Abstract
BackgroundAdrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality.MethodsA cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated.ResultsLevels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold.ConclusionsMR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.
Highlights
Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system
As septic shock still accounts for an unacceptable number of deaths in the critically ill, we reasoned that a biomarker strategy using a combination of clinical, biochemical, and physiological parameters focusing on the circulatory system may be one way of stratifying very highrisk patients
The aim of this study was to test whether MR-proADM and CT-proET-1 are associated with myocardial injury, measured using transthoracic echocardiography and High-sensitivity troponin T (hsTNT) in patients with septic shock
Summary
Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. Whilst numerous studies have investigated novel biomarkers to diagnose and risk-stratify patients with sepsis, none have become universally accepted and few have focused on the circulatory system per se. Endothelial activation is a hallmark of sepsis and thought to play a key role in the pathophysiology of septic shock In this regard, three novel biomarkers have been described that may have contributory and/or predictive roles in the development of circulatory failure – midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and high-sensitivity troponin T (hsTNT). In the largest study to date, Guignant et al [7] showed that increased plasma MRproADM was associated with 28-day mortality
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