John A. Ulatowski

Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging

The ability to measure the effects of local alterations in blood flow, blood volume and oxygenation by nuclear magnetic resonance has stimulated a surge of activity in functional MRI of many organs, particularly in its application to cognitive neuroscience. However, the exact description of these effects in terms of the interrelations between the MRI signal changes and the basic physiological parameters has remained an elusive goal. We here present this fundamental theory for spin-echo signal changes in perfused tissue and validate it in vivo in the cat brain by using the physiological alteration of hypoxic hypoxia. These experiments show that high-resolution absolute blood volume images can be obtained by using hemoglobin as a natural intravascular contrast agent. The theory also correctly predicts the magnitude of spin-echo MRI signal intensity changes on brain activation and thereby provides a sound physiological basis for these types of studies.

Treatment of refractory intracranial hypertension with 23.4% saline.

ObjectiveTo evaluate the effect of intravenous bolus administration of 23.4% saline (8008 mOsm/L) on refractory intracranial hypertension (RIH) in patients with diverse intracranial diseases.DesignRetrospective chart review.SettingA neurosciences intensive care unit in a university hospital.Patients

Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema : Effect on intracranial pressure and lateral displacement of the brain

OBJECTIVE To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema. DESIGN Retrospective chart review. SETTINGS Neurocritical care unit of a university hospital. PATIENTS Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n = 8), postoperative edema (n = 5), nontraumatic intracranial hemorrhage (n = 8), and cerebral infarction (n = 6). INTERVENTION Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L. MEASUREMENTS AND MAIN RESULTS A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2 = .91, p = .03), and postoperative edema (r2 = .82, p = .06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8 +/- 1.4 to 1.1 +/- 0.9 [SEM]) and in patients with postoperative edema (3.1 +/- 1.6 to 1.1 +/- 0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus. CONCLUSIONS Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.

A Pilot Randomized Trial of Induced Blood Pressure Elevation: Effects on Function and Focal Perfusion in Acute and Subacute Stroke

Background: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. Methods: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation (‘treated’ patients, n = 9) or conventional management (‘untreated’ patients, n = 6). Results: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6–8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. Conclusion: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

Treatment of Intraventricular Hemorrhage With Urokinase Effects on 30-Day Survival

BACKGROUND AND PURPOSE Intraventricular hemorrhage (IVH) remains associated with high morbidity and mortality. Therapy with external ventricular drainage alone has not modified outcome in these patients. METHODS Twelve pilot IVH patients who required external ventricular drainage were prospectively treated with intraventricular urokinase followed by the randomized, double-blinded allocation of 8 patients to either treatment or placebo. Observed 30-day mortality was compared with predicted 30-day mortality obtained by use of a previously validated method. RESULTS Twenty patients were enrolled; admission Glasgow Coma Scale score in 11 patients was </=8; 10 patients had pulse pressure <85 mm Hg. Mean+/-SD ICH volume in 16 patients was 6.21+/-7.53 cm(3) (range 0 to 23.88 cm(3)), and mean+/-SD intraventricular hematoma volume was 44.26+/-31.65 cm(3) (range 1.31 to 100.36 cm(3)). Four patients (20%) died within 30 days. Predicted mortality for these 20 patients was 68.42% (range 3% to 100%). Probability of observing </=4 deaths among 20 patients under a 68.42% expected mortality is 0.000012. CONCLUSIONS Intraventricular urokinase may significantly improve 30-day survival in IVH patients. On the basis of current evidence, a double-blinded, placebo-controlled, multicenter study that uses thrombolysis to treat IVH has received funding and began January 1, 2000.

Symptomatic vasospasm diagnosis after subarachnoid hemorrhage: Evaluation of transcranial Doppler ultrasound and cerebral angiography as related to compromised vascular distribution

ObjectiveTo evaluate the reliability of transcranial Doppler ultrasound in detecting symptomatic vasospasm in patients after aneurysmal subarachnoid hemorrhage and monitoring response after hypertensive and endovascular treatments. DesignRetrospective chart review. SettingNeurosciences critical care unit in a tertiary-care university hospital. PatientsAll patients admitted to a neurosciences critical care unit with the diagnosis of subarachnoid hemorrhage between January 1990 and June 1997. InterventionsNone Measurements and Main ResultsWe reviewed transcranial Doppler ultrasound data of 199 patients; 55 had symptomatic vasospasm. Clinical symptoms and corresponding vascular distributions were identified, as was angiographic vasospasm (n = 35). The sensitivity and specificity of transcranial Doppler ultrasound for anterior circulation vessels were calculated by using a mean cerebral blood flow velocity criterion of >120 cm/sec. Clinical diagnosis of symptomatic vasospasm was used as the standard to determine sensitivity and specificity of transcranial Doppler ultrasound and cerebral angiography.The sensitivity of transcranial Doppler ultrasound for anterior circulation in patients with symptomatic vasospasm was 73% with a specificity of 80%. The sensitivity of cerebral angiography was 80%. For individual vessels, the sensitivity and specificity of transcranial Doppler ultrasound were middle cerebral artery, 64% and 78%; anterior cerebral artery, 45% and 84%; and internal carotid artery, 80% and 77%, respectively. The mean times for symptomatic and transcranial Doppler ultrasound signs of vasospasm presentation were 6.4 ± 2 and 6.1 ± 3 days, respectively. In patients without symptomatic vasospasm, the mean time for mean cerebral blood flow velocities >120 cm/sec was 7.0 ± 3 days (p < .05). Symptomatic vasospasm also was associated with thickness of clot on head computed tomography scan and rapidly increasing mean cerebral blood flow velocities. Transcranial Doppler ultrasound signs of vasospasm improved after endovascular treatment in 30 patients. ConclusionsThe reliability of transcranial Doppler ultrasound was better at detecting high mean cerebral blood flow velocities in patients with symptomatic vasospasm related to middle cerebral and internal carotid artery distributions than for anterior cerebral artery distribution. Transcranial Doppler ultrasound was as sensitive as cerebral angiography at detecting symptomatic vasospasm. High mean cerebral blood flow velocities can be apparent before the presence of symptomatic vasospasm. Daily transcranial Doppler ultrasound monitoring could provide early identification of patients with aneurysmal subarachnoid hemorrhage who are at high risk for symptomatic vasospasm and may be helpful at following success of endovascular treatment.

Early identification of patients at risk for symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

Objective: To develop a scheme for early identification of individuals at risk for symptomatic vasospasm after subarachnoid hemorrhage (SAH). Design: Analysis of prospectively collected data from the placebo‐treated group in a multicenter clinical trial. Settings: Fifty‐four neurosurgical centers in North America. Measurements and Main Results: We identified independent predictors of symptomatic vasospasm using stepwise logistic regression analysis from demographic, clinical, laboratory, and neuroimaging characteristics of the participants. We developed a scoring system (symptomatic vasospasm risk index) based on a combination of these predictors. Out of 283 patients in the analysis (all treated with oral nimodipine), 93 (33%) developed symptomatic vasospasm within 14 days after SAH. There were four independent predictors of symptomatic vasospasm: thickness of subarachnoid clot on computed tomographic scan (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.8‐10.0); early rise in middle cerebral artery mean flow velocity (MCA‐MFV), defined as a value ≥110 cm/sec recorded on or before post‐SAH day 5 (OR, 1.9; 95% CI, 1.1‐3.3), Glasgow Coma Scale score <14 (OR, 1.8; 95% CI, 1.1‐3.1); and rupture of anterior cerebral or internal carotid artery aneurysm (OR, 1.9; 95% CI, 1.0‐3.4). The probability of identifying patients who would develop symptomatic vasospasm (percentage of area under receiver operating characteristics curve ± SEM) was higher with symptomatic vasospasm risk index (68% ± 8%) compared with thickness of clot (62% ± 8%; p = .08) or MCA‐MFV (45% ± 7%, p < .05) criteria alone. Conclusions: Patients at high risk for symptomatic vasospasm can be identified early in the course of SAH using a risk index. A risk index based on a combination of variables may represent a predictive paradigm superior to conventionally used criteria based on clot thickness or MCA‐MFV criteria.

Plasma exchange versus intravenous immunoglobulin treatment in myasthenic crisis

Article abstract We performed a retrospective multicenter chart review to compare the efficacy and tolerance of plasma exchange (PE) and intravenous immunoglobulin (IVIg) in treatment of 54 episodes of myasthenic crisis. After adjustment for other variables, PE (compared with IVIg) was associated with a superior ventilatory status at 2 weeks (partial F = 6.2, p = 0.02) and 1 month functional outcome (partial F = 4.5, p = 0.04). However, the complication rate was higher with PE compared with IVIg (13 versus 5 episodes, p = 0.07).

Variability in Blood and Blood Component Utilization as Assessed by an Anesthesia Information Management System

Background: Data can be collected for various purposes with anesthesia information management systems. The authors describe methods for using data acquired from an anesthesia information management system to assess intraoperative utilization of blood and blood components. Methods: Over an 18-month period, data were collected on 48,086 surgical patients at a tertiary care academic medical center. All data were acquired with an automated anesthesia recordkeeping system. Detailed reports were generated for blood and blood component utilization according to surgical service and surgical procedure, and for individual surgeons and anesthesiologists. Transfusion hemoglobin trigger and target concentrations were compared among surgical services and procedures, and between individual medical providers. Results: For all patients given erythrocytes, the mean transfusion hemoglobin trigger was 8.4 ± 1.5, and the target was 10.2 ± 1.5 g/dl. Variation was significant among surgical services (trigger range: 7.5 ± 1.2–9.5 ± 1.1, P = 0.0001; target range: 9.1 ± 1.2–11.3 ± 1.4 g/dl, P = 0.002), surgeons (trigger range: 7.2 ± 0.7–9.8 ± 1.0, P = 0.001; target range: 8.8 ± 0.9–11.8 ± 1.3 g/dl, P = 0.001), and anesthesiologists (trigger range: 7.2 ± 0.8–9.6 ± 1.2, P = 0.001; target range: 9.0 ± 0.9–11.7 ± 1.3 g/dl, P = 0.0004). The use of erythrocyte salvage, fresh frozen plasma, and platelets varied threefold to fourfold among individual surgeons compared with their peers performing the same surgical procedure. Conclusions: The use of data acquired from an anesthesia information management system allowed a detailed analysis of blood component utilization, which revealed significant variation among surgical services and surgical procedures, and among individual anesthesiologists and surgeons compared with their peers. Incorporating these methods of data acquisition and analysis into a blood management program could reduce unnecessary transfusions, an outcome that may increase patient safety and reduce costs.

Risk factors for multiple intracranial aneurysms

OBJECTIVE Risk factors that predispose to the formation of multiple intracranial aneurysms, which are present in up to 34% of patients with intracranial aneurysms, are not well defined. In this study, we examined the association between known risk factors for cerebrovascular disease and presence of multiple intracranial aneurysms. METHODS We reviewed the medical records and results of conventional angiography in all patients with a diagnosis of intracranial aneurysms admitted to the Johns Hopkins University hospital between January 1990 and June 1997. We determined the independent association between various cerebrovascular risk factors and the presence of multiple aneurysms using logistic regression analysis. RESULTS Of 419 patients admitted with intracranial aneurysms (298 ruptured and 121 unruptured), 127 (30%) had multiple intracranial aneurysms. In univariate analysis, female gender (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.1-3.3) and cigarette smoking at any time (OR = 1.8; 95% CI, 1.1-3.0) were significantly associated with presence of multiple aneurysms. In the multivariate analysis, cigarette smoking at any time (OR = 1.7; 95% CI, 1.1-2.8) and female gender (OR = 2.1; 95% CI 1.2-3.5) remained significantly associated with multiple aneurysms. Hypertension, diabetes mellitus, and alcohol and illicit drug use were not significantly associated with presence of multiple aneurysms. CONCLUSION Cigarette smoking and female gender seem to increase the risk for multiple aneurysms in patients predisposed to intracranial aneurysm formation. Further studies are required to investigate the mechanism underlying the association between cigarette smoking and intracranial aneurysm formation.