Laura Lennihan

Effect of Hypervolemic Therapy on Cerebral Blood Flow After Subarachnoid Hemorrhage A Randomized Controlled Trial

BACKGROUND AND PURPOSE Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared. METHODS On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF ((133)xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient). RESULTS HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (P=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (P=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups. CONCLUSIONS HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit.

Myocardial Injury and Left Ventricular Performance After Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE Electrocardiographic abnormalities and elevations of the creatine kinase myocardial isoenzyme (CK-MB) occur frequently after subarachnoid hemorrhage. In some patients, a reversible and presumably neurogenic form of left ventricular dysfunction is demonstrated by echocardiography. It is not known whether cardiac injury of this type adversely affects cardiovascular hemodynamic performance. METHODS We retrospectively studied 72 patients admitted to our neuro-ICU for aneurysmal subarachnoid hemorrhage over a 2.5-year period. We selected patients who met the following criteria: (1) CK-MB levels measured within 3 days of onset, (2) pulmonary artery catheter placed, (3) echocardiogram performed, and (4) no history of preexisting cardiac disease. Hemodynamic profiles were recorded on the day after surgery (n=67) or on the day of echocardiography (n=5) if surgery was not performed (mean, 3. 3+/-1.7 days after onset). The severity of cardiac injury was classified as none (peak CK-MB <1%, n=36), mild (peak CK-MB 1% to 2%, n=21), moderate (peak CK-MB >2%, n=6), or severe (abnormal left ventricular wall motion, n=9). RESULTS Abnormal left ventricular wall motion occurred exclusively in patients with peak CK-MB levels >2% (P<0.0001), poor neurological grade (P=0.002), and female sex (P=0.02). Left ventricular stroke volume index and stroke work index were elevated above the normal range in patients with peak CK-MB levels <1% and fell progressively as the severity of cardiac injury increased, with mean values for patients with abnormal wall motion below normal (both P<0.0001 by ANOVA). Cardiac index followed a similar trend, but the effect was less pronounced (P<0.0001). Using forward stepwise multiple logistic regression, we found that thick subarachnoid clot on the admission CT scan (odds ratio, 1.9; 95% confidence interval [95% CI], 1.0 to 3.4; P=0.04) and depressed cardiac index (odds ratio, 2.1; 95% CI, 1.0 to 4.1; P=0.04) were independent predictors of symptomatic vasospasm. CONCLUSIONS Myocardial enzyme release and echocardiographic wall motion abnormalities are associated with impaired left ventricular performance after subarachnoid hemorrhage. In severely affected patients, reduction of cardiac output from normally elevated levels may increase the risk of cerebral ischemia related to vasospasm.

Cardiac injury associated with neurogenic pulmonary edema following subarachnoid hemorrhage

Objective: To describe the clinical features of cardiac injury associated with neurogenic pulmonary edema (NPE) in patients with acute subarachnoid hemorrhage (SAH). Background: NPE is generally viewed as a form of noncardiogenic pulmonary edema related to massive sympathetic discharge. Methods: Case series. Results: We found echocardiography evidence of reduced global and segmental left ventricular (LV) systolic function in five women (mean age, 44; range, 36 to 57) with SAH and NPE. None had a history of heart disease. Four patients were Hunt/Hess grade III and one was grade IV. All five patients experienced (1) sudden hypotension (systolic blood pressure <110 mm Hg) following initially elevated blood pressures, (2) transient lactic acidosis, (3) borderline (2 to 4%) creatine kinase MB elevations, and (4) varied acute (< 24 hours) electrocardiographic changes followed by widespread and persistent T wave inversions. Pulmonary artery wedge pressures were normal in 3/3 patients at the onset of pulmonary edema but reached high levels (>16 mm Hg) in all four patients studied beyond this period. Reduced cardiac output and LV stroke volume were identified in three patients; the fourth patient demonstrated normal values on high doses of intravenous pressors. Cerebral infarction due to vasospasm occurred in four patients and resulted in two deaths. Follow-up echocardiography performed 2 to 6 weeks after SAH revealed normal LV function in all three survivors. Conclusions: A reversible form of cardiac injury may occur in patients with NPE following SAH and is associated with characteristic clinical findings. Impaired LV hemodynamic performance in this setting may contribute to cardiovascular instability, pulmonary edema formation, and complications from cerebral ischemia.

The role of transcranial Doppler in confirming brain death: Sensitivity, specificity, and suggestions for performance and interpretation

We performed transcranial Doppler (TCD) examinations on 54 comatose patients over a 1-year period. Of 49 patients with technically adequate TCD examinations, 23 met criteria for determination of brain death by clinical and EEG criteria (21) or clinical criteria alone (2; EEG not performed). A TCD waveform abnormality, consisting of absent or reversed diastolic flow, or small early systolic spikes, in at least 2 intracranial arteries, occurred in 21 brain-dead patients, but in none of the other patients in coma. With appropriate guidelines for performance and interpretation, TCD could be incorporated into institutional protocols as a rapid and convenient alternative to EEG for confirmation of brain death.

Neuroimaging in Stroke Recovery: A Position Paper from the First International Workshop on Neuroimaging and Stroke Recovery

Baron, Jean-Claude*Black, Sandra E.Butler, Andrew J.Carey, JamesChollet, FrancoisCohen, Leonardo G.*Corbetta, MaurizioCramer, Steven C.*Dobkin, Bruce H.*Frackowiak, RichardHeiss, W.D.Johansen-Berg, Heidi*Krakauer, John W.Lazar, Ronald M.Lennihan, Laura L.Loubinoux, Isabelle*Marshall, Randolph S.*Matthews, PaulMohr, J.P.Nelles, GereonPascual-Leone, AlvaroPomeroy, ValerieRijntjes, MichelRossini, Paolo MariaRothwell, John C.Seitz, Rudiger J.Small, Steven L.Sunderland, AlanWard, N.S.*Weiller, CorneliusWise, Richard J.S.IntroductionThe First International Workshop on Neuroimagingand Stroke Recovery was convened in February, 2004 inNew York City. The purpose of the workshop was to de-scribe the state of the field with regard to technical andanalytical methods, to discuss the use of complementaryimaging modalities, and to assess the current potential toapply functional neuroimaging to the development of ratio-nal treatment strategies for enhanced stroke recovery.Presented herein is a summary statement of topics dis-cussed at the workshop. These included (i) the clinical rel-evance of functional imaging changes after stroke for themotor and language systems; (ii) the technical challengesfaced in moving towards establishing functional neuro-imaging as a clinically useful tool; (iii) the contributions ofneurophysiological probes such as transcranial magnet-ic stimulation (TMS) to improve understanding of themechanisms underlying brain reorganization after stroke;and (iv) the potential role of neuroimaging in the assess-ment and development of rational pharmacological andbehavioral therapies.Clinical RelevanceFunctional recovery commonly occurs in survivingstroke patients in the weeks and months following theinjury. There is evidence from animal models that cere-bral reorganization underlies at least some of this recov-ery and it is hoped that an understanding of the neuro-physiological processes underlying this reorganization inthe human brain will lead to a rational approach to thetreatment of impairment. In animal models, focal braindamage triggers a number of changes at the molecular, cel-lular, and systems level, some of which alter the potentialfor cerebral reorganization and consequent functionalrecovery. Although the same techniques are not availableto study the working human brain, functional brain imag-ing has provided insights into how the human brainresponds to focal injury.

Improvement After Constraint-Induced Movement Therapy Recovery of Normal Motor Control or Task-Specific Compensation?

Background. Constraint-induced movement therapy (CIMT) has proven effective in increasing functional use of the affected arm in patients with chronic stroke. The mechanism of CIMT is not well understood. Objective. To demonstrate, in a proof-of-concept study, the feasibility of using kinematic measures in conjunction with clinical outcome measures to better understand the mechanism of recovery in chronic stroke patients with mild to moderate motor impairments who undergo CIMT. Methods. A total of 10 patients with chronic stroke were enrolled in a modified CIMT protocol over 2 weeks. Treatment response was assessed with the Action Research Arm Test (ARAT), the Upper-Extremity Fugl-Meyer score (FM-UE), and kinematic analysis of visually guided arm and wrist movements. All assessments were performed twice before the therapeutic intervention and once afterward. Results. There was a clinically meaningful improvement in ARAT from the second pre-CIMT session to the post-CIMT session compared with the change between the 2 pre-CIMT sessions. In contrast, FM-UE and kinematic measures showed no meaningful improvements. Conclusions. Functional improvement in the affected arm after CIMT in patients with chronic stroke appears to be mediated through compensatory strategies rather than a decrease in impairment or return to more normal motor control. We suggest that future large-scale studies of new interventions for neurorehabilitation track performance using kinematic analyses as well as clinical scales.

Cost and Outcome of Mechanical Ventilation for Life-Threatening Stroke

Background and Purpose Hospital mortality rates of 50% to 90% have been reported for stroke patients treated with mechanical ventilation. These data have raised serious questions about the cost-effectiveness of this intervention. We sought to determine how often stroke patients are mechanically ventilated, identify predictors of 30-day survival among ventilated patients, and evaluate the cost-effectiveness of this intervention. Methods We identified mechanically ventilated patients in a population-based multiethnic cohort of 510 incidence stroke patients who were hospitalized between July 1993 and June 1996. Factors affecting 30-day survival were identified in a multiple logistic regression analysis. We calculated the cost per patient discharged alive, life-year saved, and quality-adjusted life-year saved using a zero-cost, zero-life assumption. Results Ten percent of patients (n=52) were mechanically ventilated. Thirty-day mortality was 65% overall and did not differ significantly by stroke subtype. Glasgow Coma Scale score on the day of intubation (P <0.01) and subsequent neurological deterioration (P =0.02) were identified as predictors of 30-day mortality. The cost (1996 US dollars) of hospitalization per patient discharged alive was

Predictors of resource use after acute hospitalization The Northern Manhattan Stroke Study

89 400; the cost per year of life saved was

Lack of association between carotid plaque hematoma and ischemic cerebral symptoms.

37 600; and the cost per quality-adjusted life-year saved was

Effect of 5% albumin solution on sodium balance and blood volume after subarachnoid hemorrhage.

174 200. Functional status of most survivors was poor; at 6 months, half were severely disabled and completely dependent. In a worst-case scenario of quality of life preferences, mechanical ventilation resulted in a net deficit of meaningful survival. Conclusions Two thirds of mechanically ventilated stroke patients die during their hospitalization, and most survivors are severely disabled. Survival is particularly unlikely if patients are deeply comatose or clinically deteriorate after intubation. In our multiethnic urban population, mechanical ventilation for stroke was relatively cost-effective for extending life but not for preserving quality of life.