Relationship Between C-Reactive Protein, Systemic Oxygen Consumption, and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Abstract

Background and Purpose-Subarachnoid hemorrhage (SAH) is known to result in elevated systemic oxygen consumption (VO 2 ) and increases in high-sensitivity C-reactive protein (hsCRP), although the relationship among hsCRP, VO 2 , and delayed cerebral ischemia (DCI) after SAH remains unknown. We hypothesized that hsCRP is directly associated with VO 2 and that elevated VO 2 is a predictor of DCI after SAH. Methods-Prospective serial assessments of VO 2 and hsCRP over 4 prespecified time periods during the first 14 days after bleed in consecutive SAH patients admitted to a single academic medical center for a 2-year period. Results-One hundred ten SAH patients met study criteria (mean age, 55Ϯ16 years; 62% women), with a median admission Hunt Hess grade of 3 (interquartile range, 2-4). In multivariate generalized estimating equation model of the first 14 days after bleed, VO 2 was associated with younger age (Pϭ0.01), male gender (Pϭ0.01), and hsCRP levels (Pϭ0.03). Twenty-four (22%) patients had DCI develop, with a median onset on day 7 after bleed (interquartile range, 5-11). The mean VO 2 (291Ϯ65 mL/min versus 226Ϯ55 mL/min; Pϭ0.003) was higher in DCI patients. In a multivariable Cox proportional hazards model, younger age (hazard ratio, 1.2 per 5 years; 95% CI, 1.1-1.3), a higher modified Fisher scale score (hazard ratio, 3.4 per 1-point increase; 95% CI, 1.7-6.9), and higher VO 2 (HR, 1.2 per 50-mL/min increase; 95% CI, 1.1-1.3) were predictive of DCI. Conclusions-Systemic oxygen consumption is associated with hsCRP levels in the first 14 days after SAH and is an independent predictor of DCI. (Stroke. 2011;42:2436-2442.)

Inflammation, negative nitrogen balance, and outcome after aneurysmal subarachnoid hemorrhage

“…Taken together, findings from this and our previous studies 6,17 indicate that the metabolic sequelae, protein catabolism, and free fatty acid metabolism seen after SAH are closely linked to the acute inflammatory response.…”

“…We hypothesized that the metabolic response and nutritional status after SAH would be dependent on the inflammatory status, and our decision to allocate measurements into phases by PBD was based on previous reports of inflammatory response after SAH. 17,38 While this may have introduced measurement bias into our results, we believe our overall method of repeating Receiver operating characteristic curve for C-reactive protein and transthyretin predicting poor outcome at 3 months…”

“…Our methodology for IDC has been described previously. 17,18 In mechanically ventilated subjects, the IDC circuit system was connected to the oxygen delivery and exhaust systems of the ventilator, whereas in non-mechanically ventilated subjects, the IDC circuit was connected to an airtight canopy that covered the subject's head and neck and delivered a measured constant flow of air (21% O 2 ).…”

Free Fatty Acids and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

“…We recently demonstrated a direct relationship between systemic oxygen consumption (VO2) and inflammation after SAH and further found that acute elevation in VO2 was an independent predictor of delayed cerebral ischemia 8 . While many factors after acute brain injury can influence changes in VO2, an increase in lipid peroxidation may be the end result of the hypermetabolic state.…”

Preconditioning the Human Brain

“…Inflammatory mediators, such as interleukin-6, tumor necrosis factor, intracellular adhesion molecule, matrix metalloproteinase 9, and C-reactive protein, have been linked to DCI and are downregulated through preconditioning. [40][41][42][43][48][49][50][51][52][53][54] In addition, tissue is rendered more tolerant to ischemia through reduction of excitotoxicity and metabolic protection by enhancing mitochondrial function. Preconditioning also affects several other pathways that have been implicated in vasospasm and DCI.…”