S-Adenosylhomocysteine Is a Useful Metabolic Factor in the Early Prediction of Septic Disease Progression and Death in Critically Ill Patients: A Prospective Cohort Study

Abstract

A common final pathway of pathogenetic mechanisms in septic organ dysfunction and death is a lack or non-utilization of oxygen. Plasma concentrations of lactate serve as surrogates for the oxygen-deficiency-induced imbalance between energy supply and demand. As S-adenosylhomocysteine (SAH) was shown to reflect tissue hypoxia, we compared the ability of SAH versus lactate to predict the progression of inflammatory and septic disease to septic organ dysfunction and death. Using univariate and multiple logistic regression, we found that SAH but not lactate, taken upon patients’ inclusion in the study close to ICU admission, significantly and independently contributed to the prediction of disease progression and death. Due to the stronger increase in SAH in relation to S-adenosylmethionine (SAM), the ratio of SAM to SAH, representing methylation potential, was significantly decreased in patients with septic organ dysfunction and non-survivors compared with SIRS/sepsis patients (2.8 (IQR 2.3–3.9) vs. 8.8 (4.9–13.8); p = 0.003) or survivors (4.9 (2.8–9.5) vs. 8.9 (5.1–14.3); p = 0.026), respectively. Thus, SAH appears to be a better contributor to the prediction of septic organ dysfunction and death than lactate in critically ill patients. As SAH is a potent inhibitor of SAM-dependent methyltransferases involved in numerous vital biochemical processes, the impairment of the SAM-to-SAH ratio in severely critically ill septic patients and non-survivors warrants further studies on the pathogenetic role of SAH in septic multiple organ failure.

Predicting Critically Ill Patients Outcome in the ICU using UHPLC-HRMS Data

“…When it comes to the metabolites that were up-regulated in deceased patients, S-adenosyl-Lhomocysteine has emerged as a biomarker for severe sepsis and systemic inflammatory response syndrome in the ICU. Elevated levels of this biomarker, linked to tissue hypoxia, predict disease severity and outcome [15]. (R)-lactate and pyruvate are associated with unfavorable clinical outcomes and an increased risk of ICU mortality, particularly when present in high concentrations.…”

Mortality Prediction by Kinetic Parameters of Lactate and S-Adenosylhomocysteine in a Cohort of Critically Ill Patients

“…In the search for an alternative marker for hypoxia in critically ill patients, in addition to its association with an elevated risk of cardiovascular disease [ 37 , 38 ] and renal disease in diabetic nephropathy [ 39 ] and chronic kidney disease [ 40 ], SAH has also emerged as a metabolite reflecting tissue hypoxia [ 26 , 27 , 28 , 41 ]. Hypoxia causes the breakdown of energy-rich adenine nucleotides, leading to an intracellular accumulation of adenosine [ 27 ].…”

“…Adenosine reacts with L-homocysteine to form stable SAH [ 42 ]. Thus, SAH is considered to be a marker for a lack of perfusion-dependent oxygen supply and hence tissue hypoxia [ 26 , 27 , 28 , 41 ]. SAH was found to be a highly sensitive marker for myocardial ischemia [ 26 ].…”

“…S-adenosylhomocysteine (SAH) is another metabolite that reflects tissue hypoxia [ 26 , 27 ]. Recently, it was shown that SAH allowed for improved prediction of septic organ dysfunction and death compared with lactate when using a single value close to ICU admission [ 28 ]. To the best of our knowledge, the kinetic parameters of SAH like mean, maximum, and normalized area score have not been evaluated for mortality prediction before.…”

Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator

“…The study population was a subgroup of a 99-patient cohort recruited at the anesthesiology-led interdisciplinary surgical ICU of a tertiary care hospital (University Medical Center Mannheim) between June 2017 and May 2019 as reported (39). Briefly, for cohort inclusion F.S.C.…”