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Ann Intensive Care. 2018 Sep 17;8(1):90. doi: 10.1186/s13613-018-0435-1.

Hyperoxia toxicity in septic shock patients according to the Sepsis-3 criteria: a post hoc analysis of the HYPER2S trial.

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Médecine Intensive et Réanimation, Médecine Hyperbare, Centre Hospitalier Universitaire, 4, Rue Larrey, 49933, Angers Cedex 9, France.
LUNAM Université, Université d'Angers, Angers, France.
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Helmholtzstrasse 8-1, 89081, Ulm, Germany.
Klinik für Anästhesiologie, Abteilung Klinische Anästhesiologie, Universitätsklinikum, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Helmholtzstrasse 8-1, 89081, Ulm, Germany.
Service de Réanimation Adulte, Centre Hospitalier Intercommunal de Créteil, 40, Avenue de Verdun, 94010, Créteil Cedex, France.
Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, Service de Réanimation, Nouvel Hôpital Civil, Université de Strasbourg (UNISTRA), Strasbourg, France.
INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France.
Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK.



Criteria for the Sepsis-3 definition of septic shock include vasopressor treatment to maintain a mean arterial pressure > 65 mmHg and a lactate concentration > 2 mmol/L. The impact of hyperoxia in patients with septic shock using these criteria is unknown.


A post hoc analysis was performed of the HYPER2S trial assessing hyperoxia versus normoxia in septic patients requiring vasopressor therapy, in whom a plasma lactate value was available at study inclusion. Mortality was compared between patients fulfilling the Sepsis-3 septic shock criteria and patients requiring vasopressors for hypotension only (i.e., with lactate ≤ 2 mmol/L).


Of the 434 patients enrolled, 397 had available data for lactate at inclusion. 230 had lactate > 2 mmol/L and 167 ≤ 2 mmol/L. Among patients with lactate > 2 mmol/L, 108 and 122 were "hyperoxia"- and "normoxia"-treated, respectively. Patients with lactate > 2 mmol/L had significantly less COPD more cirrhosis and required surgery more frequently. They also had higher illness severity (SOFA 10.6 ± 2.8 vs. 9.5 ± 2.5, p = 0.0001), required more renal replacement therapy (RRT), and received vasopressor and mechanical ventilation for longer time. Mortality rate at day 28 was higher in the "hyperoxia"-treated patients with lactate > 2 mmol/L as compared to "normoxia"-treated patients (57.4% vs. 44.3%, p = 0.054), despite similar RRT requirements as well as vasopressor and mechanical ventilation-free days. A multivariate analysis showed an independent association between hyperoxia and mortality at day 28 and 90. In patients with lactate ≤ 2 mmol/L, hyperoxia had no effect on mortality nor on other outcomes.


Our results suggest that hyperoxia may be associated with a higher mortality rate in patients with septic shock using the Sepsis-3 criteria, but not in patients with hypotension alone.


Hyperlactatemia; Hyperoxia; Oxygen extraction; Oxygen transport; Sepsis-3; Septic shock

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