Christos Lazaridis

CT perfusion-guided patient selection for endovascular treatment of acute ischemic stroke is safe and effective

Background Traditional treatment in acute ischemic stroke is based on time criteria when administering intravenous and intra-arterial therapies. However, recent evidence suggests that image-based criteria may be useful for selecting patients for intra-arterial interventions. The use of CT perfusion (CTP)-based criteria, regardless of time from symptom onset, in patient selection for intra-arterial treatment of ischemic stroke was assessed. Methods Patients with ischemic stroke who presented to the emergency department at the Medical University of South Carolina with a National Institute of Health Stroke Scale score of ≥ 8, regardless of time from symptom onset, were assessed retrospectively. CTP maps were qualitatively assessed for the presence of penumbra and infarction. Selected patients underwent mechanical aspiration of their occlusion using the Penumbra system. Functional outcome was then recorded using the modified Rankin scale (mRS) at 90 days or the closest follow-up to 90 days. Results 53 patients were included in the study. The median time from symptom onset to groin vascular access was 6.3 h. Eight patients (15%) had bleeding complications including subarachnoid hemorrhage, parenchymal hemorrhage and intraventricular hemorrhage. After CTP-based selection, the patients were divided into two groups for analysis: ≤6 h and >6 h from symptom onset to endovascular procedure. No difference was found in functional outcome between the two groups (38.5% and 40.7% achieved 90-day mRS ≤2, respectively (p=1.0) and 57.7% and 51.9% achieved 90-day mRS ≤3, respectively (p=0.785)). There was no difference in the rate of intracranial hemorrhage between the two groups (11.5 vs 18.5, p=0.704). Conclusion This study demonstrated similar rates of good functional outcome and intracranial hemorrhage in patients with ischemic stroke when endovascular treatment was performed based on CTP selection rather than time-guided selection. These findings suggest that endovascular reperfusion in ischemic stroke may be effective and safe, and may allow patient selection not solely based on time from symptom onset.

Intra-Aortic Balloon Pump Counterpulsation in the Setting of Subarachnoid Hemorrhage, Cerebral Vasospasm, and Neurogenic Stress Cardiomyopathy. Case Report and Review of the Literature

BackgroundThe management of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) can be often complicated by the presence of stunned myocardium and left ventricular failure. Vasopressors and inotropes are commonly used to optimize mean arterial pressure (MAP) and cerebral perfusion pressure (CPP). Intra-aortic balloon counterpulsation pump (IABP) may be indicated in the management of these patients.MethodsWe report the case of a 55-year-old patient who suffered an aSAH complicated by severe left ventricular failure, who subsequently developed symptomatic cerebral vasospasm. Left ventricular failure precluded traditional hemodynamic augmentation, and IABP was successfully used instead, which allowed for reinstitution of hypertensive hypervolemic therapy and prevented delayed cerebral ischemia.ResultsA review of the literature conducted on symptomatic cerebral vasospasm after aSAH and severe left ventricular failure revealed seven publications describing 14 patients with aSAH treated with an IABP during the period of vasospasm.ConclusionsIntra-aortic balloon counterpulsation pump (IABP) is used for hemodynamic support of patients in cardiogenic shock and its use in the setting of aSAH, cardiomyopathy, and cerebral vasospasm can be beneficial in preventing delayed ischemic deficits.

High-osmolarity saline in neurocritical care: systematic review and meta-analysis.

Background and Purpose:Intracranial hypertension and cerebral edema are known contributors to secondary brain injury and to poor neurologic outcomes. Small volume solutions of exceedingly high osmolarity, such as 23.4% saline, have been used for the management of intracranial hypertension crises and as a measure to prevent or reverse acute brain tissue shifts. We conducted a systematic literature review on the use of 23.4% saline in neurocritically ill patients and a meta-analysis of the effect of 23.4% saline on intracranial pressure reduction. Design:We searched computerized databases, reference lists, and personal files to identify all clinical studies in which 23.4% saline has been used for the treatment of neurocritical care patients. Studies that did not directly involve either effects on cerebral hemodynamics or the treatment of patients with clinical or radiographic evidence of intracranial hypertension and/or cerebral swelling were eliminated. Measurements and Main Results:We identified 11 clinical studies meeting eligibility criteria. A meta-analysis was performed to evaluate the percent decrease in intracranial pressure and the 95% confidence intervals, from baseline to 60 minutes or nadir from the six studies from which this information could be extracted. A fixed effects meta-analysis estimated that the percent decrease in intracranial pressure from baseline to either 60 minutes or nadir after administration of 23.4% saline was 55.6% (se 5.90; 95% confidence interval, 43.99–67.12; p < 0.0001). Conclusions:Highly concentrated hypertonic saline such as 23.4% provides a small volume solution with low cost and an over 50% reduction effect on raised intracranial pressure. Side effects reported are minor overall in view of the potentially catastrophic event that is being treated. High quality data are still needed to define the most appropriate osmotherapeutic agent, the optimal dose, the safest and most effective mode of administration and to further elucidate the mechanism of action of 23.4% saline and of osmotherapy in general.

Optimal cerebral perfusion pressure: are we ready for it?

Abstract Objectives: Cerebral perfusion pressure (CPP)-oriented therapy and the Lund concept lie on opposite ends of the CPP scale, in the management of head injury. Optimization of CPP by monitoring cerebral vascular pressure reactivity is an alternative approach that may reconcile these two divergent approaches, preventing both injurious hypotension and hypertension with an individualized CPP target. Methods: Indices describing cerebral vascular reactivity or cerebral blood flow autoregulation, derived from intracranial pressure, near-infrared spectroscopy, or transcranial Doppler are reviewed in this manuscript. Results: Indices of cerebrovascular reactivity and autoregulation typically converge to a U-shape curve when viewed as a function of CPP, with the best reactivity metrics indicating optimal CPP. In a retrospective study of prospectively collected data from head-injured patients, Steiner et al. demonstrated that a greater distance between averaged over total monitoring time-CPP and optimal CPP, correlated with unfavourable outcome. A recent study of 300 head-injured patients (2003–2009) showed that hypotension below optimal CPP was associated with greater mortality rate, while hypertension above optimal CPP was associated with an increase in severe disability. Discussion: Pilot studies indicating feasibility of autoregulation-oriented CPP optimization have been performed in adult and paediatric traumatic brain injury, aneurysmal subarachnoid haemorrhage, and in patients undergoing cardiothoracic surgery. It remains to be prospectively demonstrated whether optimal CPP management is able to improve outcome.

Cerebral Blood Flow, Brain Tissue Oxygen, and Metabolic Effects of Decompressive Craniectomy

Decompressive craniectomy (DC) is used for patients with traumatic brain injury (TBI), malignant edema from middle cerebral artery infarction, aneurysmal subarachnoid hemorrhage, and non-traumatic intracerebral or cerebellar hemorrhage. The objective of the procedure is to relieve intractable intracranial hypertension and/or to prevent or reverse cerebral herniation. Decompressive craniectomy has been shown to decrease mortality in selected patients with large hemispheric infarction and to control intracranial pressure in addition to improving pressure–volume compensatory reserve after TBI. The clinical effectiveness of DC in patients with TBI is under evaluation in ongoing randomized clinical trials. There are several unresolved controversies regarding optimal candidate selection, timing, technique, and post-operative management and complications. The nature and temporal progression of alterations in cerebral blood flow, brain tissue oxygen, and microdialysis markers have only recently been researched. Elucidating the pathophysiology of pressure-flow and cerebral hemodynamic consequences of DC could assist in optimizing clinical decision making and further defining the role of decompressive craniectomy.

Clevidipine rapidly and safely reduces blood pressure in acute intracerebral hemorrhage: the ACCELERATE trial.

Background: Intracerebral hemorrhage (ICH) causes 10-15% of primary strokes, with mortality related to hematoma volume. Blood pressure (BP) reduction may attenuate hematoma expansion. ACCELERATE (the Evaluation of Patients with Acute Hypertension and Intracerebral Hemorrhage with Intravenous Clevidipine Treatment) is a pilot study representing the first evaluation of safety and efficacy of intravenous clevidipine for the rapid treatment of hypertension in ICH patients. Methods: ICH patients with a systolic BP (SBP) >160 mm Hg who present within 6 h (n = 27) or 12 h (n = 10) of symptoms were prospectively enrolled, treated with open-label clevidipine until SBP ≤160 mm Hg was achieved and then titrated to keep target SBP between 140-160 mm Hg. Results: A total of 35 patients with baseline median Glasgow Coma Scale score of 12, median NIH Stroke Scale score of 14, mean SBP of 186 mm Hg and a mean time from onset of symptoms of 5.5 h received clevidipine. Median time to achieve SBP target range was 5.5 min. All patients achieved target SBP within 30 min; 96.9% achieved target SBP with clevidipine monotherapy. CT scans showed minimal hematoma volume change for the overall population (median change 0.01 ml, -2.9%). Mild/moderate hypotension was reported in 3 patients and resolved with dose reduction or drug discontinuation. Conclusion: Clevidipine monotherapy was effective and safe for rapid BP reduction in this cohort of critically ill ICH patients. Overall, patients showed minimal hematoma expansion with BP reduction, suggesting that rapid BP control with clevidipine may have a beneficial impact on hematoma expansion and warrants further investigation.

Utilization of CT perfusion patient selection for mechanical thrombectomy irrespective of time: a comparison of functional outcomes and complications

Background Patient selection for acute ischemic stroke has been largely driven by time-based criteria, although emerging data suggest that image-based criteria may be useful. The purpose of this study was to directly compare outcomes of patients treated within a traditional time window with those treated beyond this benchmark when CT perfusion (CTP) imaging was used as the primary selection tool. Methods A prospectively collected database of all patients with acute ischemic stroke who received intra-arterial therapy at the Medical University of South Carolina was retrospectively analyzed, regardless of time from symptom onset. At presentation, CTP maps were qualitatively assessed. Selected patients underwent intra-arterial therapy. Functional outcome according to the modified Rankin scale (mRS) score at about 90 days was documented. Results 140 patients were included in the study. The median time from symptom onset to groin access was 7.0 h. Overall, 28 patients (20%) had bleeding complications, but only 10 (7.1%) were symptomatic. The average National Institute of Health Stroke Scale (NIHSS) score for patients treated ≤7 h from symptom onset was 17.3 and 30.2% had a mRS score of 0–2 at 90 days. Patients treated >7 h from symptom onset had an average NIHSS score of 15.1 and 45.5% achieved a mRS score of 0–2 at 90 days (p=0.104). Patients in the two groups had similar rates of symptomatic intracerebral hemorrhage (8.5% and 5.8%, respectively; p=0.745). Conclusions No difference was found in the rates of good functional outcome between patients treated ≤7 h and those treated >7 h from symptom onset. These data suggest that imaging-based patient selection is a safe and viable methodology.

Telestroke in South Carolina

BACKGROUND The administration of thrombolysis to eligible patients is often limited to centers with expertise. This study was intended to report on the safety and efficacy (in increasing thrombolysis availability) of telemedicine in the acute assessment and treatment of stroke patients presenting to hospitals in distant locations from a designated stroke center. METHODS A web-based telestroke tool (remote evaluation of acute ischemic stroke at Medical University of South Carolina [REACH-MUSC]), was implemented to provide acute stroke care 24 hours per day, 7 days per week to 12 community hospitals in South Carolina. RESULTS Nine hundred sixty-five consults were performed. Among the 525 patients with a National Institutes of Health Stroke Score >3, 185 (35.7%) were treated with intravenous tissue plasminogen activator (t-PA) alone, 15 (2.9%) received combination of intravenous and intra-arterial thrombolysis/thrombectomy, and 11 (2.1%) were treated with intra-arterial therapy alone. Of those who received intravenous t-PA, 119 (64.3%) were transferred to the hub; the medians (interquartile range) for onset to treatment for the intravenous t-PA and the intravenous t-PA and intra-arterial groups were 152 (range 115-193) minutes and 147 (range 107-179) minutes, respectively. Three patients (1.6%) who received intravenous t-PA alone experienced symptomatic intracerebral hemorrhage. The most common reason for not receiving thrombolysis was patient presentation outside the time window for treatment. CONCLUSIONS Telestroke can have a major impact in increasing thrombolysis rates in remote areas from specialized centers, and in particular in areas where t-PA is underutilized.

Advanced Hemodynamic Monitoring: Principles and Practice in Neurocritical Care

Advanced hemodynamic monitoring is necessary for many patients with acute brain and/or spinal cord injury. Optimizing cerebral and systemic physiology requires multi-organ system function monitoring. Hemodynamic manipulations are cardinal among interventions to regulate cerebral perfusion pressure and cerebral blood flow. The pulmonary artery catheter is not any more the sole tool available; less invasive and potentially more accurate methodologies have been developed and employed in the operating room and among diverse critically ill populations. These include transpulmonary thermodilution, arterial pressure pulse contour, and waveform analysis and bedside critical care ultrasound. A thorough understanding of hemodynamics and of the available monitoring modalities is an essential skill for the neurointensivist.

Brain tissue oxygenation, lactate-pyruvate ratio, and cerebrovascular pressure reactivity monitoring in severe traumatic brain injury: systematic review and viewpoint.

BackgroundPrevention and detection of secondary brain insults via multimodality neuromonitoring is a major goal in patients with severe traumatic brain injury (TBI).ObjectiveExplore the underlying pathophysiology and clinical outcome correlates as it pertains to combined monitoring of ≥2 from the following variables: partial brain tissue oxygen tension (PbtO2), pressure reactivity index (PRx), and lactate pyruvate ratio (LPR).MethodsData sources included Medline, EMBASE, and evidence-based databases (Cochrane DSR, ACP Journal Club, DARE, and the Cochrane Controlled Trials Register). The PRISMA recommendations were followed. Two authors independently selected articles meeting inclusion criteria. Studies enrolled adults who required critical care and monitoring in the setting of TBI. Included studies reported on correlations between the monitored variables and/or reported on correlations of the variables with clinical outcomes.ResultsThirty-four reports were included (32 observational studies and 2 randomized controlled trials) with a mean sample size of 34 patients (range 6–223), and a total of 1,161 patient-observations. Overall methodological quality was moderate. Due to inter-study heterogeneity in outcomes of interest, study design, and in both number and type of covariates included in multivariable analyses, quantitative synthesis of study results was not undertaken.ConclusionSeveral literature limitations were identified including small number of subjects, lack of clinical outcome correlations, inconsistent probe location, and overall moderate quality among the included studies. These limitations preclude any firm conclusions; nevertheless we suggest that the status of cerebrovascular reactivity is not only important for cerebral perfusion pressure optimization but should also inform interpretation and interventions targeted on PbtO2 and LPR. Assessment of reactivity can be the first step in approaching the relations among cerebral blood flow, oxygen delivery, demand, and cellular metabolism.