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Critical Care
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Procalcitonin and mortality in status epilepticus: an observational cohort study

Authors: Raoul Sutter, Martina Valença, Sarah Tschudin-Sutter, Stephan Rüegg, Stephan Marsch

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

Acute-phase proteins, such as procalcitonin (PCT), C-reactive protein (CRP) and albumin, may relate with course and outcome in status epilepticus (SE), as seizures bring about inflammation, changes of cytokine levels and blood–brain barrier breakdown. We aimed to determine the predictive value of serum levels of PCT at SE onset for the emergence of infections and unfavorable outcome in adult patients with SE. Furthermore, we sought to compare the predictive value of PCT, CRP and albumin for death.

Methods

This observational cohort study was performed in the intensive care units of the University Hospital Basel (Switzerland), a university-affiliated tertiary care center. Adult patients with SE admitted from 2005 to 2012 were included. Serum levels of PCT, CRP and albumin were assessed at SE onset. Unfavorable outcome (i.e., death and a Glasgow Outcome Score of 1 to 3) during hospital stay and mortality after 30 days were considered the primary and infections as the secondary outcome measures.

Results

In 91 SE patients, mortality was 23.1 % during hospital stay and at 30-days follow-up. Infections emerged in 30.8 % of patients. In the multivariable analysis, PCT predicted unfavorable outcome independently from possible confounders such as acute etiology, infections during SE, the Charlson Comorbidity Index, and the Status Epilepticus Severity Score (hazard ratio 1.44 per every increasing ug/L, 95 % confidence interval 1.11-1.87). Additional multivariable analysis including serum levels of PCT, CRP and albumin revealed PCT as the only biomarker independently associated with an increased hazard for unfavorable outcome. PCT levels at SE onset were not related to infections during SE.

Conclusions

Serum PCT levels measured at SE onset are independently associated with unfavorable outcome but do not predict the emergence of infections during SE. Procalcitonin may increase the predictive value of clinical scoring systems allowing for rapid risk stratification early in the course of SE.
Literature
1.
Rosenow F, Hamer HM, Knake S. The epidemiology of convulsive and nonconvulsive status epilepticus. Epilepsia. 2007;48:82–4.PubMed
2.
Sutter R, Kaplan PW, Rüegg S. Outcome predictors for status epilepticus—what really counts. Nat Rev Neurol. 2013;9:525–34.PubMed
3.
Rossetti AO, Logroscino G, Bromfield EB. A clinical score for prognosis of status epilepticus in adults. Neurology. 2006;66:1736–8.PubMed
4.
Sutter R, Kaplan PW, Rüegg S. Independent external validation of the Status Epilepticus Severity Score. Crit Care Med. 2013;41:e475–9.PubMed
5.
Leitinger M, Holler Y, Kalss G, Rohracher A, Novak HF, Hofler J, et al. Epidemiology-Based Mortality Score in Status Epilepticus (EMSE). Neurocrit Care. 2015;22:273–82.PubMed
6.
Vezzani A, Viviani B. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology. 2015;96:70–82.PubMed
7.
Devinsky O, Vezzani A, Najjar S, De Lanerolle NC, Rogawski MA. Glia and epilepsy: excitability and inflammation. Trends Neurosci. 2013;36:174–84.PubMed
8.
Sutter R, Grize L, Fuhr P, Rüegg S, Marsch S. Acute phase proteins and mortality in status epilepticus: a five-year observational cohort study. Crit Care Med. 2013;41:1526–33.PubMed
9.
Joyce CD, Fiscus RR, Wang X, Dries DJ, Morris RC, Prinz RA. Calcitonin gene-related peptide levels are elevated in patients with sepsis. Surgery. 1990;108:1097–101.PubMed
10.
Becker KL, Snider R, Nylen ES. Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target. Br J Pharmacol. 2010;159:253–64.PubMed
11.
Brunkhorst FM, Eberhard OK, Brunkhorst R. Discrimination of infectious and noninfectious causes of early acute respiratory distress syndrome by procalcitonin. Crit Care Med. 1999;27:2172–6.PubMed
12.
de Kruif MD, Limper M, Gerritsen H, Spek CA, Brandjes DP, ten Cate H, et al. Additional value of procalcitonin for diagnosis of infection in patients with fever at the emergency department. Crit Care Med. 2010;38:457–63.PubMed
13.
Deng WJ, Shen RL, Li M, Teng JF. Relationship Between Procalcitonin Serum Levels and Functional Outcome in Stroke Patients. Cell Mol Neurobiol. 2015;35:355–61.PubMed
14.
Engel H, Ben Hamouda N, Portmann K, Delodder F, Suys T, Feihl F, et al. Serum procalcitonin as a marker of post-cardiac arrest syndrome and long-term neurological recovery, but not of early-onset infections, in comatose post-anoxic patients treated with therapeutic hypothermia. Resuscitation. 2013;84:776–81.PubMed
15.
Sutter R, Tschudin-Sutter S, Grize L, Widmer AF, Marsch S, Ruegg S. Acute phase proteins and white blood cell levels for prediction of infectious complications in status epilepticus. Crit Care. 2011;15:R274.PubMedPubMedCentral
16.
Sutter R, Marsch S, Fuhr P, Kaplan PW, Rüegg S. Anesthetic drugs in status epilepticus – risk or rescue? A six-year cohort study. Neurology. 2014;82:656–64.PubMedPubMedCentral
17.
Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3–23.PubMed
18.
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC,Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7. www.​strobe-statement.​org.
19.
Sutter R, Tschudin-Sutter S, Grize L, Fuhr P, Bonten MJ, Widmer AF, et al. Associations between infections and clinical outcome parameters in status epilepticus: a retrospective 5-year cohort study. Epilepsia. 2012;53:1489–97.PubMed
20.
Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128–40.PubMed
21.
Novy J, Logroscino G, Rossetti AO. Refractory status epilepticus: a prospective observational study. Epilepsia. 2010;51:251–6.PubMed
22.
Agan K, Afsar N, Midi I, Us O, Balosso S, Aykut-Bingol C. Predictors of refractoriness in a Turkish status epilepticus data bank. Epilepsy & behavior: E&B. 2009;14:651–4.
23.
Zelano J, Moller F, Dobesberger J, Trinka E, Kumlien E. Infections in status epilepticus: a retrospective 5-year cohort study. Seizure. 2014;23:603–6.PubMed
24.
Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A, et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia. 2001;42:714–8.PubMed
25.
Sutter R, Fuhr P, Grize L, Marsch S, Rüegg S. Continuous video-EEG monitoring increases detection rate of nonconvulsive status epilepticus in the ICU. Epilepsia. 2011;52:453–7.PubMed
26.
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.PubMed
27.
Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998;279:1477–82.PubMed
28.
Carter AM, Catto AJ, Mansfield MW, Bamford JM, Grant PJ. Predictive variables for mortality after acute ischemic stroke. Stroke. 2007;38:1873–80.PubMed
29.
Di Napoli M, Parry-Jones AR, Smith CJ, Hopkins SJ, Slevin M, Masotti L, et al. C-reactive protein predicts hematoma growth in intracerebral hemorrhage. Stroke. 2014;45:59–65.PubMed
30.
Di Napoli M, Godoy DA, Campi V, Masotti L, Smith CJ, Parry Jones AR, et al. C-reactive protein in intracerebral hemorrhage: time course, tissue localization, and prognosis. Neurology. 2012;79:690–9.PubMed
31.
den Hertog HM, van Rossum JA, van der Worp HB, van Gemert HM, de Jonge R, Koudstaal PJ, et al. C-reactive protein in the very early phase of acute ischemic stroke: association with poor outcome and death. J Neurol. 2009;256:2003–8.
32.
Karlinski M, Bembenek J, Grabska K, Kobayashi A, Baranowska A, Litwin T, et al. Routine serum C-reactive protein and stroke outcome after intravenous thrombolysis. Acta Neurol Scand. 2014;130:305–11.PubMed
33.
Maegaki Y, Kurozawa Y, Tamasaki A, Togawa M, Tamura A, Hirao M, et al. Early predictors of status epilepticus-associated mortality and morbidity in children. Brain Dev. 2015;37:478–86.PubMed
34.
Ishikawa N, Kobayashi Y, Fujii Y, Kobayashi M. Increased interleukin-6 and high-sensitivity C-reactive protein levels in pediatric epilepsy patients with frequent, refractory generalized motor seizures. Seizure. 2015;25:136–40.PubMed
35.
Hayashida H, Kaneko T, Kasaoka S, Oshima C, Miyauchi T, Fujita M, et al. Comparison of the predictability of neurological outcome by serum procalcitonin and glial fibrillary acidic protein in postcardiac-arrest patients. Neurocrit Care. 2010;12:252–7.PubMed
36.
Marchi N, Angelov L, Masaryk T, Fazio V, Granata T, Hernandez N, et al. Seizure-promoting effect of blood–brain barrier disruption. Epilepsia. 2007;48:732–42.PubMedPubMedCentral
37.
Fabene PF, Navarro Mora G, Martinello M, Rossi B, Merigo F, Ottoboni L, et al. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat Med. 2008;14:1377–83.PubMedPubMedCentral
38.
Janigro D. Are you in or out? Leukocyte, ion, and neurotransmitter permeability across the epileptic blood–brain barrier. Epilepsia. 2012;53:26–34.PubMedPubMedCentral
39.
Bauer S, Köller M, Cepok S, Todorova-Rudolph A, Nowak M, Nockher WA, et al. NK and CD4+ T cell changes in blood after seizures in temporal lobe epilepsy. Exp Neurol. 2008;211:370–7.PubMed
40.
Pacifici R, Paris L, Di Carlo S, Bacosi A, Pichini S, Zuccaro P. Cytokine production in blood mononuclear cells from epileptic patients. Epilepsia. 1995;36:384–7.PubMed
41.
Heinemann U, Kaufer D, Friedman A. Blood–brain barrier dysfunction, TGFbeta signaling, and astrocyte dysfunction in epilepsy. Glia. 2012;60:1251–7.PubMedPubMedCentral
42.
Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci. 2001;2:734–44.PubMed
43.
Montgomery SL, Bowers WJ. Tumor necrosis factor-alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system. J Neuroimmune Pharmacol. 2012;7:42–59.PubMed
44.
Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7:31–40.PubMed
45.
Viviani B, Gardoni F, Marinovich M. Cytokines and neuronal ion channels in health and disease. Int Rev Neurobiol. 2007;82:247–63.PubMed
46.
Gardoni F, Boraso M, Zianni E, Corsini E, Galli CL, Cattabeni F, et al. Distribution of interleukin-1 receptor complex at the synaptic membrane driven by interleukin-1beta and NMDA stimulation. J Neuroinflammation. 2011;8:14.PubMedPubMedCentral
47.
Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci. 2005;25:3219–28.PubMedPubMedCentral
48.
Vezzani A, Friedman A. Brain inflammation as a biomarker in epilepsy. Biomark Med. 2011;5:607–14.PubMed
49.
50.
Vezzani A, Maroso M, Balosso S, Sanchez MA, Bartfai T. IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun. 2011;25:1281–9.PubMed
51.
Nguyen MD, Julien JP, Rivest S. Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci. 2002;3:216–27.PubMed
52.
Commission on Epidemiology and Prognosis of the International League Against Epilepsy. Guidelines for epidemiologic studies on epilepsy. Epilepsia. 1993;34:592–6.
Metadata
Title
Procalcitonin and mortality in status epilepticus: an observational cohort study
Authors
Raoul Sutter
Martina Valença
Sarah Tschudin-Sutter
Stephan Rüegg
Stephan Marsch
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-1072-9

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