Related Corticosteroid Insufficiency Research Articles

Current approach to diagnosing and treating necrotizing fasciitis

Introduction: Necrotizing fasciitis is an infrequent yet highly fatal bacterial infection characterized by widespread necrosis of fascia and subcutaneous fat tissue. Though initial symptoms resemble typical infection, necrotizing fasciitis progresses rapidly triggering acute phase response. Individuals with advanced age, chronically ill, immunocompromised, or abusing alcohol are especially susceptible to developing necrotizing fasciitis. In order to reduce mortality, early diagnosis and appropriate treatment are indispensable. Aim of the Study: Aim of this study is through evaluating existing literature to outline the contemporary diagnostic strategies and emerging therapy options for necrotizing fasciitis. Description of the State of Knowledge: Primary diagnostic methods involve clinical evaluation and surgical exploration, complemented by fresh frozen sections for rapid diagnosis and the finger test. Diagnostic imaging incorporates the use of magnetic resonance imaging, computed tomography and ultrasound. The treatment is mostly centered around surgical debridement and antibiotic therapy. Therapies that display potential efficacy include low-dose radiotherapy, hyperbaric oxygen therapy, and the use of intact fish skin grafts for tissue reconstruction after successful treatment. The emerging approach includes therapy targeting systemic inflammatory response syndrome, sepsis induced coagulopathy and critical illness related corticosteroid insufficiency. Conclusions: The management of necrotizing fasciitis primarily depends on traditional methods. Fast identification and proper treatment are pivotal in reducing the mortality rate. Recognizing the significance of addressing the acute phase response in necrotizing fasciitis treatment introduces new possibilities for therapeutic interventions. Further research is vital to evaluate the existing approaches to necrotizing fasciitis management and explore new diagnoistic and therapeutic alternatives.

Profiling endogenous adrenal function during veno-venous ECMO support in COVID-19 ARDS: a descriptive analysis.

Prolonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical- illness- related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS. A total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I-IV, Ang 1-7, and Ang 1-5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity. Cortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support. Oxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI.

728: OUTCOMES AND TIMING OF STRESS-DOSE HYDROCORTISONE IN PEDIATRIC SEPTIC SHOCK

Introduction: Sepsis is a major contributor to pediatric morbidity and mortality worldwide. Pediatric sepsis is defined as systemic inflammatory response syndrome (SIRS) in the presence of suspected or confirmed infection. Pediatric septic shock is defined as sepsis with cardiovascular organ dysfunction. In vasoactive-inotropic recalcitrant septic shock, stress dose corticosteroids are often administered for presumed critical illness related corticosteroid insufficiency (CIRCI). However, there is not consistent data to support the use of stress dose hydrocortisone (HCT) in septic shock. To further investigate clinical outcomes related to timing of HCT, we hypothesized that children with vasoactive-inotropic recalcitrant septic shock who received early HCT (< 6 hours) would have lower vasoactive-inotropic scores (VIS) in the first 48 hours, a decreased length of stay (LOS) and increased ventilator-free days (VFD). Methods: A retrospective chart review was performed from November 2017 to December 2021 of subjects 0 to < 18 years, admitted to the pediatric intensive care unit (PICU) meeting the definition for septic shock, requiring vasopressors and/or inotropes and given HCT for CIRCI. We measured VIS, PICU and hospital LOS and VFD. Subjects with chronic steroid use or who received etomidate were excluded. Results: Of 227 subjects screened, 23 met criteria for analysis. Seven subjects received HCT within 6 hours of vasopressor initiation (early group), while 16 received HCT >6 hours (late group). Initial VIS average was 10.96 in the early group and 10.78 in the late group. At 48 hours, average VIS in the early group was 9.51 and 1.44 in the late group. Average PICU LOS was 15.58 for the early group and 10.82 for the late group. Average hospital LOS was 37.47 for the early group and 19.76 for the late group. VFD average was 15.32 in the early group and 16.61 in the late group. Pediatric Index of Mortality 3 (PIM-3) average in the early group was 2.02 and 1.61 in the late group. Mortality incidence was 2 in 7 in the early group, and 4 in 16 in the late group. Conclusions: Preliminary data suggests there is an increased VIS at 48 hours, increased PICU and hospital LOS, and decreased VFD with early administration of HCT. Although PIM-3 scores were higher in the early group, mortality was similar between groups.

Survival Benefit of Corticosteroid Replacement in Critically Ill Patients: One Treatment Effect or Two?

Survival benefit of corticosteroid replacement in critically ill patients: one treatment effect or two? Background: In the comparison of placebo versus corticosteroid replacement therapy (CRT) among ill patients, the treatment effect (difference in 28-day mortality rate between placebo and CRT) tends to vary according to mortality in the placebo group. In this context, we treat 28-day mortality in the placebo group as a surrogate for severity of illness [1]. Hypothesis: In the present era of physiologic CRT, critical illness related corticosteroid insufficiency (CIRCI) may be defined operationally by the difference in clinical outcomes, such as 28-day mortality, between placebo and CRT treatment groups. In this simulation analysis, we examined the hypothesis that treatment effects of CRT observed in various randomized, placebo-controlled clinical trials may be explained by heterogeneous population consisting of two strata, S1 and S2, having discrete conditional probabilities of mortality when treated with CRT vs. placebo. Methods: Using published Randomized Controlled Trial (RCT) data, the relationship between treatment effect and severity of illness was analyzed using a least squares solution weighted by sample sizes. A probability model included likelihoods for outcomes (28-day mortality with placebo vs. CRT) in two population strata: (i) a minority stratum (S1) having treatment effect > 0 and (ii) a majority stratum (S2) having a treatment effect ≤ 0. In a simple simulation scenario we varied the treatment effect in S1 as function of the placebo group mortality in S2 in order to fit the relationship obtained from published RCT data. The potential impact of sensitivity and specificity on diagnostic tests to identify S1 was also addressed. Results: A hyperbolic function (y = [Mx/(K+x)] - A) provided a good fit for published RCT trials of physiologic CRT (treatment effect [y] vs. placebo group mortality rate [x]). Pooling results for S1 and S2 having population frequencies of 0.2 and 0.8, respectively, approximated the observedhyperbolic function of treatment effects and severity of illness. A significant treatment effect was maintained when S1 was identified by diagnostic tests having 75% sensitivity-specificity. Conclusions: Population heterogeneity has not been excluded as an explanation for the relatively modest treatment effect of CRT in critically ill patients. Given the possibility of harm of CRT in the majority population (S2), our model further suggests that clinical or laboratory measures that would distinguish S1 and S2 with reasonable accuracy would significantly improve clinical outcomes and reduce numbers needed to treat. Our findings also support the more general hypothesis that the treatment effects of CRT vary according to severity of illness (1).

Retrospective evaluation of the use of hydrocortisone for treatment of suspected critical illness-related corticosteroid insufficiency (CIRCI) in dogs with septic shock (2010-2017): 47 cases.

To evaluate characteristics of septic shock patients treated with hydrocortisone (HC) due to suspicion of critical illness-related corticosteroid insufficiency (CIRCI) as compared to septic shock patients without suspicion of CIRCI. Retrospective study between February 2010 and October 2017. University teaching hospital ICU. Data were collected for 47 dogs with septic shock. Twenty-one dogs were treated with HC (HC-treated) due to suspicion of CIRCI. Twenty-six dogs did not receive HC (non-HC-treated). HC was administered either as an intermittent IV bolus or as a constant rate infusion (CRI) to those patients with suspected CIRCI. Significantly higher baseline APPLEfull scores and predicted mortality were detected in the HC-treated patients compared to non-HC-treated patients (0.87vs 0.44 for predicted mortality, P=0.039). Patients in the HC-treated group were on more vasopressors and cardiotonics than those in the non-HC-treated group (2.5vs 1.5, P<0.001). All patients initially responded to vasopressor administration, with average time to resolution of hypotension being 90 minutes for the HC-treated group compared to 60 minutes for the non-HC-treated group (P=0.640). However, HC-treated patients took significantly longer to have a sustained resolution (a systolic blood pressure>90mm Hg or a mean blood pressure>65mm Hg for at least 4h) of their hypotension after starting vasopressors, as compared to their non-HC-treated counterparts (8.5vs 4h, P=0.001). Three (14.3%) HC-treated patients survived to discharge compared to 9 (34.6%) non-HC-treated patients, but this was not statistically significant. HC-treated patients had a higher baseline risk of mortality than non-HC-treated patients. There was no significant difference in survival between the HC-treated and non-HC-treated septic shock patients. Further studies are needed to evaluate the use of HC in patients with suspected CIRCI.

Place de la corticothérapie dans le choc septique

Le sepsis est un problème de santé publique majeur, associé à une morbi-mortalité conséquente. La forme la plus sévère du sepsis, le choc septique, a une physiopathologie complexe, associant entre autres anomalies une insuffisance corticotrope et une réponse inflammatoire exagérée. Les corticoïdes, médicaments aux effets pléiotropes, corrigent cette insuffisance corticotrope et exhibent un effet anti-inflammatoire. Les corticoïdes sont à l’heure actuelle un des rares médicaments possiblement capables de réduire la mortalité dans le choc septique. S’ajoute à cet effet bénéfique sur la mortalité un effet hémodynamique favorable. L’administration de corticoïdes à faibles doses et sur une courte période est associée à remarquablement peu d’effets secondaires. Un traitement par hydrocortisone 200mg/j peut être administré chez les patients en choc septique. Nous suggérons l’administration de ce traitement en bolus intraveineux intermittent pendant sept jours sans sevrage progressif à la fin de cette période. Un minéralocorticoïde, la fludrocortisone, peut être associée au traitement par hydrocortisone dans les états de choc réfractaire. La recherche de biomarqueurs permettant d’identifier précisément une population répondant aux corticoïdes dans le choc septique est une thématique porteuse.

Critical Care Implications of Adrenal Disease States

Adrenal disease in the critically ill patient can present many challenges for the intensivist. Besides primary, secondary, and tertiary adrenal insufficiency, a state known as critical care–related corticosteroid insufficiency (CIRCI) has been described. Adrenal insufficiency can pose many issues to the critically ill patient as it can decrease the patient’s ability to respond to the stress that critical illness presents to the human body. Proper recognition and diagnosis of adrenal insufficiency in the critically ill patient can be extremely important in the treatment of these patients and could be a lifesaving intervention if CIRCI is discovered. A less commonly encountered issue of adrenal disease lies in the area of adrenal hormone excess caused by a pheochromocytoma or extra-adrenal paragangliomas. These tumors can release large amounts of endogenous catecholamines that cause significant patient morbidity and mortality if not recognized early and treated appropriately. Although adrenal insufficiency and adrenal excess are less commonly encountered problems in critically ill patients, the recognition and treatment of these disease states can prevent the morbidity and mortality of critically ill patients that suffer from these disease states. This review contains 5 figures, 5 tables, and 89 references. Key words: adrenal insufficiency, hypothalamic-pituitary axis, critical illness–related corticosteroid insufficiency, pheochromocytoma, steroid replacement therapy

Critical illness - related corticosteroid insufficiency in patients after cardiac surgery and cardiologic emergencies

Critical illness - related corticosteroid insufficiency (CIRCI) is associated with elevated level of circulating biomarkers of inflammation, pro - coagulant effects, deterioration of systemic inflammatory response syndrome (SIRS) and, consequently, prolonged in - hospital stay and increased mortality of intensive care patients. Incidence of CIRCI widely varies depending on specific patient's population and applied diagnostic thresholds being as high as 30% among postoperative patients on inotropes. CIRCI is a complex clinical and pathophysiological condition with substantial influence on immediate survival and prognosis. Clinical impact of CIRCI as well as pathogenetically based therapy arouse keen interest of intensive care specialists and clinical pathologists. The specific issues of CIRCI in patients after cardiac surgery and cardiology emergencies remain largely under - recognized, so further scrutinization is needed.

Interpretation of Society of Critical Care Medicine and European Society of Intensive Care Medicine of clinical practice guideline on critical illness related corticosteroid insufficiency in 2017

Great progress of critical illness-related corticosteroid insufficiency (CIRCI) has been made in diagnosis and treatment, but it still has high mortality. Meanwhile, corticosteroids are widely used in critically ill patients. Recently, the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) published a practice guideline which had updated the diagnosis and management of CIRCI. In order to master and promote the guideline, this article interprets the new guideline to assist Chinese clinicians for better understanding CICRI at a more comprehensive level.

Steroid Replacement in Critical Care

Corticosteroids, mainly produced by the adrenal glands, regulate the response to acute and chronic stress. Acute inflammation associated with critical illness may counteract the hypothalamic-pituitary-adrenal response, resulting in a condition called critical illness–related corticosteroid insufficiency. This condition may benefit from corticosteroid replacement. As it translates into a broad variety of clinical and biological syndromes, although there is still no gold standard, critical illness–related corticosteroid insufficiency may be best recognized by a blunted cortisol response to 250 µg of corticotropin given as an intravenous bolus. Corticosteroid replacement should rely on prolonged treatment with low to moderate doses. In practice, the type and duration of corticosteroid dose may vary with the cause of critical illness (e.g., sepsis, acute respiratory distress syndrome, trauma). Finally, optimal corticosteroid replacement should also include minimization of the risk of serious adverse events mainly by careful prevention of superinfection and avoidance of drugs that may potentiate corticosteroids’ deleterious effects on body metabolism or the nervous system. Key words: Adrenals – hypothalamic pituitary adrenal axis – sepsis – inflammation – cytokines – hydrocortisone

Changes in cortisol, adrenocorticotropic hormones in term infants with critical illness and their clinical significance

Objective To investigate the changes in cortisol, adrenocorticotropic hormones(ACTH) in term infants with critical illness and to evaluate their functional status. Methods One hundred and fifty term infants who were transferred to the hospital within 72 hours after birth were involved(gestational age≥37 weeks). These term infants were evaluated by neonatal critical illness scores(NCIS) at the time of admission, and they were divided into a mild group and a severe group according to the NCIS scores.Serum cortisol and ACTH concentrations were measured at the time of admission on day 7 and day 14 after birth. Results (1)Within 72 hours after birth, the basic serum cortisol concentration of severe illness infants[(283.5±196.0) μg/L]was significantly higher than that of the infants with mild illness[(175.0±186.5) μg/L], and there was a significant difference(t=-3.830, P=0.000). The basic serum cortisol concentration of the term infants with severe illness was higher than that of the term infants with mild illness, but there was no significant difference[7 d: (94.1±41.3) μg/L vs (62.5±37.9) μg/L, 14 d: (68.6±47.7) μg/L vs (50.9±38.4) μg/L, all P>0.05]. (2) Among the infants with critical illness, the basic serum cortisol concentration within 72 hours after birth was significantly higher than those of day 7 and day 14 after birth(t=5.994, 2.848; P=0.000, 0.036). (3)Among the mild infants, the basic serum cortisol concentration within 72 hours after birth was significantly higher than those of day 7 and day 14 after birth(t=4.691, 3.076; P=0.000, 0.037). (4)The basic serum ACTH concentrations had no significant difference between the severe group and the mild group[≤72 h: (101.55±61.52) ng/L vs (85.54±59.83) ng/L, 7 d: (54.91±22.75) ng/L vs (71.07±20.51) ng/L, 14 d: (44.67±28.30) ng/L vs (44.92±24.68)ng/L, all P>0.05]. (5)The serum cortisol and ACTH concentration within 72 hours after birth of the dead infants[(351.9±179.7) μg/L, (215.5±165.9) ng/L] were significantly higher than those of the survivors[(201.4±161.4) μg/L, (83.5±54.0) ng/L], and there were significant diffe-rences(t=-2.547, -3.833; P=0.012, 0.000). (6) The basic serum cortisol concentration within 72 hours after birth had a negative correlation with NCIS(r=-0.293, P=0.043), pH(r=-0.336, P=0.000) and base excess(BE)(r=-0.261, P=0.002); but it had a positive correlation with ACTH concentration within 72 hours after birth(r=0.443, P=0.000). The serum basic ACTH within 72 hours after birth had a negative correlation with BE(r=-0.181, P=0.031), and had positive correlation with the basic serum cortisol concentration within 72 hours and day 7(r=0.443, 0.268; P=0.000, 0.048). Conclusions The term infants have the ability to response to external stimuli by regulating cortisol secretion.The basic serum cortisol concentration of term infants is related to the critical illness.The worse the condition is, the higher the base serum cortisol concentration is. Key words: Cortisol; Adrenocorticotropic hormone; Critical illness related corticosteroid insufficiency; Term infant

Measurement of Salivary Cortisol Level for the Diagnosis of Critical Illness–Related Corticosteroid Insufficiency in Children*

To compare serum total, serum free and salivary cortisol in critically ill children. Prospective observational cohort study. Tertiary pediatric critical care unit at Ronald McDonald Children's Hospital at Loyola University Medical Center. We enrolled 59 patients (4 weeks to 18 years of age) between January 2012 and May 2013. Thirty-four patients were included in the salivary to serum free cortisol correlational analysis. Blood and saliva samples were obtained simultaneously within 24 hours of admission between the hours of 6 AM and 12 PM. Salivary cortisol was tested by liquid chromatography/tandem mass spectrometry, serum free cortisol by liquid chromatography/tandem mass spectrometry followed by equilibrium dialysis, and serum total cortisol by liquid chromatography/tandem mass spectrometry. Salivary and serum free cortisol values from 34 patients had a correlation coefficient (r) of 0.87 (95% CI, 0.75-0.93; p < 0.0001). The total serum and salivary cortisol values had a correlation coefficient (r) of 0.67 (95% CI, 0.42-0.81; p < 0.0001). The total serum and serum free cortisol values had a correlation coefficient (r) of 0.83 (95% CI, 0.69-0.91; p < 0.0001). Serum free and salivary cortisol values correlate in critically ill children. Salivary cortisol can be used as a surrogate for serum free cortisol in critically ill pediatric patients. Salivary cortisol is a cost-effective and less invasive measure of bioavailable cortisol and offers an alternate and accurate method for assessing critical illness-related corticosteroid insufficiency in children.

Stress Response and Endocrine Deregulation during Critical Illness

The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that arrive through distinct pathways. Activation of the stress system leads to behavioral and physical changes that are remarkably consistent in their qualitative presentation. The stress response is mediated largely by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, which includes the sympathetic nervous system and the adrenal medulla. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The time-limited nature of this process renders its accompanying antigrowth, antireproductive, catabolic, and immunosuppressive effects temporarily beneficial and/or of no adverse consequence to the individual. However, chronic activation of the stress system as occurs in critically ill patients may lead to a number of disorders, including stress hyperglycemia, dysfunction of the HPA and hypothalamic-pituitary-thyroid (HPT) axes, and hypothalamic-pituitary growth hormone (GH) dysfunction. These disorders are reviewed in this chapter. Diagnosis of adrenal insufficiency/critical illness–related corticosteroid insufficiency and who to treat with steroids are also covered in depth. The author emphasizes the controversial management of these deregulated hormonal axes with only limited data supporting an improvement in outcome with hormonal replacement therapy. This review contains 3 Figures, 1 Table, 39 References, 5 Board-Styled MCQs, and a Teaching Slide Set for teaching and reference purposes.

Stress Response and Endocrine Deregulation during Critical Illness

The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that arrive through distinct pathways. Activation of the stress system leads to behavioral and physical changes that are remarkably consistent in their qualitative presentation. The stress response is mediated largely by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, which includes the sympathetic nervous system and the adrenal medulla. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The time-limited nature of this process renders its accompanying antigrowth, antireproductive, catabolic, and immunosuppressive effects temporarily beneficial and/or of no adverse consequence to the individual. However, chronic activation of the stress system as occurs in critically ill patients may lead to a number of disorders, including stress hyperglycemia, dysfunction of the HPA and hypothalamic-pituitary-thyroid (HPT) axes, and hypothalamic-pituitary growth hormone (GH) dysfunction. These disorders are reviewed in this chapter. Diagnosis of adrenal insufficiency/critical illness–related corticosteroid insufficiency and who to treat with steroids are also covered in depth. The author emphasizes the controversial management of these deregulated hormonal axes with only limited data supporting an improvement in outcome with hormonal replacement therapy. This review contains 3 Figures, 1 Table, 39 References, 5 Board-Styled MCQs, and a Teaching Slide Set for teaching and reference purposes.

Critical Illness – Related Corticosteroid Insufficiency

In some acute critical illnesses, the function of Hypothalamus-Pituitary-Adrenal axis can be impaired. This event is called "Critical Illness-Related Corticosteroid Insufficiency" (CIRCI). We conducted a study to determine which of the CIRCI patients need steroid therapy. This study was performed on patients who were admitted in Pediatric Intensive Care Unit (PICU) in Nemazee Hospital, affiliated to Shiraz University of Medical Sciences, Iran.&#x0D; In first 24 hour of PICU admission, Serum cortisol levels were measured immediately before, 30 and 60 minutes after IV administration of 250 μg of synthetic adrenocorticotropic hormone (Synacthen®).Their clinical conditions and paraclinical data were followed and recorded. Twenty four patients were enrolled in the study. Twelve patients (50%) had CIRCI. CIRCI was defined as Random Serum Cortisol (RSC)&lt;10 μg/dl or elevation of serum cortisol level after Synacthen administration below 9 µg/dl.The results of serum cortisol level usually were ready one day after blood sampling. Based on general condition, blood pressure and serum electrolyte levels, all CIRCI patients were improved when serum cortisol levels were determined. Therefore, steroid therapy was not started for them. Finally, all of the CIRCI patients improved and after a few days, all of them were discharged from the hospital with good conditions. Findings of our study showed that corticosteroid therapy is not needed as a routine treatment for CIRCI patients. This is in agreement with some other studies. but in contrast to some articles who recommended corticosteroid therapy for patients with CIRCI. There is lack of consensus about optimal approach to CIRCI in children, therefor; well-designed RCTs and systematic reviews are needed to determine proper treatment recommendations for these critically ill children before administration.

Critical illness-related corticosteroid insufficiency in cirrhotic patients with acute gastroesophageal variceal bleeding: risk factors and association with outcome*.

Critical illness-related corticosteroid insufficiency can adversely influence the prognosis of critically ill patients. However, its impact on the outcomes of patients with cirrhosis and acute gastroesophageal variceal bleeding remains unknown. We evaluated adrenal function using short corticotropin stimulation test in patients with cirrhosis and gastroesophageal variceal bleeding. The main outcomes analyzed were 5-day treatment failure and 6-week mortality. Prospective observational study. Ten-bed gastroenterology-specific medical ICU at a 3,613-bed university teaching hospital in Taiwan. Patients with liver cirrhosis and acute gastroesophageal variceal bleeding. None. We evaluated adrenal function using short corticotropin stimulation test in 157 episodes of gastroesophageal variceal bleeding in 143 patients with cirrhosis. Critical illness-related corticosteroid insufficiency occurred in 29.9% of patients. The patients with critical illness-related corticosteroid insufficiency had higher rates of treatment failure and 6-week mortality (63.8% vs 10.9%, 42.6% vs 6.4%, respectively; p < 0.001). The cumulative rates of survival at 6 weeks were 57.4% and 93.6% for the critical illness-related corticosteroid insufficiency group and normal adrenal function group, respectively (p < 0.001). The cortisol response to corticotropin was inversely correlated with Model for End-Stage Liver Disease and Child-Pugh scores and positively correlated with the levels of high-density lipoprotein and total cholesterol. Hypovolemic shock, high-density lipoprotein, platelet count, and bacterial infection at inclusion are independent factors predicting critical illness-related corticosteroid insufficiency, whereas critical illness-related corticosteroid insufficiency, Model for End-Stage Liver Disease score, hypovolemic shock, hepatocellular carcinoma, and active bleeding at endoscopy are independent factors to predict treatment failure. Multivariate analysis also identified Model for End-Stage Liver Disease score, hypovolemic shock, and bacterial infection at inclusion as independent factors associated with 6-week mortality. Critical illness-related corticosteroid insufficiency is common in cirrhotic patients with acute gastroesophageal variceal bleeding and is an independent factor to predict 5-day treatment failure.

Critical illness–related corticosteroid insufficiency after multiple traumas

Given that the observed prevalence and time course of critical illness-related corticosteroid insufficiency (CIRCI) remain inconsistent in trauma patients, the present study was designed to investigate the prevalence, time course, and effect of CIRCI on the outcome of critically ill patients with multiple injuries. In this multicenter, prospective cohort study, patients with multiple injuries in seven intensive care units in China were enrolled. Adrenocorticotropic hormone (ACTH) stimulation tests were performed by administering intravenously 250 μg of synthetic ACTH on Days 1, 2, 3, 5, and 7 after traumatic injury. CIRCI was defined as baseline cortisol level of less than 10 μg/dL or a Δcortisol (difference baseline and highest cortisol level at 30 or 60 minutes after ACTH stimulation) less than 9 μg/dL. The incidence and time course of CIRCI and 28-day mortality were recorded. CIRCI occurred in 54.3% (38 of 70) of the patients with multiple injuries, including 10 patients with total cortisol level of less than 10 μg/dL and 28 patients with Δcortisol of less than 9 μg/dL. Most (94.7%) diagnosis of CIRCI was made in the first 48 hours after traumatic injury. The CIRCI patients had significantly more severe illness on the day of admission. At each time point, the baseline cortisol level was comparable between the CIRCI and non-CIRCI patients, while Δcortisol in the CIRCI group was significantly lower compared with the non-CIRCI group. The CIRCI patients with a Δcortisol of less than 9 μg/dL had a significantly higher 28-day mortality (39.3%) compared with those with a baseline cortisol level of less than 10 μg/dL (10.0%) and non-CIRCI patients (6.3%). Only Δcortisol of less than 9 μg/dL but not baseline cortisol level of less than 10 μg/dL seemed to be an independent risk factor for death (odds ratio, 1.19; p = 0.023). CIRCI is common in critically ill trauma population and usually occurs in the early stages. Only the results of the ACTH stimulation test but not baseline cortisol level was associated with poor prognosis. Prognostic study, level II.

Acute neuro-endocrine profile and prediction of outcome after severe brain injury.

ObjectThe aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome.MethodsProspective study, including consecutive patients, 15–70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08–10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17–19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E.ResultsProfound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH- and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated.ConclusionProfound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.

Detection of Critical Illness–Related Corticosteroid Insufficiency Using 1 μg Adrenocorticotropic Hormone Test

Our objectives were to determine the incidence of critical illness-related corticosteroid insufficiency (CIRCI) in patients with septic shock using a 1 μg corticotropin (ACTH) test and to describe their clinical outcomes. We retrospectively identified 219 consecutive patients with septic shock assessed for CIRCI with a 1 μg ACTH test. Standardized testing involved plasma cortisol measurements at baseline (T0) and at 30 min (T30) and 60 min (T60) after ACTH administration. The maximal increase in cortisol (Δ max) was calculated as the difference between T0 and the highest cortisol value at T30 or T60. Critical illness-related corticosteroid insufficiency was defined as Δ max less than 9 μg/dL after ACTH administration. The mean age of the cohort was 63.0 ± 15.8 years, mean Acute Physiology and Chronic Health Evaluation II score was 26.3 ± 8.1, 85.6% were mechanically ventilated, and the mean number of organ failures was 3.0 ± 1.2. Critical illness-related corticosteroid insufficiency was diagnosed in 70.8% of patients. Twenty-eight-day mortality was highest in patients with baseline cortisol greater than 65 μg/dL (62.5%) and in those with baseline cortisol 34 μg/dL or greater and Δ max less than 9 μg/dL (50.0%). There was no difference in mortality in patients with and without CIRCI (53.9% vs. 36.4%, P = 0.08). Corticosteroids were administered to 69.4% of patients for 5.3 ± 3.6 days. For patients with CIRCI, intensive care unit mortality was similar for those who received corticosteroids compared with those who did not (46.0% vs. 25.0%, P = 0.166). The incidence of CIRCI based on 1 μg ACTH was high in this septic shock cohort. The highest mortality rates were observed in patients with high baseline cortisol and in those who failed to respond appropriately to ACTH. The administration of corticosteroids was not associated with a reduction in mortality.

Update on adrenal insufficiency in patients with liver cirrhosis.

Liver cirrhosis is a major cause of mortality worldwide, often with severe sepsis as the terminal event. Over the last two decades, several studies have reported that in septic patients the adrenal glands respond inappropriately to stimulation, and that the treatment with corticosteroids decreases mortality in such patients. Both cirrhosis and septic shock share many hemodynamic abnormalities such as hyperdynamic circulatory failure, decreased peripheral vascular resistance, increased cardiac output, hypo-responsiveness to vasopressors, increased levels of proinflammatory cytokines [interleukine(IL)-1, IL-6, tumor necrosis factor-alpha] and it has, consequently, been reported that adrenal insufficiency (AI) is common in critically ill cirrhotic patients. AI may also be present in patients with stable cirrhosis without sepsis and in those undergoing liver transplantation. The term hepato-adrenal syndrome defines AI in patients with advanced liver disease with sepsis and/or other complications, and it suggests that it could be a feature of liver disease per se, with a different pathogenesis from that of septic shock. Relative AI is the term given to inadequate cortisol response to stress. More recently, another term is used, namely "critical illness related corticosteroid insufficiency" to define "an inadequate cellular corticosteroid activity for the severity of the patient's illness". The mechanisms of AI in liver cirrhosis are not completely understood, although decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested. The prevalence of AI in cirrhotic patients varies widely according to the stage of the liver disease (compensated or decompensated, with or without sepsis), the diagnostic criteria defining AI and the methodology used. The effects of corticosteroid therapy on cirrhotic patients with septic shock and AI are controversial. This review aims to summarize the existing published information regarding AI in patients with liver cirrhosis.