Corticosteroids for severe sepsis: an evidence-based guide for physicians

Septic shock is characterized by uncontrolled systemic inflammation that contributes to the progression of organ failures and eventually death. There is now ample evidence that the inability of the host to mount an appropriate hypothalamic-pituitary and adrenal axis response plays a major in overwhelming systemic inflammation during infections. Proinflammatory mediators released in the inflamed sites oppose to the anti-inflammatory response, an effect that may be reversed by exogenous corticosteroids. With sepsis, via nongenomic and genomic effects, corticosteroids restore cardiovascular homeostasis, terminate systemic and tissue inflammation, restore organ function, and prevent death. These effects of corticosteroids have been consistently found in animal studies and in most recent frequentist and Bayesian meta-analyses. Corticosteroids should be initiated only in patients with sepsis who require 0.5 μg/kg per minute or more of norepinephrine and should be continued for 5 to 7 days except in patients with poor hemodynamic response after 2 days of corticosteroids and with a cortisol increment of more than 250 nmol/L after a standard adrenocorticotropin hormone (ACTH) test. Hydrocortisone should be given at a daily dose of 200 mg and preferably combined to enteral fludrocortisone at a dose of 50 μg. Blood glucose levels should be kept below 150 mg/dL

Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

BACKGROUND: The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. CASE PRESENTATION: Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD). A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. CONCLUSION: Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully

Corticotherapy for traumatic brain-injured Patients - The Corti-TC trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury (TBI) is a main cause of severe prolonged disability of young patients. Hospital acquired pneumonia (HAP) add to the morbidity and mortality of traumatic brain-injured patients. In one study, hydrocortisone for treatment of traumatic-induced corticosteroid insufficiency (CI) in multiple injured patients has prevented HAP, particularly in the sub-group of patients with severe TBI. Fludrocortisone is recommended in severe brain-injured patients suffering from acute subarachnoid hemorrhage. Whether an association of hydrocortisone with fludrocortisone protects from HAP and improves neurological recovery is uncertain. The aim of the current study is to compare corticotherapy to placebo for TBI patients with CI.</p> <p>Methods</p> <p>The CORTI-TC (Corticotherapy in traumatic brain-injured patients) trial is a multicenter, randomized, placebo controlled, double-blind, two-arms study. Three hundred and seventy six patients hospitalized in Intensive Care Unit with a severe traumatic brain injury (Glasgow Coma Scale ≤ 8) are randomized in the first 24 hours following trauma to hydrocortisone (200 mg.day^-1for 7 days, 100 mg on days 8-9 and 50 mg on day-10) with fludrocortisone (50 μg for 10 days) or double placebo. The treatment is stopped if patients have an appropriate adrenal response. The primary endpoint is HAP on day-28. The endpoint of the ancillary study is the neurological status on 6 and 12 months.</p> <p>Discussion</p> <p>The CORTI-TC trial is the first randomized controlled trial powered to investigate whether hydrocortisone with fludrocortisone in TBI patients with CI prevent HAP and improve long term recovery.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01093261">NCT01093261</a></p

Academic conflict of interest

PURPOSE: We set out to summarize the current challenges in academic conflict of interest. METHODS: This is a narrative review by a multidisciplinary, multinational panel of academic officers including deans of medical/pharmacy schools. RESULTS AND CONCLUSIONS: Disclosing conflict of interest has become the appropriate professional behavior since the 1990s in response to the necessity to fix moral and financial fences around medical activities. The nature of the conflict of interest is academic when either the conflict relates to academic duties and/or the nature of the interest is academic. People usually distinguish between real conflict of interest, when private interest overtly influences one\u27s professional obligations; potential conflict of interest, when there is no obvious direct link between a person interests and current duties without ruling out that expected changes in duties cause a situation of conflict; and apparent conflict of interest, when the risk does not really exist, but serious doubts remain. Areas at risk of academic conflict of interest include peer review process for grant evaluation or journals, scientific communications such as elaborating and disseminating clinical guidelines, lecturing at meeting, advising decision-makers, teaching activities, and mentoring. The management of academic conflict of interest should consider actions in four domains, i.e., education, prevention, measures for enforcement and solving, and communication. Academic conflicts of interest are as frequent as financial conflicts but more difficult to identify and assess, and much less addressed in the literature. Generating more evidence from high-quality research is mandated to improve the management of academic and more generally non-financial conflicts of interest

Serum macrophage migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients: an observational study

<p>Abstract</p> <p>Background</p> <p>The hypothalamo-pituitary-adrenal (HPA) axis modulates the inflammatory response during sepsis. Macrophage migration inhibitory factor (MIF), which counteracts the anti-inflammatory activity of glucocorticoid (GC), is one of the mediators of the development of inflammation. An inflammatory imbalance involving GC and MIF might be the cause or result of adrenal insufficiency. Our objective was to clarify the relationship between serum MIF and adrenal function in the HPA axis of sepsis patients using the adrenocorticotropic hormone (ACTH) stimulation test.</p> <p>Methods</p> <p>An observational study was performed in a university intensive care unit over a two-year period. Of 64 consecutive sepsis patients, 41 were enrolled. The enrolled patients underwent an ACTH stimulation test within 24 h of the diagnosis of severe sepsis or septic shock. Clinical and laboratory parameters, including serum MIF and cortisol, were measured.</p> <p>Results</p> <p>Based on their responses to the ACTH stimulation test, the patients were divided into a normal adrenal response (NAR) group (n = 22) and an adrenal insufficiency (AI) group (n = 19). The AI group had significantly more septic shock patients and higher prothrombin time ratios, serum MIF, and baseline cortisol than did the NAR group (<it>P </it>< 0.05). Serum MIF correlated significantly with the SOFA (Sequential Organ Failure Assessment) score, prothrombin time ratio, and delta max cortisol, which is maximum increment of serum cortisol concentration after ACTH stimulation test (rs = 0.414, 0.355, and -0.49, respectively, <it>P </it>< 0.05). Serum MIF also correlated significantly with the delta max cortisol/albumin ratio (rs = -0.501, <it>P </it>= 0.001). Receiver operating characteristic curve analysis identified the threshold serum MIF concentration (19.5 ng/mL, <it>P </it>= 0.01) that segregated patients into the NAR and AI groups.</p> <p>Conclusions</p> <p>The inverse correlation between serum MIF and delta max cortisol or the delta max cortisol/albumin ratio suggests that high serum MIF reflects an insufficient adrenal response in the HPA axis. Serum MIF could be a valuable clinical marker of adrenal insufficiency in sepsis patients.</p