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.

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

OBJECTIVE: Subarachnoid hemorrhage (SAH) predisposes patients to excessive natriuresis and volume contraction. We studied the effects of postoperative administration of 5% albumin solution on sodium balance and blood volume after SAH. We also sought to identify physiological variables that influence renal sodium excretion after SAH. METHODS: Forty-three patients with acute SAH were randomly assigned to receive hypervolemia or normovolemia treatment for a period of 7 days after aneurysm clipping. In addition to a base line infusion of normal saline solution (80 ml/hr), 250 ml of 5% albumin solution was administered every 2 hours for central venous pressure (CVP) values of < or =8 mm Hg (hypervolemia group, n = 19) or < or =5 mm Hg (normovolemia group, n = 24). RESULTS: Both groups demonstrated relative volume expansion in base line measurements. The hypervolemia group received significantly more total fluid, sodium, and 5% albumin solution than did the normovolemia group and had higher CVP values and serum albumin levels (all P < 0.02). Cumulative sodium balance was even in the hypervolemia group and persistently negative in the normovolemia group, because of sodium losses that occurred on Postoperative Days 2 and 3 (P = 0.03). In a multiple-regression analysis of all patients, 24-hour sodium balance correlated negatively with glomerular filtration rate (GFR) and positively with serum albumin levels, after correction for sodium intake (P < 0.0001). Hypervolemia therapy seemed to paradoxically lower GFR (P = 0.10) and had no effect on blood volume, which declined by 10% in both groups. Pulmonary edema requiring diuresis occurred in only one patient in the hypervolemia group. CONCLUSION: Supplemental 5% albumin solution given to maintain CVP values of >8 mm Hg prevented sodium and fluid losses but did not have an impact on blood volume in our patients, who were hypervolemic in base line measurements. The natriuresis that occurs after SAH may be mediated in part by elevations of GFR. In addition to acting as a colloid volume expander, 5% albumin solution lowers the GFR and promotes renal sodium retention after SAH. These properties may limit the amount of total fluid required to maintain a given CVP value and hence may minimize the frequency of pulmonary edema.

Electrocardiographic markers of abnormal left ventricular wall motion in acute subarachnoid hemorrhage.

A reversible and presumably neurogenic form of myocardial dysfunction may occur following subarachnoid hemorrhage (SAH), but the relationship of this finding to electrocardiographic abnormalities remains unclear. To clarify this issue, serial electrocardiograms (ECGs, mean 6.2 per patient) and echocardiograms (mean 3.4 days after SAH) were obtained in 57 SAH patients without preexisting cardiac disease. The goal was to determine which specific electrocardiographic changes, if any, reflect abnormal left ventricular wall motion in acute SAH. Wall motion abnormalities were identified in five (8%) of 57 patients. Four of these affected patients experienced hypotension (systolic blood pressure < 100 mm Hg) and three exhibited pulmonary edema within 6 hours of SAH, compared to none of the 52 patients with normal wall motion (p < 0.0001). Patients with abnormal wall motion were more likely than patients with normal echocardiograms to have symmetrical T wave inversion (five of five vs. seven of 52, p < 0.001) and severe (> or = 500 msec) QTc segment prolongation (five of five vs. three of 52, p < 0.001) on serial ECGs. These associations maintained their significance with analysis limited to single ECGs performed on or near the day of echocardiography. Abnormal wall motion was also associated with borderline (2% to 5%) creatine kinase MB elevation (five of five vs. three of 52, p < 0.001) and poor neurological grade (p < 0.0001). Although no combination of findings on a single ECG resulted in 100% sensitivity for abnormal wall motion, the presence of either inverted T waves or severe QTc segment prolongation on serial ECGs was associated with 100% sensitivity and 81% specificity. These results demonstrate an association between reduced left ventricular systolic function, mild creatine kinase MB elevation, and electrocardiographic repolarization abnormalities in acute SAH. Symmetrical T wave inversion and severe QTc segment prolongation best identified patients at risk for myocardial dysfunction and may serve as useful criteria for echocardiographic screening following SAH.

Noninvasive monitoring of cardiac output by Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage.

OBJECTIVE: To assess the validity and potential clinical utility of cardiac output monitoring using Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage. DESIGN: Observational study of patients in a randomized, clinical trial. SETTING: Neurologic intensive care unit. PATIENTS: Simultaneous, blinded measurements of cardiac output by thermodilution and Doppler echocardiography were performed in 48 patients 1 or 2 days after aneurysmal clipping. Follow-up Doppler echocardiography was performed an average of 3.9 days later (range 3 to 6) in 15 patients assigned to normovolemia and 24 patients assigned to hypervolemia. INTERVENTION: Patients received supplemental 5% albumin in order to maintain increased (hypervolemia) or normal (normovolemia) cardiac filling pressures. MEASUREMENTS AND MAIN RESULTS: The overall degree of correlation between the two measures was moderate (r = .67, r2 = .45, p < .0001). Bias and precision calculations (-0.75 +/- 1.34 L/min) showed a tendency for Doppler echocardiography to underestimate thermodilution, particularly when cardiac output was very high. Although hypervolemia patients received more 5% albumin than normovolemia patients, mean percent change in Doppler echocardiography cardiac output did not differ between the two groups. Multiple regression analysis showed that the percent change in Doppler echocardiography cardiac output correlated strongly with changes in heart rate (p < .0001), but not with daily net fluid balance or 5% albumin administration. CONCLUSIONS: Agreement was poor between Doppler echocardiography and thermodilution measurements of cardiac output, and trends reflected variations in heart rate rather than fluid status. Monitoring of cardiac output by this technique cannot be recommended in patients treated with volume expansion after subarachnoid hemorrhage.

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 echocardiographic 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 clinical spectrum of unruptured intracranial aneurysms.

OBJECTIVE: A retrospective study was performed to delineate the clinical characteristics of symptomatic unruptured aneurysms. DESIGN: Patient histories, operative reports, and angiograms in 111 patients with 132 unruptured aneurysms were reviewed. SETTING: Tertiary care university hospital. PATIENTS: One hundred eleven patients with 132 unruptured intracranial aneurysms were studied. There were 85 women and 26 men, with a mean age of 51.2 years (age range, 11 to 77 years). Many patients were referred by community neurologists and neurosurgeons for further evaluation and neurosurgical management. RESULTS: Fifty-four symptomatic patients were identified. Group 1 (n = 19; mean aneurysm diameter, 2.1 cm) had acute symptoms: ischemia (n = 7), headache (n = 7), seizure (n = 3), and cranial neuropathy (n = 2). Group 2 (n = 35; mean aneurysm diameter, 2.2 cm) had chronic symptoms attributed to mass effect: headache (n = 18), visual loss (n = 10), pyramidal tract dysfunction (n = 4), and facial pain (n = 3). Group 3 (n = 57; mean aneurysm diameter, 1.1 cm) had asymptomatic aneurysms. CONCLUSIONS: Acute severe headache, comparable to subarachnoid hemorrhage headache, but without nuchal rigidity, was associated with the following mechanisms: aneurysm thrombosis, localized meningeal inflammation, and unexplained. Unruptured aneurysms may be misdiagnosed as optic neuritis or migraine, or serve as a nidus for cerebral thromboembolic events. Internal carotid artery and posterior circulation aneurysms were more likely to cause focal symptoms from mass effect than were anterior cerebral artery and middle cerebral artery aneurysms. Weeks to years may elapse before their diagnosis. The absence of subarachnoid blood does not exclude an aneurysm as a cause for acute or chronic neurologic symptoms.

Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia.

A consecutive series of 145 patients with acute aneurysmal subarachnoid hemorrhage (SAH) were operated on within 7 days of SAH and were prospectively evaluated over a 4-year period to determine if the timing of aneurysm surgery influenced the development of delayed cerebral ischemia. All patients were managed with a standardized policy of urgent surgical clipping and treatment with aggressive prophylactic postoperative volume expansion. Patients with delayed ischemic symptoms were additionally treated with induced hypertension. Forty-nine patients underwent surgery on Day 0 or 1 (Group 1) post-SAH, 60 patients on Day 2 or 3 (Group 2), and 36 patients on Days 4 through 7 (Group 3). Postoperative delayed cerebral ischemia developed in 16% of (Group 1) patients, in 22% of Group 2 patients, and in 28% of Group 3 patients. Cerebral infarction resulting from delayed cerebral ischemia developed in only 4% of Group 1 patients, 10% of Group 2 patients, and 11% of Group 3 patients. A bad clinical outcome as a result of delayed cerebral ischemia occurred in one Group 1 patient (2%), two Group 2 patients (3%), and one Group 3 patient (3%). Preoperative grade was not significantly correlated with the incidence or severity of delayed cerebral ischemia at any time interval except that patients in modified Hunt and Hess Grade I or II who underwent surgery on Day 0 or 1 after SAH had no strokes or bad outcomes from delayed cerebral ischemia. This study demonstrates that there is no rationale for delaying aneurysm surgery based on the time interval between SAH and patient evaluation.

Does pimozide block the reinforcing effect of brain stimulation?

The neuroleptic pimozide produces an extinction-like decline in the runway and Skinner box performance of rats rewarded with electrical stimulation of the medial forebrain bundle (MFB) in the lateral and posterior hypothalamus. The required dose is an order of magnitude less than the dose that incapacitates. The extinction-like decline is seen even when the drug treated rats run and receive brain stimulation in a running wheel prior to runway testing. The decline is also task-specific: after extinguishing in the Skinner box, rats readily perform in the runway, but soon show extinction in this task, too. The characteristics of pimozide's effects on rewarded behavior imply that the drug, whatever other effects it may have, does block the reinforcing effect of the brain stimulation reward.