Increased brain volume among good grade patients with intracerebral hemorrhage. Results from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) study.

BACKGROUND: We ascertained the occurrence of global cerebral edema manifesting as increased brain volume in subjects with intracerebral hemorrhage (ICH) and explored the relationship between subject characteristics and three month outcomes. METHODS: A post-hoc analysis of a multicenter prospective study that recruited patients with ICH, elevated SBP ≥170 mm Hg, and Glasgow Coma Scale (GCS) score ≥8, who presented within 6 h of symptom onset was performed. Computed tomographic (CT) scans at baseline and 24 h, submitted to a core image laboratory, were analyzed to measure total brain, hematoma, and perihematoma edema volumes from baseline and 24-h CT scans using image analysis software. The increased brain volume was determined by subtracting the hematoma and perihematomal edema volumes from the total brain volume. RESULTS: A total of 18 (44 %) of 41 subjects had increased brain volume that developed between initial CT scan and 24-h CT scan. The median increase in brain volume among the 18 subjects was 35 cc ranging from 0.12 to 296 cc. The median baseline GCS score was 15 in both groups of subjects who experienced increased brain volume and those who did not, and the median hematoma volume was 10.18 and 6.73, respectively. Three of the 18 subjects with increased brain volume underwent concurrent neurological deterioration and one subject died during hospitalization. CONCLUSIONS: We found preliminary evidence of increased cerebral brain volume in subjects with good grade and small ICHs, which may be suggestive of global cerebral edema.

Levetiracetam is associated with improved cognitive outcome for patients with intracranial hemorrhage.

BACKGROUND: To date, common therapy in patients with intracranial hemorrhage (ICH) includes prophylaxis of seizure using antiepileptic drugs, commonly phenytoin. Phenytoin therapy is associated with a high incidence of cognitive disturbance. Levetiracetam is known to cause less cognitive disruption and may be a suitable alternative for seizure prophylaxis. Cognitive outcomes in ICH patients receiving seizure prophylaxis with levetiracetam or phenytoin are compared. METHOD: A retrospective chart review was conducted with 269 patients who received prophylactic levetiracetam or phenytoin between August 2005 and May 2008. A total of 85 reviewed patients met inclusion criteria (phenytoin n = 25, levetiracetam n = 60). RESULTS: Statistically significant results included higher Glasgow Coma Scores (GCS) at dismissal (median, 14 vs. 11, P = 0.023), lower seizure incidence (0.0 vs. 8%, P = 0.03) for patients receiving levetiracetam than those treated with phenytoin and patients being discharged home (21.7% vs. 16%, P = 0.03). Observed trends included greater cognitive function retention rate (56.7% vs. 36%, P = 0.08). CONCLUSION: Despite similarities in hemorrhage type and severity at onset, patients receiving levetiracetam had better cognition at discharge and fewer seizures than patients receiving phenytoin. These data suggest that levetiracetam is more effective than phenytoin for seizure prophylaxis without suppression of cognitive abilities in patients with ICH.

Association of serum glucose concentrations during acute hospitalization with hematoma expansion, perihematomal edema, and three month outcome among patients with intracerebral hemorrhage.

BACKGROUND: There is some evidence that hyperglycemia increases the rate of poor outcomes in patients with intracerebral hemorrhage (ICH). We explored the relationship between various parameters of serum glucose concentrations measured during acute hospitalization and hematoma expansion, perihematomal edema, and three month outcome among subjects with ICH. METHODS: A post-hoc analysis of a multicenter prospective study recruiting subjects with ICH and elevated systolic blood pressure (SBP) ≥170 mmHg who presented within 6 h of symptom onset was performed. The serum glucose concentration was measured repeatedly up to 5 times over 3 days after admission and change over time was characterized using a summary statistic by fitting the linear regression model for each subject. The admission glucose, glucose change between admission and 24 hour glucose concentration, and estimated parameters (slope and intercept) were entered in the logistic regression model separately to predict the functional outcome as measured by modified Rankin scale (mRS) at 90 days (0-3 vs. 4-6); hematoma expansion at 24 h (≤33 vs. >33%); and relative perihematomal edema expansion at 24 h (≤40 vs. >40%). RESULTS: A total of 60 subjects were recruited (aged 62.0 ±15.1 years; 56.7% men). The mean of initial glucose concentration (±standard deviation) was 136.7 mg/dl (±58.1). Thirty-five out of 60 (58%) subjects had a declining glucose over time (negative slope). The risk of poor outcome (mRS 4-6) in those with increasing serum glucose levels was over two-fold relative to those who had declining serum glucose levels (RR = 2.64, 95% confidence interval [CI]: 1.03, 6.75). The RRs were 2.59 (95% CI: 1.27, 5.30) for hematoma expansion >33%; and 1.25 (95% CI: 0.73, 2.13) for relative edema expansion >40%. CONCLUSIONS: Decline in serum glucose concentration correlated with reduction in proportion of subjects with hematoma expansion and poor clinical outcome. These results provide a justification for a randomized controlled clinical trial to evaluate the efficacy of aggressive serum glucose reduction in reducing death and disability among patients with ICH.

The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients.

OBJECTIVE: Previously, delirium has been identified as an independent risk factor for mortality in critically ill medical patients. We undertook this study to examine the relationships among medication usage, delirium, and clinical outcomes in a critically ill surgical/trauma population. DESIGN: Prospective, multicentered, observational study. SETTING: Two surgical intensive care units in level 1 trauma centers. PATIENTS: One hundred thirty-four consecutive surgical adult patients requiring mechanical ventilation (MV) for greater than 24 hours. INTERVENTIONS: Daily delirium assessment with the Confusion Assessment Method-Intensive Care Unit tool, outcomes assessment, and prospective data collection. MEASUREMENT AND MAIN RESULTS: Of the 134 patients who met inclusion criteria, 84 patients (63%) developed delirium at some point during their intensive care unit (ICU) stay. Delirium was associated with more MV days (9.1 vs. 4.9 days, p < 0.01), longer ICU stay (12.2 vs. 7.4 days, p < 0.01), longer hospital stay (20.6 vs. 14.7 days, p < 0.01). Additionally, greater cumulative lorazepam dose (p = 0.012), and higher cumulative fentanyl dose (p = 0.035) were administered in the delirium group. CONCLUSIONS: Delirium in the surgical/trauma ICU cohort is independently associated with more days requiring MV, longer ICU length of stay, and longer hospital length of stay. Additionally, greater amounts of lorazepam and fentanyl were administered to patients with delirium.

Use of intrathecal nicardipine for aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm.

BACKGROUND: Cerebral vasospasm leading to delayed ischemia is a common and serious complication of aneurysmal subarachnoid hemorrhage that often results in increased morbidity and mortality. Treatments for cerebral vasospasm, including triple-H therapy (therapeutic hypervolemia, hypertension, and hemodilution), nimodipine, balloon angioplasty, and intra-arterial vasodilators have limitations in their efficacy and safety profiles. Nicardipine, a calcium channel blocker, is available for intravenous administration for blood pressure reduction. A recent study reported its efficacy in the treatment of cerebral vasospasm when given intrathecally (IT). We present our experiences with IT nicardipine for treatment of cerebral vasospasm. METHODS: IT nicardipine was administered to six patients with aneurysmal subarachnoid hemorrhage after prophylactic and aggressive therapeutic management for vasospasm failed. RESULTS: In these patients, IT nicardipine treatment was followed within 8 hours by a 43.1 +/- 31.0 cm/s decrease in middle cerebral arterial flow velocity, as measured by transcranial Doppler ultrasound. CONCLUSIONS: Based on these positive results, we believe that larger scale studies evaluating the safety and efficacy of IT nicardipine for the management of cerebral vasospasm are warranted.

Cerebral venous thrombosis: a review.

BACKGROUND: Cerebral venous thrombosis (CVT) is less frequent than arterial thrombosis, presents in an atypical fashion, and is an uncommon cause of stroke. Although the functional outcome from CVT is better than arterial strokes, the outcome of CVT remains unpredictable and may lead to sequelae or even death if not recognized and treated early. REVIEW SUMMARY: The clinical presentations, time of onset, and neuroimaging findings vary. Symptoms include headache, seizures, neurologic deficits, and altered consciousness. Causes include hematologic disorders, hypercoagulable states, pregnancy, and contraceptive medications. Treatment of this infrequent condition remains controversial and includes heparin infusions, intrasinus thrombolysis, and other endovascular procedures. CONCLUSION: Further clinical trials are needed to address optimal treatment of this infrequent but potentially serious condition.

A clinical example of the "limping brain" syndrome: a case report.

We present a case report of a patient presenting with persistent aphasia for 1 week and cerebral hypoperfusion documented by single-photon emission tomography, both of which resolved completely after successful angioplasty of the symptomatic artery. This case represents a rare clinical example of "limping brain syndrome."

Systemic risk factors associated with progression of atherosclerosis from the coronary to the carotid arteries.

BACKGROUND: It is unclear why atherosclerosis remains restricted to one arterial tree in some patients whereas it is more generalized in others. Few studies have addressed the role that systemic risk factors play in the progression of atherosclerosis from one arterial tree to another. METHODS: We studied 344 consecutive patients with suggested coronary artery disease (CAD) who underwent combined coronary and carotid angiography during a 7-month period. Coronary and carotid disease was graded as absent-mild or moderate-severe based on the degree of stenosis of these vessels. Traditional vascular risk factors were compared for patients with moderate-severe CAD alone versus patients with moderate-severe CAD and carotid disease. RESULTS: Moderate-severe CAD alone was found in 162 patients and moderate-severe CAD and carotid disease was found in 100 patients. Multivariate analysis showed that hypertension (P = .007, odds ratio 2.2, 95% confidence interval 1.2-3.9), history of smoking (P = .06, odds ratio 1.8, 95% confidence interval 1.0-3.4), and diabetes (P = .09, odds ratio 1.6, 95% confidence interval 0.9-2.8) were associated with combined moderate-severe CAD and carotid disease. Patients with combined moderate-severe CAD and carotid disease were significantly more likely to have at least 2 of these 3 risk factors (P < .001) than patients with moderate-severe CAD alone. CONCLUSION: An accumulating burden of hypertension, diabetes, and smoking are important in the progression of atherosclerosis from the coronary to the carotid circulation.

Systolic blood pressure reduction and risk of acute renal injury in patients with intracerebral hemorrhage.

BACKGROUND: Aggressive systolic blood pressure reduction may precipitate acute renal injury because of underlying hypertensive nephropathy in patients with intracerebral hemorrhage. The study's objective was to determine the rate and determinants of acute renal injury during acute hospitalization among subjects with intracerebral hemorrhage using a post hoc analysis of a multicenter prospective study. METHODS: Subjects with intracerebral hemorrhage and elevated systolic blood pressure of 170 mm Hg or greater who presented within 6 hours of symptom onset and underwent treatment of acute hypertensive response and fluid management as per study and local protocols, respectively. Acute renal injury was defined post hoc using the criteria used in Acute Kidney Injury Network classifications within 72 hours of admission. Descriptive statistics and standard statistical tests were used to characterize and evaluate the effect of systolic blood pressure reduction parameters (relative to initial systolic blood pressure) and average maximum hourly dose of nicardipine on the occurrence of acute renal injury. RESULTS: A total of 60 subjects were recruited (57% were men; mean age of 62.0 ± 15.1 years). Five subjects (9%) had stage I acute renal injury according to the Acute Kidney Injury Network criteria. None of the subjects had stage II or III acute renal injury. The serum creatinine course for the first 3 days suggested that the peak elevation of creatinine was seen at 18, 30, 57, 58, and 71 hours after baseline measurements in these 5 subjects, all of which except for the first one were beyond the protocol-specified treatment period. The incidences of neurologic deterioration and symptomatic hematoma expansion were significantly greater in the subjects with stage I renal impairment. The systolic blood pressure reduction parameters (in particular, the area under the curve depicting the 24-hour systolic blood pressure summary statistic) and the higher average maximum hourly nicardipine dose were strongly associated with stage I renal impairment. CONCLUSIONS: Although acute renal injury is infrequent and mild among subjects with intracerebral hemorrhage undergoing systolic blood pressure reduction, a trend in association between systolic blood pressure reduction and renal impairment was observed in this small study. Therefore, it is important to carefully monitor the renal function when administering treatment to reduce systolic blood pressure in patients with intracerebral hemorrhage.

Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study.

BACKGROUND: Evidence indicates that systolic blood pressure (SBP) reduction may reduce hematoma expansion in patients with intracerebral hemorrhage (ICH) who are initially seen with acute hypertensive response. OBJECTIVE: To explore the relationship between different variables of SBP reduction and hematoma expansion, perihematomal edema, and 3-month outcome among patients with ICH. DESIGN: Post hoc analysis of a traditional phase 1 dose-escalation multicenter prospective study. SETTING: Emergency departments and intensive care units. PATIENTS: Patients having ICH with an elevated SBP of at least 170 mm Hg who were seen within 6 hours of symptom onset. INTERVENTION: Systolic blood pressure reduction using intravenous nicardipine hydrochloride targeting 3 tiers of sequentially escalating SBP reduction goals (170-199, 140-169, or 110-139 mm Hg). MAIN OUTCOME MEASURES: We evaluated the effect of SBP reduction (relative to initial SBP) on the following: hematoma expansion (defined as an increased intraparenchymal hemorrhage volume >33% on 24-hour vs baseline computed tomographic [CT] images), higher perihematomal edema ratio (defined as a >40% increased ratio of edema volume to hematoma volume on 24-hour vs baseline CT images), and poor 3-month outcome (defined as a modified Rankin scale score of 4-6). RESULTS: Sixty patients (mean [SD] age, 62.0 [15.1] years; 34 men) were recruited (18, 20, and 22 patients in each of the 3 SBP reduction goal tiers). The median area under the curve (AUC) (calculated as the area between the hourly SBP measurements over 24 hours and the baseline SBP) was 1360 (minimum, 3643; maximum, 45) U. Comparing patients having less vs more aggressive SBP reduction based on 24-hour AUC analysis, frequencies were 32% vs 17% for hematoma expansion, 61% vs 40% for higher perihematomal edema ratio, and 46% vs 38% for poor 3-month outcome (P > .05 for all). The median SBP reductions were 54 mm Hg at 6 hours and 62 mm Hg at 6 hours from treatment initiation. Comparing patients having equal to or less vs more than the median SBP reduction at 2 hours, frequencies were 21% vs 31% for hematoma expansion, 42% vs 57% for higher perihematomal edema ratio, and 35% vs 48% for poor 3-month outcome (P > .05 for all). CONCLUSIONS: We found no significant relationship between SBP reduction and any of the outcomes measured herein; however, the Antihypertensive Treatment of Acute Cerebral Hemorrhage study was primarily a safety study and was not powered for such end points. The consistent favorable direction of these associations supports further studies with an adequately powered randomized controlled design to evaluate the efficacy of aggressive pharmacologic SBP reduction.

Placement of external ventricular drains and intracranial pressure monitors by neurointensivists.

INTRODUCTION: External ventricular drains (EVDs) and intracranial pressure (ICP) monitors are widely used in the Neurological Critical Care Unit (NCCU) to measure ICP and divert cerebrospinal fluid (CSF). EVDs and ICP monitors have historically been placed by neurosurgeons; however, with recent staffing of NCCUs by neurointensivists, a growing number of EVDs and ICP monitors are being placed by these specialists. RESULTS: Limited data are available concerning the safety or feasibility of such placements by neurointensivists. We present our experience with EVD and ICP monitor placement by a neurointensivist in the NCCU. A retrospective chart review of 29 patients with EVD placement and 7 patients with ICP monitors--all placed by a single neurointensivist--was conducted for patients admitted to the NCCU from August 2005 to January 2008. DISCUSSION: These findings were compared to published outcomes from neurosurgeon placements. All 29 patients with EVDs remained infection-free, with CSF pleocytosis occurring in one patient (3.4%). All 7 patients receiving ICP monitors remained free from infection. Complications after drain placement occurred in 20.7% (n = 6) of patients, with all six complications being EVD tract hematoma measuring less than 5 cm(3). CONCLUSION: Patients receiving ICP monitors had no complications. These complication rates are comparable to published rates, which suggest that placement of EVDs and ICP monitors by neurointensivists may be safe and effective. However, small sample size (n = 36) prohibits definitive safety and efficacy conclusions. For this reason, further research analyzing a larger patient sample is warranted.