Septic shock with no diagnosis at 24 hours: a pragmatic multicenter prospective cohort study.
BACKGROUND
The lack of a patent source of infection after 24 hours of management of shock considered septic is a common and disturbing scenario. We aimed to determine the prevalence and the causes of shock with no diagnosis 24 hours after its onset, and to compare the outcomes of patients with early-confirmed septic shock to those of others.


METHODS
We conducted a pragmatic, prospective, multicenter observational cohort study in ten intensive care units (ICU) in France. We included all consecutive patients admitted to the ICU with suspected septic shock defined by clinical suspicion of infection leading to antibiotic prescription plus acute circulatory failure requiring vasopressor support.


RESULTS
A total of 508 patients were admitted with suspected septic shock. Among them, 374 (74 %) had early-confirmed septic shock, while the 134 others (26 %) had no source of infection identified nor microbiological documentation retrieved 24 hours after shock onset. Among these, 37/134 (28 %) had late-confirmed septic shock diagnosed after 24 hours, 59/134 (44 %) had a condition mimicking septic (septic shock mimicker, mainly related to adverse drug reactions, acute mesenteric ischemia and malignancies) and 38/134 (28 %) had shock of unknown origin by the end of the ICU stay. There were no differences between patients with early-confirmed septic shock and the remainder in ICU mortality and the median duration of ICU stay, of tracheal intubation and of vasopressor support. The multivariable Cox model showed that the risk of day-60 mortality did not differ between patients with or without early-confirmed septic shock. A sensitivity analysis was performed in the subgroup (n = 369/508) of patients meeting the Sepsis-3 definition criteria and displayed consistent results.


CONCLUSIONS
One quarter of the patients admitted in the ICU with suspected septic shock had no infection identified 24 hours after its onset and almost half of them were eventually diagnosed with a septic shock mimicker. Outcome did not differ between patients with early-confirmed septic shock and other patients.
Service de réanimation Médicale, Groupe de Recherche CARMAS, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France. damien.contou@aphp.fr.|INSERM U955, Institut Mondor de Recherche Biomedicale, Equipe 8, Faculté de Médecine de Créteil, Université Paris Est-Créteil, Créteil, France. damien.contou@aphp.fr.
Damien
D
Contou
Service de réanimation médico-chirurgicale, Centre Hospitalier Universitaire Louis Mourier, Assistance Publique-Hôpitaux de Paris, 178 rue des Renouillers, Colombes, 92700, France.
Damien
D
Roux
Service de réanimation, Centre Hospitalier Marc Jacquet, 2 rue Fréteau de Peny, Melun, 77011, France.
Sébastien
S
Jochmans
Service de réanimation médicale, Centre Hospitalier Universitaire de Poitiers, 2 rue de la Milétrie, Poitiers, 86021, France.
Rémi
R
Coudroy
Service de réanimation médicale, Centre Hospitalier Universitaire Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 20 rue Leblanc, Paris, 75015, France.
Emmanuel
E
Guérot
Service de réanimation médico-chirurgicale, Centre Hospitalier André Mignot, 177 rue de Versailles, Le Chesnay, 78150, France.
David
D
Grimaldi
Service de réanimation, Centre Hospitalier Robert Ballanger, Boulevard Robert Ballanger, Aulnay-sous-Bois, 93600, France.
Sylvie
S
Ricome
Service de réanimation médicale, Centre Hospitalier Universitaire Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 184 rue du Faubourg Saint-Antoine, Paris, 75012, France.
Eric
E
Maury
Service de réanimation polyvalente, Centre Hospitalier Victor Dupouy, 69 rue du Lieutenant-Colonel Prudhon, Argenteuil, 95107, France.
Gaëtan
G
Plantefève
Service de réanimation médicale, Centre Hospitalier Universitaire Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
Julien
J
Mayaux
Service de réanimation Médicale, Groupe de Recherche CARMAS, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France.|INSERM U955, Institut Mondor de Recherche Biomedicale, Equipe 8, Faculté de Médecine de Créteil, Université Paris Est-Créteil, Créteil, France.
Armand
A
Mekontso Dessap
Service de réanimation Médicale, Groupe de Recherche CARMAS, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France.|INSERM U955, Institut Mondor de Recherche Biomedicale, Equipe 8, Faculté de Médecine de Créteil, Université Paris Est-Créteil, Créteil, France.
Christian
C
Brun-Buisson
Service de réanimation Médicale, Groupe de Recherche CARMAS, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France.|INSERM U955, Institut Mondor de Recherche Biomedicale, Equipe 8, Faculté de Médecine de Créteil, Université Paris Est-Créteil, Créteil, France.
Nicolas
N
de Prost
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015331:Cohort Studies; D003422:Critical Care / Q000379:methods / Q000639:trends; D005602:France / Q000453:epidemiology; D007362:Intensive Care Units / Q000639:trends; D009026:Mortality / Q000639:trends; D011446:Prospective Studies; D012307:Risk Factors; D012772:Shock, Septic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D061665:Time-to-Treatment / Q000639:trends
Acute mesenteric ischemia; Intensive care; Sepsis; Sepsis mimickers; Septic shock