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Potentially modifiable factors contributing to sepsis-associated encephalopathy

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Abstract

Purpose

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes.

Methods

We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively.

Results

We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19–1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27–5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09–1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53–2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48–3.57), and S. aureus (aOR = 1.54, 95% CI 1.05–2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13–14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09–1.76).

Conclusions

Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

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Acknowledgements

Members of the OUTCOMEREA Study Group.

Scientific committee: Jean-François Timsit (Medical and Infectious Diseases ICU, Bichat-Claude Bernard Hospital, Paris, France; UMR 1137 Inserm–Paris Diderot university IAME, 75018, Paris); Elie Azoulay (Medical ICU, Saint Louis Hospital, Paris, France); Maïté Garrouste-Orgeas (ICU, Saint-Joseph Hospital, Paris, France); Jean-Ralph Zahar (Infection Control Unit, Angers Hospital, Angers, France); Christophe Adrie (Physiology, Cochin Hospital, Paris, France); Michael Darmon (Medical ICU, Saint Etienne University Hospital, St Etienne, France); and Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, and UMR 1137 Inserm –Paris Diderot university IAME, 75018, Paris, France).

Biostatistical and information system expertise: Jean-Francois Timsit (Medical and Infectious Diseases ICU, Bichat-Claude Bernard Hospital, Paris, France; UMR 1137 Inserm–Paris Diderot university IAME, 75018, Paris); Corinne Alberti (Medical Computer Sciences and Biostatistics Department, Robert Debré Hospital, Paris, France); Adrien Français (Integrated Research Center U823, Grenoble, France); Aurélien Vesin (OUTCOMEREA organization and Integrated Research Center U823, Grenoble, France); Stephane Ruckly (OUTCOMEREA organization and Inserm UMR 1137 IAME, 75018, Paris); Sébastien Bailly (Grenoble university hospital Inserm UMR 1137 IAME, 75018, Paris) and Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, and Inserm UMR 1137 IAME, 75018, Paris, France); Frederik Lecorre (Supelec, France); Didier Nakache (Conservatoire National des Arts et Métiers, Paris, France); and Aurélien Vannieuwenhuyze (Tourcoing, France).

Investigators of the OUTCOMEREA database: Christophe Adrie (ICU, CH Melun, and Physiology, Cochin Hospital, Paris, France); Carole Agasse (medical ICU, university hospital Nantes, France); Bernard Allaouchiche (ICU, Pierre benite Hospital, Lyon, France); Olivier Andremont (ICU, Bichat Hospital, Paris, France); Pascal Andreu (CHU Dijon, Dijon, France); Laurent Argaud (Medical ICU, Hospices Civils de Lyon, Lyon, France); Claire Ara-Somohano (Medical ICU, University Hospital, Grenoble, France); Elie Azoulay (Medical ICU, Saint Louis Hospital, Paris, France); Francois Barbier (medical-surgical ICU, Orleans, France), Jean-Pierre Bedos (ICU, Versailles Hospital, Versailles, France); Jérome Bedel (ICU, Versailles Hospital, Versailles, France), Julien Bohé (ICU, Hôpital Pierre Benite, Lyon France), Lila Bouadma (ICU, Bichat Hospital, Paris, France); Noel Brule (medical ICU, university hospital Nantes, France); Cédirc Brétonnière (medical ICU, university hospital Nantes, France); Christine Cheval (ICU, Hyeres Hospital, Hyeres, France); Christophe Clec’h (ICU, Avicenne Hospital, Bobigny, France); Elisabeth Coupez (ICU, G Montpied Hospital, Clermont-Ferrand, France); Michael Darmon (ICU, Saint Etienne Hospital, Saint Etienne, France); Etienne de Montmollin (ICU, Delafontaine Hospital, Saint Denis), Loa Dopeux (ICU, G Montpied Hospital, Clermont-Ferrand, France); Anne-Sylvie Dumenil (Antoine Béclère Hospital, Clamart, France); Claire Dupuis (Bichat hospital and UMR 1137 Inserm–Paris Diderot university IAME, 75018, Paris, France), Jean-Marc Forel (AP HM, Medical ICU, Hôpital Nord Marseille), Marc Gainnier (la Timone hospital, Marseille, France), Charlotte Garret (medical ICU, university hospital Nantes, France); Antoine Gros (ICU, Versailles Hospital, Versailles, France), Akim Haouache (Surgical ICU, H Mondor Hospital, Creteil, France); Romain Hernu (Medical ICU, Hospices Civils de Lyon, Lyon, France); Samir Jamali (ICU, Dourdan, Dourdan Hospital, Dourdan, France); Sébastien Jochmans (ICU, CH Melun); Jean-Baptiste Joffredo (ICU, G Montpied Hospital, Clermont-Ferrand, France); Hatem Khallel (ICU, Cayenne General Hospital, Cayenne, France); Guillaume Lacave (ICU, Versailles Hospital, Versailles, France), Alexandre Lautrette (ICU, G Montpied Hospital, Clermont-Ferrand, France); Virgine Lemiale (Medical ICU, Saint Louis Hospital, Paris, France); Mathilde Lermuzeaux (ICU, Bichat Hospital, Paris, France), Guillaume Marcotte (Surgical ICU, Hospices Civils de Lyon, Lyon, France); Eric Le Miere (ICU, Louis Mourier Hospital, Colombes, France); Jordane Lebut (ICU, Bichat Hospital, Paris, France); Maxime Lugosi (Medical ICU, University Hospital Grenoble, Grenoble, France); Eric Magalhaes (ICU, Bichat Hospital, Paris, France), Sibylle Merceron (ICU, Versailles Hospital, Versailles, France), Bruno Mourvillier (ICU, Bichat Hospital, Paris, France); Benoît Misset (ICU, Saint-Joseph Hospital, Paris, France); Delphine Moreau (ICU, Saint-Louis Hospital, Paris, France); Bruno Mourvillier (ICU, Bichat Hospital, Paris, France); Mathild Neuville (ICU, Bichat Hospital, Paris, France), Laurent Nicolet (medical ICU, university hospital Nantes, France); Laurent Papazian (Hopital Nord, Marseille, France), Benjamin Planquette (pulmonology ICU, George Pompidou hospital Hospital, Paris, France); Jean-Pierre Quenot Pascal Andreu (CHU Dijon, Dijon, France); Aguila Radjou (ICU, Bichat Hospital, Paris, France), Romain Sonneville (ICU, Bichat Hospital, Paris, France), Jean Reignier (medical ICU, university hospital Nantes, France); Bertrand Souweine (ICU, G Montpied Hospital, Clermont-Ferrand, France); Carole Schwebel (ICU, A Michallon Hospital, Grenoble, France); Roland Smonig (ICU, Bichat Hospital, Paris, France); Gilles Troché (ICU, Antoine Béclère Hospital, Clamart, France); Marie Thuong (ICU, Delafontaine Hospital, Saint Denis, France); Guillaume Thierry (ICU, Saint-Louis Hospital, Paris, France); Dany Toledano (ICU, Gonesse Hospital, Gonesse, France); Guillaume Van Der Meersch –Medical Surgical ICU, university hospital Avicenne), Marion Venot (Medical ICU, Saint Louis Hospital, Paris, France); Olivier Zambon (medical ICU, university hospital Nantes, France);.

Study monitors: Julien Fournier, Caroline Tournegros, Stéphanie Bagur, Mireille Adda, Vanessa Vindrieux, Sylvie de la Salle, Loic Ferrand, Stéphane Guessens, Helene Merle, Nadira Kaddour, Boris Berthe, Samir Bekkhouche, Kaouttar Mellouk, Mélaine Lebrazic, Carole Ouisse, Diane Maugars, Sylvie Conrozier, Igor Theodose, Manal Nouacer, Veronique Deiler, Myriam Moussa, Atika Mouaci Nassima Viguier and Sophie Letrou.

Authors’ contributions

Design and conduct of the study: R. Sonneville, S. Ruckly, and J.F. Timsit. Collection of the data: J. Poujade, M. Garrouste-Orgeas, B. Souweine, M. Darmon, E. Mariotte, L. Argaud, F. Barbier, D. Goldgran-Toledano, G. Marcotte, AS Dumenil, S. Jamali, V. Laurent, B. Mourvillier, and JF. Timsit. Management, analysis and interpretation of the data: R. Sonneville, E. de Montmollin, S. Ruckly, and J.F. Timsit. Manuscript preparation: R. Sonneville, E. de Montmollin, S. Ruckly, and J.F. Timsit. Critical revision and approval of the manuscript: All authors.

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Correspondence to Romain Sonneville.

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Take-home message:

Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy.

A list of members of the OUTCOMEREA study group is given in the Acknowledgements.

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Sonneville, R., de Montmollin, E., Poujade, J. et al. Potentially modifiable factors contributing to sepsis-associated encephalopathy. Intensive Care Med 43, 1075–1084 (2017). https://doi.org/10.1007/s00134-017-4807-z

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