Matthew E. Fink

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.

Myasthenic crisis Clinical features, mortality, complications, and risk factors for prolonged intubation

We retrospectively reviewed the hospital records of 53 patients admitted for 73 episodes of myasthenic crisis at Columbia-Presbyterian Medical Center over a period of 12 years, from 1983 to 1994. Median age at the onset of first crisis was 55 (range, 20 to 82), the ratio of women to men was 21, and the median interval from onset of symptoms to first crisis was 8 months. Infection (usually pneumonia or upper respiratory infection) was the most common precipitating factor (38%), followed by no obvious cause (30%) and aspiration (10%). Twenty-five percent of patients were extubated at 7 days, 50% at 13 days, and 75% at 31 days; the longest crisis exceeded 5 months. Using survival analysis and backward stepwise Cox regression, we identified three independent predictors of prolonged intubation: (1) pre-intubation serum bicarbonate ≥30 mg/dl (p = 0.0004, relative hazard 4.5), (2) peak vital capacity day 1 to 6 post-intubation <25 mYkg (p = 0.001, relative hazard 2.9), and (3) age >50 (p = 0.01, relative hazard 2.4). The proportion of patients intubated longer than 2 weeks was 0% among those with no risk factors, 21% with one risk factor, 46% with two risk factors, and 88% with three risk factors (p = 0.0004). Complications independently associated with prolonged intubation included atelectasis (p = 0.002), anemia treated with transfusion (p = 0.03), Clostridium diffcile infection (p = 0.011, and congestive heart failure (p = 0.03). Three episodes of crisis were fatal, for a mortality rate of 4% (3/73); four additional patients died after extubation. All seven deaths were due to overwhelming medical comorbidity. Over half of those who survived were functionally dependent (home or institutionalized) at discharge. In addition to prospective controlled studies of immuno-therapies, the prevention and treatment of medical complications offers the best opportunity for further improving the outcome of myasthenic crisis.

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.

Quantitative EEG monitoring for patients with subarachnoid hemorrhage

We evaluated the sensitivity of continuous quantitative EEG in 11 patients with subarachnoid hemorrhage (SAH). We correlated compressed spectral array (CSA) and trend analysis (TA) of total power (1-30 Hz), frequency centroid (1-30 Hz), alpha ratio and percent delta power with clinical and radiological findings. For all ischemic events (n = 11), the most sensitive TA parameter was a change in total power (91%), followed by changes in alpha ratio (64%), frequency centroid (55%), and percent delta (45%). Comparable CSA features were changes in power (44%) and slowing (39%). Total power and frequency varied independently. In 4 cases, EEG findings on TA appeared before clinical changes. Continuous quantitative EEG may be useful for monitoring and predicting ischemia following SAH. TA of individual EEG parameters is more sensitive than CSA, and total power is the most sensitive.

Harnessing hypoxic adaptation to prevent, treat, and repair stroke

The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being highly evolved in its architecture, the human brain appears to utilize phylogenetically conserved homeostatic strategies to combat hypoxia and ischemia. Specifically, several converging lines of inquiry have demonstrated that the transcription factor hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette of genes involved in adaptation to hypoxia in surviving neurons after stroke. Accordingly, pharmacological or molecular approaches that engage hypoxic adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4 hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of function. In this review, we discuss the potential mechanisms that could subserve protective and restorative effects of augmenting hypoxic adaptation in the brain. The strategy appears to involve HIF-dependent and HIF-independent pathways and more than 70 genes and proteins activated transcriptionally and post-transcriptionally that can act at cellular, local, and system levels to compensate for oxygen insufficiency. The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics.

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.

Transcranial Doppler detection of anterior cerebral artery vasospasm.

The performance of transcranial Doppler in the detection of anterior cerebral artery vasospasm and vasospasm in patients after subarachnoid haemorrhage was analysed. Transcranial Doppler and cerebral angiography were performed within the same 24 hours on each of 41 patients with acute subarachnoid haemorrhage. Sensitivity and specificity of transcranial Doppler to classify middle cerebral arteries, anterior cerebral arteries, and patients with angiographic vasospasm were determined at mean velocities of 120 and 140 cm/s. Accuracy of transcranial Doppler was better at 140 than at 120 cm/s. For the middle cerebral artery, sensitivity was 86%, specificity 98%. For the anterior cerebral artery, sensitivity was 13%, specificity 100%. Among all patients, sensitivity was 45%, specificity 96%. Among patients with anterior communicating artery aneurysms, sensitivity was 14%, specificity 90%. Therefore, transcranial Doppler accurately differentiates between middle cerebral arteries with and without vasospasm on angiography, but has a very low sensitivity for detecting anterior cerebral artery vasospasm and vasospasm in patients with anterior communicating artery aneurysms. Since vasospasm may involve anterior cerebral arteries while sparing middle cerebral arteries, especially after rupture of an anterior communicating artery aneurysm, caution should be exercised in using negative transcranial Doppler results to make treatment decisions based on the assumed absence of vasospasm.

Paroxysmal Supraventricular Tachycardia and the Risk of Ischemic Stroke

Background and Purpose— It is unknown whether supraventricular arrhythmias other than atrial fibrillation or flutter are associated with stroke. Methods— To examine the association between paroxysmal supraventricular tachycardia (PSVT) and stroke, we performed a retrospective cohort study using administrative claims data from all emergency department encounters and hospitalizations at California’s nonfederal acute care hospitals in 2009. Our cohort comprised all adult patients with ≥1 emergency department visit or hospitalization from which they were discharged alive and without a diagnosis of stroke. Our primary exposure was a diagnosis of PSVT recorded at an encounter before stroke or documented as present-on-admission at the time of stroke. To reduce confounding, we excluded patients with diagnoses of atrial fibrillation. We defined PSVT, stroke, and atrial fibrillation using International Classification of Diseases, Ninth Revision, Clinical Modification codes previously validated by detailed chart review. Results— Of 4 806 830 eligible patients, 14 121 (0.29%) were diagnosed with PSVT and 14 402 (0.30%) experienced a stroke. The cumulative rate of stroke after PSVT diagnosis (0.94%; 95% confidence interval, 0.76%–1.16%) significantly exceeded the rate among patients without a diagnosis of PSVT (0.21%; 95% confidence interval, 0.21%–0.22%). In Cox proportional hazards analysis controlling for demographic characteristics and potential confounders, PSVT was independently associated with a higher risk of subsequent stroke (hazard ratio, 2.10; 95% confidence interval, 1.69–2.62). Conclusions— In a large and demographically diverse sample of patients, we found an independent association between PSVT and ischemic stroke. PSVT seems to be a novel risk factor that may account for some proportion of strokes that are currently classified as cryptogenic.

Using Quantitative CT Perfusion for Evaluation of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH leading to permanent neurologic deficits, infarction, and death. Our aim was to prospectively evaluate the diagnostic accuracy of CTP and to determine a quantitative threshold for DCI in aneurysmal SAH. MATERIALS AND METHODS: Patients with SAH were prospectively enrolled in a protocol approved by the institutional review board. CTP was performed during the typical time period for DCI, between days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained by using standard region-of-interest placement sampling of gray matter. The reference standard for DCI is controversial and consisted of clinical and imaging criteria in this study. In a subanalysis of vasospasm, DSA was used as the reference standard. ROC curves determined the diagnostic accuracy by using AUC. Optimal threshold values were calculated by using the patient population utility method. RESULTS: Ninety-seven patients were included; 41% (40/97) had DCI. Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV. Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity) for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was 94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5 mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78% sensitivity, 70% specificity) for MTT. CONCLUSIONS: CBF and MTT have the highest overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5-second MTT are suggested for DCI on the basis of the patient population utility method. Absolute threshold values may not be generalizable due to differences in scanner equipment and postprocessing methods.