John C. Andrefsky

Cooling for Acute Ischemic Brain Damage (COOL AID) An Open Pilot Study of Induced Hypothermia in Acute Ischemic Stroke

Background and Purpose— Hypothermia is effective in improving outcome in experimental models of brain infarction. We studied the feasibility and safety of hypothermia in patients with acute ischemic stroke treated with thrombolysis. Methods— An open study design was used. All patients presented with major ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15) within 6 hours of onset. After informed consent, patients with a persistent NIHSS score of >8 were treated with hypothermia to 32±1°C for 12 to 72 hours depending on vessel patency. All patients were monitored in the neurocritical care unit for complications. A modified Rankin Scale was measured at 90 days and compared with concurrent controls. Results— Ten patients with a mean age of 71.1±14.3 years and an NIHSS score of 19.8±3.3 were treated with hypothermia. Nine patients served as concurrent controls. The mean time from symptom onset to thrombolysis was 3.1±1.4 hours and from symptom onset to initiation of hypothermia was 6.2±1.3 hours. The mean duration of hypothermia was 47.4±20.4 hours. Target temperature was achieved in 3.5±1.5 hours. Noncritical complications in hypothermia patients included bradycardia (n=5), ventricular ectopy (n=3), hypotension (n=3), melena (n=2), fever after rewarming (n=3), and infections (n=4). Four patients with chronic atrial fibrillation developed rapid ventricular rate, which was noncritical in 2 and critical in 2 patients. Three patients had myocardial infarctions without sequelae. There were 3 deaths in patients undergoing hypothermia. The mean modified Rankin Scale score at 3 months in hypothermia patients was 3.1±2.3. Conclusion— Induced hypothermia appears feasible and safe in patients with acute ischemic stroke even after thrombolysis. Refinements of the cooling process, optimal target temperature, duration of therapy, and, most important, clinical efficacy, require further study.

Intra-arterial thrombolysis for perioperative stroke after open heart surgery

Article abstract Recent major surgery is an exclusion criterion for thrombolysis. Six patients with acute ischemic stroke underwent intra-arterial thrombolysis after recent open heart surgery without clinically significant bleeding complications, although one patient developed a small, asymptomatic cerebellar hemorrhage. Intra-arterial thrombolysis may be an option for patients with cerebral embolism in the perioperative period.

Successful treatment of vancomycin-resistant enterococcus meningitis with linezolid: Case report and review of the literature

Objective To describe the successful treatment of a case of vancomycin-resistant enterococcus meningitis with linezolid. Design Case report and review of the literature. Patients The patient is a 35-yr-old man who suffered a cerebellar hemorrhage after embolization of a cerebellar arteriovenous malformation. The patient underwent ventriculostomy drainage and craniectomy. The patient was on broad-spectrum antibiotics for pneumonia including vancomycin. The patient remained febrile and grew vancomycin-resistant Enterococcus faecium from the cerebrospinal fluid. Interventions The patient was treated with intravenous chloramphenicol without success. On postoperative day 16, the patient was begun on intravenous linezolid. Main Results The patient received 4 wks of intravenous linezolid with complete eradication of the meningitis. Conclusions Intravenous linezolid appears to be a safe and effective therapy for vancomycin-resistant enterococcus meningitis.

Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial: Randomized Pilot Clinical Trial

Background and Purpose— Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. Methods— All patients with stroke were screened for eligibility (age 18–75 years, National Institutes of Health Stroke Scale ≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both ≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. Results— Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. Conclusions— HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. Clinical Trial Registration— This trial was not registered because enrollment began before July 1, 2005.

Technical refinements and drawbacks of a surface cooling technique for the treatment of severe acute ischemic stroke.

AbstractPurpose: To describe a technique for the induction of hypothermia and its complications for the treatment of acute ischemic stroke. Methods: Adults with acute (<8 hours), severe (National Institutes of Health Stroke Scale >14) ischemic stroke of the anterior circulation were enrolled. Patients were intubated, sedated, and paralyzed. Surface cooling to 32°±1°C was performed with a cooling blanket and an alcohol/ice bath. Hypothermia was maintained for 12–72 hours. Physiological parameters were measured continuously. A computed tomography scan of the brain was obtained at 24 hours. Rewarming was initiated 12 hours after middle cerebral artery recanalization at a rate of 0.25°C/hour. All complications and adverse outcomes were documented from initiation of hypothermia until hospital discharge. Results: Eighteen patients with a mean National Institutes of Health Stroke Scale =21.4±5.6 were treated. The goal temperature was reached within 3.2±1.5 hours. Cooling time was proportional to body weight (p=0.009) and decreased with immediate paralysis to prevent shivering (p=0.033). Maintenance and rewarming were characterized by fluctuations in core temperature. All patients developed a decrease in blood pressure, heart rate, and potassium values that were proportional to temperature (p<0.05). Complications were generally mild, but pneumonia and myocardial infarction or both occurred in five patients. There were trends for increased risk of complications with longer duration of hypothermia (p=0.08) and increasing age (p=0.0504). Rewarming was well-tolerated with rebound cerebral edema occurring in only one patient. Conclusion: Surface cooling for the treatment of acute ischemic stroke can be performed rapidly with early neuromuscular paralysis. Advanced age and prolonged hypothermia may be associated with an increased risk of complications.

Head computed tomography in medical intensive care unit patients: Clinical indications

Objective: To assess whether clinical variables might be useful in selecting patients who will have an acute intracranial abnormality seen in head computed tomographic scans (HCT). Design: Retrospective study. Setting: Medical intensive care unit (MICU) in a tertiary teaching hospital. Measurements: Medical records of patients admitted to the MICU who underwent HCT between January 1, 1994, and December 31, 1995, were reviewed. Patients with acute intracranial abnormalities (HCT‐positive) and those without new acute findings (HCT‐negative) were compared on various clinical variables, including demographics, indications for obtaining the HCT (mental status change, neurologic deficit, fever, seizures), coagulation profiles, when the HCT was performed (at admission or after admission), and ordering physician. Main Results: Of 297 HCTs obtained in 230 patients, 37% (109/297) were positive. When the clinical variables were examined univariately, only the presence of a neurologic deficit (70% vs. 37%; difference, 33%; p < .001) differed significantly between positive and negative HCTs. Multivariate analysis confirmed that only the frequency of a new neurologic deficit differed significantly in the two groups (p < .001; odds ratio, 3.9; 95% confidence interval, 2.3‐6.4). In patients without neurologic deficits, only the presence of seizures was associated with a positive HCT (p < .01: logistic regression). The presence of either neurologic deficit or seizures best predicted a positive HCT: sensitivity 0.81, specificity 0.53, positive predictive value 0.50, and negative predictive value 0.83. Conclusion: Among MICU patients, the presence of either neurologic deficit or seizures is associated with the presence of an acute intracranial abnormality seen in HCT, but the association is not powerful enough to reliably depend on these clinical variables to select patients for HCTs in the MICU.

Fever is Associated With Third Ventricular Shift in Intracerebral Hemorrhage

P104 Introduction: Several studies have shown the detrimental effect of fever on brain injury. Recently, the incidence and prognostic significance of fever after intracerebral hemorrhage (ICH) was reported. The underlying cause of fever remains speculative. We present data on fever after ICH, volume of ICH, 3rd ventricular shift, and patient outcome. Methods: Data from 61 patients with ICH were collected prospectively from August 1999 to April 2000 including age, admission Glasgow Coma Scale (GCS) score, ICH volume, 3rd ventricular shift, maximum temperature (Tmax) and fever (T >38.5 °C) at 24, 48, 72 and 96 hours. Patients were screened for common causes of fever. Outcome was determined by mortality at discharge and National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) at 3 months. Spearman correlation coefficient, Mann-Whitney test, and logistic regression were used to assess relationships. No adjustment was made to significance criterion for multiple comparisons over time. Results: The average age was 65 ± 16 years. The mean admission GCS score was 8.8 ± 4.8. The mean ICH volume was 48.9 ± 52.4 cc. The mean 3rd ventricular shift was 3.6 ± 4.5 mm. The mean Tmax was 38.0 ± 0.9°C. There was a correlation between ICH volume and Tmax at 24 hours (p= 0.04) and at 72 hours (p= 0.03) and fever at 24 hours (p=0.039) and at 72 hours (p=0.036). Tmax at 72 hours correlated with 3rd ventricular shift (p= 0.01). Patients with 3rd ventricular shift > 1 mm were more likely to have a fever within the first 72 hours (p= 0.049). Multivariate logistic regression analysis showed no confounding effects from intubation status, presence of infection (positive blood, sputum, or urine culture/urinalysis), abnormal chest x-ray, or DVT. Fever at 72 hours was associated with a higher mortality at discharge (p=0.046). Fever within 72 hours was associated with a trend of a worse NIHSS score (p=0.06) at 3 months but no worse outcome by BI or mRS score at 3 months. Conclusion: Fever after ICH correlates with 3rd ventricular shift and ICH volume. The underlying mechanism may be hypothalamic dysfunction. Fever may be associated with a worse outcome but more studies are needed.