cosyntropin and Sepsis

Severe systemic infection leads to hypercortisolism. Reduced cortisol binding proteins may accentuate the free cortisol elevations seen in systemic infection. Recently, low total cortisol increments after tetracosactrin have been associated with increased mortality and hemodynamic responsiveness to exogenous hydrocortisone in septic shock (SS), a phenomenon termed by some investigators as relative adrenal insufficiency (RAI).. Free plasma cortisol may correspond more closely to illness severity than total cortisol, comparing SS and sepsis (S).. This was a prospective study.. This study took place in a tertiary teaching hospital.. Patients had SS (n = 45) or S (n = 19) or were healthy controls (HCs; n = 10).. The aim of the study was to compare total with free cortisol, measured directly and estimated by Coolens' method, corticosteroid-binding globulin (CBG), and albumin in patients with SS (with and without RAI) and S during acute illness, recovery, and convalescence.. Comparing SS, S, and HC subjects, free cortisol levels reflected illness severity more closely than total cortisol (basal free cortisol, SS, 186 vs. S, 29 vs. HC, 13 nmol/liter, P < 0.001 compared with basal total cortisol, SS, 880 vs. S, 417 vs. HC, 352 nmol/liter, P < 0.001). Stimulated free cortisol increments varied greatly with illness category (SS, 192 vs. S, 115 vs. HC, 59 nmol/liter, P = 0.004), whereas total cortisol increments did not (SS, 474 vs. S, 576 vs. HC, 524 nmol/liter, P = 0.013). The lack of increase in total cortisol with illness severity is due to lower CBG and albumin. One third of patients with SS (15 of 45) but no S patients met a recently described criterion for RAI (total cortisol increment after tetracosactrin < or = 248 nmol/liter). RAI patients had higher basal total cortisol (1157 vs. 756 nmol/liter; P = 0.028) and basal free cortisol (287 vs. 140 nmol/liter; P = 0.017) than non-RAI patients. Mean cortisol increments in RAI were lower (total, 99 vs. 648 nmol/liter, P < 0.001; free, 59 vs. 252 nmol/liter, P < 0.001). These differences were not due to altered CBG or albumin levels. Free cortisol levels normalized more promptly than total cortisol in convalescence. Calculated free cortisol by Coolens' method compared closely with measured free cortisol.. Free cortisol is likely to be a better guide to cortisolemia in systemic infection because it corresponds more closely to illness severity. The attenuated cortisol increment after tetracosactrin in RAI is not due to low cortisol-binding proteins. Free cortisol levels can be determined reliably using total cortisol and CBG levels.

Topics: Adrenal Insufficiency; Aged; Cosyntropin; Female; Humans; Hydrocortisone; Male; Microdialysis; Middle Aged; Prospective Studies; Reproducibility of Results; Sepsis; Serum Albumin; Shock, Septic; Transcortin

Cardiogenic shock shares with septic shock common hemodynamic features, inflammatory patterns, and most likely similar complications such as critical illness-related corticosteroid insufficiency. The aim of this study was to evaluate the prevalence of critical illness-related corticosteroid insufficiency in cardiogenic shock patients and to secondarily assess its prognostic value on 90-day mortality.. A single-center prospective observational study conducted over a 3-year period and including all patients with cardiogenic shock. Main exclusion criteria were patients with prior cardiac arrest, sepsis, ongoing corticosteroid therapy, and etomidate administration. A short corticotropin test was performed in the first 24 h following admission. Serum cortisol levels were measured before (T0) and 60 min (T60) after administration of 250 μg of cosyntropin. Critical illness-related corticosteroid insufficiency was defined according to the 2017 consensus definition (basal total cortisol<10 μg·dL or a delta cortisol T60-T0<9 μg·dL) as well as the thresholds published in 2016 in cardiogenic shock patients associated with worst prognosis (basal total cortisol>29 μg·dL and delta cortisol T60-T0<17 μg·dL).. Seventy-nine consecutive patients hospitalized in intensive care for cardiogenic shock met the inclusion criteria. Overall mortality was 43% at day 90. Forty-two percent had critical illness-related corticosteroid insufficiency using the 2017 consensus definition and 32% using the 2016 cardiogenic shock thresholds. Presence of critical illness-related corticosteroid insufficiency was not an independent factor associated with 90-day mortality irrespective of the thresholds used.. Critical illness-related corticosteroid insufficiency is a frequent occurrence in medical cardiogenic shock. However, in this study, such insufficiency was not associated with prognosis.

Topics: Adrenal Cortex Hormones; Aged; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Sepsis; Shock, Cardiogenic

Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects.. Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data.. Single academic medical center.. Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10).. I.v. cosyntropin (250 μg).. Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004).. Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.

Topics: Academic Medical Centers; Adrenal Cortex; Adult; Aged; Aged, 80 and over; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Male; Middle Aged; Sepsis; Serum Albumin; Shock, Septic; Transcortin

Critically ill cancer patients with sepsis represent a high-risk sub-group for the development of critical illness-related corticosteroid insufficiency (CIRCI); however, the incidence of CIRCI in this population is unknown. The purpose of this study was to determine the incidence of CIRCI in cancer patients with severe sepsis or septic shock.. A single-center, retrospective, observational study was conducted in a 52-bed medical-surgical intensive care unit of a National Cancer Institute-recognized academic oncology institution. Eighty-six consecutive patients with a diagnosis of severe sepsis or septic shock who received a high-dose 250-μg cosyntropin stimulation test were included. CIRCI was identified by a maximum delta serum cortisol of 9 μg/dL or less post cosyntropin.. Overall, 59% (95% CI, 48-70%) of cancer patients with severe sepsis or septic shock were determined to have CIRCI. When compared to patients without CIRCI, patients with CIRCI had higher baseline serum cortisol (median, 26.3 versus 14.7 μg/dL; p = 0.002) and lower delta cortisol levels (median, 3.1 versus 12.5 μg/dL; p < 0.001). Mortality did not differ between the two groups. An inverse relationship was identified between baseline serum cortisol and maximum delta cortisol (maximum delta cortisol = -0.27 × baseline cortisol + 14.30; R (2) = 0.208, p < 0.001).. The incidence of CIRCI in cancer patients with severe sepsis or septic shock appears high. Further large-scale prospective trials are needed to confirm these findings.

Topics: Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Incidence; Male; Middle Aged; Retrospective Studies; Sepsis; Severity of Illness Index; Shock, Septic; Young Adult

The aim of this study was to examine opinions and practices of US critical care practitioners (USCCPs) toward corticosteroid therapy in adult patients with severe sepsis or septic shock.. A multicenter, electronic survey of USCCP members of the Society of Critical Care Medicine was conducted between March 18 and July 31, 2009.. A total of 542 USCCPs responded to the survey. The majority (83%) do not commonly use corticosteroids in adult patients with severe sepsis; however, up to 81% report use of corticosteroids for septic shock. Twenty-eight percent believe that corticosteroids reduce mortality in septic shock, whereas 27% do not and 45% are unsure. The decision to initiate therapy is based, more often, on a patient's clinical status (65%) vs serum cortisol analysis (35%). Hydrocortisone is the most common corticosteroid prescribed (93%), with a median dosage of 200 mg/d and administration via intermittent intravenous injection. The Corticosteroid Therapy of Septic Shock trial had a large impact on survey respondents, with 62% reporting a practice change. Among the 19% of practitioners who do not prescribe corticosteroids, the most common reason was lack of proven survival benefit.. Corticosteroids are commonly used by USCCPs in adult patients with septic shock; however, criteria used to initiate therapy and opinions regarding their impact vary.

Topics: Adrenal Cortex Hormones; Cosyntropin; Decision Making; Health Personnel; Health Status; Humans; Hydrocortisone; Practice Patterns, Physicians'; Sepsis; Shock, Septic; United States

Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard.. We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency.. This was an inception cohort study.. In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11beta-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11beta-deoxycortisol levels below 7 microg/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 microg/dl), Delta cortisol (< 9 microg/dl), and free cortisol (< 2 microg/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50 (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 microg/dl or less or Delta cortisol of less than 9 microg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 microg/dl or greater and Delta cortisol of 16.8 microg/dl or greater.. In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 microg/dl or delta cortisol is less than 9 microg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 microg/dl or greater or Delta cortisol is 16.8 microg/dl or greater.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Cosyntropin; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Sepsis; Serum Albumin; Shock, Septic; Transcortin

We hypothesized that hypothyroidism and adrenal insufficiency frequently occur together in critically ill patients.. A prospective observational study.. Surgical intensive care unit of a university-affiliated tertiary referral center.. Sixty-six consecutive patients with severe sepsis, septic shock, and hemorrhagic shock who required pulmonary artery catheterization for resuscitation were studied.. Thyrotropin and baseline cortisol levels were obtained at 3 am followed by intravenous injection of 250 mug of cosyntropin, a synthetic adrenocorticotropic hormone derivative. A second measurement of the cortisol level was performed 1 hour later.. Incidence of hypothyroidism and adrenal insufficiency and mortality.. Mean (SD) age was 62 (19) years. The mean (SD) Acute Physiology and Chronic Health Evaluation II score was 21 (5). Twenty-seven patients (40.9%) had severe sepsis, 31 (46.9%) had septic shock, and 8 (12.1%) had hemorrhagic shock. Five patients (7.6%) had hypothyroidism alone and 35 (53.0%) had only adrenal insufficiency. Eight patients (12.1%) had both hypothyroidism and adrenal insufficiency. All patients with endocrine abnormalities were treated. Mortality for the total group was 15 (22.7%) of 66 patients.. There is a 12% incidence of simultaneous hypothyroidism and adrenal insufficiency in our study and the routine testing for both may be indicated in this population of critically ill patients.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Hypothyroidism; Incidence; Injections, Intravenous; Male; Middle Aged; Prospective Studies; Sepsis; Shock, Hemorrhagic; Shock, Septic; Thyrotropin; Wounds and Injuries