Blood Lactate/ATP Ratio, as an Alarm Index and Real-Time Biomarker in Critical Illness

Abstract

ObjectiveThe 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.Methods and ResultsBlood 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.ConclusionBlood 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.

Sepsis impairs microvascular autoregulation and delays capillary response within hypoxic capillaries

“…However, we found the opposite as ATP efflux decreased in hypoxic septic RBCs. Consistent with this inhibition of RBC ATP efflux and decreased plasma ATP levels in septic rats is the finding that plasma ATP levels are decreased in critically ill patients [ 35 ].…”

Mitochondria Are Gate-keepers of T Cell Function by Producing the ATP That Drives Purinergic Signaling

“…We found that mitochondrial activity in lymphocytes of septic patients is impaired, which may be an underlying cause of T cell suppression in these patients. This notion is supported by findings that oxygen consumption of peripheral blood mononuclear cells is lower in sepsis patients than in patients without sepsis (48,49) and that the cellular ATP content of circulating cells is lower and lactate levels are higher in sepsis patients compared with patients without sepsis (50).…”

A Simple Method for Measuring Adenosine Triphosphate in Acute Cholangitis Patients to Determine the Need for Emergency Biliary Drainage

“…Blood cells become diluted by transfusion, and a low red blood cell (RBC) count is usually found in patients with advanced disease, resulting in a low blood level of ATP in those who are severely ill (11). Since the major source of ATP in blood is RBCs, the blood ATP levels in the present study were normalized by the level of tHgb (ATP/tHgb).…”

“…Indeed, blood ATP depletion has been identified in children with influenza-associated acute encephalopathy (9). Although released ATP cannot be accurately analyzed due to rapid degradation, the cellular ATP level, including the blood cell ATP level, is easily measured with a bedside procedure that uses the sum of ATP production and ATP degradation and/or release (10, 11).…”