• Elisabeth Knöller, Tatjana Stenzel, Friederike Broeskamp, Rouven Hornung, Angelika Scheuerle, Oscar McCook, Ulrich Wachter, Josef A Vogt, José Matallo, Martin Wepler, Holger Gässler, Michael Gröger, Martin Matejovic, Enrico Calzia, Lorenz Lampl, Michael Georgieff, Peter Möller, Pierre Asfar, Peter Radermacher, and Sebastian Hafner.
• 1Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm, Ulm, Germany. 2Institut für Pathologie, Universitätsklinikum Ulm, Ulm, Germany. 3Klinik für Anästhesiologie, Universitätsklinikum Ulm, Ulm, Germany. 4Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. 5Abteilung X Anästhesie und Intensivmedizin, Bundeswehrkrankenhaus Ulm, Ulm, Germany. 6Department of Internal Medicine I, Biomedical Centre and Karlova Univerzita Praha, Plzeň, Czech Republic. 7Laboratoire HIFIH, UPRES EA 3859, PRES l'UNAM, IFR 132, CNRS UMR 6214, INSERM U1083, Université Angers, Angers, France. 8Département de Réanimation Médicale et de Médecine Hyperbare, Centre Hospitalier Universitaire, Angers, France.
• Crit. Care Med. 2016 May 1; 44 (5): e264-77.

ObjectiveHemorrhagic shock-induced tissue hypoxia induces hyperinflammation, ultimately causing multiple organ failure. Hyperoxia and hypothermia can attenuate tissue hypoxia due to increased oxygen supply and decreased demand, respectively. Therefore, we tested the hypothesis whether mild therapeutic hypothermia and hyperoxia would attenuate postshock hyperinflammation and thereby organ dysfunction.DesignProspective, controlled, randomized study.SettingUniversity animal research laboratory.SubjectsThirty-six Bretoncelles-Meishan-Willebrand pigs of either gender.InterventionsAfter 4 hours of hemorrhagic shock (removal of 30% of the blood volume, subsequent titration of mean arterial pressure at 35 mm Hg), anesthetized and instrumented pigs were randomly assigned to "control" (standard resuscitation: retransfusion of shed blood, fluid resuscitation, norepinephrine titrated to maintain mean arterial pressure at preshock values, mechanical ventilation titrated to maintain arterial oxygen saturation > 90%), "hyperoxia" (standard resuscitation, but FIO2, 1.0), "hypothermia" (standard resuscitation, but core temperature 34°C), or "combi" (hyperoxia plus hypothermia) (n = 9 each).Measurements And Main ResultsBefore, immediately at the end of and 12 and 22 hours after hemorrhagic shock, we measured hemodynamics, blood gases, acid-base status, metabolism, organ function, cytokine production, and coagulation. Postmortem kidney specimen were taken for histological evaluation, immunohistochemistry (nitrotyrosine, cystathionine γ-lyase, activated caspase-3, and extravascular albumin), and immunoblotting (nuclear factor-κB, hypoxia-inducible factor-1α, heme oxygenase-1, inducible nitric oxide synthase, B-cell lymphoma-extra large, and protein expression of the endogenous nuclear factor-κB inhibitor). Although hyperoxia alone attenuated the postshock hyperinflammation and thereby tended to improve visceral organ function, hypothermia and combi treatment had no beneficial effect.ConclusionsDuring resuscitation from near-lethal hemorrhagic shock, hyperoxia attenuated hyperinflammation, and thereby showed a favorable trend toward improved organ function. The lacking efficacy of hypothermia was most likely due to more pronounced barrier dysfunction with vascular leakage-induced circulatory failure.

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