Background: Targeting a cerebral perfusion pressure optimal for cerebral autoregulation (CPPopt) has been gaining more attention to prevent secondary damage after acute neurological injury. Brain tissue oxygenation (PbtO ₂ ) can identify insufficient cerebral blood flow and secondary brain injury. Defining the relationship between CPPopt and PbtO ₂ after aneurysmal subarachnoid hemorrhage may result in (1) mechanistic insights into whether and how CPPopt-based strategies might be beneficial and (2) establishing support for the use of PbtO ₂ as an adjunctive monitor for adequate or optimal local perfusion. Methods: We performed a retrospective analysis of a prospectively collected 2-center dataset of patients with aneurysmal subarachnoid hemorrhage with or without later diagnosis of delayed cerebral ischemia (DCI). CPPopt was calculated as the cerebral perfusion pressure (CPP) value corresponding to the lowest pressure reactivity index (moving correlation coefficient of mean arterial and intracranial pressure). The relationship of (hourly) deltaCPP (CPP−CPPopt) and PbtO ₂ was investigated using natural spline regression analysis. Data after DCI diagnosis were excluded. Brain tissue hypoxia was defined as PbtO ₂ <20 mmHg. Results: One hundred thirty-one patients were included with a median of 44.0 (interquartile range, 20.8–78.3) hourly CPPopt/PbtO2 datapoints. The regression plot revealed a nonlinear relationship between PbtO ₂ and deltaCPP ( P <0.001) with PbtO ₂ decrease with deltaCPP <0 mmHg and stable PbtO ₂ with deltaCPP ≥0mmHg, although there was substantial individual variation. Brain tissue hypoxia (34.6% of all measurements) was more frequent with deltaCPP <0 mmHg. These dynamics were similar in patients with or without DCI. Conclusions: We found a nonlinear relationship between PbtO ₂ and deviation of patients’ CPP from CPPopt in aneurysmal subarachnoid hemorrhage patients in the pre-DCI period. CPP values below calculated CPPopt were associated with lower PbtO ₂ . Nevertheless, the nature of PbtO ₂ measurements is complex, and the variability is high. Combined multimodality monitoring with CPP/CPPopt and PbtO ₂ should be recommended to redefine individual pressure targets (CPP/CPPopt) and retain the option to detect local perfusion deficits during DCI (PbtO ₂ ), which cannot be fulfilled by both measurements interchangeably.

This study aims to investigate the characteristics of patients with mild aneurysmal and non-aneurysmal perimesencephalic and non-perimesencephalic subarachnoid hemorrhage (aSAH, pmSAH, npmSAH) with emphasis on admission biomarkers, clinical course, and outcome. A prospective cohort of 115 patients with aSAH (Hunt and Hess 1–3) and of 35 patients without aneurysms (16 pmSAH and 19 npmSAH) admitted between January 2014 and January 2020 was included. Demographic data, blood samples on admission, complications (hydrocephalus, shunt dependency, delayed cerebral ischemia DCI, DCI-related infarction, and mortality), and outcome after 6 months were analyzed. Demographic data was comparable between all groups except for age (aSAH 55 [48–65] vs. npmSAH 60 [56–68] vs. pmSAH 52 [42–60], p = 0.032) and loss of consciousness (33% vs. 0% vs. 0%, p = 0.0004). Admission biomarkers showed poorer renal function and highest glucose levels for npmSAH patients. Complication rate in npmSAH was high and comparable to that of aSAH patients (hydrocephalus, shunt dependency, DCI, DCI-related infarction, mortality), but nearly absent in patients with pmSAH. Favorable outcome after 6 months was seen in 92.9% of pmSAH, 83.3% of npmSAH, and 62.7% of aSAH (p = 0.0264). In this prospective cohort of SAH patients, npmSAH was associated with a complicated clinical course, comparable to that of patients with aSAH. In contrast, such complications were nearly absent in pmSAH patients, suggesting fundamental differences in the pathophysiology of patients with different types of non-aneurysmal hemorrhage. Our findings underline the importance for a precise terminology according the hemorrhage etiology as a basis for more vigilant management of npmSAH patients. NCT02142166, 05/20/2014, retrospectively registered.

Despite extensive research on aneurysm treatment and neurocritical care, aneurysmal subarachnoid hemorrhage (SAH) is still a life-threatening disease, often leaving survivors with lasting neurological and cognitive impairments. Early brain injury (EBI) and delayed cerebral ischemia (DCI) are the main contributors to brain damage, with neuroinflammation being a critical shared pathophysiological process. While numerous inflammatory markers and their temporal profiles in cerebrospinal fluid (CSF) have already been identified, comparisons with age- and sex-matched controls are limited. This study analyzed CSF from 17 SAH patients requiring an external ventricular drain (EVD) due to symptomatic hydrocephalus, sampled on days 4 and 10 post-ictus. An age- and sex-matched control group included 17 cerebrovascularly healthy patients requiring lumbar drains during aortic surgery. Chemokines and cytokines were quantified using immunoassays. Significantly elevated markers in SAH patients across both time points included MCP-1, CXCL-13, Eotaxin-1, CXCL-10, IL-8, and MIF. MIP-1α and MIP-1β showed significant differences at particular time points, indicating a distinct temporal profile for each parameter. These findings highlight neuroinflammation’s key role in intracranial and systemic pathophysiology following SAH, emphasizing its complexity and individual variability. Knowing demographic factors impact the specific manifestations of pathophysiological processes, the comparison with an age- and sex-matched control group is meaningful.

Background: Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN. However, evidence in this regard is largely lacking. We investigated the effects of a classical (iHTN+IAN) and modified (IAN _only ) treatment protocol for refractory DCI in an observational study. Methods: Rescue treatment for DCI was initiated with iHTN (target >180 mm Hg systolic) and escalated to IAN in refractory cases. Until July 2018, both iHTN and IAN were offered in cases refractory to iHTN alone. After protocol modification, iHTN target was preemptively lowered to >120 mm Hg when IAN was initiated (IAN _only ). Primary outcome was noradrenaline demand. Secondary outcomes included noradrenaline-associated complications, brain tissue oxygenation, DCI-related infarction and favorable 6-month outcome (Glasgow Outcome Scale 4–5). Results: N=29 and n=20 patients were treated according to the classical and modified protocol, respectively. Protocol modification resulted in a significant reduction of noradrenaline demand (iHTN+IAN 0.70±0.54 µg/kg per minute and IAN _only 0.26±0.20 µg/kg per minute, P <0.0001) and minor complications (15.0% versus 48.3%, unadjusted odds ratio, 0.19 [95% CI, 0.05–0.79]; P <0.05) with comparable rates of major complications (20.0% versus 20.7%, odds ratio, 0.96 [0.23–3.95]; P =0.95). Incidence of DCI-related infarction (45.0% versus 41.1%, odds ratio, 1.16 [0.37–3.66]; P =0.80) and favorable clinical outcome (55.6% versus 40.0%, odds ratio, 1.88 [0.55–6.39]; P =0.32) were similar. Brain tissue oxygenation was significantly higher with IANonly (26.6±12.8, 39.6±15.4 mm Hg; P <0.01). Conclusions: Assuming the potential of iHTN to be exhausted in case of refractory hypoperfusion, additional IAN may serve as a last-resort measure to bridge hypoperfusion in the DCI phase. With close monitoring, preemptive lowering of pressure target after induction of IAN may be a safe alternative to alleviate total noradrenaline load and potentially reduce complication rate.

Background: Cerebral autoregulation (CA) can be impaired in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). The Pressure Reactivity Index (PRx, correlation of blood pressure and intracranial pressure) and Oxygen Reactivity Index (ORx, correlation of cerebral perfusion pressure and brain tissue oxygenation, PbtO₂) are both believed to estimate CA. We hypothesized that CA could be poorer in hypoperfused territories during DCI and that ORx and PRx may not be equally effective in detecting such local variances. Methods: ORx and PRx were compared daily in 76 patients with aSAH with or without DCI until the time of DCI diagnosis. The ICP/PbtO₂-probes of DCI patients were retrospectively stratified by being in or outside areas of hypoperfusion via CT perfusion image, resulting in three groups: DCI + /probe + (DCI patients, probe located inside the hypoperfused area), DCI + /probe−  (probe outside the hypoperfused area), DCI−  (no DCI). Results: PRx and ORx were not correlated (r = − 0.01, p = 0.56). Mean ORx but not PRx was highest when the probe was located in a hypoperfused area (ORx DCI + /probe + 0.28 ± 0.13 vs. DCI + /probe−  0.18 ± 0.15, p < 0.05; PRx DCI + /probe + 0.12 ± 0.17 vs. DCI + /probe−  0.06 ± 0.20, p = 0.35). PRx detected poorer autoregulation during the early phase with relatively higher ICP (days 1–3 after hemorrhage) but did not differentiate the three groups on the following days when ICP was lower on average. ORx was higher in the DCI + /probe + group than in the other two groups from day 3 onward. ORx and PRx did not differ between patients with DCI, whose probe was located elsewhere, and patients without DCI (ORx DCI + /probe−  0.18 ± 0.15 vs. DCI−  0.20 ± 0.14; p = 0.50; PRx DCI + /probe−  0.06 ± 0.20 vs. DCI−  0.08 ± 0.17, p = 0.35). Conclusions: PRx and ORx are not interchangeable measures of autoregulation, as they likely measure different homeostatic mechanisms. PRx represents the classical cerebrovascular reactivity and might be better suited to detect disturbed autoregulation during phases with moderately elevated ICP. Autoregulation may be poorer in territories affected by DCI. These local perfusion disturbances leading up to DCI may be more readily detected by ORx than PRx. Further research should investigate their robustness to detect DCI and to serve as a basis for autoregulation-targeted treatment after aSAH.