Clinical Study
Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage

https://doi.org/10.1016/j.jocn.2009.09.003Get rights and content

Abstract

Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of cerebral dysfunction that were associated with poor admission clinical grade. Between 1997 and 2008, 850 consecutive SAH patients were enrolled in our prospective database. Demographic data, physiological parameters, and location and volume of blood were recorded. After univariate analysis, significant variables were entered into a logistic regression model to identify significant associations with poor admission clinical grade (Hunt–Hess grade 4–5). Independent predictors of poor admission grade included a SAH sum score >15/30 (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.5–3.6), an intraventricular hemorrhage sum score >1/12 (OR 3.1, 95% CI 2.1–4.8), aneurysm size >10 mm (OR 1.7, 95% CI 1.1–2.6), body temperature ⩾38.3 °C (OR 2.5, 95% CI 1.1–5.4), and hyperglycemia >200 mg/dL (OR 2.7, 95% CI 1.6–4.5). In a large, consecutive series of prospectively enrolled patients with SAH, the inflammatory response at the time of aneurysm rupture, as reflected by the volume and location of the hemoglobin burden, hyperthermia, and perturbed glucose metabolism, independently predicts poor admission Hunt–Hess grade. Strategies for mitigating the inflammatory response to aneurysmal rupture in the hyper-acute setting may improve the admission clinical grade, which may in turn improve outcomes.

Introduction

Aneurysmal subarachnoid hemorrhage (aSAH) affects nearly 30 000 individuals each year in the United States.[1], [2] Although early surgical and neuroendovascular interventions, as well as aggressive postoperative management strategies, have improved outcomes, mortality in the acute phase following aneurysm rupture is significant: 12% of aSAH patients die within the first 24 hours and 25% within the first 48 hours.3 Early brain injury (EBI) is a recently coined term that describes the immediate injury to the brain after aneurysm rupture and the response to hemorrhage within the subarachnoid space.[4], [5], [6], [7], [8], [9] A number of critical, interrelated pathways have been implicated in EBI, including apoptotic mechanisms and ischemic pathways, which lead to neuronal cell death, cerebral edema, and a global cerebral inflammatory process.[6], [7], [10] This early inflammatory response may underlie the host of metabolic, hormonal, neuronal, and vascular derangements that occur following SAH, including cerebral vasospasm, myocardial stunning, acute lung injury, cerebral salt wasting, perturbed glucose metabolism and alterations in thermal regulation.[6], [7], [10] Treatment strategies that target these complications in isolation, such as those used in recent trials for the treatment and prevention of vasospasm, have failed to yield improvements in morbidity and mortality,[11], [12], [13] perhaps because they fail to address inflammation as the putative underlying etiology.

Poor admission clinical grade (Hunt–Hess) is one of the most important determinants of outcome after aSAH.14 We hypothesized that poor admission clinical grade may reflect the extent of ultra-early brain injury and the cerebral inflammatory response initiated at the time of aneurysm rupture. Therefore, we sought to identify factors known to contribute to cerebral inflammation, and markers of early cerebral dysfunction, in one of the largest clinical series of patients with aSAH presented to date, in an effort to test the hypothesis that early brain injury and inflammation are associated with poor admission clinical grade in this patient population.

Section snippets

Patient population

As part of the Columbia University Subarachnoid Hemorrhage Outcomes Project, 850 consecutive patients with SAH admitted to the Neurological Intensive Care Unit of Columbia University Medical Center between 15 September 1997 and 14 July 2008 were prospectively enrolled.[15], [16] The study was approved by the Columbia University Institutional Review Board. The diagnosis of SAH was established on the basis of computed tomography (CT) scans obtained at admission or xanthochromia of the

Results

Between 15 September 1997 and 14 July 2008, 850 patients were admitted to the Neurological Intensive Care Unit of Columbia University Medical Center with a diagnosis of aSAH. The median age of these patients was 54 years, with a 25th percentile of 44 years and a 75th percentile of 64 years. Fifty-one percent were Caucasian, and 67% were female. Twenty-five percent of these patients (n = 213) were admitted with Hunt–Hess grade 4–5 (Table 1).

Patients with a poor admission clinical grade (poor-grade

Discussion

Despite recent advances in the treatment of patients after SAH, morbidity and mortality rates have failed to improve significantly.7 Vasospasm is one of the most significant causes of morbidity and mortality after SAH, yet recent trials aimed at improving cerebral blood flow or mitigating vasospasm following aSAH have had limited success in improving overall outcome.[11], [12], [13] These failures may be explained in part by a perspective that incorporates cerebral vasospasm as but one sequela

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