Top

Published in:

Open Access 01-12-2013 | Review

Understanding brain dysfunction in sepsis

Authors: Romain Sonneville, Franck Verdonk, Camille Rauturier, Isabelle F Klein, Michel Wolff, Djillali Annane, Fabrice Chretien, Tarek Sharshar

Published in: Annals of Intensive Care | Issue 1/2013

Abstract

Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.

Available only for authorised users

Eidelman LA, Putterman D, Putterman C, Sprung CL: The spectrum of septic encephalopathy. Definitions, etiologies, and mortalities. JAMA 1996, 275: 470–473. 10.1001/jama.1996.03530300054040PubMed

Sprung CL, Peduzzi PN, Shatney CH, Schein RM, Wilson MF, Sheagren JN, Hinshaw LB: Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration systemic sepsis cooperative study group. Crit Care Med 1990, 18: 801–806. 10.1097/00003246-199008000-00001PubMed

Milbrandt EB, Angus DC: Potential mechanisms and markers of critical illness-associated cognitive dysfunction. Curr Opin Crit Care 2005, 11: 355–359. 10.1097/01.ccx.0000170508.63067.04PubMed

Jaber S, Chanques G, Altairac C, Sebbane M, Vergne C, Perrigault PF, Eledjam JJ: A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes. Chest 2005, 128: 2749–2757. 10.1378/chest.128.4.2749PubMed

Heymann A, Sander M, Krahne D, Deja M, Weber-Carstens S, MacGuill M, Kastrup M, Wernecke KD, Nachtigall I, Spies CD: Hyperactive delirium and blood glucose control in critically ill patients. J Int Med Res 2007, 35: 666–677. 10.1177/147323000703500511PubMed

Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, et al.: Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001, 286: 2703–2710. 10.1001/jama.286.21.2703PubMed

Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004, 291: 1753–1762. 10.1001/jama.291.14.1753PubMed

Tracey KJ: The inflammatory reflex. Nature 2002, 420: 853–859. 10.1038/nature01321PubMed

Sharshar T, Annane D: Endocrine effects of vasopressin in critically ill patients. Best Pract Res Clin Anaesthesiol 2008, 22: 265–273. 10.1016/j.bpa.2008.02.005PubMed

10.

Semmler A, Hermann S, Mormann F, Weberpals M, Paxian SA, Okulla T, Schafers M, Kummer MP, Klockgether T, Heneka MT: Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J Neuroinflammation 2008, 5: 38. 10.1186/1742-2094-5-38PubMedCentralPubMed

11.

Stellwagen D, Malenka RC: Synaptic scaling mediated by glial TNF-alpha. Nature 2006, 440: 1054–1059. 10.1038/nature04671PubMed

12.

Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M: Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA 2010, 107: 20518–20522. 10.1073/pnas.1014557107PubMedCentralPubMed

13.

Terrando N, Rei Fidalgo A, Vizcaychipi M, Cibelli M, Ma D, Monaco C, Feldmann M, Maze M: The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction. Crit Care 2010, 14: R88. 10.1186/cc9019PubMedCentralPubMed

14.

Chavan SS, Huerta PT, Robbiati S, Valdes-Ferrer SI, Ochani M, Dancho M, Frankfurt M, Volpe BT, Tracey KJ, Diamond B: HMGB1 mediates cognitive impairment in sepsis survivors. Mol Med 2012, 18: 930–937.PubMedCentralPubMed

15.

van Gool WA, van de Beek D, Eikelenboom P: Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet 2010, 375: 773–775. 10.1016/S0140-6736(09)61158-2PubMed

16.

Henry CJ, Huang Y, Wynne AM, Godbout JP: Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun 2009, 23: 309–317. 10.1016/j.bbi.2008.09.002PubMedCentralPubMed

17.

Hannestad J, Gallezot JD, Schafbauer T, Lim K, Kloczynski T, Morris ED, Carson RE, Ding YS, Cosgrove K: Endotoxin-induced systemic inflammation activates microglia: [(11)C]PBR28 positron emission tomography in nonhuman primates. Neuroimage 2012, 63: 232–239. 10.1016/j.neuroimage.2012.06.055PubMedCentralPubMed

18.

Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW: Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun 2008, 22: 301–311. 10.1016/j.bbi.2007.08.014PubMedCentralPubMed

19.

Barrientos RM, Higgins EA, Biedenkapp JC, Sprunger DB, Wright-Hardesty KJ, Watkins LR, Rudy JW, Maier SF: Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging 2006, 27: 723–732. 10.1016/j.neurobiolaging.2005.03.010PubMed

20.

Imamura Y, Wang H, Matsumoto N, Muroya T, Shimazaki J, Ogura H, Shimazu T: Interleukin-1beta causes long-term potentiation deficiency in a mouse model of septic encephalopathy. Neuroscience 2011, 187: 63–69.PubMed

21.

Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M: Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol 2010, 68: 360–368. 10.1002/ana.22082PubMed

22.

Semmler A, Okulla T, Sastre M, Dumitrescu-Ozimek L, Heneka MT: Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J Chem Neuroanat 2005, 30: 144–157. 10.1016/j.jchemneu.2005.07.003PubMed

23.

Semmler A, Frisch C, Debeir T, Ramanathan M, Okulla T, Klockgether T, Heneka MT: 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. 10.1016/j.expneurol.2007.01.003PubMed

24.

Weberpals M, Hermes M, Hermann S, Kummer MP, Terwel D, Semmler A, Berger M, Schafers M, Heneka MT: NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci 2009, 29: 14177–14184. 10.1523/JNEUROSCI.3238-09.2009PubMed

25.

Semmler A, Widmann CN, Okulla T, Urbach H, Kaiser M, Widman G, Mormann F, Weide J, Fliessbach K, Hoeft A, et al.: Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry 2013, 84: 62–69. 10.1136/jnnp-2012-302883PubMed

26.

Handa O, Stephen J, Cepinskas G: Role of endothelial nitric oxide synthase-derived nitric oxide in activation and dysfunction of cerebrovascular endothelial cells during early onsets of sepsis. Am J Physiol Heart Circ Physiol 2008, 295: H1712–1719. 10.1152/ajpheart.00476.2008PubMedCentralPubMed

27.

Taccone FS, Castanares-Zapatero D, Peres-Bota D, Vincent JL, Berre J, Melot C: Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock. Neurocrit Care 2010, 12: 35–42. 10.1007/s12028-009-9289-6PubMed

28.

Alexander JJ, Jacob A, Cunningham P, Hensley L, Quigg RJ: TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1. Neurochem Int 2008, 52: 447–456. 10.1016/j.neuint.2007.08.006PubMedCentralPubMed

29.

Sharshar T, Carlier R, Bernard F, Guidoux C, Brouland JP, Nardi O, de la Grandmaison GL, Aboab J, Gray F, Menon D, Annane D: Brain lesions in septic shock: a magnetic resonance imaging study. Intensive Care Med 2007, 33: 798–806. 10.1007/s00134-007-0598-yPubMed

30.

Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA: Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 2010, 85: 427–432. 10.4065/mcp.2009.0590PubMedCentralPubMed

31.

Bozza FA, Garteiser P, Oliveira MF, Doblas S, Cranford R, Saunders D, Jones I, Towner RA, Castro-Faria-Neto HC: Sepsis-associated encephalopathy: a magnetic resonance imaging and spectroscopy study. J Cereb Blood Flow Metab 2010, 30: 440–448. 10.1038/jcbfm.2009.215PubMedCentralPubMed

32.

Pandharipande PP, Morandi A, Adams JR, Girard TD, Thompson JL, Shintani AK, Ely EW: Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med 2009, 35: 1886–1892. 10.1007/s00134-009-1573-6PubMedCentralPubMed

33.

Adams Wilson JR, Morandi A, Girard TD, Thompson JL, Boomershine CS, Shintani AK, Ely EW, Pandharipande PP: The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*. Crit Care Med 2012, 40: 835–841. 10.1097/CCM.0b013e318236f62dPubMedCentralPubMed

34.

Sharshar T, Annane D, de la Grandmaison GL, Brouland JP, Hopkinson NS, Francoise G: The neuropathology of septic shock. Brain Pathol 2004, 14: 21–33.PubMed

35.

Sharshar T, Gray F, Lorin de la Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, Orlikowski D, Raphael JC, Gajdos P, Annane D: Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 2003, 362: 1799–1805. 10.1016/S0140-6736(03)14899-4PubMed

36.

Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Ruegg S, Strebel SP, Marsch SC, Pargger H, Steiner LA: Cerebral perfusion in sepsis-associated delirium. Crit Care 2008, 12: R63. 10.1186/cc6891PubMedCentralPubMed

37.

Hshieh TT, Fong TG, Marcantonio ER, Inouye SK: Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci 2008, 63: 764–772. 10.1093/gerona/63.7.764PubMedCentralPubMed

38.

Jansson A, Olin K, Yoshitake T, Hagman B, Herrington MK, Kehr J, Permert J: Effects of isoflurane on prefrontal acetylcholine release and hypothalamic Fos response in young adult and aged rats. Exp Neurol 2004, 190: 535–543. 10.1016/j.expneurol.2004.08.027PubMed

39.

Field RH, Gossen A, Cunningham C: Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory deficits: reconciling inflammatory and cholinergic hypotheses of delirium. J Neurosci 2012, 32: 6288–6294. 10.1523/JNEUROSCI.4673-11.2012PubMedCentralPubMed

40.

Kadoi Y, Saito S: An alteration in the gamma-aminobutyric acid receptor system in experimentally induced septic shock in rats. Crit Care Med 1996, 24: 298–305. 10.1097/00003246-199602000-00020PubMed

41.

Pavlov VA, Ochani M, Gallowitsch-Puerta M, Ochani K, Huston JM, Czura CJ, Al-Abed Y, Tracey KJ: Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA 2006, 103: 5219–5223. 10.1073/pnas.0600506103PubMedCentralPubMed

42.

Basler T, Meier-Hellmann A, Bredle D, Reinhart K: Amino acid imbalance early in septic encephalopathy. Intensive Care Med 2002, 28: 293–298. 10.1007/s00134-002-1217-6PubMed

43.

van Eijk MM, Roes KC, Honing ML, Kuiper MA, Karakus A, van der Jagt M, Spronk PE, van Gool WA, van der Mast RC, Kesecioglu J, Slooter AJ: 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 randomised trial. Lancet 2010, 376: 1829–1837. 10.1016/S0140-6736(10)61855-7PubMed

44.

Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW: Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006, 104: 21–26. 10.1097/00000542-200601000-00005PubMed

45.

Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW: 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. 10.1186/cc8916PubMedCentralPubMed

46.

Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, et al.: Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007, 298: 2644–2653. 10.1001/jama.298.22.2644PubMed

47.

Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J: Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012, 307: 1151–1160. 10.1001/jama.2012.304PubMed

48.

Dahmani S, Rouelle D, Gressens P, Mantz J: Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions. Anesthesiology 2005, 103: 969–977. 10.1097/00000542-200511000-00011PubMed

49.

Dahmani S, Rouelle D, Gressens P, Mantz J: Characterization of the postconditioning effect of dexmedetomidine in mouse organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation. Anesthesiology 2010, 112: 373–383. 10.1097/ALN.0b013e3181ca6982PubMed

50.

Degos V, Charpentier TL, Chhor V, Brissaud O, Lebon S, Schwendimann L, Bednareck N, Passemard S, Mantz J, Gressens P: Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression. Anesthesiology 2013, 118: 1123–1132. 10.1097/ALN.0b013e318286cf36PubMed

51.

Barichello T, Fortunato JJ, Vitali AM, Feier G, Reinke A, Moreira JC, Quevedo J, Dal-Pizzol F: Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation. Crit Care Med 2006, 34: 886–889. 10.1097/01.CCM.0000201880.50116.12PubMed

52.

Barichello T, Machado RA, Constantino L, Valvassori SS, Reus GZ, Martins MR, Petronilho F, Ritter C, Quevedo J, Dal-Pizzol F: Antioxidant treatment prevented late memory impairment in an animal model of sepsis. Crit Care Med 2007, 35: 2186–2190. 10.1097/01.CCM.0000281452.60683.96PubMed

53.

Comim CM, Barichello T, Grandgirard D, Dal-Pizzol F, Quevedo J, Leib SL, Comim CM, Barichello T, Grandgirard D, Dal-Pizzol F, Quevedo J, Leib SL: Caspase-3 mediates in part hippocampal apoptosis in sepsis. Mol Neurobiol 2013, 47: 39–48.

54.

Polito A, Brouland JP, Porcher R, Sonneville R, Siami S, Stevens RD, Guidoux C, Maxime V, de la Grandmaison GL, Chretien FC, et al.: Hyperglycaemia and apoptosis of microglial cells in human septic shock. Crit Care 2011, 15: R131. 10.1186/cc10244PubMedCentralPubMed

55.

McGrane S, Girard TD, Thompson JL, Shintani AK, Woodworth A, Ely EW, Pandharipande PP: Procalcitonin and C-reactive protein levels at admission as predictors of duration of acute brain dysfunction in critically ill patients. Crit Care 2011, 15: R78. 10.1186/cc10070PubMedCentralPubMed

56.

van den Boogaard M, Kox M, Quinn KL, van Achterberg T, van der Hoeven JG, Schoonhoven L, Pickkers P: Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients. Crit Care 2011, 15: R297. 10.1186/cc10598PubMedCentralPubMed

57.

Sonneville R, den Hertog HM, Guiza F, Gunst J, Derese I, Wouters PJ, Brouland JP, Polito A, Gray F, Chretien F, et al.: Impact of hyperglycemia on neuropathological alterations during critical illness. J Clin Endocrinol Metab 2012, 97: 2113–2123. 10.1210/jc.2011-2971PubMed

58.

Hopkins RO, Suchyta MR, Snow GL, Jephson A, Weaver LK, Orme JF: Blood glucose dysregulation and cognitive outcome in ARDS survivors. Brain Inj 2010, 24: 1478–1484. 10.3109/02699052.2010.506861PubMed

59.

Mikkelsen ME, Christie JD, Lanken PN, Biester RC, Thompson BT, Bellamy SL, Localio AR, Demissie E, Hopkins RO, Angus DC: The ARDS Cognitive Outcomes Study (ACOS): long-term neuropsychological function in acute lung injury survivors. Am J Respir Crit Care Med 2012, 185: 1307–15. 10.1164/rccm.201111-2025OCPubMedCentralPubMed

60.

Janz DR, Abel TW, Jackson JC, Gunther ML, Heckers S, Ely EW: Brain autopsy findings in intensive care unit patients previously suffering from delirium: a pilot study. J Crit Care 2010,25(538):e537–512.

61.

Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW: Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010, 38: 1513–1520. 10.1097/CCM.0b013e3181e47be1PubMedCentralPubMed

62.

Sharshar T, Porcher R, Siami S, Rohaut B, Bailly-Salin J, Hopkinson NS, 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. 10.1097/CCM.0b013e31821b843bPubMed

63.

Engelhard K, Werner C, Eberspacher E, Bachl M, Blobner M, Hildt E, Hutzler P, Kochs E: The effect of the alpha 2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg 2003, 96: 524–531. table of contentsPubMed

64.

65.

Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, Gajdos P: Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med 1999, 160: 458–465. 10.1164/ajrccm.160.2.9810073PubMed

66.

Iacobone E, Bailly-Salin J, Polito A, Friedman D, Stevens RD, Sharshar T: Sepsis-associated encephalopathy and its differential diagnosis. Crit Care Med 2009, 37: S331–336.PubMed

67.

Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y: Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 2001, 27: 859–64. 10.1007/s001340100909PubMed

68.

Piazza O, Russo E, Cotena S, Esposito G, Tufano R: Elevated S100B levels do not correlate with the severity of encephalopathy during sepsis. Br J Anaesth 2007, 99: 518–521. 10.1093/bja/aem201PubMed

69.

Nguyen DN, 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. 10.1097/01.CCM.0000217218.51381.49PubMed

70.

Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J: Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol 2006, 27: 2179–2190.PubMed

71.

Morandi A, Rogers BP, Gunther ML, Merkle K, Pandharipande P, Girard TD, Jackson JC, Thompson J, Shintani AK, Geevarghese S, et al.: The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*. Crit Care Med 2012, 40: 2182–2189. 10.1097/CCM.0b013e318250acdcPubMedCentralPubMed

72.

Gunther ML, Morandi A, Krauskopf E, Pandharipande P, Girard TD, Jackson JC, Thompson J, Shintani AK, Geevarghese S, Miller RR 3rd, 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. 10.1097/CCM.0b013e318250acc0PubMedCentralPubMed

73.

Oddo M, Carrera E, Claassen J, Mayer SA, Hirsch LJ: Continuous electroencephalography in the medical intensive care unit. Crit Care Med 2009, 37: 2051–2056. 10.1097/CCM.0b013e3181a00604PubMed

74.

Foreman B, Claassen J, Abou Khaled K, Jirsch J, Alschuler DM, Wittman J, Emerson RG, Hirsch LJ: Generalized periodic discharges in the critically ill: a case–control study of 200 patients. Neurology 2012, 79: 1951–1960. 10.1212/WNL.0b013e3182735cd7PubMedCentralPubMed

75.

Watson PL, Shintani AK, Tyson R, Pandharipande PP, Pun BT, Ely EW: Presence of electroencephalogram burst suppression in sedated, critically ill patients is associated with increased mortality. Crit Care Med 2008, 36: 3171–3177. 10.1097/CCM.0b013e318186b9cePubMedCentralPubMed

76.

Young GB, Bolton CF, Archibald YM, Austin TW, Wells GA: The electroencephalogram in sepsis-associated encephalopathy. J Clin Neurophysiol 1992, 9: 145–152. 10.1097/00004691-199201000-00016PubMed

77.

Ong C, Gilmore E, Claassen J, Foreman B, Mayer SA: Impact of prolonged periodic epileptiform discharges on coma prognosis. Neurocrit Care 2012, 17: 39–44. 10.1007/s12028-012-9728-7PubMed

78.

Awissi DK, Lebrun G, Coursin DB, Riker RR, Skrobik Y: Alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary. Intensive Care Med 2013, 39: 16–30. 10.1007/s00134-012-2758-yPubMed

79.

Sechi G, Serra A: Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007, 6: 442–455. 10.1016/S1474-4422(07)70104-7PubMed

80.

Lucidarme O, Seguin A, Daubin C, Ramakers M, Terzi N, Beck P, Charbonneau P, du Cheyron D: Nicotine withdrawal and agitation in ventilated critically ill patients. Crit Care 2010, 14: R58. 10.1186/cc8954PubMedCentralPubMed

81.

Zaal IJ, Spruyt CF, Peelen LM, van Eijk MM, Wientjes R, Schneider MM, Kesecioglu J, Slooter AJ: Intensive care unit environment may affect the course of delirium. Intensive Care Med 2012, 39: 481–488.PubMed

82.

McPherson JA, Wagner CE, Boehm LM, Hall JD, Johnson DC, Miller LR, Burns KM, Thompson JL, Shintani AK, Ely EW, Pandharipande PP: Delirium in the cardiovascular ICU: exploring modifiable risk factors. Crit Care Med 2012, 41: 405–413.

83.

Sonneville R, Mirabel M, Hajage D, Tubach F, Vignon P, Perez P, Lavoue S, Kouatchet A, Pajot O, Dessap AM, et al.: Neurologic complications and outcomes of infective endocarditis in critically ill patients: the ENDOcardite en REAnimation prospective multicenter study. Crit Care Med 2011, 39: 1474–1481. 10.1097/CCM.0b013e3182120b41PubMed

84.

Klein I, Iung B, Labreuche J, Hess A, Wolff M, Messika-Zeitoun D, Lavallee P, Laissy JP, Leport C, Duval X: Cerebral microbleeds are frequent in infective endocarditis: a case–control study. Stroke 2009, 40: 3461–3465. 10.1161/STROKEAHA.109.562546PubMed

85.

Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH: Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009, 180: 1092–1097. 10.1164/rccm.200904-0537OCPubMedCentralPubMed

86.

Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW: Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004, 32: 955–962. 10.1097/01.CCM.0000119429.16055.92PubMed

87.

Iwashyna TJ, Ely EW, Smith DM, Langa KM: Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010, 304: 1787–1794. 10.1001/jama.2010.1553PubMedCentralPubMed

88.

Hopkins RO, Herridge MS: Quality of life, emotional abnormalities, and cognitive dysfunction in survivors of acute lung injury/acute respiratory distress syndrome. Clin Chest Med 2006, 27: 679–689. abstract x 10.1016/j.ccm.2006.06.003PubMed

89.

Hopkins RO, Jackson JC: Assessing neurocognitive outcomes after critical illness: are delirium and long-term cognitive impairments related? Curr Opin Crit Care 2006, 12: 388–394. 10.1097/01.ccx.0000244115.24000.f5PubMed

90.

Hopkins RO, Jackson JC: Short- and long-term cognitive outcomes in intensive care unit survivors. Clin Chest Med 2009, 30: 143–153. ix 10.1016/j.ccm.2008.11.001PubMed

91.

Boer KR, van Ruler O, van Emmerik AA, Sprangers MA, de Rooij SE, Vroom MB, de Borgie CA, Boermeester MA, Reitsma JB: Factors associated with posttraumatic stress symptoms in a prospective cohort of patients after abdominal sepsis: a nomogram. Intensive Care Med 2008, 34: 664–674. 10.1007/s00134-007-0941-3PubMedCentralPubMed

92.

Girard TD, Pandharipande PP, Ely EW: Delirium in the intensive care unit. Crit Care 2008,12(Suppl 3):S3. 10.1186/cc6149PubMedCentralPubMed

93.

Spapen H, Nguyen DN, Troubleyn J, Huyghens L, Schiettecatte J: Drotrecogin alfa (activated) may attenuate severe sepsis-associated encephalopathy in clinical septic shock. Crit Care 2010, 14: R54. 10.1186/cc8947PubMedCentralPubMed

94.

Schelling G, Roozendaal B, Krauseneck T, Schmoelz M, DEQ D, Briegel J: Efficacy of hydrocortisone in preventing posttraumatic stress disorder following critical illness and major surgery. Ann N Y Acad Sci 2006, 1071: 46–53. 10.1196/annals.1364.005PubMed

95.

Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y: Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007, 33: 66–73. 10.1007/s00134-006-0399-8PubMed

96.

Kress JP, Pohlman AS, O’Connor MF, Hall JB: Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000, 342: 1471–1477. 10.1056/NEJM200005183422002PubMed

97.

Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, et al.: Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008, 371: 126–134. 10.1016/S0140-6736(08)60105-1PubMed

98.

Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG: Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009, 301: 489–499. 10.1001/jama.2009.56PubMed

99.

Payen JF, Bosson JL, Chanques G, Mantz J, Labarere J: Pain assessment is associated with decreased duration of mechanical ventilation in the intensive care unit: a post Hoc analysis of the DOLOREA study. Anesthesiology 2009, 111: 1308–1316. 10.1097/ALN.0b013e3181c0d4f0PubMed

100.

Awissi DK, Begin C, Moisan J, Lachaine J, Skrobik Y: I-SAVE study: impact of sedation, analgesia, and delirium protocols evaluated in the intensive care unit: an economic evaluation. Ann Pharmacother 2012, 46: 21–28. 10.1345/aph.1Q284PubMed

101.

Woods JC, Mion LC, Connor JT, Viray F, Jahan L, Huber C, McHugh R, Gonzales JP, Stoller JK, Arroliga AC: Severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes. Intensive Care Med 2004, 30: 1066–1072. 10.1007/s00134-004-2193-9PubMed

102.

Inouye SK, Bogardus ST Jr, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, Cooney LM Jr: A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 1999, 340: 669–676. 10.1056/NEJM199903043400901PubMed

103.

Micek ST, Anand NJ, Laible BR, Shannon WD, Kollef MH: Delirium as detected by the CAM-ICU predicts restraint use among mechanically ventilated medical patients. Crit Care Med 2005, 33: 1260–1265. 10.1097/01.CCM.0000164540.58515.BFPubMed

104.

Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L, Miller M, Franczyk M, Deprizio D, et al.: Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009, 373: 1874–1882. 10.1016/S0140-6736(09)60658-9PubMed

105.

Kadoi Y, Goto F: Selective inducible nitric oxide inhibition can restore hemodynamics, but does not improve neurological dysfunction in experimentally-induced septic shock in rats. Anesth Analg 2004, 99: 212–220. 10.1213/01.ANE.0000118111.94913.22PubMed

106.

Esen F, Erdem T, Aktan D, Orhan M, Kaya M, Eraksoy H, Cakar N, Telci L: Effect of magnesium sulfate administration on blood–brain barrier in a rat model of intraperitoneal sepsis: a randomized controlled experimental study. Crit Care 2005, 9: R18–23. 10.1186/cc3004PubMedCentralPubMed

107.

Toklu HZ, Uysal MK, 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. 10.1016/j.jss.2008.03.013PubMed

108.

Avtan SM, Kaya M, Orhan N, Arslan A, Arican N, Toklu AS, Gurses C, Elmas I, Kucuk M, Ahishali B: The effects of hyperbaric oxygen therapy on blood–brain barrier permeability in septic rats. Brain Res 2011, 1412: 63–72.PubMed

109.

Wratten ML: Therapeutic approaches to reduce systemic inflammation in septic-associated neurologic complications. Eur J Anaesthesiol Suppl 2008, 42: 1–7.PubMed

110.

Esen F, Senturk E, Ozcan PE, Ahishali B, Arican N, Orhan N, Ekizoglu O, Kucuk M, Kaya M: Intravenous immunoglobulins prevent the breakdown of the blood–brain barrier in experimentally induced sepsis. Crit Care Med 2012, 40: 1214–1220. 10.1097/CCM.0b013e31823779caPubMed

Title: Understanding brain dysfunction in sepsis
Authors: Romain Sonneville
Franck Verdonk
Camille Rauturier
Isabelle F Klein
Michel Wolff
Djillali Annane
Fabrice Chretien
Tarek Sharshar
Publication date: 01-12-2013
Publisher: Springer Paris
Published in: Annals of Intensive Care / Issue 1/2013
Electronic ISSN: 2110-5820
DOI: https://doi.org/10.1186/2110-5820-3-15

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Understanding brain dysfunction in sepsis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2013

Acute microcirculatory effects of medium frequency versus high frequency neuromuscular electrical stimulation in critically ill patients - a pilot study

How caregivers view patient comfort and what they do to improve it: a French survey

How is intensive care reimbursed? A review of eight European countries

The pain, agitation, and delirium practice guidelines for adult critically ill patients: a post-publication perspective

Demographics and outcomes of critically ill patients transferred from other hospitals to a tertiary care academic referral center in Saudi Arabia

Does vasopressor therapy have an indication in hemorrhagic shock?