Early Brain Injury After Subarachnoid Hemorrhage: Incidence and Mechanisms.

Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.

Inhalational Versus Intravenous Anesthetic Conditioning for Subarachnoid Hemorrhage-Induced Delayed Cerebral Ischemia.

BACKGROUND: Inhalational anesthetics were associated with reduced incidence of angiographic vasospasm and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). Whether intravenous anesthetics provide similar level of protection is not known. METHODS: Anesthetic data were collected retrospectively for patients with SAH who received general anesthesia for aneurysm repair between January 1, 2014 and May 31, 2018, at 2 academic centers in the United States (one employing primarily inhalational and the other primarily intravenous anesthesia with propofol). We compared the outcomes of angiographic vasospasm, DCI, and neurological outcome (measured by disposition at hospital discharge), between the 2 sites, adjusting for potential confounders. RESULTS: We compared 179 patients with SAH receiving inhalational anesthetics at one institution to 206 patients with SAH receiving intravenous anesthetics at the second institution. The rates of angiographic vasospasm between inhalational versus intravenous anesthetic groups were 32% versus 52% (odds ratio, 0.49 [CI, 0.32-0.75]; P=0.001) and DCI were 21% versus 40% (odds ratio, 0.47 [CI, 0.29-0.74]; P=0.001), adjusting for imbalances between sites/groups, Hunt-Hess and Fisher grades, type of aneurysm treatment, and American Society of Anesthesiology status. No impact of anesthetics on neurological outcome at time of discharge was noted with rates of good discharge outcome between inhalational versus intravenous anesthetic groups at (78% versus 72%, P=0.23). CONCLUSIONS: Our data suggest that those who received inhalational versus intravenous anesthetic for ruptured aneurysm repair had significant protection against SAH-induced angiographic vasospasm and DCI. Although we cannot fully disentangle site-specific versus anesthetic effects in this comparative study, these results, when coupled with preclinical data demonstrating a similar protective effect of inhalational anesthetics on vasospasm and DCI, suggest that inhalational anesthetics may be preferable for patients with SAH undergoing aneurysm repair. Additional investigations examining the effect of inhalational anesthetics on other SAH outcomes such as early brain injury and long-term neurological outcomes are warranted.

Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH. METHODS: We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome. RESULTS: Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3-11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients. CONCLUSIONS: Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

Role of Anesthetics and Their Adjuvants in Neurovascular Protection in Secondary Brain Injury after Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or endovascular repair of their aneurysm. Given the potential impact certain anesthetics have on secondary brain injury after SAH, appropriate selection of anesthetics may prove impactful on overall outcome of these patients. This narrative review focuses on the available evidence of anesthetics and their adjuvants in neurovascular protection in aneurysmal subarachnoid hemorrhage and discusses current impact on clinical care and future investigative directions.

Role of SIRT1 in Isoflurane Conditioning-Induced Neurovascular Protection against Delayed Cerebral Ischemia Secondary to Subarachnoid Hemorrhage.

We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. The aim of our current study is to examine the role of SIRT1 in isoflurane conditioning-induced neurovascular protection against SAH-induced DCI. Mice were divided into four groups: sham, SAH, or SAH with isoflurane conditioning (with and without EX-527). Experimental SAH via endovascular perforation was performed. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. EX-527, a selective SIRT1 inhibitor, 10 mg/kg was injected intraperitoneally immediately after SAH in the EX-527 group. SIRT1 mRNA expression and activity levels were measured. Vasospasm, microvessel thrombosis, and neurological outcome were assessed. SIRT1 mRNA expression was downregulated, and no difference in SIRT1 activity was noted after isoflurane exposure. Isoflurane conditioning with and without EX-527 attenuated vasospasm, microvessel thrombosis and improved neurological outcomes. Our data validate our previous findings that isoflurane conditioning provides strong protection against both the macro and micro vascular deficits induced by SAH, but this protection is likely not mediated through the SIRT1 pathway.

Effects of Hypoxic and Ischemic Clinical Conditions on the Outcomes of Acute Ischemic Stroke Patients.

BACKGROUND: Several studies have shown the neuroprotective role afforded by hypoxic and ischemic preconditioning in cerebrovascular disorders. There are several clinical conditions which simulate the hypoxic and ischemic conditioning in humans. The aim of this retrospective study is to identify whether the presence of any clinical scenarios mimicking the hypoxic and ischemic conditions prior to the current acute ischemic stroke (AIS) has a neuroprotective role in these patients. MATERIALS AND METHODS: Data were collected for patients >18 years of age who underwent endovascular treatment for AIS from January 2009 to June 2015. A good outcome was defined as modified Rankin score (mRS) of 0 to 3 at discharge and a poor outcome as mRS of 4-6. A logistic regression analysis was performed to identify independent predictors of outcomes at discharge in both groups. A p value of <0.05 was considered statistically significant for all analyses. RESULTS: A total of 102 patients, aged 67 ± 16 years with median preprocedural National Institute of Health Stroke Scale (NIHSS) score 17.5 (1-36), were included. Twenty-one (21%) patients had a good outcome (mRS: 0-3) and 81 (79%) had a poor outcome (mRS: 4-6). A logistic regression analysis identified higher NIHSS score [odds ratio (OR): 1.251, confidence interval (CI): 1.11-1.40, p = 0.0002] and history of transient ischemic attack (TIA; OR: 7.881, CI: 1.05-21.01, p < 0.04) as predictors of a poor outcome at discharge. CONCLUSION: Our data suggest that the occurrence of TIA preceding an AIS may be associated with the poor outcomes in patients with AIS, although this finding needs confirmation in larger studies. HOW TO CITE THIS ARTICLE: Athiraman U, Tempelhoff R, Karanikolas M. Effects of Hypoxic and Ischemic Clinical Conditions on the Outcomes of Acute Ischemic Stroke Patients. Indian J Crit Care Med 2020;24(2):104-108.

Anesthetic management of 877 pediatric patients undergoing muscle biopsy for neuromuscular disorders: a 20-year review.

BACKGROUND: The objectives are to review the anesthetic management and anesthetic-related adverse events in patients undergoing muscle biopsy for a broad spectrum of neuromuscular disorders (NMD). AIM: The study aims to assess the hypothesis that perceived awareness of potential anesthesia-induced hyperkalemia and MH in patients with NMD reduces the frequency of such events. METHODS: A 20-year retrospective review of 877 consecutive patients undergoing muscle biopsy to establish diagnoses of NMD has been performed. Patients were categorized prebiopsy into six groups: M (myopathy and muscular dystrophy), MM (mitochondrial or metabolic myopathy), N (neurodegenerative, peripheral neuropathy or spinal muscular atrophy disorder), D (dermatomyositis), C (cardiomyopathy), or S (seizure disorder). Data were collected for demographics, anesthetic management, pre- and postoperative anesthesia-induced muscle injury, postbiopsy histopathologic diagnosis, and concordance comparisons between pre- and postbiopsy diagnoses. RESULTS: There were 513 males (58.5%) and 364 females (41.5%) (1.4:1) with 137 individuals (15.6%) operated on under 1 year of age and two-thirds by 6 years of age. NMD diagnosis was reached in 409 (46.6%) while 468 (53.4%) had no specific pathology. No patients exhibited signs of anesthesia-induced muscle injury (malignant hyperthermia, rhabdomyolysis, cardiac arrest, or postoperative deterioration of weakness). MM was the largest group pre biopsy (367, 41.8%). Anesthetic agents were: nitrous oxide in 657 (74.9%); volatile agents in 139 (15.8%); intravenous agents in 836 (95.3%) (primarily propofol, midazolam, and fentanyl); nondepolarizing muscle relaxants in 404 (46.1%); and regional anesthesia in 112 (12.8%) [most commonly spinal anesthesia in 80 (71.4%)]. Comparing preoperative diagnostic category with postoperative diagnosis, there was a concordance of 78% (319/409) between the two for cases with a definitive diagnosis and 89.7% (787/877) for all cases. CONCLUSIONS: In this retrospective study, no patient exhibited signs or symptoms of hyperkalemia or MH probably because the incidence is very low and becomes even less likely due to the selection of the various anesthetic agents and strategies administered.

Performance of computer simulated inhalational anesthetic uptake model in comparison with real time isoflurane concentration.

Gas Man software was developed to enhance our understanding of the pharmacokinetics of inhalational anaesthetics. To date the Gas Man software has not been validated in humans. In this study we compared the Gas Man software with real time measured end tidal isoflurane concentrations while using a semi closed circle system in anesthetised patients. Thirty-four ASA I and II patients 18-60 years of age were selected for the study. After a standardized induction anesthesia was maintained with N2O + O2 mixture and isoflurane using the circle system. The fresh gas flow or dial setting of Isoflurane vaporizer were changed at random. The inspired and end-tidal concentration values of isoflurane measured at 1 min intervals were retrieved from the patient monitor. Real time anesthetic settings for the patient were simultaneously simulated in the Gas Man software to generate the inspired and end-tidal concentration of isoflurane values at every minute for comparison. Varvel's criteria have been used to assess this model. The median absolute performance error was 9.39 %, median performance error was -5.30 %, wobble was 5.16 %, and divergence was -1.82 %. All criteria were within limits of the acceptable performance of the model. The end-tidal concentration values of isoflurane in real patients are very close to those predicted by Gas Man software. The pharmocokinetics of inhalational anesthetic administration in patients can be taught accurately using Gas Man technology. This technology may also help in developing different kinetic models of inhalational agents in the body.

Isoflurane preconditioning induced genomic changes in mouse cortex.

Background: Altered patterns of genetic expression induced by isoflurane preconditioning in mouse brain have not yet been investigated. The aim of our pilot study is to examine the temporal sequence of changes in the transcriptome of mouse brain cortex produced by isoflurane preconditioning. Methods: Twelve-wk-old wild-type (C57BL/6J) male mice were randomly assigned for the experiments. Mice were exposed to isoflurane 2% in air for 1 h and brains were harvested at the following time points-immediately (0 h), and at 6, 12, 24, 36, 48, and 72 h after isoflurane exposure. A separate cohort of mice were exposed to three doses of isoflurane on days 1, 2, and 3 and brains were harvested after the third exposure. The NanoString mouse neuropathology panel was used to analyse isoflurane-induced gene expression in the cortex. The neuropathology panel included 760 genes covering pathways involved in neurodegeneration and other nervous system diseases, and 10 internal reference genes for data normalisation. Results: Genes involving several pathways were upregulated and downregulated by isoflurane preconditioning. Interestingly, a biphasic response was noted, meaning, an early expression of genes (until 6 h), followed by a transient pause (until 24 h), and a second wave of genomic response beginning at 36 h of isoflurane exposure was noted. Conclusions: Isoflurane preconditioning induces significant alterations in the genes involved in neurodegeneration and other nervous system disorders in a temporal sequence. These data could aid in the identification of molecular mechanisms behind isoflurane preconditioning-induced neuroprotection in various central nervous system diseases.

Role of microglia after subarachnoid hemorrhage.

Subarachnoid hemorrhage is a devastating sequela of aneurysm rupture. Because it disproportionately affects younger patients, the population impact of hemorrhagic stroke from subarachnoid hemorrhage is substantial. Secondary brain injury is a significant contributor to morbidity after subarachnoid hemorrhage. Initial hemorrhage causes intracranial pressure elevations, disrupted cerebral perfusion pressure, global ischemia, and systemic dysfunction. These initial events are followed by two characterized timespans of secondary brain injury: the early brain injury period and the delayed cerebral ischemia period. The identification of varying microglial phenotypes across phases of secondary brain injury paired with the functions of microglia during each phase provides a basis for microglia serving a critical role in both promoting and attenuating subarachnoid hemorrhage-induced morbidity. The duality of microglial effects on outcomes following SAH is highlighted by the pleiotropic features of these cells. Here, we provide an overview of the key role of microglia in subarachnoid hemorrhage-induced secondary brain injury as both cytotoxic and restorative effectors. We first describe the ontogeny of microglial populations that respond to subarachnoid hemorrhage. We then correlate the phenotypic development of secondary brain injury after subarachnoid hemorrhage to microglial functions, synthesizing experimental data in this area.

Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage - A critical review.

Aneurysmal subarachnoid hemorrhage (SAH) carries significant mortality and morbidity, with nearly half of SAH survivors having major cognitive dysfunction that impairs their functional status, emotional health, and quality of life. Apart from the initial hemorrhage severity, secondary brain injury due to early brain injury and delayed cerebral ischemia plays a leading role in patient outcome after SAH. While many strategies to combat secondary brain injury have been developed in preclinical studies and tested in late phase clinical trials, only one (nimodipine) has proven efficacious for improving long-term functional outcome. The causes of these failures are likely multitude, but include use of therapies targeting only one element of what has proven to be multifactorial brain injury process. Conditioning is a therapeutic strategy that leverages endogenous protective mechanisms to exert powerful and remarkably pleiotropic protective effects against injury to all major cell types of the CNS. The aim of this article is to review the current body of evidence for the use of conditioning agents in SAH, summarize the underlying neuroprotective mechanisms, and identify gaps in the current literature to guide future investigation with the long-term goal of identifying a conditioning-based therapeutic that significantly improves functional and cognitive outcomes for SAH patients.

Quality assurance for focused ultrasound-induced blood-brain barrier opening procedure using passive acoustic detection.

BACKGROUND: Focused ultrasound (FUS) combined with microbubbles is a promising technique for noninvasive, reversible, and spatially targeted blood-brain barrier opening, with clinical trials currently ongoing. Despite the fast development of this technology, there is a lack of established quality assurance (QA) strategies to ensure procedure consistency and safety. To address this challenge, this study presents the development and clinical evaluation of a passive acoustic detection-based QA protocol for FUS-induced blood-brain barrier opening (FUS-BBBO) procedure. METHODS: Ten glioma patients were recruited to a clinical trial for evaluating a neuronavigation-guided FUS device. An acoustic sensor was incorporated at the center of the FUS device to passively capture acoustic signals for accomplishing three QA functions: FUS device QA to ensure the device functions consistently, acoustic coupling QA to detect air bubbles trapped in the acoustic coupling gel and water bladder of the transducer, and FUS procedure QA to evaluate the consistency of the treatment procedure. FINDINGS: The FUS device passed the device QA in 9/10 patient studies. 4/9 cases failed acoustic coupling QA on the first try. The acoustic coupling procedure was repeatedly performed until it passed QA in 3/4 cases. One case failed acoustic coupling QA due to time constraints. Realtime passive cavitation monitoring was performed for FUS procedure QA, which captured variations in FUS-induced microbubble cavitation dynamics among patients. INTERPRETATION: This study demonstrated that the proposed passive acoustic detection could be integrated with a clinical FUS system for the QA of the FUS-BBBO procedure. FUNDING: National Institutes of Health R01CA276174, R01MH116981, UG3MH126861, R01EB027223, R01EB030102, and R01NS128461.

A Global Review of the Perioperative Care of Patients With Aneurysmal Subarachnoid Hemorrhage Undergoing Microsurgical Repair of Ruptured Intracerebral Aneurysm.

INTRODUCTION: To describe the perioperative care of patients with aneurysmal subarachnoid hemorrhage (aSAH) who undergo microsurgical repair of a ruptured intracerebral aneurysm. METHODS: An English language survey examined 138 areas of the perioperative care of patients with aSAH. Reported practices were categorized as those reported by <20%, 21% to 40%, 41% to 60%, 61% to 80%, and 81% to 100% of participating hospitals. Data were stratified by Worldbank country income level (high-income or low/middle-income). Variation between country-income groups and between countries was presented as an intracluster correlation coefficient (ICC) and 95% confidence interval (CI). RESULTS: Forty-eight hospitals representing 14 countries participated in the survey (response rate 64%); 33 (69%) hospitals admitted ≥60 aSAH patients per year. Clinical practices reported by 81 to 100% of the hospitals included placement of an arterial catheter, preinduction blood type/cross match, use of neuromuscular blockade during induction of general anesthesia, delivering 6 to 8 mL/kg tidal volume, and checking hemoglobin and electrolyte panels. Reported use of intraoperative neurophysiological monitoring was 25% (41% in high-income and 10% in low/middle-income countries), with variation between Worldbank country-income group (ICC 0.15, 95% CI 0.02-2.76) and between countries (ICC 0.44, 95% CI 0.00-0.68). The use of induced hypothermia for neuroprotection was low (2%). Before aneurysm securement, variable in blood pressure targets was reported; systolic blood pressure 90 to 120 mm Hg (30%), 90 to 140 mm Hg (21%), and 90 to 160 mmHg (5%). Induced hypertension during temporary clipping was reported by 37% of hospitals (37% each in high and low/middle-income countries). CONCLUSIONS: This global survey identifies differences in reported practices during the perioperative management of patients with aSAH.

Automated Quantification of Compartmental Blood Volumes Enables Prediction of Delayed Cerebral Ischemia and Outcomes After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: The role of hemorrhage volume in risk of vasospasm, delayed cerebral ischemia (DCI), and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH) is well established. However, the relative contribution of blood within individual compartments is unclear. We present an automated technique for measuring not only total but also volumes of blood in each major compartment after SAH. METHODS: We trained convolutional neural networks to identify compartmental blood (cisterns, sulci, and ventricles) from baseline computed tomography scans of patients with SAH. We compared automated blood volumes against traditional markers of bleeding (modified Fisher score [mFS], Hijdra sum score [HSS]) in 190 SAH patients for prediction of vasospasm, DCI, and functional status (modified Rankin Scale) at hospital discharge. RESULTS: Combined cisternal and sulcal volume was better correlated with mFS and HSS than cisternal volume alone (ρ = 0.63 vs. 0.58 and 0.75 vs. 0.70, P < 0.001). Only blood volume in combined cisternal plus sulcal compartments was independently associated with DCI (OR 1.023 per mL, 95% CI 1.002-1.048), after adjusting for clinical factors while ventricular blood volume was not. Total and specifically sulcal blood volume was strongly associated with poor outcome (OR 1.03 per mL, 1.01-1.06, P = 0.006 and OR 1.04, 1.00-1.08 for sulcal) as was HSS (OR 1.06 per point, 1.00-1.12, P = 0.04), while mFS was not (P = 0.24). CONCLUSIONS: An automated imaging algorithm can measure the volume of bleeding after SAH within individual compartments, demonstrating cisternal plus sulcal (and not ventricular) blood contributes to risk of DCI/vasospasm. Automated blood volume was independently associated with outcome, while qualitative grading was not.

Propofol Affords No Protection against Delayed Cerebral Ischemia in a Mouse Model of Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is an important contributor to poor outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. We previously showed that volatile anesthetics such as isoflurane, sevoflurane and desflurane provided robust protection against SAH-induced DCI, but the impact of a more commonly used intravenous anesthetic agent, propofol, is not known. The goal of our current study is to examine the neurovascular protective effects of propofol on SAH-induced DCI. Twelve-week-old male wild-type mice were utilized for the study. Mice underwent endovascular perforation SAH or sham surgery followed one hour later by propofol infusion through the internal jugular vein (2 mg/kg/min continuous intravenous infusion). Large artery vasospasm was assessed three days after SAH. Neurological outcome assessment was performed at baseline and then daily until animal sacrifice. Statistical analysis was performed via one-way ANOVA and two-way repeated measures ANOVA followed by the Newman-Keuls multiple comparison test with significance set at p < 0.05. Intravenous propofol did not provide any protection against large artery vasospasm or sensory-motor neurological deficits induced by SAH. Our data show that propofol did not afford significant protection against SAH-induced DCI. These results are consistent with recent clinical studies that suggest that the neurovascular protection afforded by anesthetic conditioning is critically dependent on the class of anesthetic agent.

Intraoperative Blood Pressure and Carbon Dioxide Values during Aneurysmal Repair and the Outcomes after Aneurysmal Subarachnoid Hemorrhage.

Cerebral autoregulation impairment is a critical aspect of subarachnoid hemorrhage (SAH)-induced secondary brain injury and is also shown to be an independent predictor of delayed cerebral ischemia (DCI) and poor neurologic outcomes. Interestingly, intraoperative hemodynamic and ventilatory parameters were shown to influence patient outcomes after SAH. The aim of the current study was to evaluate the association of intraoperative hypotension and hypocapnia with the occurrence of angiographic vasospasm, DCI, and neurologic outcomes at discharge. Intraoperative data were collected for 390 patients with aneurysmal SAH who underwent general anesthesia for aneurysm clipping or coiling between January 2010 and May 2018. We measured the mean intraoperative blood pressure and end-tidal carbon dioxide (ETCO2), as well as the area under the curve (AUC) for the burden of hypotension: SBP below 100 or MBP below 65 and hypocapnia (ETCO2 < 30), during the intraoperative period. The outcome measures were angiographic vasospasm, DCI, and the neurologic outcomes at discharge as measured by the modified Rankin scale score (an mRS of 0-2 is a good outcome, and 3-6 is a poor outcome). Univariate and logistic regression analyses were performed to evaluate whether blood pressure (BP) and ETCO2 variables were independently associated with outcome measures. Out of 390 patients, 132 (34%) developed moderate-to-severe vasospasm, 114 (29%) developed DCI, and 46% (169) had good neurologic outcomes at discharge. None of the measured intraoperative BP and ETCO2 variables were associated with angiographic vasospasm, DCI, or poor neurologic outcomes. Our study did not identify an independent association between the degree of intraoperative hypotension or hypocapnia in relation to angiographic vasospasm, DCI, or the neurologic outcomes at discharge in SAH patients.

The Regional Cerebral Oxygen Saturation Effect of Inotropes/Vasopressors Administered to Treat Intraoperative Hypotension: A Bayesian Network Meta-analysis.

One of the main concerns of intraoperative hypotension is adequacy of cerebral perfusion, as cerebral blood flow decreases passively when mean arterial pressure falls below the lower limit of cerebral autoregulation. Treatment of intraoperative hypotension includes administration of drugs, such as inotropes and vasopressors, which have different pharmacological effects on cerebral hemodynamics; there is no consensus on the preferred drug to use. We performed a network meta-analysis (NMA) to pool and analyze data comparing the effect on cerebral oxygen saturation (ScO 2 ) measured by cerebral oximetry of various inotropes/vasopressors used to treat intraoperative hypotension. We searched randomized control trials in Embase, Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that enrolled adult patients undergoing surgery under general/spinal anesthesia that compared at least 2 inotropes/vasopressors to treat hypotension. We reviewed 51 full-text manuscripts and included 9 randomized controlled trials in our study. The primary outcome was change in ScO 2 . Our results showed the likelihood that dopamine, ephedrine, and norepinephrine had the lowest probability of decreasing ScO 2 . The suggested rank order to maintain ScO 2 , from higher to lower, was dopamine

The Association Between Illness Severity Scores and In-hospital Mortality After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: The purpose of this study was to examine the association with in-hospital mortality of 8 illness severity scores in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In a retrospective cohort study, we investigated the association with in-hospital mortality of admission Hunt and Hess (HH) score, Fisher grade, severity of illness and risk of mortality scores, and serial Glasgow coma scale (GCS) score in patients with aSAH. We also explored the changes in GCS between admission and discharge using a multivariate model adjusting for age, clinical vasospasm, and external ventricular drain status. RESULTS: Data from 480 patients with aSAH, of which 383 (79.8%) aneurysms were in the anterior circulation, were included in analysis. Patients were female (n=340, 70.8%) with a median age of 56 (interquartile range: 48 to 66) years. The majority (n=332, 69.2%) had admission HH score 3 to 5, Fisher grade 3 to 4 (n=437, 91%), median severity of illness 3 (range: 1 to 4), median risk of mortality 3 (range: 1 to 4), and median admission GCS of 13 (interquartile range: 7 to 15). Overall, 406 (84.6%) patients received an external ventricular drain, 469 (97.7%) underwent aneurysm repair, and 60 died (12.5%). Compared with admission HH score, GCS 24 hours after admission (area under the curve: 0.84, 95% confidence interval [CI]: 0.79-0.88) and 24 hours after aneurysm repair (area under the curve: 0.87, 95% CI: 0.82-0.90) were more likely to be associated with in-hospital mortality. Among those who died, the greatest decline in GCS was noted between 24 hours after aneurysm repair and discharge (-3.38 points, 95% CI: -4.17, -2.58). CONCLUSIONS: Compared with admission HH score, GCS 24 hours after admission (or 24 h after aneurysm repair) is more likely to be associated with in-hospital mortality after aSAH.

Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) Quality Metrics in Patients Undergoing Decompressive Craniectomy and Endoscopic Clot Evacuation after Spontaneous Supratentorial Intracerebral Hemorrhage: A Retrospective Observational Study.

BACKGROUND: We report adherence to 6 Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) quality metrics (QMs) relevant to patients undergoing decompressive craniectomy or endoscopic clot evacuation after spontaneous supratentorial intracerebral hemorrhage (sICH). METHODS: In this retrospective observational study, we describe adherence to the following ASPIRE QMs: acute kidney injury (AKI-01); mean arterial pressure < 65 mm Hg for less than 15 minutes (BP-03); myocardial injury (CARD-02); treatment of high glucose (> 200 mg/dL, GLU-03); reversal of neuromuscular blockade (NMB-02); and perioperative hypothermia (TEMP-03). RESULT: The study included 95 patients (70% male) with median (interquartile range) age 55 (47 to 66) years and ICH score 2 (1 to 3) undergoing craniectomy (n=55) or endoscopic clot evacuation (n=40) after sICH. In-hospital mortality attributable to sICH was 23% (n=22). Patients with American Society of Anesthesiologists physical status class 5 (n=16), preoperative reduced glomerular filtration rate (n=5), elevated cardiac troponin (n=21) and no intraoperative labs with high glucose (n=71), those who were not extubated at the end of the case (n=62) or did not receive a neuromuscular blocker given (n=3), and patients having emergent surgery (n=64) were excluded from the analysis for their respective ASPIRE QM based on predetermined ASPIRE exclusion criteria. For the remaining patients, the adherence to ASPIRE QMs were: AKI-01, craniectomy 34%, endoscopic clot evacuation 1%; BP-03, craniectomy 72%, clot evacuation 73%; CARD-02, 100% for both groups; GLU-03, craniectomy 67%, clot evacuation 100%; NMB-02, clot evacuation 79%, and; TEMP-03, clot evacuation 0% with hypothermia. CONCLUSION: This study found variable adherence to ASPIRE QMs in sICH patients undergoing decompressive craniectomy or endoscopic clot evacuation. The relatively high number of patients excluded from individual ASPIRE metrics is a major limitation.

First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound.

Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome cell-free DNA (cfDNA) fragments (120-280 bp), 1.9-fold for the patient-specific tumor variant ctDNA level, and 5.6-fold for the TERT mutation ctDNA level. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication modulated cell physical structure-related genes. Only 2 out of 17,982 total detected genes related to the immune pathways were upregulated. These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.