title: Blood lactate/ATP ratio, as an alarm index and real-time biomarker in critical illness.
abstract: OBJECTIVE
  The acute physiology, age and chronic health evaluation (APACHE) II score and other related scores have been used for evaluation of illness severity in the intensive care unit (ICU), but there is still a need for real-time and sensitive prognostic biomarkers. Recently, alarmins from damaged tissues have been reported as alarm-signaling molecules. Although ATP is a member of the alarmins and its depletion in tissues closely correlates with multiple-organ failure, blood ATP level has not been evaluated in critical illness. To identify real-time prognostic biomarker of critical illness, we measured blood ATP levels and the lactate/ATP ratio (ATP-lactate energy risk score, A-LES) in critically ill patients.
  
  
  RESULTS
  Blood samples were collected from 42 consecutive critically ill ICU patients and 155 healthy subjects. The prognostic values of blood ATP levels and A-LES were compared with APACHE II score. The mean ATP level (SD) in healthy subjects was 0.62 (0.19) mM with no significant age or gender differences. The median ATP level in severely ill patients at ICU admission was significantly low at 0.31 mM (interquartile range 0.25 to 0.44) than the level in moderately ill patient at 0.56 mM (0.38 to 0.70) (P<0.01). Assessment with ATP was further corrected by lactate and expressed as A-LES. The median A-LES was 2.7 (2.1 to 3.3) in patients with satisfactory outcome at discharge but was significantly higher in non-survivors at 38.9 (21.0 to 67.9) (P<0.01). Receiver operating characteristic analysis indicated that measurement of blood ATP and A-LES at ICU admission are as useful as APACHE II score for prediction of mortality.
  
  
  CONCLUSIONS
  Blood ATP levels and A-LES are sensitive prognostic biomarkers of mortality at ICU admission. In addition, A-LES provided further real-time evaluation score of illness severity during ICU stay particularly for critically ill patients with APACHE II scores of ≥20.0.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Chida
authors.forename: Rie
authors.initials: R
authors.lastname: Ono
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamane
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Hiyoshi
authors.forename: Masaji
authors.initials: M
authors.lastname: Nishimura
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Onodera
authors.forename: Emiko
authors.initials: E
authors.lastname: Nakataki
authors.forename: Koichi
authors.initials: K
authors.lastname: Shichijo
authors.forename: Masatami
authors.initials: M
authors.lastname: Matushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D004734:Energy Metabolism; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007362:Intensive Care Units; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012016:Reference Values; D012306:Risk; D013997:Time Factors; D014680:Veins / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D019344:Lactic Acid; D000255:Adenosine Triphosphate