title: Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.
abstract: Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy.
authors: Politecnico di Milano, Milan, Italy.
authors: Manuela
authors: M
authors: Ferrario
authors: Politecnico di Milano, Milan, Italy.
authors: Alice
authors: A
authors: Cambiaghi
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Laura
authors: L
authors: Brunelli
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Silvia
authors: S
authors: Giordano
authors: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda -Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.|Dipartimento di Anestesia, Rianimazione, ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors: Pietro
authors: P
authors: Caironi
authors: Azienda Ospedaliera di Desio, Desio, Italy.
authors: Luca
authors: L
authors: Guatteri
authors: Azienda Ospedaliera Luigi Sacco, Milan, Italy.
authors: Ferdinando
authors: F
authors: Raimondi
authors: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda -Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.|Dipartimento di Anestesia, Rianimazione, ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors: Luciano
authors: L
authors: Gattinoni
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Roberto
authors: R
authors: Latini
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Serge
authors: S
authors: Masson
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Giuseppe
authors: G
authors: Ristagno
authors: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors: Roberta
authors: R
authors: Pastorelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D015331:Cohort Studies; D005260:Female; D020404:Glycerophospholipids / Q000097:blood; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D006801:Humans; D007362:Intensive Care Units; D007737:Kynurenine / Q000097:blood; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D010865:Pilot Projects; D012772:Shock, Septic / Q000382:microbiology / Q000401:mortality* / Q000473:pathology; D013107:Sphingolipids / Q000097:blood; D016019:Survival Analysis
chemical_list: D000596:Amino Acids; D020404:Glycerophospholipids; D013107:Sphingolipids; C116917:acylcarnitine; D007737:Kynurenine; D002331:Carnitine