Inter-observer agreement on the diagnosis of neurocardiogenic injury following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Neurocardiogenic injury results from increased sympathetic nervous system activation following acute brain injury. No diagnostic criteria for neurocardiogenic injury exist, and agreement has not been tested. We investigated the agreement by neurointensivists for the presence of neurocardiogenic injury on routine cardiac studies. METHODS: Six neurointensivists rated 100 consecutive cases of aneurysmal subarachnoid hemorrhage (aSAH) for the presence of neurocardiogenic injury. A fixed-panel design was employed for the agreement among the whole cohort, as well as stratified by modified Fisher Scale (mFs), Hunt and Hess grade, gender, and the presence of elevated cardiac enzymes. Overall percent agreement, paired agreement, and agreement above change (Fleiss' Kappa) were calculated. Overall percent agreement between groups was compared using Chi square tests. RESULTS: Six raters completed the survey for a total 600 responses. Overall percent agreement was 79.3 %, and agreement among cases at least one rater thought had neurocardiogenic injury was 66.5 % (paired agreement). Fleiss' Kappa was 0.66 (95 % CI, 0.1-0.71; p < 0.0001), indicating substantial agreement above chance. Similarly, on subgroup analysis, significant agreement beyond chance was seen in all groups (p < 0.001). Overall percent agreement was significantly better among mFs 3-4 compared to mFs ≤ 2 (81.3 vs. 63.6 %; p = 0.018) and among cases with positive cTI (96.9 vs. 70.1 %; p ≤ 0.001). CONCLUSIONS: Overall, we demonstrated substantial agreement for the presence of neurocardiogenic injury on early cardiac studies following aSAH. However, inter-observer variability increased when evaluating patients without the objective finding of elevated cTI and among those with lower clinical and radiographic grades.

Relationship between hemoglobin concentrations and outcomes across subgroups of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Anemia predicts poor outcome following aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that this association would be stronger among patients with more severe SAH, since these patients are likely to be more vulnerable to secondary brain injury in the form of reduced cerebral oxygen delivery. METHODS: Daily nadir hemoglobin (Hb) concentrations over 2 weeks following SAH were retrieved in 245 consecutive patients, and compared between those with a favorable versus unfavorable outcome. The analysis was repeated with patients dichotomized as follows: WFNS score 4-5 vs. 1-3; modified Fisher score (MFS) 4 vs. 0-3; and vasospasm present vs. absent. Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data with repeated measures. RESULTS: Patients with an unfavorable outcome consistently had lower Hb concentrations, especially between days 6-11 following SAH (P ranging from <0.001 to 0.009), as well as a greater fall in Hb over time (beta = -0.07, P < 0.001). This was true regardless of WFNS score, MFS, or the presence or absence of vasospasm. However, the effect was somewhat more pronounced among patients with higher WFNS and modified Fisher scores. CONCLUSION: Lower Hb levels are associated with worse outcomes regardless of SAH severity or the development of vasospasm. This finding may imply that a lower Hb concentration is largely a marker for a greater degree of systemic illness, rather than necessarily causing direct harm. However, the association is somewhat stronger among patients with more severe SAH. Thus, if there is a benefit for maintaining higher Hb levels with transfusions or erythropoietin, it may be more pronounced among these patients.

Implications of early versus late bilateral pulmonary infiltrates in patients with aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Bilateral pulmonary infiltrates occur frequently following aneurysmal subarachnoid hemorrhage (SAH), and may be associated with worse outcomes. The etiology, natural history, and prognosis of infiltrates occurring soon after SAH may differ from the characteristics of infiltrates developing at a later time. METHODS: We performed a retrospective cohort study involving 245 consecutive patients with a ruptured cerebral aneurysm to assess the association between "early" (< or = 72 h) or "late" (>72 h) bilateral pulmonary infiltrates and subsequent death or neurologic impairment. We used logistic regression models to adjust for baseline differences in age, level of consciousness, amount of blood on computed tomography, and the presence or absence of clinical vasospasm. RESULTS: Sixty-seven patients (27%) developed bilateral pulmonary infiltrates. Of these, 36 (54%) had early infiltrates, 24 (36%) had late infiltrates, and 7 (10%) had both. Twenty-eight patients (11% of entire cohort) met criteria for acute respiratory distress syndrome (ARDS). Patients with early infiltrates were more likely to have presented with stupor or coma than patients who developed infiltrates later (64% vs. 29%, P < 0.01). In multivariable analysis, late pulmonary infiltrates were strongly predictive of poor outcome (OR 5.0, 95% CI 1.9-13.6, P < 0.01), while early infiltrates were not (OR 1.2, 95% CI 0.5-3.0, P = 0.66). CONCLUSIONS: Bilateral pulmonary infiltrates after SAH most often occur within three days of aneurysm rupture. However, only infiltrates occurring beyond this time are independently associated with poor outcome. Increased emphasis on the prevention of late pulmonary complications has the potential to improve outcomes in SAH.

A comparison of 3 radiographic scales for the prediction of delayed ischemia and prognosis following subarachnoid hemorrhage.

OBJECT: Delayed cerebral ischemia is a major cause of morbidity and death following aneurysmal subarachnoid hemorrhage and requires timely intervention for a successful outcome to be achieved. In this study the investigators compared the commonly used Fisher scale with 2 newer radiographic scales for the prediction of vasospasm, delayed infarction, and poor outcome. METHODS: This was a single-center, retrospective cohort study involving 271 consecutive patients with a ruptured cerebral aneurysm. Without knowledge of subsequent events, admission CT scans were each assigned scores by using 3 different grading schemes: the Fisher, modified Fisher, and Claassen scales. For each of the scales, the relationship between an increasing score and the risk of later complications was assessed in univariate and multiple logistic regression analyses. RESULTS: With the Fisher scale, the risk of complications was relatively high when the score was 3, but not for other scores. In contrast, using the other scales, there was a more linear relationship between a rising score and the frequency of complications. This was particularly true for the modified Fisher scale, in which each stepwise increase was associated with an escalating risk of vasospasm, delayed infarction, and poor prognosis. Kappa scores measuring interobserver variability among 4 CT readers were also slightly better with the newer scales. CONCLUSIONS: Although the modified Fisher and Claassen scales have yet to be prospectively validated, the authors' findings suggest that the clinical performance of these systems is superior to that of the Fisher scale.

Complications associated with anemia and blood transfusion in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Patients with subarachnoid hemorrhage (SAH) frequently develop delayed cerebral ischemia and may be especially vulnerable to the effects of anemia. However, the potentially harmful effects of allogeneic red blood cells are increasingly being recognized. The optimal transfusion threshold is unknown, but current practice most often uses a liberal approach. We assessed the association between anemia or transfusion and subsequent adverse outcomes. DESIGN: Retrospective cohort study. SETTING: Neuroscience intensive care unit of a university hospital. PATIENTS: A total of 245 consecutive patients with aneurysmal SAH. INTERVENTIONS: None. MEASUREMENTS: Logistic regression models were used to adjust for baseline differences in age, severity of neurologic impairment, and amount of blood on computed tomography. Patients were dichotomized based on whether symptomatic vasospasm was diagnosed. MAIN RESULTS: Individually, anemia (nadir hemoglobin <10 g/dL) and the use of transfusions were both associated with the combined outcome of death, severe disability, or delayed infarction (odds ratio [OR] for anemia, 2.7; 95% confidence interval [CI] 1.5-5; p < .01; OR for transfusion, 4.8; 95% CI, 2.5-9.1; p < .01). When both variables were together introduced into a logistic regression model, only transfusion remained significantly predictive (OR, 4.3; 95% CI, 1.5-9.3; p < .01). The relationship between anemia and adverse outcomes was stronger among patients diagnosed with vasospasm, whereas for transfusion, it was stronger among patients without vasospasm. Transfusion also was associated with the development of nosocomial infections (OR, 3.2; 95% CI, 1.7-5.5; p < .01). There was no statistically significant difference in complications based on the duration of blood storage before transfusion. CONCLUSIONS: Although anemia is predictive of adverse outcomes in patients with SAH, this observation cannot be considered justification for a liberal transfusion strategy. Appropriate transfusion thresholds may vary depending on the presence or absence of clinical vasospasm. Randomized trials that compare liberal and restrictive transfusion strategies in patients with SAH are needed.

Statin use was not associated with less vasospasm or improved outcome after subarachnoid hemorrhage.

OBJECTIVE: The development of delayed ischemia caused by cerebral vasospasm remains a common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Preliminary studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of vasospasm, but additional study is required. METHODS: Beginning in May 2006, our treatment protocol for patients presenting with subarachnoid hemorrhage was altered to routinely include the use of 80 mg of simvastatin per day for 14 days. Before this time, only patients with other indications for statins were treated. The charts of 203 consecutive patients over a period of 27 months were retrospectively reviewed, and 150 patients were included in the analysis, of whom 71 patients received statins. These patients were compared with 79 untreated patients to determine whether or not the use of statins was associated with a reduction in the occurrence of vasospasm, delayed infarction, or poor outcome (death, vegetative state, or severe disability). RESULTS: Patients who were treated with statins and those who were not had similar baseline characteristics, although more patients in the former group were managed with endovascular coil embolization. There were no statistically significant differences in the proportion of patients developing at least moderate radiographic vasospasm (41% with statins versus 42% without, P = 0.91), symptomatic vasospasm (32% with statins versus 25% without, P = 0.34), delayed infarction (23% with statins versus 28% without, P = 0.46), or poor outcome (39% with statins versus 35% without, P = 0.61). After adjustment for differences in baseline characteristics, including the method of aneurysm treatment, statins were still not significantly protective. CONCLUSION: The addition of statins to standard care was not associated with any reduction in the development of vasospasm or improvement in outcomes after aneurysmal subarachnoid hemorrhage. If there is a benefit to statin use, it may be smaller than suggested by previous studies. However, further randomized controlled trials are awaited.