Jose I. Suarez

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.

Exercise echocardiography versus 201Tl single-photon emission computed tomography in evaluation of coronary artery disease. Analysis of 292 patients.

BackgroundExercise echocardiography (digital cine-loop technique) and 201TI single-photon emission computed tomography (SPECT) were performed simultaneously in 292 patients being evaluated for coronary artery disease. Methods and ResultsPretreadmill and posttreadmill echocardiographic images of diagnostic quality were obtained in 289 patients, and the left ventricle was divided into anterior, inferior, and lateral regions. Any wall motion or perfusion abnormality observed within each region was classified as totally reversible, fixed, or partially reversible. Exercise echocardiography and SPECT were normal in 137 patients and abnormal in 118 (88% agreement). Equal numbers of regional abnormalities were detected by one test when missed by the other. The two tests had an 82% agreement in detecting the same type of finding within the regions analyzed. SPECT detected more reversible abnormalities than echocardiography, whereas echocardiography detected more fixed abnormalities than SPECT. Regions with a fixed abnormality by echocardiography frequently showed partial reversibility of a perfusion defect by SPECT. Nearly one third of regions with fixed perfusion defects by SPECT demonstrated normal resting function or reversible abnormalities by echocardiography. Sensitivity for coronary artery disease by angiography (≥50% diameter stenosis) in 112 patients was similar for the two tests, ranging from 58% and 61% (echocardiography and SPECT, respectively) for one-vessel disease to 94% for three-vessel disease. The specificities for echocardiography and SPECT were 88% and 81%, respectively. ConclusionsExercise echocardiography had a diagnostic accuracy comparable to that of SPECT for the detection of regional abnormalities produced by significant coronary artery disease. A greater number of abnormal regions were detected with the combined use of both tests.

Intensive blood-pressure lowering in patients with acute cerebral hemorrhage

BACKGROUND Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage. METHODS We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments. RESULTS Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002). CONCLUSIONS The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).

Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions.

Objective: To determine the short‐ and long‐term outcomes after successful reversal of transtentorial herniation by medical treatment. Although it has been recognized that aggressive medical management can reverse transtentorial herniation, it is believed that overall outcome in such patients is poor. Design: Prospective cohort study. Setting: Neurocritical care unit of a university hospital. Patients: A total of 28 consecutive patients who underwent an episode of transtentorial herniation (defined as decrease in level of consciousness accompanied by pupillary dilation) secondary to a supratentorial mass lesion followed by successful reversal. Intervention: Herniation was reversed by using a combination of hyperventilation, mannitol and hypertonic saline. Measurements and Main Results: The following outcomes were analyzed: risk of second herniation, radiologic evidence of structural damage or vascular compromise related to herniation on post‐herniation computed tomographic scan, in‐hospital mortality, and long‐term functional outcome using Rankin score and Barthel index. A total of 32 episodes of transtentorial herniations were reversed in 28 patients during a 14‐month period. The most common precipitating cause were edema (n = 23) or new/expanding intracerebral hematoma (n = 5). After first reversal of transtentorial herniation in 28 patients, a second herniation episode was observed in 16 patients after a mean interval of 88.2 hrs (range, 23‐432 hrs); four were successfully reversed. On follow‐up computed tomographic scan, hypodense lesion in mid‐brain (n = 6), temporal lobe contusion (n = 2), posterior cerebral artery (n = 3), and middle cerebral artery (n = 1) infarction were visualized in a minority of patients. The in‐hospital mortality was 60% (n = 15) with brain death being the cause of death in 13 patients; care was withdrawn in eight patients. Second episode of herniation (p = .002) and midbrain involvement during herniation (p = .02) were associated with in‐hospital mortality. During a mean follow‐up period of 11.4 ± 4.2 months, two patients died of cerebral neoplasm and human immunodeficiency virus‐related sepsis, respectively. Of the 11 survivors, 7 were functionally independent (Rankin score <3 and Barthel index >60). Conclusions: Although mortality after transtentorial herniation is high, we found a prominent potential for meaningful recovery with aggressive medical reversal of transtentorial herniation. Our study implies that timely medical intervention for reversing transtentorial herniation can result in preservation of neurologic function.

Prothrombin Complex Concentrates for Oral Anticoagulant Therapy-Related Intracranial Hemorrhage: A Review of the Literature

Warfarin-related intracranial hemorrhage carries a high mortality and poor neurological outcome. Rapid reversal of coagulopathy is a cornerstone of medical therapy to halt bleeding progression; however the optimal approach remains undefined. Prothrombin complex concentrates have promising features that may rapidly reverse coagulopathy, but remain relatively unstudied. We aim to review the literature regarding the use of prothrombin complex concentrates in patients with warfarin-related intracranial hemorrhage. A comprehensive review of the literature was conducted using PUBMED and Google Scholar databases to identify the use of PCC in patients with warfarin-related intracranial hemorrhage. The characteristics abstracted included the type of PCC, dosing, study design, type of intracranial hemorrhage, changes in the INR, and adverse effects. Prothrombin complex concentrates are heterogenous in regards to factor concentration. PCC consistently reversed the INR in patients with intracranial hemorrhage. There is some evidence that PCC may reverse the INR more rapidly compared to fresh frozen plasma. Serious adverse effects were uncommon and included mainly thromboembolism. PCC has features which make it a promising therapy for patients with warfarin-related intracranial hemorrhage, and deserves more rigorous study in prospective-randomized controlled trials.

Intra-Arterial Thrombolytic Therapy in Peri-Coronary Angiography Ischemic Stroke

Background— Intra-arterial thrombolysis (IAT) for peri-coronary angiography (CA) stroke may be safe and efficacious. However, IAT may increase the risk of intracranial hemorrhage (ICH). Methods— A retrospective study was performed involving 3 university hospitals. All peri-CA IAT-treated cases were identified. Patient demographics, stroke severity, angiographic findings, thrombolytic use, modified Rankin Scale (mRS), ICH, and mortality were determined. Results— A total of 21 patients with post–left CA stroke were treated with IAT (mean age 71.8±12.3 years). Arterial occlusion was found in 14 (66.7%) and 7 (33.3%) of the anterior and posterior circulation, respectively. Mean time-to-therapy was 36±12 minutes from the time the neurological deficit was noted. mRS ≤2 occurred in 10 of 21 (48%) patients. Patients with younger age and shorter time-to-IAT had more complete arterial recanalization and clinical recovery. Symptomatic ICH occurred in 3 (14%) cases, and 4 (19%) patients died. Conclusions— Peri-CA IAT appears to be feasible and safe without increased risk of symptomatic ICH and death when compared with the previously reported IAT literature.

Older age does not increase risk of hemorrhagic complications after intravenous and/or intra-arterial thrombolysis for acute stroke.

BACKGROUND The elderly have significantly higher incidence of ischemic stroke and have higher mortality and morbidity compared with younger patients. Intracranial hemorrhage (ICH) after thrombolysis is one of the causes of unfavorable outcome. However, it is unclear whether age over 80 years is a predictor for hemorrhagic transformation after intravenous, intra-arterial, or a combination of both thrombolytic therapies. METHODS A database of 488 consecutive patients with ischemic stroke who received thrombolytic therapy was analyzed using logistic regression model to determine whether factors such as age over 80 years, demographic characteristics, onset to treatment time, severity of neurologic deficits, route of administration, blood glucose, or mean arterial pressure were associated with symptomatic ICH. RESULTS The rates of symptomatic hemorrhage were 12.82% and 10.4% in older and younger groups, respectively. The odds of symptomatic hemorrhage after thrombolytic therapy for patients over 80 years of age after adjusting for route of administration, National Institutes of Health Stroke Scale score, mean arterial pressure, and glucose was not significantly different from that of the younger age group (odds ratio [OR] = 1.64; 95% confidence interval [CI]: 0.729-3.66). Hyperglycemia (>150 mg/dL) was associated with increased odds of symptomatic ICH (OR = 2.32; 95% CI: 1.09-4.93). Patients older than 80 years had similar rates of recanalization (OR = 0.8; 95% CI: 0.4-1.8) and rates of asymptomatic ICH (OR = 2.40; 95% CI: 0.89-6.5). CONCLUSIONS Risks of ICH after thrombolysis for acute ischemic stroke are similar in patients over and under 80 years of age. Our data suggest that the decision to provide thrombolytic therapy should not be solely based on patients age.

Seizures and Anticonvulsants after Aneurysmal Subarachnoid Hemorrhage

Seizures and seizure-like activity may occur in patients experiencing aneurysmal subarachnoid hemorrhage. Treatment of these events with prophylactic antiepileptic drugs remains controversial. An electronic literature search was conducted for English language articles describing the incidence and treatment of seizures after aneurysmal subarachnoid hemorrhage from 1980 to October 2010. A total of 56 articles were included in this review. Seizures often occur at the time of initial presentation or aneurysmal rebleeding before aneurysm treatment. Seizures occur in about 2% of patients after invasive aneurysm treatment, with a higher incidence after surgical clipping compared with endovascular repair. Non-convulsive seizures should be considered in patients with poor neurological status or deterioration. Seizure prophylaxis with antiepileptic drugs is controversial, with limited data available for developing recommendations. While antiepileptic drug use has been linked to worse prognosis, studies have evaluated treatment with almost exclusively phenytoin. When prophylaxis is used, 3-day treatment seems to provide similar seizure prevention with better outcome compared with longer-term treatment.

Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey.

IntroductionAnemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown.MethodsWe performed a survey of North American academic neurointensivists, vascular neurosurgeons and multidisciplinary intensivists who regularly care for patients with SAH to determine hemoglobin (Hb) concentrations which commonly trigger a decision to initiate transfusion. We also assessed minimum and maximum acceptable Hb goals in the context of a clinical trial and how decision-making is influenced by advanced neurological monitoring, clinician characteristics and patient-specific factors.ResultsThe survey was sent to 531 clinicians, of whom 282 (53%) responded. In a hypothetical patient with high-grade SAH (WFNS 4), the mean Hb concentration at which clinicians administered RBCs was 8.19 g/dL (95% CI, 8.07 to 8.30 g/dL). Transfusion practices were comparatively more restrictive in patients with low-grade SAH (mean Hb 7.85 g/dL (95% CI, 7.73 to 7.97 g/dL)) (P < 0.0001) and more liberal in patients with delayed cerebral ischemia (DCI) (mean Hb 8.58 g/dL (95% CI, 8.45 to 8.72 g/dL)) (P < 0.0001). In each setting, there was a broad range of opinions. The majority of respondents expressed a willingness to study a restrictive threshold of ≤8 g/dL (92%) and a liberal goal of ≥10 g/dl (75%); in both cases, the preferred transfusion thresholds were significantly higher for patients with DCI (P < 0.0001). Neurosurgeons expressed higher minimum Hb goals than intensivists, especially for patients with high-grade SAH (β = 0.46, P = 0.003), and were more likely to administer two rather than one unit of RBCs (56% vs. 19%; P < 0.0001). Institutional use of transfusion protocols was associated with more restrictive practices. More senior clinicians preferred higher Hb goals in the context of a clinical trial. Respondents were more likely to transfuse patients with brain tissue oxygen tension values <15 mmHg and lactate-to-pyruvate ratios >40.ConclusionsThere is widespread variation in the use of RBC transfusions in SAH patients. Practices are heavily influenced by the specific dynamic clinical characteristics of patients and may be further modified by clinician specialty and seniority, the use of protocols and advanced neurological monitoring.

Ubiquitous expression of human SCA2 gene under the regulation of the SCA2 self promoter cause specific Purkinje cell degeneration in transgenic mice

The objective of this work was the generation of an animal model of the SCA2 disease for future studies on the benefits of therapeutic molecules and neuropathological mechanisms that underline this human disorder. The transgenic fragment was microinjected into pronuclei of B6D2F1 X OF1 mouse hybrid strain. For Northern blots, RNAs were hybridized with a human cDNA fragment from the SCA2 gene and a mouse beta-actin cDNA fragment. Monoclonal antibody directed to the N-terminal of the ataxin 2 protein with 22Q was used for Western blot analysis. A rotating rod apparatus was utilized to measure motor coordination of mice. Immunohistochemical detection of Purkinje neurons was performed with anti-calbindin 28K as primary antibody. Ubiquitous expression of the SCA2 transgene with 75 CAG repeats regulated by the SCA2 self promoter was obtained after generation of our transgenic mice. Analysis of transgenic mice revealed significant differences of motor coordination compared with the wild type littermates. Specific degeneration of Purkinje neurons and transgene over-expression in the brain, liver and skeletal muscle, rather than in lungs and kidneys was also observed, resembling the expression pattern of the ataxin 2 in humans.