Optimal oxygenation during and after cardiopulmonary resuscitation.
ABSTRACT Reversal of tissue hypoxia, particularly in the heart and brain, is a fundamental goal of cardiopulmonary resuscitation. However, a growing body of evidence suggests that hyperoxia, especially after return of spontaneous circulation (ROSC), may worsen outcomes. The purpose of this review is to describe the current evidence supporting the concept of controlled oxygenation during and after cardiac arrest.
Animal studies over the last two decades have built a compelling case that arterial hyperoxemia during the first hour after ROSC causes increased oxidative damage, increased neuronal death, and worse neurologic function. However, human data are limited. The only prospective randomized clinical trial comparing different inspired oxygen concentrations in post-cardiac arrest patients was underpowered to detect a difference in survival or neurologic outcome. More recently a retrospective analysis of data from a multicenter registry found that initial arterial hyperoxemia (paO2 ≥ 300 mmHg) was associated with increased mortality and worse functional outcome in patients admitted to the ICU after cardiac arrest. The existing evidence, though limited, has contributed to new guidelines for oxygen therapy in patients resuscitated from cardiac arrest.
The benefit of supplemental oxygen during cardiopulmonary resuscitation remains uncertain. However, in patients who achieve ROSC after cardiac arrest, available evidence supports adjusting inspired oxygen content to avoid arterial hyperoxemia while providing adequate arterial oxyhemoglobin saturation. This strategy is likely to be most effective when initiated as soon as possible after ROSC and appears to be most important during the first hour. Definitive clinical trials are needed to determine the ultimate impact on outcome.
- SourceAvailable from: Fabrizio Proietti[Show abstract] [Hide abstract]
ABSTRACT: Isoprostanes, neuroprostanes, isofurans, and neurofurans have all become attractive biomarkers of oxidative damage and lipid peroxidation in brain tissue. Asphyxia and subsequent reoxygenation cause a burst of oxygen free radicals. Isoprostanes and isofurans are generated by free radical attacks of esterified arachidonic acid. Neuroprostanes and neurofurans are derived from the peroxidation of docosahexanoic acid, which is abundant in neurons and could therefore more selectively represent oxidative brain injury. Newborn piglets (age 12-36 h) underwent hypoxia until the base excess reached -20 mmol/L or the mean arterial blood pressure dropped below 15 mm Hg. They were randomly assigned to receive resuscitation with 21, 40, or 100% oxygen for 30 min and then ventilation with air. The levels of isoprostanes, isofurans, neuroprostanes, and neurofurans were determined in brain tissue (ng/g) isolated from the prefrontal cortex using gas chromatography-mass spectrometry (GC/MS) with negative ion chemical ionization (NICI) techniques. A control group underwent the same procedures and observations but was not submitted to hypoxia or hyperoxia. Hypoxia and reoxygenation significantly increased the levels of isoprostanes, isofurans, neuroprostanes, and neurofurans in the cerebral cortex. Nine hours after resuscitation with 100% oxygen for 30 min, there was nearly a 4-fold increase in the levels of isoprostanes and isofurans compared to the control group (P=0.007 and P=0.001) and more than a 2-fold increase in neuroprostane levels (P=0.002). The levels of neuroprostanes and neurofurans were significantly higher in the piglets that were resuscitated with supplementary oxygen (40 and 100%) compared to the group treated with air (21%). The significance levels of the observed differences in neuroprostanes for the 21% vs 40% comparison and the 21% vs 100% comparison were P<0.001 and P=0.001, respectively. For neurofurans, the P values of the 21% vs 40% comparison and the 21% vs 100% comparison were P=0.036 and P=0.025, respectively. Supplementary oxygen used for the resuscitation of newborns increases lipid peroxidation in brain cortical neurons, a result that is indicative of oxidative brain damage. These novel findings provide new knowledge regarding the relationships between oxidative brain injury and resuscitation with oxygen.Free Radical Biology and Medicine 07/2012; 53(5):1061-7. DOI:10.1016/j.freeradbiomed.2012.07.022 · 5.71 Impact Factor
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ABSTRACT: Nox family NADPH oxidases serve a variety of functions requiring reactive oxygen species (ROS) generation, including antimicrobial defense, biosynthetic processes, oxygen sensing, and redox-based cellular signaling. We explored targeting, assembly, and activation of several Nox family oxidases, since ROS production appears to be regulated both spatially and temporally. Nox1 and Nox3 are similar to the phagocytic (Nox2-based) oxidase, functioning as multicomponent superoxide-generating enzymes. Factors regulating their activities include cytosolic activator and organizer proteins and GTP-Rac. Their regulation varies, with the following rank order: Nox2 > Nox1 > Nox3. Determinants of subcellular targeting include: (a) formation of Nox-p22(phox) heterodimeric complexes allowing plasma membrane translocation, (b) phospholipids-binding specificities of PX domain-containing organizer proteins (p47(phox) or Nox organizer 1 (Noxo1 and p40(phox)), and (c) variably splicing of Noxo1 PX domains directing them to nuclear or plasma membranes. Dual oxidases (Duox1 and Duox2) are targeted by different mechanisms. Plasma membrane targeting results in H(2)O(2) release, not superoxide, to support extracellular peroxidases. Human Duox1 and Duox2 have no demonstrable peroxidase activity, despite their extensive homology with heme peroxidases. The dual oxidases were reconstituted by Duox activator 2 (Duoxa2) or two Duoxa1 variants, which dictate maturation, subcellular localization, and the type of ROS generated by forming stable complexes with Duox.Antioxidants & Redox Signaling 05/2009; 11(10):2607-19. DOI:10.1089/ARS.2009.2637 · 7.67 Impact Factor
Article: Periodische Fieber- Syndrome[Show abstract] [Hide abstract]
ABSTRACT: Periodische Fiebersyndrome gelten seit Langem als klinische Entitäten, doch als genetische Dysfunktionen sind sie erst seit Ende des vergangenen Jahrhunderts bekannt. Inzwischen sind etwa ein halbes Dutzend pathogene Genveränderungen mit multiplen Mutationen identifiziert, die periodische Fiebersyndrome verursachen und zur wachsenden Familie der „Autoinflammatorischen Erkrankungen“ gezählt werden.