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13 - Global brain ischemia and reperfusion
- from Part III - The pathophysiology of global ischemia and reperfusion
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- By Brian J. O'Neil, Department of Emergency Medicine, William Beaumont Hospital, Royal Oak, MI, USA, Raymond C. Koehler, Department of Anesthesiology, Johns Hopkins University, Baltimore, MD, USA, Robert W. Neumar, Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, Uwe Ebmeyer, Klinik für Anaesthesiologie und Intensivtherapie, Otto-von-Guericke Universität, Magdeburg, Germany, Gary S. Krause, Department of Emergency Medicine, Wayne State University, Detroit, MI, USA
- Edited by Norman A. Paradis, University of Colorado, Denver, Henry R. Halperin, The Johns Hopkins University School of Medicine, Karl B. Kern, University of Arizona, Volker Wenzel, Douglas A. Chamberlain, Cardiff University
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- Book:
- Cardiac Arrest
- Published online:
- 06 January 2010
- Print publication:
- 18 October 2007, pp 236-281
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- Chapter
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Summary
Introduction
Sudden, unexpected death claims nearly 1000 lives each day in the United States and is the fifth leading cause of all deaths in the western world. Cardiac arrest occurs over 300 000 times per year both in the United States and Europe with the risk for persons 35 years and older estimated at 1 per 1000. In those patients resuscitated from cardiac arrest, nearly 60% die from a neurological cause. Despite every effort, only 3%–10% of all resuscitated patients are able to resume their former lifestyles.
To date, there are no clinically effective pharmacologic tools for amelioration of brain damage by ischemia and reperfusion. Clinical trials conducted more than a decade ago utilizing postresuscitation treatment with barbiturates or calcium antagonists were disappointing. More recently, clinical treatment of stroke with a radical scavenger (trilazad), intercellular adhesion molecule-1 antagonist (Enlimomab), glutamate receptor antagonist (Aptiganel, gavestinel), glutamate release inhibitor (Lubeluzole), ganglioside administration (GM1), calcium channel blockade, or upregulation of the GABA receptor (Clomethiazole) were all found ineffective. This suggests that our understanding of the mechanisms involved in damage and repair in neurons remains incomplete and further therapeutic progress will require the delineation of the primary mechanisms involved in neuronal injury and repair.
Although the picture is still incomplete, a few things are clear.
The majority of damage occurs not during ischemia but during reperfusion. Nevertheless, the two processes work sequentially to increase neuronal damage (i.e., lipolysis during ischemia potentiates the radicalmediated peroxidation of polyunsaturated fatty acids (PUFAs) during reperfusion).
[…]
51 - Bringing it all together: brain-oriented postresuscitation critical care
- from Part V - Postresuscitation disease and its care
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- By Uwe Ebmeyer, Clinic for Anaesthesiology and Intensive Therapy, Otto-von-Guericke, Laurence M. Katz, Department of Emergency Medicine and University, Magdeburg, Germany, Kevin R. Ward, University of North Carolina Department of Emergency Medicine, Virginia Commonwealth University, Detroit, MI, USA, Robert W. Neumar, Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
- Edited by Norman A. Paradis, University of Colorado, Denver, Henry R. Halperin, The Johns Hopkins University School of Medicine, Karl B. Kern, University of Arizona, Volker Wenzel, Douglas A. Chamberlain, Cardiff University
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- Book:
- Cardiac Arrest
- Published online:
- 06 January 2010
- Print publication:
- 18 October 2007, pp 902-918
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- Chapter
- Export citation
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Summary
Multiple brain-damaging processes occur both during cardiac arrest and after return of spontaneous circulation (ROSC). The first aspect, the actual arrest, is best treated by rapid institution of artificial circulation/ventilation and early ROSC. The details and physiologic background for these procedures are discussed in previous chapters. This chapter will focus on the early period after restoration of spontaneous circulation and treatment aimed to prevent or minimize postischemic brain damage after restoration of spontaneous circulation. The ultimate importance of the postreperfusion (after ROSC) phase for long-term outcome is often underestimated. Currently it is believed that the majority of brain-injuring processes occur not during the no-flow state (cardiac arrest) but during resuscitative reperfusion. This latter stage includes a trickle-, a low-, and a temporary high-flow period. Since significant injury occurs during the resuscitation period, there is a window of opportunity to intervene and affect outcome. Nevertheless, the development of treatments for the multifactorial postresuscitation syndrome is complex and time-consuming and has thus far led to disappointing results. Numerous treatments effective in the laboratory have failed or been shown to have an almost undetectable benefit in clinical studies. Large multicenter studies – the only way to detect small(er) benefits – are extremely expensive and time-consuming and require an enormous administrative and financial investment. Sometimes ethical concerns about obtaining informed consent make clinical resuscitation research increasingly difficult. Nevertheless, definitive clinical studies are the only way to prove the effectiveness of resuscitation and postresuscitation treatment; clinically relevant laboratory studies may only help to select those that are most promising.