Sepsis-Associated Brain Dysfunction: A Review of Current Literature

Piotr F Czempik, Michał P Pluta, Łukasz J Krzych, Piotr F Czempik, Michał P Pluta, Łukasz J Krzych

Abstract

Sepsis-associated brain dysfunction (SABD) may be the most common type of encephalopathy in critically ill patients. SABD develops in up to 70% of septic patients and represents the most frequent organ insufficiency associated with sepsis. It presents with a plethora of acute neurological features and may have several serious long-term psychiatric consequences. SABD might cause various pathological changes in the brain through numerous mechanisms. Clinical neurological examination is the basic screening method for SABD, although it may be challenging in subjects receiving with opioids and sedative agents. As electrographic seizures and periodic discharges might be present in 20% of septic patients, screening with electroencephalography (EEG) might be useful. Several imaging techniques have been suggested for non-invasive assessment of structure and function of the brain in SABD patients; however, their usefulness is rather limited. Although several experimental therapies have been postulated, at the moment, no specific treatment exists. Clinicians should focus on preventive measures and optimal management of sepsis. This review discusses epidemiology, clinical presentation, pathology, pathophysiology, diagnosis, management, and prevention of SABD.

Keywords: diagnosis; epidemiology; management; pathophysiology; prevention; sepsis-associated brain dysfunction; sepsis-associated encephalopathy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed pathophysiologic changes in sepsis-associated brain dysfunction.

References

    1. Rhodes A., Evans L.E., Alhazzani W., Levy M.M., Antonelli M., Ferrer R., Kumar A., Sevransky J.E., Sprung C.L., Nunnally M.E., et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit. Care Med. 2017;43:304–377. doi: 10.1007/s00134-017-4683-6.
    1. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.-D., Coopersmith C.M., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287.
    1. Salluh J.I., Soares M., Teles J.M., Ceraso D., Raimondi N., Nava V.S., Blasquez P., Ugarte S., Ibanez-Guzman C., Centeno J.V., et al. Delirium epidemiology in critical care (DECCA): An international study. Crit. Care. 2010;14:R210. doi: 10.1186/cc9333.
    1. Gofton T.E., Young G.B. Sepsis-associated encephalopathy. Nat. Rev. Neurol. 2012;8:557–566. doi: 10.1038/nrneurol.2012.183.
    1. Bolton C.F., Young G.B., Zochodne D.W. The neurological complications of sepsis. Ann. Neurol. 1993;33:94–100. doi: 10.1002/ana.410330115.
    1. Bolton C.F., Young G.B. Managing the nervous system effects of sepsis. Chest. 2007;131:1273–1274. doi: 10.1378/chest.07-0367.
    1. Young G.B., Bolton C.F., Austin T.W., Archibald Y.M., Gonder J., Wells G.A. The encephalopathy associated with septic illness. Clin. Investig. Med. 1990;13:297–304.
    1. Zhang L.N., Wang X.T., Ai Y.H., Guo Q.L., Huang L., Liu Z.Y., Yao B. Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients: 2008–2011. Chin. Med. J. 2012;125:828–831.
    1. Eidelman L.A., Putterman D., Putterman C., Sprung C.L. The spectrum of septic encephalopathy: Definitions, etiologies, and mortalities. JAMA. 1996;75:470–473. doi: 10.1001/jama.1996.03530300054040.
    1. Mikkelsen M.E., Christie J.D., Lanken P.N., Biester R.C., Thompson B.T., Bellamy S.L., Localio A.R., Demissie E., Hopkins R.O., Angus D.C. The adult respiratory distress syndrome cognitive outcomes study: Long-term neuropsychological function in survivors of acute lung injury. Am. J. Respir. Crit. Care Med. 2012;185:1307–1315. doi: 10.1164/rccm.201111-2025OC.
    1. Semmler A., Frisch C., Debeir T., Ramanathan M., Okulla T., Klockgether T., Heneka M.T. Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp. Neurol. 2007;204:733–740. doi: 10.1016/j.expneurol.2007.01.003.
    1. Soriano F.G. Quality of life: Late sequela in sepsis. Crit. Care Med. 2005;33:262–263. doi: 10.1097/.
    1. Lazosky A., Young G.B., Zirul S., Phillips R. Quality of life after septic illness. J. Crit. Care. 2010;25:406–412. doi: 10.1016/j.jcrc.2009.10.001.
    1. Feng Q., Ai Y.H., Gong H., Wu L., Ai M.L., Deng S.Y., Huang L., Peng Q.Y., Zhang L.N. Characterization of Sepsis and Sepsis-Associated Encephalopathy. J. Intensive Care Med. 2019;34:938–945. doi: 10.1177/0885066617719750.
    1. Wintermann G.B., Brunkhorst F.M., Petrowski K., Strauss B., Oehmichen F., Pohl M., Rosendahl J. Stress disorders following prolonged critical illness in survivors of severe sepsis. Crit. Care Med. 2015;43:1213–1222. doi: 10.1097/CCM.0000000000000936.
    1. Mostel Z., Perl A., Marck M., Mehdi S.F., Lowell B., Bathija S., Santosh R., Pavlov V.A., Chavan S.S., Roth J. Post-sepsis syndrome—An evolving entity that afflicts survivors of sepsis. Mol. Med. 2019;26:6. doi: 10.1186/s10020-019-0132-z.
    1. Lund-Sorensen H., Benros M.E., Madsen T., Sorensen H.J., Eaton W.W., Postolache T.T., Nordentoft M., Erlangsen A. A Nationwide Cohort Study of the Association between Hospitalization with Infection and Risk of Death by Suicide. JAMA Psychiatry. 2016;73:912–919. doi: 10.1001/jamapsychiatry.2016.1594.
    1. Annane D., Sharshar T. Cognitive decline after Sepsis. Lancet Respir. Med. 2015;3:61–69. doi: 10.1016/S2213-2600(14)70246-2.
    1. Sharshar T., Annane D., de la Grandmaison G.L., Brouland J.P., Hopkinson N.S., Françoise G. The Neuropathology of Septic Shock. Brain Pathol. 2004;14:21–33. doi: 10.1111/j.1750-3639.2004.tb00494.x.
    1. Jackson A.C., Gilbert J.J., Young G.B., Bolton C.F. The encephalopathy of sepsis. Can. J. Neurol. Sci. 1985;12:303–307. doi: 10.1017/S0317167100035381.
    1. Sharshar T., Polito A., Checinski A., Stevens R.D. Septic-associated encephalopathy-everything starts at a microlevel. Crit. Care. 2010;14:199. doi: 10.1186/cc9254.
    1. Wilson J.X., Young G.B. Progress in clinical neurosciences: Sepsis-associated encephalopathy: Evolving concepts. Can. J. Neurol. Sci. 2003;30:98–105. doi: 10.1017/S031716710005335X.
    1. Sonneville R., Derese I., Marques M.B., Langouche L., Derde S., Chatre L., Chrétien F., Annane D., Sharshar T., Van den Berghe G., et al. Neuropathological Correlates of Hyperglycemia During Prolonged Polymicrobial Sepsis in Mice. Shock. 2015;44:245–251. doi: 10.1097/SHK.0000000000000403.
    1. Sharshar T., Porcher R., Siami S., Rohaut B., Bailly-Salin J., Hopkinson N.S., Clair B., Guidoux C., Iacobone E., Sonneville R., et al. Brainstem Responses Can Predict Death and Delirium in Sedated Patients in Intensive Care Unit. Crit. Care Med. 2011;39:1960–1967. doi: 10.1097/CCM.0b013e31821b843b.
    1. Stare J., Siami S., Trudel E., Prager-Khoutorsky M., Sharshar T., Bourque C.W. Effects of peritoneal sepsis on rat central osmoregulatory neurons mediating thirst and vasopressin release. J. Neurosci. 2015;35:12188–12197. doi: 10.1523/JNEUROSCI.5420-13.2015.
    1. Muscatell K.A., Dedovic K., Slavich G.M., Jarcho M.R., Breen E.C., Bower J.E., Irwin M.R., Eisenberger N.I. Greater amygdala activity and dorsomedial prefrontal-amygdala coupling are associated with enhanced inflammatory responses to stress. Brain Behav. Immun. 2015;43:46–53. doi: 10.1016/j.bbi.2014.06.201.
    1. van Gool W.A., van de Beek D., Eikelenboom P. Systemic infection and delirium: When cytokines and acetylcholine collide. Lancet. 2010;375:773–775. doi: 10.1016/S0140-6736(09)61158-2.
    1. Jacob A., Brorson J.R., Alexander J.J. Septic encephalopathy: Inflammation in man and mouse. Neurochem. Int. 2011;58:472–476. doi: 10.1016/j.neuint.2011.01.004.
    1. Berg R.M., Moller K., Bailey D.M. Neuro-oxidative-nitrosative stress in sepsis. J. Cereb. Blood Flow Metab. 2011;31:1532–1544. doi: 10.1038/jcbfm.2011.48.
    1. Azevedo L.C. Mitochondrial dysfunction during sepsis. Endocr. Metab. Immune Disord. Drug Targets. 2010;10:214–223. doi: 10.2174/187153010791936946.
    1. Brealey D., Karyampudi S., Jacques T.S., Novelli M., Stidwill R., Taylor V., Smolenski R.S., Singer M. Mitochondrial Dysfunction in a Long-Term Rodent Model of Sepsis and Organ Failure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004;286:491–497. doi: 10.1152/ajpregu.00432.2003.
    1. Cepinskas G., Wilson J.X. Inflammatory response in microvascular endothelium in sepsis: Role of oxidants. J. Clin. Biochem. Nutr. 2008;42:175–184. doi: 10.3164/jcbn.2008026.
    1. Burkhart C.S., Siegemund M., Steiner L.A. Cerebral perfusion in sepsis. Crit. Care. 2010;14:215. doi: 10.1186/cc8856.
    1. Szatmari S., Vegh T., Csomos A., Hallay J., Takacs I., Molnar C., Fülesdi B. Impaired Cerebrovascular Reactivity in Sepsis-Associated Encephalopathy Studied by Acetazolamide Test. Crit. Care. 2010;14:R50. doi: 10.1186/cc8939.
    1. Taccone F.S., Castanares-Zapatero D., Peres-Bota D., Vincent J.-L., Berre J., Melot C. Cerebral Autoregulation Is Influenced by Carbon Dioxide Levels in Patients With Septic Shock. Neurocrit. Care. 2010;12:35–42. doi: 10.1007/s12028-009-9289-6.
    1. Berg R.M., Taudorf S., Bailey D.M., Lundby C., Larsen F.S., Pedersen B.K., Møller K. Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans. Crit. Care. 2010;14:R16. doi: 10.1186/cc8873.
    1. Davies D.C. Blood-brain Barrier Breakdown in Septic Encephalopathy and Brain Tumours. J. Anat. 2002;200:639–646. doi: 10.1046/j.1469-7580.2002.00065.x.
    1. Sprung C.L., Cerra F.B., Freund H.R., Schein R.M., Konstantinides F.N., Marcial E.H., Pena M. Amino acid alterations and encephalopathy in the sepsis syndrome. Crit. Care Med. 1991;19:753–757. doi: 10.1097/00003246-199106000-00004.
    1. van Eijk M.M., Roes K.C., Honing M.L., Kuiper M.A., Karakus A., van der Jagt M., Spronk P.E., van Gool W.A., van der Mast R.C., Kesecioglu J., et al. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: A multicentre, double-blind, placebo-controlled randomized trial. Lancet. 2010;376:1829–1837. doi: 10.1016/S0140-6736(10)61855-7.
    1. Girard T., Exline M.C., Carson S.S., Hough C.L., Rock P. Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N. Engl. J. Med. 2018;379:2506–2516. doi: 10.1056/NEJMoa1808217.
    1. Reade M.C., Eastwood G.M., Peck L., Bellomo R., Baldwin I. Routine use of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) by bedside nurses may underdiagnose delirium. Crit. Care Resusc. 2011;13:217–224.
    1. van Eijk M.M., van den Boogaard M., van Marum R.J., Benner P., Eikelenboom P., Honing M.L., van der Hoven B., Horn J., Izaks G.J., Kalf A., et al. Routine use of the confusion assessment method for the intensive care unit: A multicenter study. Am. J. Respir. Crit. Care Med. 2011;184:340–344. doi: 10.1164/rccm.201101-0065OC.
    1. Young G.B., Bolton C.F., Archibald Y.M., Austin T.W., Wells G.A. The electroencephalogram in sepsis-associated encephalopathy. J. Clin. Neurophysiol. 1992;9:145–152. doi: 10.1097/00004691-199201000-00016.
    1. Kaplan P.W. The EEG in metabolic encephalopathy and coma. J. Clin. Neurophysiol. 2004;21:307–318.
    1. Azabou E., Magalhaes E., Braconnier A., Yahiaoui L., Moneger G., Heming N., Annane D., Mantz J., Chrétien F., Durand M.-C., et al. Early standard electroencephalogram abnormalities predict mortality in septic intensive care unit patients. PLoS ONE. 2015;10:e0139969. doi: 10.1371/journal.pone.0139969.
    1. Luitse M.J., van Asch C.J., Klijn C.J. Deep coma and diffuse white matter abnormalities caused by sepsis-associated encephalopathy. Lancet. 2013;381:2222. doi: 10.1016/S0140-6736(13)60682-0.
    1. Sharshar T., Carlier R., Bernard F., Guidoux C., Brouland J.-P., Nardi O., de la Grandmaison G.L., Aboab J., Gray F., Menon D., et al. Brain lesions in septic shock: A magnetic resonance imaging study. Intensive Care Med. 2007;33:798–806. doi: 10.1007/s00134-007-0598-y.
    1. Ahmed M., Sureka J., Mathew V., Jakkani R.K., Abhilash K.P. Magnetic resonance imaging findings in a fatal case of Salmonella typhi-associated encephalopathy: A case report and literature review. Neurol. India. 2011;59:270–272. doi: 10.4103/0028-3886.79145.
    1. Gunther M.L., Morandi A., Krauskopf E., Pandharipande P., Girard T.D., Jackson J.C., Thompson J., Shintani A.K., Geevarghese S., Miller R.R., et al. The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: The VISIONS cohort magnetic resonance imaging study. Crit. Care Med. 2012;40:2022–2032. doi: 10.1097/CCM.0b013e318250acc0.
    1. Kulkarni A.A., Sharma V.K. Role of transcranial Doppler in cerebrovascular disease. Neurol. India. 2016;64:995–1001. doi: 10.4103/0028-3886.190265.
    1. Pierrakos C., Attou R., Decorte L., Kolyviras A., Malinverni S., Gottignies P., Devriendt J., De Bels D. Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients. BMC Anesthesiol. 2014;14:45. doi: 10.1186/1471-2253-14-45.
    1. Czempik P.F., Gąsiorek J., Bąk A., Krzych L.J. Ultrasonic Assessment of Optic Nerve Sheath Diameter in Patients at Risk of Sepsis-Associated Brain Dysfunction: A Preliminary Report. Int. J. Environ. Res. Public Health. 2020;17:3656. doi: 10.3390/ijerph17103656.
    1. Nguyen D.N., Spapen H., Su F., Schiettecatte J., Shi L., Hachimi-Idrissi S., Huyghens L. Elevated serum levels of S-100beta protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock. Crit. Care Med. 2006;34:1967–1974. doi: 10.1097/01.CCM.0000217218.51381.49.
    1. Moss R.F., Parmar N.K., Tighe D., Davies D.C. Adrenergic agents modify cerebral edema and microvessel ultrastructure in porcine sepsis. Crit. Care Med. 2004;32:1916–1921. doi: 10.1097/01.CCM.0000139917.26914.DD.
    1. Toklu H.Z., Uysal M.K., Kabasakal L., Sirvanci S., Ercan F., Kaya M. The Effects of Riluzole on Neurological, Brain Biochemical, and Histological Changes in Early and Late Term of Sepsis in Rats. J. Surg. Res. 2009;152:238–248. doi: 10.1016/j.jss.2008.03.013.
    1. Andonegui G., Zelinski E.L., Schubert C.L., Knight D., Craig L.A., Winston B.W., Spanswick S.C., Petri B., Jenne C.N., Sutherland J.C., et al. Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment. JCI Insight. 2018;3:e99364. doi: 10.1172/jci.insight.99364.
    1. Pfister D., Schmidt B., Smielewski P., Siegemund M., Strebel S.P., Ruegg S., Marsch S.C.U., Pargger H., Steiner L.A. Intracranial pressure in patients with sepsis. Acta Neurochir. Suppl. 2008;102:71–75. doi: 10.1007/978-3-211-85578-2_14.
    1. Pandharipande P.P., Sanders R.D., Girard T.D., McGrane S., Thompson J.L., Shintani A.K., Herr D.L., Maze M., Ely W.E. MENDS investigators Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: An a priori-designed analysis of the MENDS randomized controlled trial. Crit. Care. 2010;14:R38. doi: 10.1186/cc8916.
    1. Vincent J.-L., Shehabi Y., Walsh T.S., Pandharipande P.P., Ball J.A., Spronk P., Longrois D., Strøm T., Conti G., Funk G.-C. Comfort and Patient-Centred Care without Excessive Sedation: The eCASH Concept. Intensive Care Med. 2016;42:962–9671. doi: 10.1007/s00134-016-4297-4.
    1. Sonneville R., de Montmollin E., Poujade J., Garrouste-Orgeas M., Souweine B., Darmon M., Mariotte E., Argaud L., Barbier F., Goldgran-Toledano D., et al. Potentially modifiable factors contributing to sepsis-associated encephalopathy. Intensive Care Med. 2017;43:1075–1084. doi: 10.1007/s00134-017-4807-z.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere