Paul Vespa

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods— A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Councils Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. Results— Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. Conclusions— aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.

Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging.

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra‐arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion‐weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8–38 cm3) and decreased to 10 cm3 (95% CI, 3–17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2–16 cm3) at baseline to 1 cm3 (95% CI, 0.4–2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality. Ann Neurol 2000;47:462–469.

Guidelines for the Evaluation and Management of Status Epilepticus

Status epilepticus (SE) treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. To provide guidance for the acute treatment of SE in critically ill patients, the Neurocritical Care Society organized a writing committee to evaluate the literature and develop an evidence-based and expert consensus practice guideline. Literature searches were conducted using PubMed and studies meeting the criteria established by the writing committee were evaluated. Recommendations were developed based on the literature using standardized assessment methods from the American Heart Association and Grading of Recommendations Assessment, Development, and Evaluation systems, as well as expert opinion when sufficient data were lacking.

Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study

Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO2) and cerebral microdialysis (MD) at a mean time of 36 h after injury. Microdialysis values were compared with the regional mean PET values adjacent to the probe. Longitudinal MD data revealed a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR)>40) but only a 2.4% incidence rate of ischemia. Positron emission tomography imaging revealed a 1% incidence of ischemia across all voxels as measured by oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO2). In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO2 (P<0.001), but not with OEF or CvO2. Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.

Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference

Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs. SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team. A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients. The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines. Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury. Recommendations were developed using the GRADE system. Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice. Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data.

Acute seizures after intracerebral hemorrhage A factor in progressive midline shift and outcome

Objective: To determine whether early seizures that occur frequently after intracerebral hemorrhage (ICH) lead to increased brain edema as manifested by increased midline shift. Methods: A total of 109 patients with ischemic stroke (n = 46) and intraparenchymal hemorrhage (n = 63) prospectively underwent continuous EEG monitoring after admission. The incidence, timing, and factors associated with seizures were defined. Serial CT brain imaging was conducted at admission, 24 hours, and 48 to 72 hours after hemorrhage and assessed for hemorrhage volume and midline shift. Outcome at time of discharge was assessed using the Glasgow Outcome Scale score. Results: Electrographic seizures occurred in 18 of 63 (28%) patients with ICH, compared with 3 of 46 (6%) patients with ischemic stroke (OR = 5.7, 95% CI 1.4 to 26.5, p < 0.004) during the initial 72 hours after admission. Seizures were most often focal with secondary generalization. Seizures were more common in lobar hemorrhages but occurred in 21% of subcortical hemorrhages. Posthemorrhagic seizures were associated with neurologic worsening on the NIH Stroke Scale (14.8 vs 18.6, p < 0.05) and with an increase in midline shift (+ 2.7 mm vs −2.4 mm, p < 0.03). There was a trend toward increased poor outcome (p < 0.06) in patients with posthemorrhagic seizures. On multivariate analysis, age and initial NIH Stroke Scale score were independent predictors of outcome. Conclusion: Seizures occur commonly after ICH and may be nonconvulsive. Seizures are independently associated with increased midline shift after intraparenchymal hemorrhage.

Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis

Objective: To determine whether nonconvulsive electrographic post‐traumatic seizures result in increases in intracranial pressure and microdialysis lactate/pyruvate ratio. Design: Prospective monitoring with retrospective data analysis. Setting: Single center academic neurologic intensive care unit. Patients: Twenty moderate to severe traumatic brain injury patients (Glasgow Coma Score 3–13). Measurements and Main Results: Continuous electroencephalography and cerebral microdialysis were performed for 7 days after injury. Ten patients had seizures and were compared with a matched cohort of traumatic brain injury patients without seizures. The seizures were repetitive and constituted status epilepticus in seven of ten patients. Using a within‐subject design, post‐traumatic seizures resulted in episodic increases in intracranial pressure (22.4 ± 7 vs. 12.8 ± 4.3 mm Hg; p < .001) and an episodic increase in lactate/pyruvate ratio (49.4 ± 16 vs. 23.8 ± 7.6; p < .001) in the seizure group. Using a between‐subjects comparison, the seizure group demonstrated a higher mean intracranial pressure (17.6 ± 6.5 vs. 12.2 ± 4.2 mm Hg; p < .001), a higher mean lactate/pyruvate ratio (38.6 ± 18 vs. 27 ± 9; p < .001) compared with nonseizure patients. The intracranial pressure and lactate/pyruvate ratio remained elevated beyond postinjury hour 100 in the seizure group but not the nonseizure group (p < .02). Conclusion: Post‐traumatic seizures result in episodic as well as long‐lasting increases in intracranial pressure and microdialysis lactate/pyruvate ratio. These data suggest that post‐traumatic seizures represent a therapeutic target for patients with traumatic brain injury.

Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury

Objective:To determine that intensive glycemic control does not reduce microdialysis glucose concentration brain metabolism of glucose. Design:Prospective monitoring followed by retrospective data analysis of cerebral microdialysis and global brain metabolism. Setting:Single center, academic neurointensive care unit. Patients:Forty-seven moderate to severe traumatic brain injury patients. Interventions:A nonrandomized, consecutive design was used for glycemic control with loose insulin (n = 33) for the initial 2 yrs or intensive insulin therapy (n = 14) for the last year. Measurements and Main Results:In 14 patients treated with intensive insulin therapy, there was a reduction in microdialysis glucose by 70% of baseline concentration compared with a 15% reduction in 33 patients treated with a loose insulin protocol. Despite this reduction in microdialysis glucose, the global metabolic rate of glucose did not change. However, intensive insulin therapy was associated with increased incidence of microdialysis markers of cellular distress, namely elevated glutamate (38 ± 37% vs. 10 ± 17%, p < .01), elevated lactate/pyruvate ratio (38 ± 37% vs. 19 ± 26%, p < .03) and low glucose (26 ± 17% vs. 11 ± 15%, p < .05, and increased global oxygen extraction fraction. Mortality was similar in the intensive and loose insulin treatment groups (14% vs. 15%, p = .9), as was 6-month clinical outcome (p = .3). Conclusions:Intensive insulin therapy results in a net reduction in microdialysis glucose and an increase in microdialysis glutamate and lactate/pyruvate without conveying a functional outcome advantage.

Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study.

Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. Levels of glucose, lactate, pyruvate, glutamate, and urea were analyzed hourly. The 6-month Glasgow Outcome Scale extended (GOSe6) score was assessed for each patient. In regions of increased glucose utilization defined by positron emission tomography, the extracellular glucose concentration was less than 0.2 mmol/l. Extracellular glucose values were less than 0.2 mmol during postinjury days 0 to 7 in 19% to 30% of hourly samples on each day. Transient decreases in glucose levels occurred with electrographic seizures and nonischemic reductions in cerebral perfusion pressure and jugular venous oxygen saturation. Glutamate levels were elevated in the majority of low-glucose samples, but the lactate/pyruvate ratio did not indicate focal ischemia. Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.

Analysis of Thrombi Retrieved From Cerebral Arteries of Patients With Acute Ischemic Stroke

Background and Purpose— Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. Methods— This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. Results— The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. “Red” clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. Conclusions— Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.