggesting neutrophil extravasation into the meninges is inhibited (79 ± 20 vs. 28 ± 24, p < 0.01). Interestingly, the intraperitoneal route of administration has a larger effect than the intrathecal route suggesting that MPO inhibition is best administered systemically not in the central nervous system. Second, mice administered AZD5904 intraperitoneal for 4 consecutive days starting 2 days after the hemorrhage do not develop delayed spatial memory dysfunction (two-way analysis of variance, p > 0.001 F [2, 22] = 10.11).

Conclusions: Systemic MPOi prevents neutrophil entry into the meninges and prevents spatial memory dysfunction. MPOi is a promising strategy for translation to patients with aneurysmal SAH.

Prognostication is fundamental to determining the intensity of care offered for many critically ill patients with severe acute brain injury (SABI). Inherent uncertainties linked to predicting outcomes for patients with SABI primarily arise from a lack of complete data regarding the natural disease/injury progression that follows various forms of SABI, stemming from early withdrawal of life-sustaining treatment. This potential bias has led to limitations in using outcome data associated with clinical grading scales and a risk of perpetuating high mortality following SABI, leading to self-fulfilling prophecies. The aims of this article are to (1) review contemporary prognostication practices among clinicians for patients with SABI, (2) discuss inherent challenges in prognosticating outcomes following SABI, (3) summarize statements and guidelines from professional societies regarding SABI prognostication, and (4) identify directions for future research in prognostication after SABI.

Background: The 'CPPopt-Guided Therapy: Assessment of Target Effectiveness' (COGiTATE) randomised controlled trial demonstrated the feasibility and safety of targeting an automated cerebral perfusion pressure (CPP) tailored to optimize cerebrovascular autoregulation (CPPopt) in patients with traumatic brain injury (TBI) requiring intracranial pressure management. The average values of the autoregulation index known as the pressure reactivity index (PRx) were not different between the intervention (CPP target = CPPopt) and control (CPP target = 60-70 mmHg) groups of the trial. This secondary analysis was performed to investigate whether: (1) in the intervention group, PRx was closer to PRxopt (PRx at CPPopt) values, indicating a more preserved reactivity, as opposed to in the control group; (2) in the intervention group, patients experienced lower hourly PRx when CPP was close to the CPPopt-based target.

Methods: We analyzed data from the 28 and 32 patients randomized to the control and intervention groups of the COGiTATE study, respectively. We compared hourly averaged ΔPRx (PRx minus PRxopt, where PRxopt is PRx at CPPopt) between the two groups, focusing on periods of globally preserved/homogeneous autoregulation (negative PRxopt). For each patient in the intervention group, PRx values in periods when ΔCPP (CPP minus CPPopt target) was between -5 and + 5 mm Hg were compared to values in periods when ΔCPP was outside this range.

Results: The median ΔPRx was significantly lower in the intervention group for negative PRxopt (Mann-Whitney U-test, p < 0.001). For each patient in this group, the median PRx was lower in periods when CPP was close to the CPPopt-based target (Wilcoxon test, p < 0.001).

Conclusions: Despite no statistically significant difference in the grand mean PRx, our results suggest that targeting CPPopt does provide a way of improving cerebrovascular reactivity in patients with TBI, offering a rational intervention for trials that address this issue. We also bring insight into aspects of the PRx/CPP relationship that should be considered for autoregulation-guided management for future clinical protocols and trials design.

Despite improvements in survival after illnesses requiring extracorporeal life support, cerebral injury continues to hinder successful outcomes. Cerebral autoregulation (CA) is an innate protective mechanism that maintains constant cerebral blood flow in the face of varying systemic blood pressure. However, it is impaired in certain disease states and, potentially, following initiation of extracorporeal circulatory support. In this review, we first discuss patient-related factors pertaining to venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and their potential role in CA impairment. Next, we examine factors intrinsic to ECMO that may affect CA, such as cannulation, changes in pulsatility, the inflammatory and adaptive immune response, intracranial hemorrhage, and ischemic stroke, in addition to ECMO management factors, such as oxygenation, ventilation, flow rates, and blood pressure management. We highlight potential mechanisms that lead to disruption of CA in both pediatric and adult populations, the challenges of measuring CA in these patients, and potential associations with neurological outcome. Altogether, we discuss individualized CA monitoring as a potential target for improving neurological outcomes in extracorporeal life support.