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Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update.

ABSTRACT: This review summarizes the (patho)-physiological effects of ventilation with high FiO2 (0.8-1.0), with a special focus on the most recent clinical evidence on its use for the management of circulatory shock and during medical emergencies. Hyperoxia is a cornerstone of the acute management of circulatory shock, a concept which is based on compelling experimental evidence that compensating the imbalance between O2 supply and requirements (i.e., the oxygen dept) is crucial for survival, at least after trauma. On the other hand, "oxygen toxicity" due to the increased formation of reactive oxygen species limits its use, because it may cause serious deleterious side effects, especially in conditions of ischemia/reperfusion. While these effects are particularly pronounced during long-term administration, i.e., beyond 12-24 h, several retrospective studies suggest that even hyperoxemia of shorter duration is also associated with increased mortality and morbidity. In fact, albeit the clinical evidence from prospective studies is surprisingly scarce, a recent meta-analysis suggests that hyperoxia is associated with increased mortality at least in patients after cardiac arrest, stroke, and traumatic brain injury. Most of these data, however, originate from heterogenous, observational studies with inconsistent results, and therefore, there is a need for the results from the large scale, randomized, controlled clinical trials on the use of hyperoxia, which can be anticipated within the next 2-3 years. Consequently, until then, "conservative" O2 therapy, i.e., targeting an arterial hemoglobin O2 saturation of 88-95 % as suggested by the guidelines of the ARDS Network and the Surviving Sepsis Campaign, represents the treatment of choice to avoid exposure to both hypoxemia and excess hyperoxemia.

SUBMITTER: Hafner S

PROVIDER: S-EPMC4653126 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update.

Hafner Sebastian S Beloncle François F Koch Andreas A Radermacher Peter P Asfar Pierre P

Annals of intensive care 20151119 1

This review summarizes the (patho)-physiological effects of ventilation with high FiO2 (0.8-1.0), with a special focus on the most recent clinical evidence on its use for the management of circulatory shock and during medical emergencies. Hyperoxia is a cornerstone of the acute management of circulatory shock, a concept which is based on compelling experimental evidence that compensating the imbalance between O2 supply and requirements (i.e., the oxygen dept) is crucial for survival, at least af ...[more]

PMID: 26585328

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Project description:Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde's two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

Dataset Information

Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update.

Publications

Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update.

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