Proven infection-related sepsis induces a differential stress response early after ICU admission

Abstract

IntroductionNeuropeptides arginine-vasopressin (AVP), apelin (APL), and stromal-derived factor-1α (SDF-1α) are involved in the dysfunction of the corticotropic axis observed in septic ICU patients. Study aims were: (i) to portray a distinctive stress-related neuro-corticotropic systemic profile of early sepsis, (ii) to propose a combination data score, for aiding ICU physicians in diagnosing sepsis on admission.MethodsThis prospective one-center observational study was carried out in a medical intensive care unit (MICU), tertiary teaching hospital. Seventy-four out of 112 critically ill patients exhibiting systemic inflammatory response syndrome (SIRS) were divided into two groups: proven sepsis and non sepsis, based on post hoc analysis of microbiological criteria and final diagnosis, and compared to healthy volunteers (n = 14). A single blood sampling was performed on admission for measurements of AVP, copeptin, APL, SDF-1α, adrenocorticotropic hormone (ACTH), cortisol baseline and post-stimulation, and procalcitonin (PCT).ResultsBlood baseline ACTH/cortisol ratio was lower and copeptin higher in septic vs. nonseptic patients. SDF-1α was further increased in septic patients vs. normal patients. Cortisol baseline, ACTH, PCT, APACHE II and sepsis scores, and shock on admission, were independent predictors of sepsis diagnosis upon admission. Using the three first aforementioned categorical bio-parameters, a probability score for predicting sepsis yielded an area under the Receiver Operating Curve (ROC) curves better than sepsis score or PCT alone (0.903 vs 0.727 and 0.726: P = 0.005 and P < 0.04, respectively).ConclusionsThe stress response of early admitted ICU patients is different in septic vs. non-septic conditions. A proposed combination of variable score analyses will tentatively help in refining bedside diagnostic tools to efficiently diagnose sepsis after further validation.

The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF)

“…Serum concentrations of D-DT and MIF were measured in 85 healthy individuals and in 37 septic patients hospitalized in the medical intensive care unit (56). The median APACHE II score at the time of intensive care unit admission was 22 points (range: 10−36 points).…”

Copeptin as a diagnostic biomarker for sepsis-related deaths

“…Most related deaths result from multiple organ dysfunction/failure occurring in advanced stages of septic shock [12].…”

“…Numerous pathophysiological mechanisms have been postulated as contributing to cardiovascular failure in patients with severe sepsis and septic shock. Vascular tone loss and the subsequent decrease in arterial blood pressure and tissue perfusion were indicated as the result of an altered balance of endogenous vasopressor/vasodilator mediators, qualitative and quantitative downregulation of endogenous vasoconstrictor hormone receptors, and inappropriately low levels of neuroendocrine stress hormones, such as arginine vasopressin (AVP) and cortisol [5,6,12,14,21,27].…”

Selective Histone Deacetylase-6 Inhibition Attenuates Stress Responses and Prevents Immune Organ Atrophy in a Lethal Septic Model

“…6 Septic patients exhibit higher baseline cortisol levels and decreased blood ACTH-to-cortisol ratio, compared to non-septic patients. 24 The pituitary gland is activated through systematic proinflammatory mediators and complex interactions between the autonomic nervous system and the immune cells. 25 Within a few minutes of onset, sepsis induces the secretion of ACTH, growth hormone and prolactin, and inhibits the secretion of luteinizing and thyroid-stimulatory hormones.…”