Abstract
Introduction
Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce the systemic inflammatory response syndrome (SIRS). This may promote both extra-cerebral organ dysfunction and delayed cerebral ischemia, contributing to worse outcome. We ascertained the frequency and predictors of SIRS after spontaneous SAH, and determined whether degree of early systemic inflammation predicted the occurrence of vasospasm and clinical outcome.
Methods
Retrospective analysis of prospectively collected data on 276 consecutive patients admitted to a neurosciences intensive care unit with acute, non-traumatic SAH between 2002 and 2005. A daily SIRS score was derived by summing the number of variables meeting standard criteria (HR >90, RR >20, Temperature >38°C, or <36°C, WBC count <4,000 or >12,000). SIRS was considered present if two or more criteria were met, while SIRS burden over the first four days was calculated by averaging daily scores. Regression modeling was used to determine the relationship among SIRS burden (after controlling for confounders including infection, surgery, and corticosteroid use), symptomatic vasospasm, and outcome, determined by hospital disposition.
Results
SIRS was present in over half the patients on admission and developed in 85% within the first four days. Factors associated with SIRS included poor clinical grade, thick cisternal blood, larger aneurysm size, higher admission blood pressure, and surgery for aneurysm clipping. Higher SIRS burden was independently associated with death or discharge to nursing home (OR 2.20/point, 95% CI 1.27–3.81). All of those developing clinical vasospasm had evidence of SIRS, with greater SIRS burden predicting increased risk for delayed ischemic neurological deficits (OR 1.77/point, 95% CI 1.12–2.80).
Conclusions
Systemic inflammatory activation is common after SAH even in the absence of infection; it is more frequent in those with more severe hemorrhage and in those who undergo surgical clipping. Higher burden of SIRS in the initial four days independently predicts symptomatic vasospasm and is associated with worse outcome.
Similar content being viewed by others
References
Gruber A, Rossler K, Graninger W, Donner A, Illievich U, Czech T. Ventricular cerebrospinal fluid and serum concentrations of sTNFR-I, IL-1ra, and IL-6 after aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 2000;12:297–306.
Bone RC, Balk RA, Cerra FB, Fein AM, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644–55.
Napolitano LM, Ferrer T, McCarter RJ Jr, Scalea TM. Systemic inflammatory response syndrome score at admission independently predicts mortality and length of stay in trauma patients. J Trauma 2000;49:647–52; discussion 652–643.
Ni Choileain N, Redmond HP. Cell response to surgery. Arch Surg 2006;141:1132–40.
Levy MM, Fink MP, Marshall JC, Abraham E, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003;29:530–8.
Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003;101:3765–77.
Malham GM, Souter MJ. Systemic inflammatory response syndrome and acute neurological disease. Br J Neurosurg 2001;15:381–7.
Dilraj A, Botha JH, Rambiritch V, Miller R, van Dellen JR. Levels of catecholamine in plasma and cerebrospinal fluid in aneurysmal subarachnoid hemorrhage. Neurosurgery 1992;31:42–51.
Naredi S, Lambert G, Eden E, et al. Increased sympathetic nervous system activity in patients with nontraumatic subarachnoid hemorrhage. Stroke 2000;31:901–6.
Moynihan J, Kruszewska B, Madden K, Callahan T. Sympathetic nervous system regulation of immunity. J Neuroimmunol 2004;147:87–90.
Gruber A, Reinprecht A, Illievich U, et al. Extracerebral organ dyfsunction and neurologic outcome after aneurysmal subarachnoid hemorrhage. Crit Care Med 1999;27:505–14.
Oliveira-Filho J, Ezzeddine MA, Segal AZ, et al. Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome. Neurology 2001;56:1299–1304.
Parkinson D, Stephenson S. Leukocytosis and subarachnoid hemorrhage. Surg Neurol 1984;21:132–4.
Weir B, Disney L, Grace M, Roberts P. Daily trends in white blood cell count and temperature after subarachnoid hemorrhage from aneurysm. Neurosurgery 1989;25:161–5.
McGirt MJ, Mavropoulos JC, McGirt LY, et al. Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 2003;98:1222–6.
Yoshimoto Y, Tanaka Y, Hoya K. Acute systemic inflammatory response syndrome in subarachnoid hemorrhage. Stroke 2001;32:1989–93.
Dumont AS, Dumont RJ, Chow MM, et al. Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 2003;53:123–35.
Hughes JT, Schianchi PM. Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. J Neurosurg 1978;48:515–25.
Fassbender K, Hodapp B, Rossol S, Bertsch T, et al. Endothelin-1 in subarachnoid hemorrhage: an acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke 2000;31:2971–5.
Chyatte D. Prevention of chronic cerebral vasospasm in dogs with ibuprofen and high-dose methylprednisolone. Stroke 1989;20:1021–6.
Miller JA, Dacey RG Jr, Diringer MN. Safety of hypertensive hypervolemic therapy with phenylephrine in the treatment of delayed ischemic deficits after subarachnoid hemorrhage. Stroke 1995;26:2260–6.
Teasdale GM, Drake CG, Hunt W, et al. A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. J Neurol Neurosurg Psychiatry 1988;51:1457.
Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6:1–9.
Hijdra A, Brouwers PJ, Vermeulen M, van Gijn J. Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke 1990;21:1156–61.
Sebha FA, Bederson JB. Mechanisms of acute brain injury after subarachnoid hemorrhage. Neurol Res 2006;28:381–98.
Naredi S, Lambert G, Friberg P, et al. Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage. Intensive Care Med 2006;32:1955–61.
McKeating EG, Andrews PJ, Signorini DF, Mascia L. Transcranial cytokine gradients in patients requiring intensive care after acute brain injury. Br J Anaesth 1997;78:520–3.
Minambres E, Cemborain A, Sanchez-Velasco P, et al. Correlation between transcranial interleukin-6 gradient and outcome in patients with acute brain injury. Crit Care Med 2003;31:933–8.
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448–54.
Rothoerl RD, Axmann C, Pina A-L, Woertgen C, Brawanksi A. Possible role of C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 2006;18:68–72.
de Oliveira JG, Beck J, Ulrich C, Rathert J, Raabe A, Seifert V. Comparison between clipping and coiling on the incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Neurosurg Rev 2007;30:22–30; discussion 30–21.
Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, et al. Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 2001;70:534–7.
Peterson JW, Kwun BD, Teramura A, et al. Immunological reaction against the aging human subarachnoid erythrocyte. A model for the onset of cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 1989;71:718–26.
Bowton DL, Bertels NH, Prough DS, Stump DA. Cerebral blood flow is reduced in patients with sepsis syndrome. Crit Care Med 1989;17:399–403.
Suarez JI, Qureshi AI, Yahia AB, et al. Symptomatic vasospasm diagnosis after subarachnoid hemorrhage: evaluation of transcranial Doppler ultrasound and cerebral angiography as related to compromised vascular distribution. Crit Care Med 2002;30:1348–55.
O’Connor E, Venkatesh B, Mashongonyika C, Lipman J, Hall J, Thomas P. Serum procalcitonin and c-reactive protein as markers of sepsis and outcome in patients with neurotrauma and subarachnoid haemorrhage. Anaesth Intensive Care 2004;32:465–70.
Gosling P, Czyz J, Nightingale P, Manji M. Microalbuminuria in the intensive care unit: clinical correlates and association with outcomes in 431 patients. Crit Care Med 2006;34:2158–66.
Bavbek M, Polin R, Kwan AL, Arthur AS, Kassell NF, Lee KS. Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Stroke 1998;29:1930–5; discussion 1935–1936.
Clatterbuck RE, Gailloud P, Ogata L, et al. Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates. J Neurosurg 2003;99:376–82.
German JW, Gross CE, Giclas P, Watral W, Bednar MM. Systemic complement depletion inhibits experimental cerebral vasospasm. Neurosurgery 1996;39:141–5; discussion 145–146.
Lynch JR, Wang H, McGirt MJ, et al. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke 2005;36:2024–6.
Neil-Dwyer G, Walter P, Cruickshank JM. Beta-blockade benefits patients following a subarachnoid hemorrhage. Eur J Clin Pharmacol 1985;28(Suppl):25–9.
Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke 2005;36:1627–32.
McGirt MJ, Lynch JR, Parra A, et al. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke 2002;33:2950–6.
McGirt MJ, Pradilla G, Legnani FG, et al. Systemic administration of simvastatin after the onset of experimental subarachnoid hemorrhage attenuates cerebral vasospasm. Neurosurgery 2006;58:945–51; discussion 945–951.
Chello M, Patti G, Candura D, et al. Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery. Crit Care Med 2006;34:660–7.
Author information
Authors and Affiliations
Corresponding author
Additional information
Financial support: Supported by NIH-N535906 (MND).
Rights and permissions
About this article
Cite this article
Dhar, R., Diringer, M.N. The Burden of the Systemic Inflammatory Response Predicts Vasospasm and Outcome after Subarachnoid Hemorrhage. Neurocrit Care 8, 404–412 (2008). https://doi.org/10.1007/s12028-008-9054-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12028-008-9054-2