Zusammenfassung
Die Anwendung einer therapeutischen Hypothermie nach verschiedenen Arten von hypoxisch-ischämischen Ereignissen zählt seit langer Zeit zu den Konzepten einer unspezifischen Zellprotektion. Nachdem Versuche mit tiefen Hypothermieformen nach Herz-Kreislauf-Stillstand im letzten Jahrhundert keine positiven Ergebnisse erbrachten, sind jetzt aktuelle Daten zum Einsatz der milden Hypothermie verfügbar, die den klinischen Nutzen eindeutig belegen. Sowohl Daten der europäischen Multicenteruntersuchung als auch jene aus Australien zeigen einen deutlichen Überlebensvorteil für Patienten, die für 12 bzw. 24 h auf 32–34°C gekühlt wurden. Dies führte 2003 zu der Aufnahme der milden Hypothermie (32–34°C) als klare Empfehlung in die International Liaison Committee on Resuscitation- (ILCOR-)Guidelines zur Behandlung von bewusstlosen Patienten nach prähospitalem Herz-Kreislauf-Stillstand. Dieser Artikel gibt eine Übersicht über bestehende Konzepte und zukünftige Perspektiven der therapeutischen milden Hypothermie.
Abstract
The use of therapeutic hypothermia following different hypoxic-ischaemic insults has played an important role in various concepts of non-specific protection of cells for a long time. Although the use of deep therapeutic hypothermia after cardiac arrest in the last century did not lead to an improved outcome, recent data have demonstrated very positive effects of mild therapeutic hypothermia. The data from the European multicenter trial as well as those from Australia have clearly demonstrated a decrease in mortality and a better neurological outcome for patients being cooled to 32–34°C for 12 or 24 h. In 2003, this led to the implementation of mild therapeutic hypothermia (32–34°C) into the International Liaison Committee on Resuscitation (ILCOR) recommendations and guidelines for the treatment of unconscious patients after prehospital cardiac arrest. This article gives an overview on existing concepts and future perspectives of therapeutic mild hypothermia.
Literatur
Adrie C, Adib-Conquy M, Laurent I et al. (2002) Successful cardiopulmonary resuscitation after cardiac arrest as a „sepsis-like“ syndrome. Circulation 106:562–568
Agardh CD, Zhang H, Smith ML, Siesjo BK (1991) Free radical production and ischemic brain damage: influence of postischemic oxygen tension. Int J Dev Neurosci 9:127–138
Aibiki M, Maekawa S, Yokono S (2000) Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans. Crit Care Med 28:3902–3906
Al-Senani FM, Graffagnino C, Grotta JC et al. (2004) A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard system and icy catheter following cardiac arrest. Resuscitation 62:143–150
Behringer W, Kentner R, Wu X et al. (2001) Thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs. An exploratory study. Resuscitation 49:83–97
Behringer W, Safar P, Wu X et al. (2003) Survival without brain damage after clinical death of 60–120 min in dogs using suspended animation by profound hypothermia. Crit Care Med 31:1523–1531
Bellamy R, Safar P, Tisherman SA et al. (1996) Suspended animation for delayed resuscitation. Crit Care Med 24:S24–47
Benson DW, Williams GR Jr, Spencer FC, Yates AJ (1959) The use of hypothermia after cardiac arrest. Anesth Analg 38:423–428
Berger C, Schäbitz WR, Georgiadis D, Steiner T, Aschoff A, Schwab S (2002) Effects of hypothermia on excitatory amino acids and metabolism in stroke patients: a microdialysis study. Stroke 33:519–524
Berghe G van den, Wouters P, Weekers F et al. (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367
Bernard S, Buist M, Monteiro O, Smith K (2003) Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report. Resuscitation 56:9–13
Bernard SA, Jones BM, Horne MK (1997) Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 30:146–153
Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563
Bigelow WG, Callaghan JC, Hopps JA (1950) General hypothermia for experimental intracardiac surgery. The use of electrophrenic respirations, an artificial pacemaker for cardiac standstill and radio-frequency rewarming in general hypothermia. Ann Surg 132:531–539
Biggart MJ, Bohn DJ (1990) Effect of hypothermia and cardiac arrest on outcome of near-drowning accidents in children. J Pediatr 117:179–183
Bohn DJ, Biggar WD, Smith CR, Conn AW, Barker GA (1986) Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning. Crit Care Med 14:529–534
Böttiger BW, Grabner C, Bauer H, Bode C, Weber T, Motsch J, Martin E (1999) Long term outcome after out-of-hospital cardiac arrest with physician staffed emergency medical services: the Utstein style applied to a midsized urban/suburban area. Heart 82:674–679
Böttiger BW, Teschendorf P, Krumnikl JJ et al. (1999) Global cerebral ischemia due to cardiocirculatory arrest in mice causes neuronal degeneration and early induction of transcription factor genes in the hippocampus. Brain Res Mol Brain Res 65:135–142
Botterell EH, Lougheed WM, Scott JW, Vandewater SL (1956) Hypothermia, and interruption of carotid, or carotid and vertebral circulation, in the surgical management of intracranial aneurysms. J Neurosurg 13:1–42
Botterell EH, Lougheed WM, Morley TP, Vandewater SL (1958) Hypothermia in the surgical treatment of ruptured intracranial aneurysms. J Neurosurg 15:4–18
Broman M, Kallskog O, Nygren K, Wolgast M (1998) The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat. Acta Physiol Scand 162:475–480
Busto R, Globus M, Dietrich W, Martinez E, Valdes I, Ginsberg M (1989) Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 20:904–910
Choi DW (1992) Excitotoxic cell death. J Neurobiol 23:1261–1276
Clifton GL, Allen S, Berry J, Koch SM (1992) Systemic hypothermia in treatment of brain injury. J Neurotrauma 9 [Suppl 2]:S487–495
Clifton GL, Allen S, Barrodale P et al. (1993) A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma 10:263–271
Clifton GL, Choi SC, Miller ER et al. (2001) Intercenter variance in clinical trials of head trauma—Experience of the National Acute Brain Injury Study: hypothermia. J Neurosurg 95:751–755
Clifton GL, Miller ER, Choi SC et al. (2001) Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 344:556–563
Cummins RO, Chamberlain DA, Abramson NS et al. (1991) Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein style. A statement for health professionals from a task force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council. Circulation 84:960–975
Dae MW, Gao DW, Ursell PC, Stillson CA, Sessler DI (2003) Safety and efficacy of endovascular cooling and rewarming for induction and reversal of hypothermia in human-sized pigs. Stroke 34:734–738
Damian MS, Ellenberg D, Gildemeister R, Lauermann J, Simonis G, Sauter W, Georgi C (2004) Coenzyme Q10 combined with mild hypothermia after cardiac arrest: a preliminary study. Circulation 110:3011–3016
Farstad M, Heltne JK, Rynning SE, Onarheim H, Mongstad A, Eliassen F, Husby P (2004) Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets? J Thorac Cardiovasc Surg 127:525–534
Fay T (1945) Observation on generalized refrigeration in cases of severe cerebral trauma. Res Publ Assoc Res Nerv Ment Dis 4:611–619
Fischer M, Böttiger BW, Popov-Cenic S, Hossmann KA (1996) Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat. Intensive Care Med 22:1214–1223
Fischer S, Renz D, Wiesnet M, Schaper W, Karliczek GF (1999) Hypothermia abolishes hypoxia-induced hyperpermeability in brain microvessel endothelial cells. Brain Res Mol Brain Res 74:135–144
Fukuda H, Tomimatsu T, Kanagawa T et al. (2003) Postischemic hyperthermia induced caspase-3 activation in the newborn rat brain after hypoxia-ischemia and exacerbated the brain damage. Biol Neonate 84:164–171
Georgiadis D, Schwarz S, Kollmar R, Schwab S (2001) Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke 32:2550–2553
Gordon CJ (2001) The therapeutic potential of regulated hypothermia. Emerg Med J 18:81–89
Hachimi-Idrissi S, Corne L, Ebinger G, Michotte Y, Huyghens L (2001) Mild hypothermia induced by a helmet device: a clinical feasibility study. Resuscitation 51:275–281
Hachimi-Idrissi S, Hemelrijck A van, Michotte A et al. (2004) Postischemic mild hypothermia reduces neurotransmitter release and astroglial cell proliferation during reperfusion after asphyxial cardiac arrest in rats. Brain Res 1019:217–225
Hashimoto T, Yonetani M, Nakamura H (2003) Selective brain hypothermia protects against hypoxic-ischemic injury in newborn rats by reducing hydroxyl radical production. Kobe J Med Sci 49:83–91
Hayashi N, Hirayama T, Udagawa A, Daimon W, Ohata M (1994) Systemic management of cerebral edema based on a new concept in severe head injury patients. Acta Neurochir Suppl 60:541–543
Hein OV, Triltsch A, Buch C von, Kox WJ, Spies C (2004) Mild hypothermia after near drowning in twin toddlers. Crit Care 8:R353–357
Hekimian G, Baugnon T, Thuong M et al. (2004) Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation. Shock 22:116–119
Husby P, Andersen KS, Owen-Falkenberg A, Steien E, Solheim J (1990) Accidental hypothermia with cardiac arrest: complete recovery after prolonged resuscitation and rewarming by extracorporeal circulation. Intensive Care Med 16:69–72
Hypothermia After Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556
Illievich UM, Zornow MH, Choi KT, Scheller MS, Strnat MA (1994) Effects of hypothermic metabolic suppression on hippocampal glutamate concentrations after transient global cerebral ischemia. Anesth Analg 78:905–911
Jiang J, Yu M, Zhu C (2000) Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases. J Neurosurg 93:546–549
Kass LE, Eitel DR, Sabulsky NK, Ogden CS, Hess DR, Peters KL (1994) One-year survival after prehospital cardiac arrest: the Utstein style applied to a rural-suburban system. Am J Emerg Med 12:17–20
Katz LM, Young A, Frank JE, Wang Y, Park K (2004) Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia. Crit Care Med 32:806–810
Kil HY, Zhang J, Piantadosi CA (1996) Brain temperature alters hydroxyl radical production during cerebral ischemia/reperfusion in rats. J Cereb Blood Flow Metab 16:100–106
Kornberger E, Lindner KH, Mayr VD et al. (2001) Effects of epinephrine in a pig model of hypothermic cardiac arrest and closed-chest cardiopulmonary resuscitation combined with active rewarming. Resuscitation 50:301–308
Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H (1993) Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 21:1348–1358
Larrey I (1814) 156–164. In: Larrey I (ed) Memoirs of military service and campaigns of the French armies, 2. edn. Cushing, Baltimore
Le F, Cusack B, Richelson E (1996) The neurotensin receptor: is there more than one subtype? Trends Pharmacol Sci 17:1–3
Leonov Y, Sterz F, Safar P, Radovsky A, Oku K, Tisherman S, Stezoski SW (1990) Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J Cereb Blood Flow Metab 10:57–70
Lin SR (1979) Changes of plasma volume and hematocrit after circulatory arrest: an experimental study in dogs. Invest Radiol 14:202–206
Lombardi G, Gallagher J, Gennis P (1994) Outcome of out-of-hospital cardiac arrest in New York City. The Pre-Hospital Arrest Survival Evaluation (PHASE) Study. JAMA 271:678–683
Love S, Barber R, Srinivasan A, Wilcock GK (2000) Activation of caspase-3 in permanent and transient brain ischaemia in man. Neuroreport 11:2495–2499
Marion DW, Penrod LE, Kelsey SF et al. (1997) Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 336:540–546
McIntyre LA, Fergusson DA, Hebert PC, Moher D, Hutchison JS (2003) Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review. Jama 289:2992–2999
Mouritzen CV, Andersen MN (1966) Mechanisms of ventricular fibrillation during hypothermia. Relative changes in myocardial refractory period and conduction velocity. J Thorac Cardiovasc Surg 51:579–584
Mullner M, Sterz F, Binder M, Schreiber W, Deimel A, Laggner AN (1997) Blood glucose concentration after cardiopulmonary resuscitation influences functional neurological recovery in human cardiac arrest survivors. J Cereb Blood Flow Metab 17:430–436
Nagao K, Hayashi N, Kanmatsuse K, Arima K, Ohtsuki J, Kikushima K, Watanabe I (2000) Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital. J Am Coll Cardiol 36:776–783
Nakashima K, Todd MM (1996) Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke 27:913–918
Nilsson L, Kogure K, Busto R (1975) Effects of hypothermia and hyperthermia on brain energy metabolism. Acta Anaesthesiol Scand 19:199–205
Nolan JP, Morley PT, Hoek TL, Hickey RW (2003) Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advancement Life Support Task Force of the International Liaison Committee on Resuscitation. Resuscitation 57:231–235
Nolan JP, Morley PT, Vanden Hoek TL et al. (2003) Therapeutic hypothermia after cardiac arrest: an advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation 108:118–121
Padosch SA, Böttiger BW (2003) Neuronal apoptosis following cerebral ischaemia: pathophysiology and possible therapeutic implications. Curr Opin Anaesth 16:439–445
Padosch SA, Vogel P, Böttiger BW (2001) Neuronale Apoptose nach zerebraler Ischamie. Grundlagen, Pathophysiologie und Interventionsmoglichkeiten. Anaesthesist 50:905–920
Padosch SA, Kern KB, Böttiger BW (2002) Therapeutic hypothermia after cardiac arrest. N Engl J Med 347:63–65
Padosch SA, Popp E, Vogel P, Böttiger BW (2003) Altered protein expression levels of Fas/CD95 and Fas ligand in differentially vulnerable brain areas in rats after global cerebral ischemia. Neurosci Lett 338:247–251
Polderman KH, Girbes AR (2002) Potential mechanisms of hypothermia-induced electrolyte depletion. Crit Care Med 30:1932
Polderman KH, Tjong Tjin Joe R, Peerdeman SM, Vandertop WP, Girbes AR (2002) Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury. Intensive Care Med 28:1563–1573
Popp E, Padosch SA, Vogel P, Schäbitz WR, Schwab S, Böttiger BW (2004) Effects of intracerebroventricular application of brain-derived neurotrophic factor on cerebral recovery after cardiac arrest in rats. Crit Care Med 32:S359–365
Poulos ND, Mollitt DL (1991) The nature and reversibility of hypothermia-induced alterations of blood viscosity. J Trauma 31:996–998
Rohrer MJ, Natale AM (1992) Effect of hypothermia on the coagulation cascade. Crit Care Med 20:1402–1405
Rosomoff HL (1959) Experimental brain injury during hypothermia. J Neurosurg 16:177–187
Rosomoff HL (1959) Protective effects of hypothermia against pathological processes of the nervous system. Ann N Y Acad Sci 80:475–486
Rosomoff HL, Holaday DA (1954) Cerebral blood flow and cerebral oxygen consumption during hypothermia. Am J Physiol 179:85–88
Safar P, Xiao F, Radovsky A et al. (1996) Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. Stroke 27:105–113
Safar P, Tisherman SA, Behringer W et al. (2000) Suspended animation for delayed resuscitation from prolonged cardiac arrest that is unresuscitable by standard cardiopulmonary-cerebral resuscitation. Crit Care Med 28 [11 Suppl]:N214–218
Safar P, Behringer W, Böttiger BW, Sterz F (2002) Cerebral resuscitation potentials for cardiac arrest. Crit Care Med 30:140–144
Schwab S, Schwarz S, Aschoff A, Keller E, Hacke W (1998) Moderate hypothermia and brain temperature in patients with severe middle cerebral artery infarction. Acta Neurochir Suppl 71:131–134
Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W (1998) Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 29:2461–2466
Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA (2001) Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 32:2033–2035
Sessler DI (2001) Complications and treatment of mild hypothermia. Anesthesiology 95:531–543
Shimohama S, Tamura Y, Akaike A, Tsukahara T, Ohara O, Watanabe S, Kimura J (1993) Brain-derived neurotrophic factor pretreatment exerts a partially protective effect against glutamate-induced neurotoxicity in cultured rat cortical neurons. Neurosci Lett 164:55–58
Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T (1993) Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:363–368
Shiozaki T, Hayakata T, Taneda M et al. (2001) A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan. J Neurosurg 94:50–54
Southwick FS, Dalglish PH Jr (1980) Recovery after prolonged asystolic cardiac arrest in profound hypothermia. A case report and literature review. JAMA 243:1250–1253
Steinberg GK, Ogilvy CS, Shuer LM et al. (2004) Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair. Neurosurgery 55:307–314
Sterz F, Safar P, Tisherman S, Radovsky A, Kuboyama K, Oku K (1991) Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med 19:379–389
Takasu A, Carrillo P, Stezoski SW, Safar P, Tisherman SA (1999) Mild or moderate hypothermia but not increased oxygen breathing prolongs survival during lethal uncontrolled hemorrhagic shock in rats, with monitoring of visceral dysoxia. Crit Care Med 27:1557–1564
Takino M, Okada Y (1991) Hyperthermia following cardiopulmonary resuscitation. Intensive Care Med 17:419–420
Tanaka K, Hori K, Wada-Tanaka N, Nomura M, Ogawa N (2001) FK506 ameliorates the discrimination learning impairment due to preventing the rarefaction of white matter induced by chronic cerebral hypoperfusion in rats. Brain Res 906:184–189
Theard MA, Tempelhoff R, Crowder CM, Cheng MA, Todorov A, Dacey RG Jr (1997) Convection versus conduction cooling for induction of mild hypothermia during neurovascular procedures in adults. J Neurosurg Anesthesiol 9:250–255
Tiainen M, Roine RO, Pettila V, Takkunen O (2003) Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke 34:2881–2886
Virkkunen I, Yli-Hankala A, Silfvast T (2004) Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringer’s solution: a pilot study. Resuscitation 62:299–302
Vogel P, Putten H, Popp E et al. (2003) Improved resuscitation after cardiac arrest in rats expressing the baculovirus caspase inhibitor protein p35 in central neurons. Anesthesiology 99:112–121
Wang H, Olivero W, Lanzino G et al. (2004) Rapid and selective cerebral hypothermia achieved using a cooling helmet. J Neurosurg 100:272–277
Weinrauch V, Safar P, Tisherman S, Kuboyama K, Radovsky A (1992) Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke 23:1454–1462
Williams GR Jr, Spencer FC (1958) The clinical use of hypothermia following cardiac arrest. Ann Surg 148:462–468
Xu L, Yenari MA, Steinberg GK, Giffard RG (2002) Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 22:21–28
Yan Y, Tang W (2001) Changes of evoked potentials and evaluation of mild hypothermia for treatment of severe brain injury. Chin J Traumatol 4:8–13
Zeiner A, Holzer M, Sterz F et al. (2000) Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group. Stroke 31:86–94
Zhang K, Wang J (2000) Comparative study on mild hypothermia for treatment of severe head injury and the most severe head injury. Inner Mongol Med J 32:4–6
Zimmerman JM, Spencer FC (1958) The influence of hypothermia on cerebral injury resulting from circulatory occlusion. Surg Forum 9:216–218
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Popp, E., Sterz, F. & Böttiger, B.W. Therapeutische milde Hypothermie nach Herz-Kreislauf-Stillstand. Anaesthesist 54, 96–106 (2005). https://doi.org/10.1007/s00101-004-0790-1
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DOI: https://doi.org/10.1007/s00101-004-0790-1