Aktuelle Therapie der Sepsis auf der neurologischen Intensivstation

Zusammenfassung

Aktuell steigen die Fallzahlen der Sepsis in den industrialisierten Ländern um jährlich etwa 5 % an und haben mittlerweile eine Inzidenz von 300/100 000 Einwohnern p. a. erreicht. Erklärt wird dies vor allem durch die demografische Alterung, der Häufung von Patienten mit immunkompromittierenden Erkrankungen und der größeren Verbreitung multiresistenter Keime. Eine septische Enzephalopathie tritt meistens schon vor den definierenden Sepsissymptomen auf. Da vor allem die frühe Therapieeinleitung mit einer besseren Prognose des Krankheitsverlaufs assoziiert ist, kommt dem Neurologen in der Erkennung der Enzephalopathie eine besondere Rolle zu. Darüber hinaus ist ein besseres neurologisches Verständnis der septischen Enzephalopathie wichtig, da das Gehirn nicht nur Opfer einer Sepsis ist, sondern auch das inflammatorische Geschehen auf mehreren Ebenen aktiv beeinflusst. Diese aktuelle Übersicht wird auf die zerebralen Aspekte der septischen Enzephalopathie näher eingehen und zukünftige klinische und wissenschaftliche Aspekte beleuchten.

Abstract

Currently, sepsis cases are on the increase in industrialised countries by approximately 5 % each year reaching an overall incidence of 300/100,000 per year. This is explained by demographic ageing, higher number of patients with immune-compromised diseases, and increased dissemination of multiresistant bacteria. Septic encephalopathy mostly precedes other sepsis-defining symptoms. Because an early treatment improves the outcome, the neurologist plays a crucial role in the early detection of septic encephalopathy. Furthermore, a better neurological understanding of septic encephalopathy is important, as the brain is not only a sepsis victim but also influences the inflammatory processes at several levels. The present overview focuses on cerebral aspects of septic encephalopathy and addresses evolving clinical and research aspects.

Schlüsselwörter

Sepsis - Intensivstation - Inflammation - Sepsis bundle - Leitlinien

Keywords

sepsis - ICU - inflammation - sepsis bundles - guidelines

• Literatur

• 1 Consales G, De Gaudio AR. Sepsis associated encephalopathy. Minerva anestesiologica 2005; 71: 39-52
• 2 Wilson JX, Young GB. Progress in clinical neurosciences: sepsis-associated encephalopathy: evolving concepts. Can Jo Neurol Sci 2003; 30: 98-105
• 3 Chromik AM, Janot M, Sulberg D et al. [Distal pancreatectomy: radical or spleen-preserving?]. Chirurg 2008; 79: 1123-1133
• 4 American College of Chest Physicians/Society of Critical Care Medicine. Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 864-874
• 5 Levy MM, Fink MP, Marshall JC et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256
• 6 Thibeault I, Laflamme N, Rivest S. Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokines. J Comp Neurol 2001; 434: 461-477
• 7 Ikeda-Matsuo Y, Ikegaya Y, Matsuki N et al. Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. J Neurochem 2005; 94: 1546-1558
• 8 Tollner B, Roth J, Storr B et al. The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide. Pflugers Arch 2000; 440: 925-932
• 9 Damm J, Wiegand F, Harden LM et al. Fever, sickness behavior, and expression of inflammatory genes in the hypothalamus after systemic and localized subcutaneous stimulation of rats with the Toll-like receptor 7 agonist imiquimod. Neuroscience 2012; 201: 166-183
• 10 Sikora JP. Immunotherapy in the management of sepsis. Arch Immunol Ther Exp (Warsz) 2002; 50: 317-324
• 11 Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med 2007; 42: 153-164
• 12 Huet O, Cherreau C, Nicco C et al. Pivotal role of glutathione depletion in plasma-induced endothelial oxidative stress during sepsis. Crit Care Med 2008; 36: 2328-2334
• 13 Okamoto H, Ito O, Roman RJ et al. Role of inducible nitric oxide synthase and cyclooxygenase-2 in endotoxin-induced cerebral hyperemia. Stroke 1998; 29: 1209-1218
• 14 Rosengarten B, Wolff S, Klatt S et al. Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model. Crit Care 2009; 13: R139
• 15 Hofer S, Bopp C, Hoerner C et al. Injury of the blood brain barrier and up-regulation of icam-1 in polymicrobial sepsis. J Surg Res 2008; 146: 276-281
• 16 Hoffmann JN, Vollmar B, Inthorn D et al. A chronic model for intravital microscopic study of microcirculatory disorders and leukocyte/endothelial cell interaction during normotensive endotoxemia. Shock 1999; 12: 355-364
• 17 Puranapanda V, Hinshaw LB, O’Rear EA et al. Erythrocyte deformability in canine septic shock and the efficacy of pentoxifylline and a leukotriene antagonist. Proc Soc Exp Biol Med 1987; 185: 206-210
• 18 Nguyen HB, Corbett SW, Steele R et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007; 35: 1105-1112
• 19 Kortgen A, Niederprum P, Bauer M. Implementation of an evidence-based “standard operating procedure” and outcome in septic shock. Crit Care Med 2006; 34: 943-949
• 20 Hernandez G, Bruhn A, Ince C. Microcirculation in sepsis: new perspectives. Curr Vasc Pharmacol 2013; 11: 161-169
• 21 Teboul JL, Duranteau J. Alteration of microcirculation in sepsis: a reality but how to go further?. Crit Care Med 2012; 40: 1653-1654
• 22 Ince C. The microcirculation is the motor of sepsis. Crit Care 2005; 9 (Suppl. 04) S13-19
• 23 Pullamsetti SS, Maring D, Ghofrani HA et al. Effect of nitric oxide synthase (NOS) inhibition on macro- and microcirculation in a model of rat endotoxic shock. Thrombosis and haemostasis 2006; 95: 720-727
• 24 De Backer D, Donadello K, Sakr Y et al. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med 2013; 41: 791-799
• 25 Rivers EP, Katranji M, Jaehne KA et al. Early interventions in severe sepsis and septic shock: a review of the evidence one decade later. Minerva Anestesiol 2012; 78: 712-724
• 26 Mesquida J, Espinal C, Gruartmoner G et al. Prognostic implications of tissue oxygen saturation in human septic shock. Intens Care Med 2012; 38: 592-597
• 27 Taccone FS, Scolletta S, Franchi F et al. Brain perfusion in sepsis. Curr Vasc Pharmacol 2013; 11: 170-186
• 28 Kuschinsky W. Capillary perfusion in the brain. Pflugers Arch 1996; 432: R42-46
• 29 Burkhart CS, Siegemund M, Steiner LA. Cerebral perfusion in sepsis. Crit Care 2010; 14: 215
• 30 Szatmari S, Vegh T, Csomos A et al. Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. Crit Care 2010; 14: R50
• 31 Mihaylova S, Killian A, Mayer K et al. Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats. J Neuroinflammation 2012; 9: 183
• 32 Hossmann KA, Traystman RJ. Cerebral blood flow and the ischemic penumbra. Handb Clin Neurol 2009; 92: 67-92
• 33 Flierl MA, Stahel PF, Rittirsch D et al. Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis. Crit Care 2009; 13: R12
• 34 Papadopoulos MC, Lamb FJ, Moss RF et al. Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex. Clin Sci (Lond) 1999; 96: 461-466
• 35 Davies DC. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anatomy 2002; 200: 639-646
• 36 Fernandes A, Silva RF, Falcao AS et al. Cytokine production, glutamate release and cell death in rat cultured astrocytes treated with unconjugated bilirubin and LPS. J Neuroimmunology 2004; 153: 64-75
• 37 Hewett SJ, Csernansky CA, Choi DW. Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS. Neuron 1994; 13: 487-494
• 38 Dora E, Kovach AG. Effect of topically administered epinephrine, norepinephrine, and acetylcholine on cerebrocortical circulation and the NAD/NADH redox state. J Cereb Blood Flow Metab 1983; 3: 161-169
• 39 Berg RM, Taudorf S, Bailey DM et al. Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans. Crit Care 2010; 14: R16
• 40 Hasselgren PO, Fischer JE. Septic encephalopathy. Etiology and management. Intens Care Med 1986; 12: 13-16
• 41 d'Avila JC, Santiago AP, Amancio RT et al. Sepsis induces brain mitochondrial dysfunction. Crit Care Med 2008; 36: 1925-1932
• 42 Correa TD, Vuda M, Blaser AR et al. Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis. Crit Care Med 2012; 40: 2841-2849
• 43 Li J, Iadecola C. Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex. Neuropharmacology 1994; 33: 1453-1461
• 44 Zingarelli B, Day BJ, Crapo JD et al. The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock. Br J Pharmacol 1997; 120: 259-267
• 45 Messaris E, Memos N, Chatzigianni E et al. Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis. Crit Care Med 2004; 32: 1764-1770
• 46 Zhou G, Kamenos G, Pendem S et al. Ascorbate protects against vascular leakage in cecal ligation and puncture-induced septic peritonitis. Am J Physiol Regul Integr Comp Physiol 2012; 302: R409-416
• 47 Vaz AR, Silva SL, Barateiro A et al. Pro-inflammatory cytokines intensify the activation of NO/NOS, JNK1/2 and caspase cascades in immature neurons exposed to elevated levels of unconjugated bilirubin. Exp Neurol 2010; 229: 381-390
• 48 Gotz T, Gunther A, Witte OW et al. Long-term sequelae of severe sepsis: cognitive impairment and structural brain alterations – an MRI study (LossCog MRI). BMC Neurology 2014; 14: 145
• 49 Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 2006; 6: 813-822
• 50 Semmler A, Okulla T, Sastre M et al. Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J Chem Neuroanat 2005; 30: 144-157
• 51 Fuller S, Steele M, Munch G. Activated astroglia during chronic inflammation in Alzheimer's disease – do they neglect their neurosupportive roles?. Mutation research 2010; 690: 40-49
• 52 Widmann CN, Heneka MT. Long-term cerebral consequences of sepsis. Lancet neurology 2014; 13: 630-636
• 53 Semmler A, Widmann CN, Okulla T et al. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry 2013; 84: 62-69
• 54 Iwashyna TJ, Ely EW, Smith DM et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010; 304: 1787-1794
• 55 Jackson JC, Hopkins RO, Miller RR et al. Acute respiratory distress syndrome, sepsis, and cognitive decline: a review and case study. Southern medical journal 2009; 102: 1150-1157
• 56 Busija DW, Leffler CW, Pourcyrous M. Hyperthermia increases cerebral metabolic rate and blood flow in neonatal pigs. Am J Physiol 1988; 255: H343-H346
• 57 Nybo L. Cycling in the heat: performance perspectives and cerebral challenges. Scand J Med Sci Sports 2010; 20 (Suppl. 03) 71-79
• 58 Roth J, Rummel C, Barth SW et al. Molecular aspects of fever and hyperthermia. Neurologic clinics 2006; 24: 421-439, v
• 59 Tracey KJ. Reflex control of immunity. Nat Rev Immunol 2009; 9: 418-428
• 60 Gamboa A, Okamoto LE, Diedrich A et al. Sympathetic activation and nitric oxide function in early hypertension. Am J Physiol Heart Circ Physiol 2012; 302: H1438-1443
• 61 Borovikova LV, Ivanova S, Zhang M et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405: 458-462
• 62 Trzeciak S, Dellinger RP, Parrillo JE et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 2007; 49: 88-98, 98 e81-82
• 63 Adam N, Kandelman S, Mantz J et al. Sepsis-induced brain dysfunction. Expert Rev Anti Infect Ther 2013; 11: 211-221
• 64 Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368-1377
• 65 Bayer O, Reinhart K, Kohl M et al. Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal, fluid balance, and patient outcomes in patients with severe sepsis: a prospective sequential analysis. Crit Care Med 2012; 40: 2543-2551
• 66 Finfer S, Norton R, Bellomo R et al. The SAFE study: saline vs. albumin for fluid resuscitation in the critically ill. Vox sanguinis 2004; 87 (Suppl. 02) 123-131
• 67 Filippi L, Gozzini E, Daniotti M et al. Rescue treatment with terlipressin in different scenarios of refractory hypotension in newborns and infants. Pediatr Crit Care Med 2011; 12: e237-241
• 68 Launey Y, Nesseler N, Malledant Y et al. Clinical review: fever in septic ICU patients – friend or foe?. Crit Care 2011; 15: 222
• 69 Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 2008; 371: 1955-1969
• 70 Saini M, Saqqur M, Kamruzzaman A et al. Effect of hyperthermia on prognosis after acute ischemic stroke. Stroke 2009; 40: 3051-3059
• 71 Manthous CA, Hall JB, Olson D et al. Effect of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med 1995; 151: 10-14
• 72 Geurts M, Macleod MR, Kollmar R et al. Therapeutic hypothermia and the risk of infection: a systematic review and meta-analysis. Crit Care Med 2014; 42: 231-242
• 73 Arons MM, Wheeler AP, Bernard GR et al. Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med 1999; 27: 699-707
• 74 Sprung CL, Cerra FB, Freund HR et al. Amino acid alterations and encephalopathy in the sepsis syndrome. Crit Care Med 1991; 19: 753-757
• 75 Sprung CL, Peduzzi PN, Shatney CH et al. Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. Crit Care Med 1990; 18: 801-806
• 76 Mayer K, Fegbeutel C, Hattar K et al. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation. Intensive Care Med 2003; 29: 1472-1481
• 77 Pontes-Arruda A, Martins LF, de Lima SM et al. Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT study. Crit Care 2011; 15: R144
• 78 Rice TW, Wheeler AP, Thompson BT et al. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA 2011; 306: 1574-1581
• 79 Mussack T, Briegel J, Schelling G et al. Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and polymorphonuclear elastase levels in human septic shock. Clin Chem Lab Med 2005; 43: 259-268
• 80 Plaschke K, Bent F, Wagner S. In contrast to its anti-inflammatory and anti-apoptotic peripheral effect, levosimendan failed to induce a long-term neuroprotective effect in a rat model of mild septic encephalopathy: a pilot study. Neuroscience letters 2014; 560: 117-121
• 81 Zhou TF, Yu JG. Recombinant human erythropoietin attenuates neuronal apoptosis and cognitive defects via JAK2/STAT3 signaling in experimental endotoxemia. J Surgical Res 2013; 183: 304-312
• 82 Gunther ML, Morandi A, Krauskopf E 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
• 83 Lindlau A, Widmann CN, Putensen C et al. Predictors of hippocampal atrophy in critically ill patients. Eur J Neurol 2015; 22: 410-415