Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study

Abstract

IntroductionAdrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase.MethodsWe prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests.ResultsPatients with low (<250 nM) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar.ConclusionsEven though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

“…The lower the cost of an intervention compared to the alternative and other costs related to the decision-i.e., fewer resources consumed-the more likely a strong recommendation prospective cohort studies in adults with or without sepsis [11] and in patients with multiple trauma [12] found that patients with CIRCI, i.e., total cortisol levels <10 µg/ dl or delta cortisol <9 µg/dl, had poorer outcomes than patients without CIRCI. Likewise, a large multicenter prospective cohort study found that critically ill children with a delta cortisol <9 µg/dl after the low-dose ACTH stimulation test required higher-dose and prolonged treatment with catecholamines, a higher amount of fluid, and had a higher mortality rate [13].…”

Fluid Overload Is Associated With Late Poor Outcomes in Neonates Following Cardiac Surgery*

“…In a prospective trial, Ricci et al randomized infants with congenital heart disease to receive either furosemide or ethacrynic acid following elective cardiac surgery. They found that ethacrynic acid was slightly more effective at augmenting urine output without any significant differences in post-operative serum creatinine or incidence of AKI (based on pRIFLE) (31). In a study of 30 pediatric patients with congestive heart failure already receiving inotropic and diuretic therapy, administration of synthetic B-type natriuretic peptide resulted in improved diuresis without significant increase in S Cr (32).…”

Strain Echocardiography Parameters Correlate With Disease Severity in Children and Infants With Sepsis*

“…Consequently recommendations in the Surviving Sepsis Guidelines emphasize the importance of lactate clearance during the resuscitation of septic patients [18]. Associations between depressed SE parameters and lactate in this study may lend insights on the mechanical contribution of cardiac dysfunction to hyperlactatemia in the context of the current literature [34, 35, 42]. Therefore further investigation into the utility of SE as a noninvasive assessment tool for cardiac function in children with sepsis is potentially useful.…”