Annual Update in Intensive Care and Emergency Medicine 2011
The Annual Update compiles the most recent developments in experimental and clinical research and practice in one comprehensive reference book. The chapters are written by well recognized experts in the field of intensive care and emergency medi
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Mitochondrial Function in Septic Shock M.A. Puskarich and A.E. Jones
Introduction Shock is the result of failure of the circulatory system to adequately deliver oxygen and nutrients to tissues. At the bedside, the clinician synthesizes data from the history, signs of hypoperfusion on physical exam, vital signs and urine output, and laboratory markers of the adequacy of substrate provision to determine the presence of shock. However, prior to the onset of clinically evident shock, the insult is first experienced at a subcellular level by the mitochondria, leading to their description as “canaries in a coal mine” [1]. Ultimately, shock is the result of failure of adequate oxygen delivery (DO2) and utilization within mitochondria, which collectively are responsible for nearly all the oxygen consumption and energy production in the body. Traditionally, resuscitation of the patient in shock focuses on therapies to improve tissue perfusion. This strategy is usually accomplished by focusing attention on normalization or optimization of macrocirculatory physiologic parameters such as mean arterial pressure (MAP). In the case of septic shock, the overarching goal of such resuscitation is to provide adequate DO2 to meet the metabolic demands of the tissues. Early resuscitation strategies aimed at rapidly achieving predefined goals in the early stages of sepsis using structured protocols (i.e., quantitative resuscitation) have been shown to lead to improvements in patient outcomes [2]. Despite improvements in patient outcomes, mortality rates of patients with septic shock treated with quantitative resuscitation protocols remain in excess of 20 % [2], leaving substantial room for clinical improvement. After macrocirculatory resuscitation, many patients still demonstrate multisystem organ dysfunction and shock physiology. The recent landscape of sepsis research is focusing on two separate, though potentially linked, mechanisms that may explain the persistence of the shock state. The first is the expanding understanding of the role of the microcirculation in the body, and the heterogeneous response of various circulatory beds to the insults of sepsis. The second is the observation that cells and mitochondria receiving adequate perfusion and oxygenation may still have a decreased ability to properly utilize energy to form ATP, referred to as cytopathic hypoxia [3], which can lead to profound metabolic alterations and the inability to supply energy to tissues. These two fields, the microcirculation and the mitochondria, represent attractive targets for novel adjunctive resuscitative agents in the treatment of septic shock.
J.-L. Vincent (ed.), Annual Update in Intensive Care and Emergency Medicine 2011 DOI 10.1007/978-3-642-18081-1, ˇ Springer Science+Business Media LLC 2011
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M.A. Puskarich and A.E. Jones
Role of the Microcirculation
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Effective resuscitation requires rapid identification of tissue hypoperfusion and timely interventions for the restoration of adequate perfusion. Although septic shock research has c
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