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OBJECTIVE Recent guidelines recommend targeting a systolic blood pressure (SBP) < 140 mm Hg in the early management of patients with spontaneous intracerebral hemorrhage (ICH). The optimal SBP targets for ICH patients after hematoma evacuation (HE) remain unclear. Here, the authors aimed to define the optimal SBP range based on multimodal neuromonitoring data. METHODS Forty poor-grade ICH patients who had undergone HE and then monitoring of intracerebral pressure, brain tissue oxygen tension (PbtO2), and cerebral metabolism (via cerebral microdialysis [CMD]) were prospectively included. Episodes of brain tissue hypoxia (BTH) (1-hour averaged PbtO2 < 20 mm Hg) and metabolic distress (CMD–lactate/pyruvate ratio [LPR] ≥ 40) were identified and linked to corresponding parameters of hemodynamic monitoring (SBP and cerebral perfusion pressure [CPP]). Multivariable regression analysis was performed using generalized estimating equations to identify associations between SBP levels, PbtO2, and brain metabolism. RESULTS The mean patient age was 60 (range 51–66) years and the median [IQR] initial ICH volume was 47 [29–60] ml. In multivariable models adjusted for Glasgow Coma Scale score, probe location, ICH volume, and age, lower SBP was independently associated with a higher risk of BTH (≤ 120 mm Hg: adjusted OR 2.9, p = 0.007; 120–130 mm Hg: adj OR 2.4, p = 0.002; 130–140 mm Hg: adj OR 1.6, p = 0.017) compared to a reference range of 140–150 mm Hg at the level of the foramen interventriculare Monroi, which corresponded to a CPP of 70–80 mm Hg and SBP levels between 150 and 160 mm Hg at the heart level. After exclusion of episodes with mitochondrial dysfunction, SBP targets < 140 mm Hg were associated with higher odds of cerebral metabolic distress (≤ 130 mm Hg: OR 2.5, p = 0.041; 130–140 mm Hg: OR 2.3, p = 0.033). Patients with a modified Rankin Scale score ≥ 5 at neurological ICU discharge more often exhibited BTH than patients with better outcomes (51% vs 10%, p = 0.003). CONCLUSIONS These data suggest that lower SPB and CPP levels are associated with a higher risk for BTH. Further studies are needed to evaluate whether a higher SPB target may prevent BTH and improve outcomes.

Purpose Hyperactive delirium is common after subarachnoid hemorrhage (SAH). We aimed to identify risk factors for delirium and to evaluate its impact on outcome. Methods We collected daily Richmond Agitation Sedation Scale (RASS) and Intensive Care Delirium Screening Checklist (ICDSC) scores in 276 SAH patients. Hyperactive delirium was defined as ICDSC ≥4 when RASS was >0. We investigated risk factors for delirium and its association with 3-month functional outcome using generalized linear models. Results Patients were 56 (IQR 47–67) years old and had a HuntH 95%-CI = 1.89–10.56; p = 0.001), the detection of an aneurysm (adjOR = 4.38; 95%-CI = 1.48–12.97; p = 0.008), a lower HH 95%-CI = 0.48–0.83; p = 0.001) and a pre-treated psychiatric disorder (adjOR = 3.17; 95%-CI = 1.14–8.83; p = 0.027) were associated with the development of delirium. Overall, delirium was not associated with worse outcome (p = 0.119). Interestingly, patients with delirium more often had a modified Rankin Scale Score (mRS) of 1–3 (77%) compared to an mRS of 0 (14%) or 4–6 (9%). Conclusion Our data indicate that hyperactive delirium is common after SAH patients and requires a certain degree of brain connectivity based ono the highest prevalence found in SAH patients with intermediate outcomes.

Objectives Patients suffering from spontaneous subarachnoid hemorrhage frequently require mechanical ventilation. Here, we aimed to identify factors associated with prolonged mechanical ventilation in subarachnoid hemorrhage patients and to create a new predictive score for prolonged mechanical ventilation. Design Prospective cohort study with retrospective data analysis. Setting Neurocritical care unit at a tertiary academic medical center. Patients Two hundred ninety-seven consecutive nontraumatic adult subarachnoid hemorrhage patients. Methods In patients with mechanical ventilation, we identified factors associated with mechanical ventilation greater than 48 hours, greater than 7 days, and greater than 14 days compared with mechanical ventilation less than or equal to 48 hours, less than or equal to 7 days, or less than or equal to 14 days in multivariable generalized linear models. Ventilated patients who died before 48 hours, 7 days, or 14 days and those never ventilated were excluded from the respective analysis. We incorporated those factors into a new prognostic score (the RAISE score) to predict prolonged mechanical ventilation greater than 7 days. The calculation was based on a random dataset of 60% of subarachnoid hemorrhage patients and was internally validated. Interventions None. Measurements and main results Patients were 57 years old (interquartile range, 47-68 yr) and presented with a median Hunt and Hess grade of 3 (1-5). Two hundred forty-two patients (82%) required mechanical ventilation for 9 days (2-20 d). In multivariable analysis, a higher Acute Physiology Score was associated with mechanical ventilation greater than 48 hours, greater than 7 days, and greater than 14 days, a higher Hunt and Hess grade with greater than 7 days and greater than 14 days. Early neuroimaging findings were associated with mechanical ventilation greater than 48 hours (hydrocephalus; high-grade Subarachnoid Hemorrhage Early Brain Edema Score), greater than 7 days (high-grade Subarachnoid Hemorrhage Early Brain Edema Score, co-occurrence of intracerebral bleeding) but not with prolonged mechanical ventilation greater than 14 days. The RAISE score, including age, Acute Physiology Score, Hunt and Hess grade, Subarachnoid Hemorrhage Early Brain Edema Score, and the co-occurrence of intracerebral hemorrhage accurately stratified patients by prolonged mechanical ventilation greater than 7 days (C-statistic 0.932). A RAISE score of 12 predicted 60% likelihood of mechanical ventilation greater than 7 days. Conclusions Initial disease severity and neuroimaging findings detected within 24 hours after ICU admission were associated with the need for prolonged mechanical ventilation in patients with subarachnoid hemorrhage. These results may be helpful for patient families and caregivers to better anticipate the course of therapy.

Purpose Cardiac complications are common after spontaneous intracerebral hemorrhage (ICH). In this study we intended to investigate factors associated with higher alterations in heart rate and their impact on outcome. Methods Eighty-eight ICH patients were included. A simplified approach to calculate heart rate variability (HRSD) in analogy to systolic blood pressure variability (SBPSD) with daily standard deviations of HR in the acute (first 24 h) and subacute phase (day1-day7) was used. Using multivariable regression, factors associated with higher HRSD and the association between higher HRSD and poor 3-month outcome (modified Rankin Scale > 3) were analyzed. All models were adjusted for age, atrial fibrillation, mechanical ventilation, vasopressor administration, and mean HR. Results Patients were 71 (IQR = 60–79) years old and presented with an admission ICH-Score of 2 (IQR = 1–3). In multivariable analysis, intraventricular hemorrhage (adjOR = 8.66, 95%-CI = 1.89–39.60, p = 0.005), a QRS complex >120 ms (adjOR = 19.02; 95%-CI = 2.08–175.05, p = 0.009) and female sex (adjOR = 4.24; 95%-CI = 1.08–16.64, p = 0.038) were associated with higher HRSD in the acute phase. A higher HRSD (adjOR = 1.29, 95%-CI = 1.01–1.66, p = 0.045) in the acute but not in the subacute phase (p = 0.764) was associated with poor 3-month outcome. Conclusion The study suggests that a higher variation in heart rate in the early phase after ICH may discriminate patients with poor outcome.

Background/objective Monitoring of brain tissue oxygen tension (PbtO2) provides insight into brain pathophysiology after intracerebral hemorrhage (ICH). Integration of probe location is recommended to optimize data interpretation. So far, little is known about the importance of PbtO2 catheter location in ICH patients. Methods We prospectively included 40 ICH patients after hematoma evacuation (HE) who required PbtO2-monitoring. PbtO2-probe location was evaluated in all head computed tomography (CT) scans within the first 6 days after HE and defined as location in the healthy brain tissue or perilesional when the catheter tip was located within 1 cm of a focal lesion (hypodense or hyperdense). Generalized estimating equations were used to investigate levels of PbtO2 in relation to different probe locations. Results Patients were 60 [51–66] years old and had a median ICH-volume of 47 [29–60] mL. Neuromonitoring probes remained for a median of 6 [2–11] days. PbtO2-probes were located in healthy brain tissue in 18/40 (45%) patients and in perilesional brain tissue in 22/40 (55%) patients. In the acute phase after HE (0–72 h), PbtO2 levels were significantly lower (21 ± 12 mmHg vs. 29 ± 10 mmHg, p = 0.010) and brain tissue hypoxia (BTH) was more common in the perilesional area as compared to healthy brain tissue (46% vs. 19%, adjOR 4.0, 95% CI 1.54–10.58, p = 0.005). Episodes of BTH significantly decreased over time in patients with probes in perilesional location (p = 0.001) but remained stable in normal appearing area (p = 0.485). A significant association between BTH and poor functional outcome was only found when probes were located in the perilesional brain tissue (adjOR 6.6, 95% CI 1.3–33.8, p = 0.023). Conclusions In the acute phase, BTH was more common in the perilesional area compared to healthy brain tissue. The improvement of BTH in the perilesional area over time may be the result of targeted treatment interventions and tissue regeneration. Due to the localized measurement of invasive neuromonitoring devices, integration of probe location in the clinical management of ICH patients and in research protocols seems mandatory.

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 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.

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p delta +0.18°C, IQR −0.01 – 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate ( p = 0.003) and CMD-lactate ( p delta was significantly lower (0°C, IQR −0.2 – 0.1; p delta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH.

Background Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH) and its contribution to hospital complications, length of intensive care unit stay, and functional outcome. Methods This is a retrospective analysis of an ongoing prospective cohort study. Swallowing ability was assessed in consecutive non-traumatic SAH patients admitted to our neurological intensive care unit using the Bogenhausen Dysphagia Score (BODS). A BODS > 2 points indicated dysphagia. Functional outcome was assessed 3 months after the SAH using the modified Rankin Scale with a score > 2 defined as poor functional outcome. Results Two-hundred and fifty consecutive SAH patients comprising all clinical severity grades with a median age of 57 years (interquartile range 47–67) were eligible for analysis. Dysphagia was diagnosed in 86 patients (34.4%). Factors independently associated with the development of dysphagia were poor clinical grade on admission (Hunt & Hess grades 4–5), SAH-associated parenchymal hematoma, hydrocephalus, detection of an aneurysm, and prolonged mechanical ventilation (> 48 h). Dysphagia was independently associated with a higher rate of pneumonia (OR = 4.32, 95% CI = 2.35–7.93), blood stream infection (OR = 4.3, 95% CI = 2.0–9.4), longer ICU stay [14 (8–21) days versus 29.5 (23–45) days, p Conclusions Dysphagia is a frequent complication of non-traumatic SAH and associated with poor functional outcome, infectious complications, and prolonged stay in the intensive care unit. Early identification of high-risk patients is needed to timely stratify individual patients for dysphagia treatment.

Fever may aggravate secondary brain injury after traumatic brain injury (TBI). The aim of this study was to identify episodes of temperature increases through visual plot analysis and algorithm supported detection, and to describe associated patterns of changes in on brain tissue oxygen tension (PbtO2). Data derive from the high-resolution cohort of the multicenter prospective Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Temperature increases (≥0.5°C) were visually identified in 33 patients within the first 11 days of monitoring. Generalized estimating equations were used to detect significant changes of systemic and neuromonitoring parameters from baseline to the highest temperature. Patients were median 50 (interquartile range [IQR], 35-62) years old, and presented with a Glasgow Coma Scale (GCS) of 8 (IQR, 4-10). In 202 episodes of temperature increases, mean temperature rose by 1.0°C ± 0.5°C within 4 hours. Overall, PbtO2 slightly increased (ΔPbtO2 = 0.9 ± 6.1 mmHg, p = 0.022) during temperature increases. PbtO2 increased in 35% (p < 0.001), was stable in 49% (p = 0.852), and decreased in 16% (p < 0.001) of episodes. During episodes of temperature increases and simultaneous drops in PbtO2, cerebral perfusion pressure (CPP) decreased (ΔCPP -6.3 ± 11.5 mmHg; p < 0.001). Brain tissue hypoxia (PbtO2

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 (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.

Diabetes mellitus (DM) is a risk factor for cardiovascular disease. However, its effect on procedural and follow-up performance after transcatheter aortic valve replacement (TAVR) remains controversial. We performed an observational study of all consecutive patients treated with a transfemoral TAVR in a single-center cohort (n = 1818). All patients were stratified by diabetes status and gender. All-cause 3-year mortality was the primary endpoint. Male patients with DM were identified to have substantially increased 3-year mortality [125/314 (39.8%)] compared to males without DM [142/478 (29.7%), p

Background: Infectious complications (IC) commonly occur in patients with intracerebral hemorrhage (ICH) and are associated with increased length of hospitalization (LOS) and poor long-term outcome. Little is known about early ICH-related predictors for the development of IC to allow appropriate allocation of resources and timely initiation of preventive measures.Methods: We prospectively enrolled 229 consecutive patients with non-traumatic ICH admitted to the neurocritical care unit (NICU) of a tertiary care hospital. Patients were screened daily for IC. Multivariable regression models using generalized linear models were used to identify associated factors with the occurrence of IC and to study their impact on functional outcome, which was assessed using the modified Rankin Scale Score (mRS) after 3 months. Unfavorable outcome was defined as mRS ≥3.Results: The most common IC were pneumonia (n = 64, 28%) and urinary tract infection (n = 54, 24%), followed by sepsis (n = 9, 4%) and ventriculitis (n = 4, 2%). Patients with a higher admission ICH Score (>2) had higher odds to develop any IC during NICU stay (OR = 1.7, 95% CI 1.2–2.3, p = 0.02). Moreover, early-onset pneumonia (≤48 h after admission) was predictive of sepsis occurring at a later time-point (median at day 11 [IQR = 6–34 days], adjOR = 22.5, 95% CI 4.88–103.6, p < 0.001). Having at least one IC and pneumonia itself were independently associated with unfavorable 3-months outcome (adjOR = 3.0, 95% CI 1.41–6.54, p = 0.005; adjOR = 4.2, 95% CI 1.33–13.19, p = 0.015, respectively). All patients with sepsis died or had poor functional outcome.Conclusions: Infectious complications are common in ICH patients and independently associated with unfavorable outcome. An ICH Score >2 on admission and early pneumonia may help to early identify patients at high risk of IC to allocate resources and start careful surveillance.

Intravenous nonsteroidal anti-inflammatory drugs and nonopioid analgesics are used to achieve normothermia or relieve pain in patients with aneurysmal subarachnoid hemorrhage (aSAH). We investigated the effects of paracetamol (1 g), diclofenac (75 mg) and metamizole (1 g) on systemic and cerebral hemodynamics and temperature during febrile and nonfebrile episodes after aSAH. Prospectively collected data from 77 consecutive poor-grade aSAH patients with invasive neuromonitoring were included. The burden and occurrence of hypotension (mean arterial pressure70 mmHg), brain tissue hypoxia (P

Background Impaired left ventricular (LV) ejection fraction is a common finding in patients with aortic stenosis and serves as a predictor of morbidity and mortality after transcatheter aortic valve replacement. However, conflicting data on the most accurate measure for LV function exist. We wanted to examine the impact of LV ejection fraction, mean pressure gradient, and stroke volume index on the outcome of patients treated by transcatheter aortic valve replacement. Methods and Results Patients treated by transcatheter aortic valve replacement were primarily separated into normal flow ( NF ; stroke volume index >35 mL/m 2 ) and low flow ( LF ; stroke volume index ≤35 mL/m 2 ). Afterwards, patients were divided into 5 groups: “NF–high gradient,” “NF–low gradient” ( NF ‐ LG ), “LF–high gradient,” “paradoxical LF‐LG,” and “classic LF‐LG.” The 3‐year mortality was the primary end point. Of 1600 patients, 789 (49.3%) were diagnosed as having LF , which was characterized by a higher 30‐day ( P =0.041) and 3‐year ( P LF was an independent predictor of all‐cause (hazard ratio, 1.29; 95% confidence interval, 1.03–1.62; P =0.03) and cardiovascular (hazard ratio, 1.37; 95% confidence interval, 1.06–1.77; P =0.016) mortality. Neither mean pressure gradient nor LV ejection fraction was an independent predictor of mortality. Patients with paradoxical LF‐LG (35.0%), classic LF‐LG (35.1%) and LF –high gradient (38.1%) had higher all‐cause mortality at 3 years compared with NF –high gradient (24.8%) and NF ‐ LG (27.9%) ( P =0.001). However, surviving patients showed a similar improvement in symptoms regardless of aortic stenosis entity. Conclusions LF is a common finding within the aortic stenosis population and, in contrast to LV ejection fraction or mean pressure gradient, an independent predictor of all‐cause and cardiovascular mortality. Despite increased long‐term mortality, high procedural success and excellent functional improvement support transcatheter aortic valve replacement in patients with LF severe aortic stenosis.

Studies of infective endocarditis (IE) in transcatheter aortic valve replacement patients are limited by univariate analysis of predictors [(1)][1], incomplete patient data (particularly non-IE cases [[2]][2]), or low number of endpoints [(3)][3]. We aimed to investigate the incidence, treatment