Plasma endothelin and big endothelin concentrations and serum endothelin-converting enzyme activity following aneurysmal subarachnoid hemorrhage

OBJECT: Pathogenesis of delayed ischemia after aneurysmal subarachnoid hemorrhage (SAH) seems to be complex. An important mediator of chronic vasospasm may be endothelin (ET)-1 with its powerful and long-lasting vasoconstricting activity. In this prospective study the author investigated the correlations between serial plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 molar concentration ratio and serum endothelin-converting enzyme (ECE)-1 activity, and ischemic complications after SAH. METHODS: To measure plasma ET-1 (51 patients), big ET-1 immunoreactivity (22 patients), and serum ECE-1 activity (13 patients), blood samples were obtained on admission, in the morning after aneurysm surgery, and during the 2nd week after hemorrhage in 51 consecutive patients (28 men and 23 women, with a mean age of 50.8 years) with aneurysmal SAH. Mean plasma concentrations of ET-1 in patients with SAH (mean +/- standard deviation: on admission, 4.2 +/- 2 pg/ml; after surgery, 4.3 +/- 2.2 pg/ml; and during the 2nd week after SAH, 3.7 +/- 1.9 pg/ml) differed from those in healthy volunteers (2.9 +/- 1.2 pg/ml; p < 0.01). Plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 ratio did not change significantly with elapsed time following SAH; however, serum ECE-1 activity during the 2nd week after SAH was higher in patients with SAH than that in controls (162 +/- 43 compared with 121 +/- 56 pg/ml, respectively; p = 0.028). Plasma ET-1 concentrations (p < 0.05) and the ET-1/big ET-1 ratios (p = 0.063) were higher but plasma big ET-1 concentrations were lower (p < 0.05) in patients who experienced symptomatic delayed cerebral ischemia, compared with other patients with SAH. In addition, in cases in which follow-up computerized tomography scans or magnetic resonance images demonstrated permanent ischemic lesions attributable to vasospasm, patients had higher ET-1 concentrations than did other patients with SAH. CONCLUSIONS: The plasma ET-1 concentration correlates with delayed cerebral ischemia after SAH, suggesting that an increased ET conversion rate in the endothelium predicts ischemic symptoms. Increased serum ECE-1 activity during the 2nd week may reflect the severity of endothelial injury to cerebral arteries.     

Hypomagnesemia after aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypomagnesemia frequently occurs in hospitalized patients, and it is associated with poor outcome. We assessed the frequency and time distribution of hypomagnesemia after aneurysmal subarachnoid hemorrhage (SAH) and its relationship to the severity of SAH, delayed cerebral ischemia (DCI), and outcome after 3 months. METHODS: Serum magnesium was measured in 107 consecutive patients admitted within 48 hours after SAH. Hypomagnesemia (serum magnesium <0.70 mmol/L) at admission was related to clinical and initial computed tomographic characteristics by means of the Mann-Whitney U test. Hypomagnesemia at admission and during the DCI onset period (Days 2-12) was related to the occurrence of DCI and hypomagnesemia at admission, and hypomagnesemia that occurred any time during the first 3 weeks after SAH was related to outcome. RESULTS: Hypomagnesemia at admission was found in 41 patients (38%) and was associated with more cisternal (P = 0.006) and ventricular (P = 0.005) blood, a longer duration of unconsciousness (P = 0.007), and a worse World Federation of Neurosurgical Societies scale score at admission (P = 0.001). The crude hazard ratio for DCI with hypomagnesemia at admission was 2.4 (95% confidence interval, 1.0-5.6), and after multivariate adjustment it was 1.9 (95% confidence interval, 0.7-4.7). The hazard ratio of hypomagnesemia from Days 2 to 12 for patients with DCI was 3.2 (range, 1.1-8.9) after multivariate adjustment. The crude odds ratio for poor outcome (Glasgow Outcome Scale score, 1-3) with hypomagnesemia at admission was 2.5 (range, 1.1-5.5). Hypomagnesemia at admission did not contribute to the prediction of outcome in the multivariate model. CONCLUSION: Hypomagnesemia is frequently present after SAH and is associated with severity of SAH. Hypomagnesemia occurring between Days 2 and 12 after SAH predicts DCI.     

Acute hydrocephalus after aneurysmal subarachnoid hemorrhage

Hydrocephalus, defined as a bicaudate index above the 95th percentile for age, was found in 34 (20%) of 174 prospectively studied patients with subarachnoid hemorrhage (SAH) who survived the first 24 hours and who underwent computerized tomography (CT) scanning within 72 hours. The occurrence of acute hydrocephalus was related to the presence of intraventricular blood, and not to the extent of cisternal hemorrhage. The level of consciousness was depressed in 30 of the 34 patients. Characteristic clinical features were present in 19 patients, including a gradual obtundation after the initial hemorrhage in 16 patients and small nonreactive pupils in nine patients (all with a Glasgow Coma Scale score of 7 or less). In the remaining 15 patients (44%), the diagnosis could be made only by CT scanning. After 1 month, 20 of the 34 patients had died: six from rebleeding (four after shunting), 11 from cerebral infarction (eight after an initial improvement), and three from other or mixed causes. Only one of nine patients in whom a shunt was placed survived, despite rapid improvement in all immediately after shunting. The mortality rate among patients with acute hydrocephalus was significantly higher than in those without, with the higher incidence caused by cerebral infarction (11 of 34 versus 12 of 140 cases, respectively; p less than 0.001). Death from infarction could not be attributed to the extent of cisternal hemorrhage, the use of antifibrinolytic drugs, or failure to apply surgical drainage, but could often be explained by the development of hyponatremia, probably accompanied by hypovolemia.     

Cardiac complications after aneurysmal subarachnoid hemorrhage

BACKGROUND: Cardiac complications are frequently encountered by neurointensivists caring for patients with SAH. Our aim was to better characterize the natural history of various cardiac abnormalities in this population. We sought to determine the risk factors for cardiac abnormalities, patient outcome, and impact of treatment type on cardiac abnormalities. METHODS: We performed a single center retrospective review of admissions of patients with aneurysmal SAH to the neurosurgical ICU in a large university hospital. Patient demographics, pertinent history, cardiac tests, hospital LOS, intervention type, and discharge outcome were collected. RESULTS: Data from 266 patients were available for analysis. Of these patients, 50% (n = 133) demonstrated cardiac abnormalities as indicated by abnormal EKG, ECHO, or troponin I. Only age was determined to be an independent statistically significant predictor of cardiac abnormality (P = .01). There was no difference in mortality between the cardiac abnormality and control groups (P = .33). However, there was increased morbidity in the cardiac abnormality group as demonstrated by worse discharge disposition, in addition to increased length of hospital stay (22.6 vs 17.1 days, P < .01). The incidence of cardiac abnormalities was the same among surgical and endovascular treatment groups. CONCLUSIONS: Cardiac abnormalities, including those that meet ACC criteria for MI, are common among patients with SAH. However, in contrast to cardiac events outside the context of SAH, these abnormalities do not increase mortality. They do, however, adversely affect discharge disposition and prolong hospital LOS. The type of aneurysm treatment does not affect the incidence or outcome of cardiac abnormalities.     

Magnesium sulfate therapy after aneurysmal subarachnoid hemorrhage

OBJECT: Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH. METHODS: A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II-IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test. Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 +/- 0.68 in the MgSO4 treatment group and 2.3 +/- 0.73 in the control group (mean +/- standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 +/- 27 cm/second in MgSO4-treated patients and 102 +/- 34 cm/second in the control group (mean +/- SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 +/- 1.6 and 3.6 +/- 1.5 (mean +/- SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur. CONCLUSIONS: Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further.     

Defining survivorship after high-grade aneurysmal subarachnoid hemorrhage

BACKGROUND: Outcome after high-grade aneurysmal SAH is poor. Various treatment paradigms have been advanced to improve treatment outcome and preserve resources, but none have addressed the potential salvageable life lost. METHODS: We retrospectively reviewed all patients with high-grade (H&H score, 4-5) aneurysmal SAH admitted to our institution from January 1998 to June 2002, all aggressively managed, to determine what clinical/radiographic criteria predicted favorable survival. RESULTS: There were 50 patients analyzed. All underwent emergency ventriculostomies or clot evacuations. Twenty-three patients (46%) improved and 7 (14%) worsened; 41 survived to receive definitive therapy. Twenty-one patients (42%) overall achieved a favorable outcome (GOS, 4-5). In the multivariate analysis (stepwise logistic regression), the postresuscitation GCSm alone predicted outcome (P= .004) with 70% cases correctly identified, whereas age, location of aneurysm (anterior circulation or not), presence of intraventricular hemorrhage, time to definitive intervention, clot on computerized tomography, type of therapy used (coil vs clip), pupillary abnormalities, and preresuscitation GCSm did not. Because the sole predictive parameter is obtained postresuscitation, no clinical or radiographic factor on presentation appears valid to determine eligibility for definitive care. CONCLUSION: Overall treatment outcome of our series is comparable with those of other articles. Our experience, as well as review of literature, does not support the existence of a validated "triage" schema to selectively treat patients with high-grade subarachnoid hemorrhage, implying that all such patients should be managed aggressively.     

Circulatory and vascular changes after aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a major complication that afflicts approximately 30% of patients who suffer an aneursymal subarachnoid hemorrhage (SAH). DCI is often associated with neurological infarction, poor outcome and mortality. Though the pathogenesis of DCI is not yet clear, it is traditionally been attributed to angiographic vasospasm. Unfortunately, clinical trials based on this premise have mostly been disappointing, predominantly unable to prevent ischemic damage and improve patient outcome despite reducing angiographic vasospasm. More recently, increasing concern that vasospasm could not fully account for DCI development has incited novel proposals as to the pathogenesis of DCI. A general theme exists among these theories (microcirculatory constriction, cortical spreading depression, blood brain barrier breakdown, microthrombosis) in that a majority seems to revolve around dysfunction and changes to the microvasculature. This purpose of this review was then to juxtapose macrovascular and microvascular changes after SAH, and provide an overview of current and prospective treatments.     

Preoperative ventriculostomy and rebleeding after aneurysmal subarachnoid hemorrhage

OBJECT: Despite the widespread use of ventriculostomy in the treatment of acute hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH), there is no consensus regarding the risk of rebleeding associated with ventriculostomy before aneurysm repair. This present study was conducted to assess the risk of rebleeding after preoperative ventriculostomy in patients with aneurysmal SAH. METHODS: The authors reviewed the records of all patients with acute SAH who were treated at a single institution between 1990 and 1997. Thus, the records of 304 consecutive patients in whom an aneurysmal SAH source was documented on angiographic studies and who had presented to the authors' institution within 7 days of ictus were analyzed. Re-bleeding was confirmed by evidence of recurrent hemorrhage on computerized tomography scans in all cases. Forty-five patients underwent ventriculostomy for acute hydrocephalus after aneurysmal SAH at least 24 hours before aneurysm repair. Ventriculostomy was performed within 24 hours of SAH in 38 patients, within 24 to 48 hours in three patients, and more than 48 hours after SAH in four patients. The mean time interval between SAH and surgery in patients who did not undergo ventriculostomy was no different from the mean interval between ventriculostomy and surgery in patients who underwent preoperative ventriculostomy (3.6 compared with 3.8 days, p = 0.81). Fourteen (5.4%) of the 259 patients who did not undergo ventriculostomy suffered preoperative aneurysm rebleeding, whereas two (4.4%) of the 45 patients who underwent preoperative ventriculostomy had aneurysm rebleeding. CONCLUSIONS: No evidence was found that preoperative ventriculostomy performed after aneurysmal SAH is associated with an increased risk of aneurysm rebleeding when early aneurysm surgery is performed.     

Factors related to hydrocephalus after aneurysmal subarachnoid hemorrhage

OBJECTIVE: The purpose of this study was to identify factors predictive of shunt-dependent hydrocephalus among patients with aneurysmal subarachnoid hemorrhage. The data can be used to predict which patients in this group have a high probability of requiring permanent cerebrospinal fluid diversion. METHODS: Seven hundred eighteen patients with aneurysmal subarachnoid hemorrhage who were treated between 1990 and 1999 were retrospectively studied, to identify factors contributing to shunt-dependent hydrocephalus. With these data, a stepwise logistic regression procedure was used to determine the effect of each variable on the development of hydrocephalus and to create a scoring system. RESULTS: Overall, 152 of the 718 patients (21.2%) underwent shunting procedures for treatment of hydrocephalus. Four hundred seventy-nine of the patients (66.7%) were female. Of the factors investigated, the following were associated with shunt-dependent hydrocephalus, as determined with a variety of statistical methods: 1) increasing age (P < 0.001), 2) female sex (P = 0.015), 3) poor admission Hunt and Hess grade (P < 0.001), 4) thick subarachnoid hemorrhage on admission computed tomographic scans (P < 0.001), 5) intraventricular hemorrhage (P < 0.001), 6) radiological hydrocephalus at the time of admission (P < 0.001), 7) distal posterior circulation location of the ruptured aneurysm (P = 0.046), 8) clinical vasospasm (P < 0.001), and 9) endovascular treatment (P = 0.013). The presence of intracerebral hematomas, giant aneurysms, or multiple aneurysms did not influence the development of shunt-dependent hydrocephalus. CONCLUSION: The results of this study can help identify patients with a high risk of developing shunt-dependent hydrocephalus. This may help neurosurgeons expedite treatment, may decrease the cost and length of hospital stays, and may result in improved outcomes.     

Reversible arterial hypotension after acute aneurysmal subarachnoid hemorrhage

The authors report five patients who developed transient arterial hypotension immediately after the rupture of cerebral aneurysms. They manifested deep coma (three cases), abnormal electrocardiogram (four cases), and remarkable pulmonary edema (two cases). The level of consciousness in all three patients who were in deep coma improved with the normalization of blood pressure. Although two patients died of recurrent hemorrhage, the other three patients were discharged in satisfactory condition. Serious clinical conditions that are not terminal and are caused by arterial hypotension immediately after the rupture of cerebral aneurysms are sometimes reversible with adequate treatment.