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Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3-5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 ( P < 0.001) and remained stable thereafter ( P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia ( P = 0.001), episodes of metabolic distress ( P = 0.002) and mitochondrial dysfunction ( P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32-5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16-9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days ( P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Fluid management in patients after subarachnoid hemorrhage (SAH) aims at the optimization of cerebral blood flow and brain oxygenation. In this study, we investigated the effects of hemodynamic management on brain oxygenation by integrating advanced hemodynamic and invasive neuromonitoring., Methods: This observational cohort bi-center study included data of consecutive poor-grade SAH patients who underwent pulse contour cardiac output (PiCCO) monitoring and invasive neuromonitoring. Fluid management was guided by the transpulmonary thermodilution system and aimed at euvolemia (cardiac index, CI ≥ 3.0 L/min/m 2 ; global end-diastolic index, GEDI 680-800 mL/m 2 ; stroke volume variation, SVV < 10%). Patients were managed using a brain tissue oxygenation (P bt O 2 ) targeted protocol to prevent brain tissue hypoxia (BTH, P bt O 2  < 20 mmHg). To assess the association between CI and P bt O 2 and the effect of fluid challenges on CI and P bt O 2 , we used generalized estimating equations to account for repeated measurements., Results: Among a total of 60 included patients (median age 56 [IQRs 47-65] years), BTH occurred in 23% of  the monitoring time during the first 10 days since admission. Overall, mean CI was within normal ranges (ranging from 3.1 ± 1.3 on day 0 to 4.1 ± 1.1 L/min/m 2 on day 4). Higher CI levels were associated with higher P bt O 2 levels (Wald = 14.2; p < 0.001). Neither daily fluid input nor fluid balance was associated with absolute P bt O 2 levels (p = 0.94 and p = 0.85, respectively) or the occurrence of BTH (p = 0.68 and p = 0.71, respectively). P bt O 2 levels were not significantly different in preload dependent patients compared to episodes of euvolemia. P bt O 2 increased as a response to fluid boluses only if BTH was present at baseline (from 13 ± 6 to 16 ± 11 mmHg, OR = 13.3 [95% CI 2.6-67.4], p = 0.002), but not when all boluses were considered (p = 0.154)., Conclusions: In this study a moderate association between increased cardiac output and brain oxygenation was observed. Fluid challenges may improve P bt O 2 only in the presence of baseline BTH. Individualized hemodynamic management requires advanced cardiac and brain monitoring in critically ill SAH patients., (© 2021. The Author(s).)

Background: Endotracheal suctioning (ES) provokes a cumulative hemodynamic response by activation of sympathetic and parasympathetic circuits in the central nervous system. In this proof-of-concept study, we aimed to analyze hemodynamic changes during ES in ventilated subarachnoid hemorrhage (SAH) patients and investigated whether the associated hemodynamic changes relate to the time to arousal and functional outcome., Methods: For the current observational study, 191 SAH patients admitted to the neurological intensive care unit of a tertiary hospital requiring mechanical ventilation were included. One thousand eighty ES episodes during the first 72 h of admission were analyzed. Baseline median heart rate (HR) and mean arterial pressure (MAP) were compared to peak HR and MAP during ES based on 5-min averaged data (ΔHR and ΔMAP). Multivariable analysis to assess associations between ΔHR and ΔMAP and time to arousal (time to Richmond Agitation Sedation Scale ≥ 0, RASS) and poor functional outcome (modified Rankin Scale Score > 2, mRS) was performed using generalized estimating equations., Results: Patients were 59 (IQR, 50-70) years old and presented with a median admission H&H grade of 4 (IQR, 3-5). In-hospital mortality was 22% (25% at 3 months) and median time to arousal was 13 (IQR, 4-21) days. HR increased by 2.3 ± 7.1 beats per minute (bpm) from 75.1 ± 14.8 bpm at baseline. MAP increased by 3.2 ± 7.8 mmHg from baseline 80.9 ± 9.8 mmHg. In multivariable analysis, ΔHR (p < 0.001) was significantly lower in patients who regained consciousness at a later time point and a lower ΔHR was associated with poor functional 3-month outcome independent of RASS (adjOR = 0.95; 95% CI = 0.93-0.98) or midazolam dose (adjOR = 0.96; 95% CI = 0.94-0.98). ΔMAP was neither associated with the time to regain consciousness (p = 0.087) nor with functional outcome (p = 0.263)., Conclusion: Augmentation in heart rate may quantify the hemodynamic response during endotracheal suctioning in brain-injured patients. The value as a biomarker to early discriminate the time to arousal and functional outcome in acutely brain-injured patients needs prospective confirmation.

Background and Purpose- Global cerebral edema occurs in up to 57% of patients with subarachnoid hemorrhage (SAH) and is associated with prolonged hospital stay and poor outcome. Recently, admission brain edema was successfully graded using a simplified computed tomography-based semiquantitative score (subarachnoid hemorrhage early brain edema score [SEBES]). Longitudinal evaluation of the SEBES grade may discriminate patients with rapid and delayed edema resolution after SAH. Here, we aimed to describe the resolution of brain edema and to study the relationship between this radiographic biomarker and hospital course and outcome after SAH. Methods- For the current observational cohort study, computed tomography scans of 283 consecutive nontraumatic SAH patients admitted to the neurological intensive care unit of a tertiary hospital were graded based on the absence of visible sulci at 2 predefined brain tissue levels in each hemisphere (SEBES ranging from 0 to 4). A score of ≥3 was defined as high-grade SEBES. Multivariable regression models using generalized linear models were used to identify associated factors with delayed edema resolution based on the median time to resolution (SEBES ≤2) in SAH survivors. Results- Patients were 57 years old (interquartile range, 48-68) and presented with a median admission Hunt and Hess grade of 3 (interquartile range, 1-5). High-grade SEBES was common (106/283, 37%) and resolved within a median of 8 days (interquartile range, 4-15) in survivors (N=80). Factors associated with delayed edema resolution were early (<72 hours) hypernatremia (>150 mmol/L; adjusted odds ratio [adjOR], 4.88; 95% CI, 1.68-14.18), leukocytosis (>15 G/L; adjOR, 3.14; 95% CI, 1.24-8.77), hyperchloremia (>121 mmol/L; adjOR, 5.24; 95% CI, 1.64-16.76), and female sex (adjOR, 3.71; 95% CI, 1.01-13.64) after adjusting for admission Hunt and Hess grade and age. Delayed brain edema resolution was an independent predictor of worse functional 3-month outcome (adjOR, 2.52; 95% CI, 1.07-5.92). Conclusions- Our data suggest that repeated quantification of the SEBES can identify SAH patients with delayed edema resolution. Based on its' prognostic value as radiographic biomarker, the SEBES may be integrated in future trials aiming to improve edema resolution after SAH.