Uticaj promene reaktivnosti hipotalamo-hipofizno-adrenalne osovine na ishod kod bolesnika sa sistemskim inflamatornim odgovorom

Abstract

Uvod: Sindrom sistemskog inflamatornog odgovora (SIRS) predstavlja inflamatorno stanje uzrokovano infekcijom ili sepsom i koje se širi na ceo organizam. SIRS se smatra delom „citokinske oluje“ i manifestuje se disregulacijom različiutih citokina. Ozbiljnost bolesti se najbolje prediktuje korišćenjem APACHE II skora (Acute Physiology and Chronic Health Evaluation II) dok se ishod kod pacijenta, odnosno organska disfunkcija ili insuficijencija prediktuje pomoću SOFA skora (Sequential Organ Failure Assessment). SIRS dovodi do značajnih promena u dinamici kortizola ukazujući na disocijaciju između adrenalnog korteksa i hipotalamo-hipofizne jedinice. Navedena promena se manifestuje visokim koncentracijama kortizola i ACTH odmah nakon početka SIRS-a. Međutim, nekoliko dana kasnije, ACTH se spušta do veoma niskih koncentracija dok koncentracije kortizola ostaju visoke. Navedeno se objašnjava direktnim efektom citokina, kao što je interleukin 6 (IL-6), na koru nadbubrega koji stimulišu oslobađanje glukokortikoida. Odgovor kortizola na stimulaciju sa ACTH predstavlja važan prediktor ishoda kod kritično bolesnih. Bolesnici sa neadekvatnim odgovorom kortizola na stimulaciju sa ACTH imaju visoku stopu mortaliteta. Stimulacija sa 250 μg ACTH se smatra zlatnim standardom u proceni adrenalne funkcije. Međutim, niskodozni test sa 1 μg ACTH (NDT) predstavlja senzitivniji test u detekciji specifičnih formi adrenalne insuficijencije kao što je hipotalamo-hipofizna disfunkcija. Upotreba NDT u kritično obolelih nije jasno definisana jer postoji mali broj podataka za formiranje jasne preporuke...

Introduction: Systemic inflammatory response syndrome (SIRS) represens inflamatory condition caused bz infection or sepsis that spreads all over the body. SIRS is considered a part of the „cytokine storm“ and is manifested by dysregulation of different cytokines. The severity of the disease is best predicted using Acute Physiology and Chronic Health Evaluation II (APACHE II) score while the patient’s outcome, namely organ dysfunction/failure during Intensive Care Unit (ICU) monitoring is predicted using Sequential Organ Failure Assessment (SOFA) score. SIRS leads to significant changes in cortisol dynamics indicating on the disociation between adrenal cortex and the hypothalamo-pituitary unit. This is manifested by the very high concentrations of cortisol and ACTH immediatly after commencement of SIRS. However, a few days later ACTH falls to the very low concentration while the concentrations of cortisol remains high. This is explained by direct effect of cytokines, as it is interleukin 6 (IL-6), on the adrenal cortex that is simulating glucocorticoid realease. Cortisol response on the stimulation with ACTH was shown to be important predictor of the outcome in critically ill patients. Patients with inadequate cortisol response on stimulation with ACTH had high mortality rate. Stimulation with 250 μg of ACTH is considered to be gold standard test for the assessment of adrenal function. However, the low-dose (1 μg) test (LDT) represents a more sensitive test for detecting specific forms of adrenal insufficiency as it is hypothalamo-pituitary disfunction. The use of LDT in critically ill patients is not clearly defined as the data on LDT are limited and not sufficient for the clear recommendation...