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Einsatz von Ketamin bei Sepsis und systemischen Entzündungsreaktionen

Role of ketamine in sepsis and systemic inflammatory response syndrome

  • Intensivmedizin
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Zusammenfassung

Ketamin führt über eine Stimulation des sympathischen Nervensystems, eine Inhibition adenosintriphosphatsensitiver Kaliumkanäle und eine Interaktion mit dem Stickstoffmonoxidsystem als einziges intravenöses Anästhetikum zu einer Steigerung des mittleren arteriellen Blutdrucks, ohne dabei das Herzzeitvolumen zu beeinträchtigen. Des Weiteren haben experimentelle und klinische Untersuchungen gezeigt, dass Ketamin antiinflammatorische Eigenschaften besitzt, indem es insbesondere die Freisetzung proinflammatorischer Zytokine, wie Tumor-Nekrose-Faktor-α und Interleukin-6 inhibiert. Außerdem konnte in tierexperimentellen Sepsismodellen eine Mortalitätsenkung durch frühzeitige Ketaminapplikation nachgewiesen werden. Im Hinblick auf die derzeit verfügbare Literatur stellt Ketamin somit möglicherweise eine sinnvolle Therapieoption für die Langzeitsedierung von Patienten mit arterieller Hypotension bei Sepsis und systemischen Entzündungsreaktionen (SIRS) dar. Eine potenzielle Nebenwirkung von Ketamin ist die Inhibition der endothelialen Stickstoffmonoxidsynthase; hierdurch wird die bei septischen Patienten per se gestörte Mikrozirkulation möglicherweise weiter beeinträchtigt. Weitere klinische Studien sind erforderlich, um die Bedeutung von Ketamin in der Behandlung von Patienten mit Sepsis und SIRS kritisch zu evaluieren.

Abstract

Ketamine is the only intravenous anesthetic that causes an increase in mean arterial pressure without compromising cardiac output. These beneficial effects are basically linked to stimulation of the sympathetic nervous system, inhibition of adenosine triphosphate-sensitive potassium channels and interactions with the nitric oxide pathway. Experimental and clinical studies have shown that ketamine exerts antiinflammatory properties by inhibiting the release of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-6. In addition, there is increasing evidence that early ketamine administration reduces mortality in experimental sepsis models. In view of the current literature ketamine appears to represent a beneficial therapeutic option for long-term sedation of patients with arterial hypotension resulting from sepsis and systemic inflammatory response syndrome (SIRS). However, it has to be taken into account that ketamine inhibits endothelial nitric oxide synthase, thereby potentially aggravating impaired (micro) regional blood flow in sepsis. Future studies are required to investigate the role of ketamine in the treatment of patients with sepsis and SIRS.

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Literatur

  1. Adams HA (1998) Wirkmechanismen von Ketamin. Anaesthesiol Reanim 23: 60–63

    PubMed  Google Scholar 

  2. Adams HA, Werner C (1997) Vom Razemat zum Eutomer: (S)-Ketamin. Renaissance einer Substanz? Anaesthesist 46: 1026–1042

    Article  PubMed  Google Scholar 

  3. Adams HA, Claussen E, Gebhardt B et al. (1991) Die Analgosedierung katecholaminpflichtiger Beatmungspatienten mit Ketamin und Midazolam. Anaesthesist 40: 238–244

    PubMed  Google Scholar 

  4. Adams HA, Thiel A, Jung A et al. (1992) Untersuchungen mit S-(+)-Ketamin an Probanden. Endokrine und Kreislaufreaktionen, Aufwachverhalten und Traumerlebnisse. Anaesthesist 41: 588–596

    PubMed  Google Scholar 

  5. Adams HA, Bauer R, Gebhardt B et al. (1994) TIVA mit S-(+)-Ketamin in der orthopädischen Alterschirurgie. Endokrine Stressreaktion, Kreislauf- und Aufwachverhalten. Anaesthesist 43: 92–100

    Article  PubMed  Google Scholar 

  6. Akata T, Izumi K, Nakashima M (2001) Mechanisms of direct inhibitory action of ketamine on vascular smooth muscle in mesenteric resistance arteries. Anesthesiology 95: 452–462

    Article  PubMed  Google Scholar 

  7. Angus DC, Linde-Zwirble WT, Lidicker J et al. (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29: 1303–1310

    Article  PubMed  Google Scholar 

  8. Annetta MG, Iemma D, Garisto C et al. (2005) Ketamine: new indications for an old drug. Curr Drug Targets 6: 789–794

    Article  PubMed  Google Scholar 

  9. Appel E, Dudziak R, Palm D, Wnuk A (1979) Sympathoneuronal and sympathoadrenal activation during ketamine anesthesia. Eur J Clin Pharmacol 16: 91–95

    PubMed  Google Scholar 

  10. Astiz ME, Rackow EC (1998) Septic shock. Lancet 351: 1501–1505

    Article  PubMed  Google Scholar 

  11. Bell RF, Dahl JB, Moore RA, Kalso E (2005) Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand 49: 1405–1428

    Article  PubMed  Google Scholar 

  12. Booke M, Westphal M, Hinder F et al. (2003) Cerebral blood flow is not altered in sheep with Pseudomonas aeruginosa sepsis treated with norepinephrine or nitric oxide synthase inhibition. Anesth Analg 96: 1122–1128

    PubMed  Google Scholar 

  13. Brookes ZL, Reilly CS, Brown NJ (2004) Differential effects of propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation of normotensive and hypertensive rats in vivo. Br J Anaesth 93: 249–256

    Article  PubMed  Google Scholar 

  14. Burchardi H, Schneider H (2004) Economic aspects of severe sepsis: a review of intensive care unit costs, cost of illness and cost effectiveness of therapy. Pharmacoeconomics 22: 793–813

    Article  PubMed  Google Scholar 

  15. Chen RM, Chen TL, Lin YL et al. (2005) Ketamine reduces nitric oxide biosynthesis in human umbilical vein endothelial cells by down-regulating endothelial nitric oxide synthase expression and intracellular calcium levels. Crit Care Med 33: 1044–1049

    Article  PubMed  Google Scholar 

  16. Chernow B, Roth BL (1986) Pharmacologic manipulation of the peripheral vasculature in shock: clinical and experimental approaches. Circ Shock 18: 141–155

    PubMed  Google Scholar 

  17. Church J, Zeman S, Lodge D (1988) The neuroprotective action of ketamine and MK-801 after transient cerebral ischemia in rats. Anesthesiology 69: 702–709

    PubMed  Google Scholar 

  18. Doenicke A, Angster R, Mayer M et al. (1992) Die Wirkung von S-(+)-Ketamin auf Katecholamine und Cortisol im Serum. Vergleich zu Ketamin-Razemat. Anaesthesist 41: 597–603

    PubMed  Google Scholar 

  19. Doenicke A, Kugler J, Mayer M et al. (1992) Ketamin-Razemat oder S-(+)-Ketamin und Midazolam. Die Einflüsse auf Vigilanz, Leistung und subjektives Befinden. Anaesthesist 41: 610–618

    PubMed  Google Scholar 

  20. Fitzal S (1997) Ketamin und Neuroprotektion. Klinischer Ausblick. Anaesthesist 46 [Suppl 1]: S65–70

  21. Freye E, Knufermann V (1994) Keine Hemmung der intestinalen Motilität nach Ketamin-/Midazolamnarkose. Ein Vergleich zur Narkose mit Enfluran und Fentanyl/Midazolam. Anaesthesist 43: 87–91

    Article  PubMed  Google Scholar 

  22. Gelissen HP, Epema AH, Henning RH et al. (1996) Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle. Anesthesiology 84: 397–403

    Article  PubMed  Google Scholar 

  23. Gibbs JM (1972) The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth 44: 1298–1302

    PubMed  Google Scholar 

  24. Gonzales JM, Loeb AL, Reichard PS, Irvine S (1995) Ketamine inhibits glutamate-, N-methyl-D-aspartate-, and quisqualate-stimulated cGMP production in cultured cerebral neurons. Anesthesiology 82: 205–213

    Article  PubMed  Google Scholar 

  25. Gurfinkel R, Czeiger D, Douvdevani A et al. (2007) Ketamine improves survival in burn followed by sepsis in rats. Anesth Analg (in press)

  26. Heinz P, Geelhoed GC, Wee C, Pascoe EM (2006) Is atropine needed with ketamine sedation? A prospective, randomised, double blind study. Emerg Med J 23: 206–209

    Article  PubMed  Google Scholar 

  27. Himmelseher S, Durieux ME (2005) Revising a dogma: ketamine for patients with neurological injury? Anesth Analg 101: 524–534

    Article  PubMed  Google Scholar 

  28. Hirota K, Sato T, Rabito SF et al. (1996) Relaxant effect of ketamine and its isomers on histamine-induced contraction of tracheal smooth muscle. Br J Anaesth 76: 266–270

    PubMed  Google Scholar 

  29. Hoff G, Bauer I, Larsen B, Bauer M (2001) Modulation of endotoxin-stimulated TNF-alpha gene expression by ketamine and propofol in cultured human whole blood. Anaesthesist 50: 494–499

    Article  PubMed  Google Scholar 

  30. Ince C, Sinaasappel M (1999) Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 27: 1369–1377

    Article  PubMed  Google Scholar 

  31. Ivani G, Vercellino C, Tonetti F (2003) Ketamine: a new look to an old drug. Minerva Anestesiol 69: 468–471

    PubMed  Google Scholar 

  32. Ivankovich AD, Miletich DJ, Reimann C et al. (1974) Cardiovascular effects of centrally administered ketamine in goats. Anesth Analg 53: 924–933

    PubMed  Google Scholar 

  33. Kawano T, Oshita S, Takahashi A et al. (2005) Molecular mechanisms underlying ketamine-mediated inhibition of sarcolemmal adenosine triphosphate-sensitive potassium channels. Anesthesiology 102: 93–101

    Article  PubMed  Google Scholar 

  34. Kawasaki C, Kawasaki T, Ogata M et al. (2001) Ketamine isomers suppress superantigen-induced proinflammatory cytokine production in human whole blood. Can J Anaesth 48: 819–823

    PubMed  Google Scholar 

  35. Kawasaki T, Ogata M, Kawasaki C et al. (1999) Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro. Anesth Analg 89: 665–669

    Article  PubMed  Google Scholar 

  36. Knaus WA, Sun X, Nystrom O, Wagner DP (1992) Evaluation of definitions for sepsis. Chest 101: 1656–1662

    PubMed  Google Scholar 

  37. Koga K, Ogata M, Takenaka I et al. (1994) Ketamine suppresses tumor necrosis factor-alpha activity and mortality in carrageenan-sensitized endotoxin shock model. Circ Shock 44: 160–168

    PubMed  Google Scholar 

  38. Kongsayreepong S, Cook DJ, Housmans PR (1993) Mechanism of the direct, negative inotropic effect of ketamine in isolated ferret and frog ventricular myocardium. Anesthesiology 79: 313–322

    PubMed  Google Scholar 

  39. Kress HG (1994) NMDA- und Opiatrezeptor-unabhängige Wirkungen von Ketamin. Anaesthesist 43 [Suppl 2]: S15–24

  40. Kress HG (1997) Wirkmechanismen von Ketamin. Anaesthesist 46 [Suppl 1]: S8–19

  41. Lacza Z, Puskar M, Figueroa JP et al. (2001) Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia. Free Radic Biol Med 31: 1609–1615

    Article  PubMed  Google Scholar 

  42. Landry DW, Oliver JA (1992) The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. J Clin Invest 89: 2071–2074

    PubMed  Google Scholar 

  43. Landry DW, Oliver JA (2001) The pathogenesis of vasodilatory shock. N Engl J Med 345: 588–595

    Article  PubMed  Google Scholar 

  44. Landry DW, Levin HR, Gallant EM et al. (1997) Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 95: 1122–1125

    PubMed  Google Scholar 

  45. Lange M, Szabo B, Aken H van et al. (2007) Short-time effects of glipizide (an ATP-sensitive potassium channel inhibitor) on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. Shock (in press)

  46. Lewis E, Rogachev B, Shaked G, Douvdevani A (2001) The in vitro effects of ketamine at large concentrations can be attributed to a nonspecific cytostatic effect. Anesth Analg 92: 927–929

    Article  PubMed  Google Scholar 

  47. Linden P van der, Gilbart E, Engelman E et al. (1990) Comparison of halothane, isoflurane, alfentanil, and ketamine in experimental septic shock. Anesth Analg 70: 608–617

    PubMed  Google Scholar 

  48. Lundy PM, Lockwood PA, Thompson G, Frew R (1986) Differential effects of ketamine isomers on neuronal and extraneuronal catecholamine uptake mechanisms. Anesthesiology 64: 359–363

    PubMed  Google Scholar 

  49. Martin CM, Yaghi A, Sibbald WJ et al. (1993) Differential impairment of vascular reactivity of small pulmonary and systemic arteries in hyperdynamic sepsis. Am Rev Respir Dis 148: 164–172

    PubMed  Google Scholar 

  50. Martin J, Bäsell K, Bürkle H et al. (2005) Analgesie und Sedierung in der Intensivmedizin. S2-Leitlinien der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin. Anaesthesiol Intensivmed 46 [Suppl]: S1–20

  51. Martin J, Parsch A, Franck M et al. (2005) Practice of sedation and analgesia in German intensive care units: results of a national survey. Crit Care 9: R117–123

    Article  PubMed  Google Scholar 

  52. Mazar J, Rogachev B, Shaked G et al. (2005) Involvement of adenosine in the antiinflammatory action of ketamine. Anesthesiology 102: 1174–1181

    Article  PubMed  Google Scholar 

  53. Mehrabi A, Golling M, Kashfi A et al. (2005) Negative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantation. Liver Transpl 11: 174–187

    Article  PubMed  Google Scholar 

  54. Modig J (1987) Positive effects of ketamine v. metomidate anesthesia on cardiovascular function, oxygen delivery and survival. Studies with a porcine endotoxin model. Acta Chir Scand 153: 7–13

    PubMed  Google Scholar 

  55. Nelson MT (1993) Ca2+-activated potassium channels and ATP-sensitive potassium channels as modulators of vascular tone. Trend Cardiovasc Med 3: 54–60

    Article  Google Scholar 

  56. Nelson MT, Quayle JM (1995) Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268: C799–822

    PubMed  Google Scholar 

  57. Ogawa K, Tanaka S, Murray PA (2001) Inhibitory effects of etomidate and ketamine on endothelium-dependent relaxation in canine pulmonary artery. Anesthesiology 94: 668–677

    Article  PubMed  Google Scholar 

  58. Pabelick CM, Rehder K, Jones KA et al. (1997) Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle. Br J Pharmacol 121: 1378–1382

    PubMed  Google Scholar 

  59. Patschke D, Bruckner JB, Gethmann JW et al. (1975) Einfluss der Ketaminnarkose auf die Hämodynamik und den myokardialen Sauerstoffverbrauch narkotisierter Hunde. Prakt Anaesth 10: 325–334

    PubMed  Google Scholar 

  60. Pfenninger E, Himmelseher S (1997) Neuroprotektion durch Ketamin auf zellularer Ebene. Anaesthesist 46 [Suppl 1]: S47–54

  61. Pfenninger E, Ahnefeld FW, Grunert A (1985) Untersuchung zum intrakraniellen Druckverhalten unter Ketaminapplikation bei erhaltener Spontanatmung. Eine tierexperimentelle Untersuchung. Anaesthesist 34: 191–196

    PubMed  Google Scholar 

  62. Radke J (1992) Analgosedierung des Intensivpatienten. Anaesthesist 41: 793–808

    PubMed  Google Scholar 

  63. Rangel-Frausto MS, Pittet D, Costigan M et al. (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273: 117–123

    Article  PubMed  Google Scholar 

  64. Reich DL, Silvay G (1989) Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 36: 186–197

    PubMed  Google Scholar 

  65. Reinhart K, Engel C, Brunkhorst FM et al. (2004) Epidemiology of severe sepsis and septic shock in Germany – Preliminary data from the German „Prevalence“ Study (abstract). Intensivmed Notfallmed 41: 11

    Google Scholar 

  66. Rivers E, Nguyen B, Havstad S et al. (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345: 1368–1377

    Article  PubMed  Google Scholar 

  67. Roytblat L, Talmor D, Rachinsky M et al. (1998) Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg 87: 266–271

    Article  PubMed  Google Scholar 

  68. Salt PJ, Barnes PK, Beswick FJ (1979) Inhibition of neuronal and extraneuronal uptake of noradrenaline by ketamine in the isolated perfused rat heart. Br J Anaesth 51: 835–838

    PubMed  Google Scholar 

  69. Schmidt H, Ebeling D, Bauer H et al. (1995) Ketamine attenuates endotoxin-induced leukocyte adherence in rat mesenteric venules. Crit Care Med 23: 2008–2014

    Article  PubMed  Google Scholar 

  70. Sehdev RS, Symmons DA, Kindl K (2006) Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas 18: 37–44

    Article  PubMed  Google Scholar 

  71. Shaked G, Czeiger D, Dukhno O et al. (2004) Ketamine improves survival and suppresses IL-6 and TNF-alpha production in a model of Gram-negative bacterial sepsis in rats. Resuscitation 62: 237–242

    Article  PubMed  Google Scholar 

  72. Shimaoka M, Iida T, Ohara A et al. (1996) Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells. Br J Anaesth 77: 238–242

    PubMed  Google Scholar 

  73. Standen NB, Quayle JM, Davies NW et al. (1989) Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science 245: 177–180

    PubMed  Google Scholar 

  74. Subramaniam K, Subramaniam B, Steinbrook RA (2004) Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg 99: 482–495

    Article  PubMed  Google Scholar 

  75. Taniguchi T, Shibata K, Yamamoto K (2001) Ketamine inhibits endotoxin-induced shock in rats. Anesthesiology 95: 928–932

    Article  PubMed  Google Scholar 

  76. Taniguchi T, Takemoto Y, Kanakura H et al. (2003) The dose-related effects of ketamine on mortality and cytokine responses to endotoxin-induced shock in rats. Anesth Analg 97: 1769–1772

    Article  PubMed  Google Scholar 

  77. Task Force of the American College of Critical Care Medicine SoCCM (1999) Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med 27: 639–660

    PubMed  Google Scholar 

  78. Taylor BS, Geller DA (2000) Molecular regulation of the human inducible nitric oxide synthase (iNOS) gene. Shock 13: 413–424

    PubMed  Google Scholar 

  79. Weigand MA, Schmidt H, Zhao Q et al. (2000) Ketamine modulates the stimulated adhesion molecule expression on human neutrophils in vitro. Anesth Analg 90: 206–212

    Article  PubMed  Google Scholar 

  80. Worek FS, Blumel G, Zeravik J et al. (1988) Comparison of ketamine and pentobarbital anesthesia with the conscious state in a porcine model of pseudomonas aeruginosa septicemia. Acta Anaesthesiol Scand 32: 509–515

    PubMed  Google Scholar 

  81. Yu Y, Zhou Z, Xu J et al. (2002) Ketamine reduces NFkappaB activation and TNFalpha production in rat mononuclear cells induced by lipopolysaccharide in vitro. Ann Clin Lab Sci 32: 292–298

    PubMed  Google Scholar 

  82. Zielmann S, Kazmaier S, Schnull S, Weyland A (1997) S-(+)-Ketamin und Kreislauf. Anaesthesist 46 [Suppl 1]: S43–46

  83. Zilberstein G, Levy R, Rachinsky M et al. (2002) Ketamine attenuates neutrophil activation after cardiopulmonary bypass. Anesth Analg 95: 531–536

    Article  PubMed  Google Scholar 

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  1. Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum, Albert-Schweitzer-Str. 33, 48149, Münster

    M. Lange, K. Bröking, H. van Aken, C. Hucklenbruch, H.-G. Bone & M. Westphal

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Lange, M., Bröking, K., van Aken, H. et al. Einsatz von Ketamin bei Sepsis und systemischen Entzündungsreaktionen. Anaesthesist 55, 883–891 (2006). https://doi.org/10.1007/s00101-006-1048-x

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