The effect of nimodipine on pulmonary function in artificially ventilated patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Nimodipine is routinely administered in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the effect of nimodipine on oxygen exchange in the lungs is insufficiently explored. METHODS: The study explored nimodipine medication in artificially ventilated patients with aSAH. The data collection period was divided into nimodipine-dependent (ND) and nimodipine-independent (NID) periods. Values for arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) were collected and compared between the periods. Patients were divided in those with lung injury (LI), defined as median Horowitz index (PaO2/FiO2) ≤40 kPa (≤300 mmHg), and without and in those with lower respiratory tract infection (LRTI) and without. RESULTS: A total of 53 out of 150 patients were artificially ventilated, and in 29 patients, the Horowitz index could be compared between ND and NID periods. A linear mixed model showed that during ND period the Horowitz index was 2.3 kPa (95% CI, 1.0-3.5 kPa, P<0.001) lower when compared to NID period. The model suggested that in the presence of LI, ND period is associated with a decrease of the index by 2.8 kPa (95% CI, 1.2-4.3 kPa, P<0.001). The decrease was more pronounced with LRTI than without: 3.4 kPa (95% CI, 0.8-6.1 kPa) vs. 2.1 kPa (95% CI, 0.7-3.4 kPa), P=0.011 and P=0.002, respectively. CONCLUSIONS: In patients with LI or LRTI in the context of aSAH, pulmonary function may worsen with nimodipine treatment. The drop of 2 to 3 kPa of the Horowitz index in patients with no lung pathology may not outweigh the benefits of nimodipine. However, in individuals with concomitant lung injury, the effect may be clinically relevant.

Outcome, Return to Work and Health-Related Costs After Aneurysmal Subarachnoid Hemorrhage.

OBJECT: Data on health-related costs after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim was to evaluate outcome, return to work and costs after aSAH with focus on differences between high- and low-grade aSAH (defined as World Federation of Neurological Surgeons [WFNS] grades 4-5 and WFNS 1-3, respectively). METHODS: A cross-sectional study was performed, including all consecutive survivors of aSAH over a 4-year period. A telephone interview was conducted to assess the Glasgow Outcome Scale Extended and employment status before and after aSAH. Direct costs were calculated by multiplying the length of hospitalization by the average daily costs. Indirect costs were calculated for productivity losses until retirement age according to the human capital approach. RESULTS: Follow-up was performed 2.7 years after aSAH (range 1.3-4.6). Favorable outcome was achieved in 114 of 150 patients (76%) and work recovery in 61 of 98 patients (62%) employed prior to aSAH. High-grade compared to low-grade aSAH resulted less frequently in favorable outcome (52% vs. 85%; p < 0.001) and work recovery (39% vs. 69%; p = 0.013). The total costs were € 344.277 (95% CI 268.383-420.171) per patient, mainly accounted to indirect costs (84%). The total costs increased with increasing degree of disability and were greater for high-grade compared to low-grade aSAH (€ 422.496 vs. € 329.193; p = 0.039). The effective costs per patient with favorable outcome were 2.1-fold greater for high-grade compared to low-grade aSAH (€ 308.625 vs. € 134.700). CONCLUSION: Favorable outcome can be achieved in a considerable proportion of high-grade aSAH patients, but costs are greater compared to low-grade aSAH. Further cost-effectiveness studies in the current era of aSAH management are needed.

Automated False Alarm Reduction in a Real-Life Intensive Care Setting Using Motion Detection.

BACKGROUND: Contemporary monitoring systems are sensitive to motion artifacts and cause an excess of false alarms. This results in alarm fatigue and hazardous alarm desensitization. To reduce the number of false alarms, we developed and validated a novel algorithm to classify alarms, based on automatic motion detection in videos. METHODS: We considered alarms generated by the following continuously measured parameters: arterial oxygen saturation, systolic blood pressure, mean blood pressure, heart rate, and mean intracranial pressure. The movements of the patient and in his/her surroundings were monitored by a camera situated at the ceiling. Using the algorithm, alarms were classified into RED (true), ORANGE (possibly false), and GREEN alarms (false, i.e., artifact). Alarms were reclassified by blinded clinicians. The performance was evaluated using confusion matrices. RESULTS: A total of 2349 alarms from 45 patients were reclassified. For RED alarms, sensitivity was high (87.0%) and specificity was low (29.6%) for all parameters. As the sensitivities and specificities for RED and GREEN alarms are interrelated, the opposite was observed for GREEN alarms, i.e., low sensitivity (30.2%) and high specificity (87.2%). As RED alarms should not be missed, even at the expense of false positives, the performance was acceptable. The low sensitivity for GREEN alarms is acceptable, as it is not harmful to tag a GREEN alarm as RED/ORANGE. It still contributes to alarm reduction. However, a 12.8% false-positive rate for GREEN alarms is critical. CONCLUSIONS: The proposed system is a step forward toward alarm reduction; however, implementation of additional layers, such as signal curve analysis, multiple parameter correlation analysis and/or more sophisticated video-based analytics are needed for improvement.

Sevoflurane sedation attenuates early cerebral oedema formation through stabilisation of the adherens junction protein beta catenin in a model of subarachnoid haemorrhage: A randomised animal study.

BACKGROUND: Severe neurological impairment is a problem after subarachnoid haemorrhage (SAH). Although volatile anaesthetics, such as sevoflurane, have demonstrated protective properties in many organs, their use in cerebral injury is controversial. Cerebral vasodilation may lead to increased intracranial pressure (ICP), but at the same time volatile anaesthetics are known to stabilise the SAH-injured endothelial barrier. OBJECTIVE: To test the effect of sevoflurane on ICP and blood-brain barrier function. DESIGN: Randomised study. PARTICIPANTS: One hundred male Wistar rats included, 96 analysed. INTERVENTIONS: SAH was induced by the endoluminal filament method under ketamine/xylazine anaesthesia. Fifteen minutes after sham surgery or induction of SAH, adult male Wistar rats were randomised to 4 h sedation with either propofol or sevoflurane. MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), ICP, extravasation of water (small), Evan's blue (intermediate) and IgG (large molecule) were measured. Zonula occludens-1 (ZO-1) and beta-catenin (ß-catenin), as important representatives of tight and adherens junction proteins, were determined by western blot. RESULTS: Propofol and sevoflurane sedation did not affect MAP or ICP in SAH animals. Extravasation of small molecules was higher in SAH-propofol compared with SAH-sevoflurane animals (79.1 ±â€Š0.9 vs. 78.0 ±â€Š0.7%, P = 0.04). For intermediate and large molecules, no difference was detected (P = 0.6 and P = 0.2). Both membrane and cytosolic fractions of ZO-1 as well as membrane ß-catenin remained unaffected by the injury and type of sedation. Decreased cytosolic fraction of ß-catenin in propofol-SAH animals (59 ±â€Š15%) was found to reach values of sham animals (100%) in the presence of sevoflurane in SAH animals (89 ±â€Š21%; P = 0.04). CONCLUSION: This experiment demonstrates that low-dose short-term sevoflurane sedation after SAH in vivo did not affect ICP and MAP and at the same time may attenuate early brain oedema formation, potentially by preserving adherens junctions. TRIAL REGISTRATION: No 115/2014 Veterinäramt Zürich.

Changes in the cerebrospinal fluid lipid profile following subarachnoid hemorrhage in a closed cranium model: Correlations to cerebral vasospasm, neuronal cell death and Interleukin-6 synthesis. A pilot study.

BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.

Proximal arterial diameters on CT angiography and digital subtraction angiography correlate both at admission and in the vasospasm period after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Comparison of artery diameters between CT angiography (CTA) and subtraction arteriography (DSA) has the limitation that measurements on DSA are provided as relative units, making a quantitative comparison difficult. On CTA, artery diameters may depend on windowing settings and may lead to false measurements. This study assesses the correlation between CTA and DSA based on measurements in a basic imaging viewer using normalized DSA values, and assesses whether the validity is time dependent. METHODS: Patients with aneurysmal subarachnoid hemorrhage (aSAH) were included if they underwent both CTA and DSA within 24 h. The analysis was performed using the basic imaging application Centricity Enterprise PACS viewer (GE Healthcare). A total of 15 arterial locations were assessed on CTA and DSA and a specific measurement protocol with normalization of all artery diameters to the cavernous segment of the internal carotid artery was used. Pearson correlation analysis was calculated to access the correlation of normalized arterial diameters measured with both methods at admission and at clinical onset of CVS. RESULTS: A total of 627 arteries in 38 patients were analyzed in both CTA and DSA. There was a significant correlation coefficient (R = 0.706) of artery diameters between CTA and DSA measures (p < 0.0001). This correlation remained high when comparing CTA and DSA at admission (correlation coefficient: 0.641; p < 0.0001) vs. in the vasospasm period (0.835; p < 0.0001). The correlation was good in all proximal artery segments and lost significance only when distal vessel segments were considered. CONCLUSION: Using basic imaging viewers, mostly accessible for clinicians, CTA is a noninvasive and reliable method to assess proximal arterial diameters of the brain in the management of cerebral vasospasm in the acute phase after aSAH. Significance is reached, independent of whether CTA is obtained in the acute phase or during the period of vasospasm, by normalization of basal cerebral artery diameters to a non-variable anatomic landmark, i.e., the petrous or cavernous internal carotid artery diameter.

Mouse model of subarachnoid hemorrhage: technical note on the filament perforation model.

Experiments using genetically engineered mice are regarded as indispensable to gaining a better understanding of the molecular pathophysiology in neuronal injury after subarachnoid hemorrhage (SAH). Therefore, mouse SAH models are becoming increasingly important. The circle of Willis perforation (cWp) model is the most frequently used mouse SAH model. We report and discuss the technical surgical approach, results, and difficulties associated with the cWp model, with reference to the existing literature. Our results largely confirmed previously published results. This model may be the first choice at present, because important pathologies can be reproduced in this model and most findings in the literature are based on it.

The rabbit blood shunt subarachnoid haemorrhage model.

The recently introduced rabbit blood shunt subarachnoid haemorrhage model is based on the two standard procedures of subclavian artery cannulation and transcutaneous cisterna magna puncture. An extracorporeal shunt placed in between the arterial system and the subarachnoid space allows examiner-independent SAH in a closed cranium. Despite its straightforwardness, it is worth examining some specific features and characteristics of the model. We outline technical considerations to successfully perform the model with minimal mortality and morbidity. In addition, we discuss outcome measures, advantages and limitations, and the applicability of the model for the study of early brain injury and delayed cerebral vasospasm after SAH.

The impact of nonsteroidal anti-inflammatory drugs on inflammatory response after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The degree of inflammatory response with cytokine release is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). Previously, we reported on an association between systemic IL-6 levels and clinical outcome in patients with aneurysmal SAH. The intention was to assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the inflammatory response after SAH. METHODS: Our method involved exploratory analysis of data and samples collected within a previous study. In 138 patients with SAH, systemic interleukin (IL-6) and c-reactive protein (CRP) were measured daily up to day 14 after SAH. The correlations among the cumulatively applied amount of NSAIDs, inflammatory parameters, and clinical outcome were calculated. RESULTS: An inverse correlation between cumulatively applied NSAIDs and both IL-6 and CRP levels was found (r = -0.437, p < 0.001 and r = -0.369, p < 0.001 respectively). Multivariable linear regression analysis showed a cumulative amount of NSAIDs to be independently predictive for systemic IL-6 and CRP levels. The cumulative amount of NSAIDs reduced the odds for unfavorable outcome, defined as Glasgow outcome scale 1-3. CONCLUSIONS: The results indicate a potential beneficial effect of NSAIDs in patients with SAH in terms of ameliorating inflammatory response, which might have an impact on outcome.

Early systemic procalcitonin levels in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Early (≤24 h) systemic procalcitonin (PCT) levels are predictive for unfavorable neurological outcome in patients after out-of-hospital cardiac arrest (OHCA). Subarachnoid hemorrhage (SAH) due to aneurysm rupture might lead to a cerebral perfusion stop similar to OHCA. The current study analyzed the association of early PCT levels and outcome in patients after SAH. METHODS: Data from 109 consecutive patients, admitted within 24 h after SAH, were analyzed. PCT levels were measured within 24 h after ictus. Clinical severity was determined using the World Federation of Neurological Societies (WFNS) scale and dichotomized into severe (grade 4-5) and non-severe (1-3). Neurological outcome after 3 months was assessed by the Glasgow outcome scale and dichotomized into unfavorable (1-3) and favorable (4-5). The predictive value was assessed using receiver operating curve (ROC) analysis. RESULTS: Systemic PCT levels were significantly higher in patients with severe SAH compared to those with non-severe SAH: 0.06 ± 0.04 versus 0.11 ± 0.11 µg/l (median ± interquartile range; p < 0.01). Patients with unfavorable outcome had significantly higher PCT levels compared to those with favorable outcome 0.09 ± 0.13 versus 0.07 ± 0.15 ng/ml (p < 0.01). ROC analysis showed an area under the curve of 0.66 (p < 0.01) for PCT, which was significantly lower than that of WFNS with 0.83 (p < 0.01). CONCLUSIONS: Early PCT levels in patients with SAH might reflect the severity of the overall initial stress response. However, the predictive value is poor, especially compared to the reported predictive values in patients with OHCA. Early PCT levels might be of little use in predicting neurological outcome after SAH.

Filament perforation model for mouse subarachnoid hemorrhage: surgical-technical considerations.

OBJECTIVE: Mouse subarachnoid hemorrhage (SAH) models are becoming increasingly important. We aimed to report and discuss the detailed technical-surgical approach and difficulties associated with the circle of Willis perforation (cWp) model, with reference to the existing literature. METHODS: First, the cWp model was reproduced using ddY mice following scarification at 0 h, Days 1, 2, and 3 after SAH. Second, C57BL/6 mice were subjected to SAH with histological examination on Days 1, 2, and 3. Sham-operated mice were sacrificed on Day 2. Neurological performance, amount of subarachnoid blood, cerebral vasospasm (CVS), and neuronal injury were assessed. Relevant articles found in the MEDLINE database were reviewed. RESULTS: Induction of SAH was successfully reproduced. The volume of subarachnoid blood decreased with time due to resorption. Neurological performance was worse in SAH compared with sham. Signs of CVS could be confirmed on Days 2 and 3, but not Day 1. The cumulative number of microthrombi was significantly higher on Days 2 and 3, but not Day 1. Apoptotic and degenerative neurons were found in the cortex and hippocampal area. Our review of the literature revealed the cWp model to be the most frequently used. The present findings largely confirmed previously published results. However, detailed technical-surgical description and its discussion were sparse, which we provide here. CONCLUSIONS: The current study provides additional useful information characterizing the cWp model. This model may be of first choice at present, as important pathologies can be reproduced and most findings in the literature are based on it.

Monitoring of cerebral hemodynamics and oxygenation to detect delayed ischemic neurological deficit after aneurysmal subarachnoid hemorrhage.

One of the major goals in the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH) is early detection and treatment of delayed ischemic neurologic deficits (DINDs) to prevent cerebral infarction and thus poor outcome or even death. The complex changes of cerebral metabolism, hemodynamics, and oxygenation after SAH are underestimated if they are considered exclusively based on angiographic cerebral vasospasm (CVS). The discrepancies on one hand may arise from the heterogeneous and complex pathophysiology of DINDs. On the other hand, the occurrence of DINDs may depend on the relationship between local cerebral oxygen delivery and demand, which can only be determined if cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)) can be measured. We briefly review the most relevant methods for monitoring cerebral hemodynamics and oxygenation and discuss the limitations associated with early diagnosis of DINDs in patients with severe aSAH not amenable for clinical neurological examination.

Systemic interleukin-6 levels reflect illness course and prognosis of patients with spontaneous nonaneurysmal subarachnoid hemorrhage.

BACKGROUND: Patients with nonaneurysmal -subarachnoid hemorrhage (SAH) show either perimesencephal (pm)SAH or nonperimesencephalic (non-pm)SAH, with hemorrhage extending into adjacent cisterns. Patients with non-pmSAH have higher risk for a complicated clinical course with cerebral vasospasm (CVS) and worse outcome. Systemic inflammatory response has been linked to CVS occurrence and worse outcome in aneurysmal SAH. We analyzed whether levels of interleukin (IL)-6, a proinflammatory cytokine, differ in patients with pmSAH compared with non-pmSAH. METHODS: The clinical course with attention to symptomatic CVS occurrence and clinical outcome was assessed. Daily systemic IL-6 levels and leukocyte counts (Lc) were measured in the acute phase in 11 patients with pmSAH and in 9 patients with non-pmSAH. RESULTS: Patients with non-pmSAH had significantly higher IL-6 levels compared to patients with pmSAH (14.7 ± 3.2 vs. 3.0 ± 0.6 pg/ml, p = 0.001). Lc counts did not differ (11.5 ± 0.5 vs. 11.2 ± 0.6 × 10(3)/µl, p = 0.485). Patients with non-pmSAH stayed significantly longer in the neurocritical care unit (16.4 ± 2.1 vs. 10.2 ± 1.1 days, p = 0.012). Symptomatic CVS occurred in two patients with non-pmSAH. Patients with pmSAH had a significantly more favorable outcome, defined as Glasgow Outcome Scale 5. CONCLUSION: Higher IL-6 levels in patients with non-pmSAH supports the common observation of more complicated illness course with higher incidence of CVS compared to patients with pmSAH.

The concept of a hybrid operating room: applications in cerebrovascular surgery.

The use of intraoperative digital substraction angiography (iDSA) is a tool in cerebrovascular surgery. According to recent studies, iDSA has been shown to alter surgical treatment in approximately 12% of cases. Moreover, it has been demonstrated that even experienced cerebrovascular surgeons might not accurately predict the need for iDSA. Intraoperative DSA prevents unnecessary surgical manipulations after occlusion of aneurysms and accurately demonstrates occlusion rates. We present our preliminary experience using routine iDSA within the concept of a hybrid operating room for cerebrovascular surgery. A total of 99 patients underwent iDSA in our hybrid operating room. Indications included intraoperative evaluation of occlusion rate of clipped aneurysms and patency of vicinity vessels (n = 82), chemical angioplasty with papaverin (n = 4), and balloon angioplasty (n = 1). In four (5%) patients, a reposition of the clip was needed due to neck remnant and perfusion of the aneurysm sack after clipping. A total of five cases underwent combined microsurgical and endovascular treatment of ruptured aneurysms and arteriovenous malformations (AVMs). The concept of a hybrid operating room has been considered in the planning and design of operation rooms dedicated to cerebrovascular surgery. Hybrid procedures combining endovascular with microsurgical strategies within the same surgical session are feasible and safe. These procedures are associated with cost-benefit advantages.

ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion.

Reperfusion after brain ischemia causes thrombus formation and microcirculatory disturbances, which are dependent on the platelet glycoprotein Ib-von Willebrand factor (VWF) axis. Because ADAMTS13 cleaves VWF and limits platelet-dependent thrombus growth, ADAMTS13 may ameliorate ischemic brain damage in acute stroke. We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion model in Adamts13(-/-) and wild-type mice. After reperfusion for 0.5 hours, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13(-/-) mice compared with wild-type mice (P < .05), which also resulted in a larger infarct volume after 24 hours for Adamts13(-/-) compared with wild-type mice (P < .01). Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion. These results indicate that ADAMTS13 may be a useful therapeutic agent for stroke.

Novel treatments for vasospasm after subarachnoid hemorrhage.

PURPOSE OF REVIEW: Cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage remains a considerable challenge in neurocritical care medicine. This review aims to cover the recent novel aspects and results in CVS treatment. RECENT FINDINGS: On the basis of the recent literature, treatment focusing on CVS alone is outdated. A considerable amount of evidence suggests CVS not to be the sole cause of delayed cerebral ischemia (DCI) and poor outcome. Early brain injury, cortical spreading depolarization, inflammation and microthrombosis have recently been discussed as additional factors. The results of a well designed phase III trial, using an endothelin-1 antagonist, indicated a decrease in the occurrence of CVS but did not change the clinical outcome significantly. Induced hypertension is currently recommended for treating suspected DCI, whereas hemodilution and hypervolemia are not. Endovascular intervention is only recommended in case of refractory symptomatic CVS. A couple of newer treatment strategies are under evaluation. Phase III trials are underway for magnesium sulfate and statins. Clinical trials aiming specifically at recently discussed factors other than CVS have not been reported. SUMMARY: Reviewing the recent literature, there have been some updates on recommendations and newer treatment modalities are under evaluation. However, a novel treatment with convincing evidence has not been reported so far.

ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury.

Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia-reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia-reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24 h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24 h after MCAO (p < 0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia-reperfusion (p < 0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia-reperfusion injury by regulating VWF-dependent inflammation as well as microvascular plugging.

Functional relationship of arterial blood pressure, central venous pressure and intracranial pressure in the early phase after subarachnoid hemorrhage.

BACKGROUND: Intracranial pressure (ICP) and arterial blood pressure (ABP) are related to each other through cerebral autoregulation. Central venous pressure (CVP) is often measured to estimate cardiac filling pressures as an approximate measure for the volume status of a patient. Prior modelling efforts have formalized the functional relationship between CVP, ICP and ABP. However, these models were used to explain short segments of data during controlled experiments and have not yet been used to explain the slowly evolving ICP increase that occurs typically in patients after aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To analyze the functional relationship between ICP, ABP and CVP recorded from SAH patients in the first five days after aneurysm. METHODS: Two methods were used to elucidate this relationship on the running average of the signals: First, using Spearman correlation coefficients calculated over 30 min segments Second, for each patient, linear state space models of ICP as the output and ABP and CVP as inputs were estimated. RESULTS: The mean and variance of the data and the correlation coefficients between ICP-ABP and ICP-CVP vary over time as the patient progresses through their stay in the ICU. On average, after an SAH event, the models show that a) ABP is the bigger driver of changes in ICP than CVP and that increasing ABP leads to reduction in ICP and (b) increasing CVP leads to an increase in ICP. CONCLUSIONS: Finding a) agrees with the hypothesis that patients with subarachnoid hemorrhage have defective autoregulation, and b) agrees with the positive correlation observed between central venous pressure and intracranial pressure in the literature.

ICU Cockpit: a platform for collecting multimodal waveform data, AI-based computational disease modeling and real-time decision support in the intensive care unit.

ICU Cockpit: a secure, fast, and scalable platform for collecting multimodal waveform data, online and historical data visualization, and online validation of algorithms in the intensive care unit. We present a network of software services that continuously stream waveforms from ICU beds to databases and a web-based user interface. Machine learning algorithms process the data streams and send outputs to the user interface. The architecture and capabilities of the platform are described. Since 2016, the platform has processed over 89 billion data points (N = 979 patients) from 200 signals (0.5-500 Hz) and laboratory analyses (once a day). We present an infrastructure-based framework for deploying and validating algorithms for critical care. The ICU Cockpit is a Big Data platform for critical care medicine, especially for multimodal waveform data. Uniquely, it allows algorithms to seamlessly integrate into the live data stream to produce clinical decision support and predictions in clinical practice.

Extracranial-intracranial bypass in atherosclerotic cerebrovascular disease: report of a single centre experience.

Despite the failure of the international extracranial-intracranial (EC-IC) bypass study in showing the benefit of bypass procedure for prevention of stroke recurrence, it has been regarded to be beneficial in a subgroup of well-selected patients with haemodynamic impairment. This report includes the EC-IC bypass experience of a single centre over a period of 14 years. All consecutive 72 patients with atherosclerotic occlusive cerebrovascular lesions associated with haemodynamic compromise treated by EC-IC bypass surgery were retrospectively reviewed. Pre-operatively, 61% of patients presented with minor stroke and the remaining 39% with recurrent transient ischemic attacks (TIAs) despite maximal medical therapy. Angiography revealed a unilateral internal carotid artery (ICA) stenosis/occlusion in 79%, bilateral ICA stenosis/occlusion in 15%, MCA stenosis/occlusion in 3% and other multiple vessel stenosis/occlusion in 3% of the cases. H(2)(15)O positron emission tomography (PET) or 99mTc-HMPAO SPECT with acetazolamide challenge was performed for haemodynamic evaluation of the cerebral blood flow (CBF). All the patients had impaired haemodynamics pre-operatively in terms of reduced regional cerebrovascular reserve capacity and rCBF. Standard STA-MCA bypass procedure was performed in all patients. A total of 68 patients with 82 bypasses were reviewed with a mean follow-up period of 34 months. Stroke recurrence took place in 10 patients (15%) resulting in an annual stroke risk of 5%. Improved cerebral haemodynamics was documented in 81% of revascularised hemispheres. Patients with unchanged or worse haemodynamic parameters had significantly more post-operative TIAs or strokes when compared to those with improved perfusion reserves (30% vs.5% of patients, p<0.05). In conclusion, EC-IC bypass procedure in selected patients with occlusive cerebrovascular lesions associated with haemodynamic impairment has revealed to be effective for prevention of further cerebral ischemia, when compared with a stroke risk rate of 15% reported to date in patients only under antiplatelet agents or anticoagulant therapy.