***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT AND OBJECTIVE Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome ( MODS ) and death . Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock , with the aim of halting the progression towards MODS and death . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study , developed in a surgical intensive care unit at Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo . METHODS The study involved 29 patients with septic shock . All eligible patients were prospect ively r and omized to receive either a dose of 0.2 mg/kg of dexamethasone ( group D ) or placebo ( group P ) , given three times at intervals of 36 hours . The patients were monitored over a seven-day period by means of the sequential organ failure assessment score . RESULTS Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group ( p = 0.043 ) . Seven-day mortality was 67 % in group P ( 10 out of 15 ) and 21 % in group D ( 3 out of 14 ) ( relative risk = 0.31 , 95 % confidence interval 0.11 to 0.88 ) . Dexamethasone enhanced the effects of vasopressor drugs . CONCLUSIONS Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality CONTEXT Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock . In addition , the benefit of adding fludrocortisone in this setting is unclear . OBJECTIVES To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone  and to assess , as a secondary objective , the benefit of fludrocortisone . DESIGN , SETTING , AND PATIENTS A multicenter , 2 x 2 factorial , r and omized trial , involving 509 adults with septic shock who presented with multiple organ dysfunction , as defined by a Sequential Organ Failure Assessment score of 8 or more , and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France . INTERVENTIONS Patients were r and omly assigned to 1 of 4 groups : continuous intravenous insulin infusion with hydrocortisone alone , continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone , conventional insulin therapy with hydrocortisone alone , or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone . Hydrocortisone was administered in a 50-mg bolus every 6 hours , and fludrocortisone was administered orally in 50-microg tablets once a day , each for 7 days . MAIN OUTCOME MEASURE In-hospital mortality . RESULTS Of the 255 patients treated with intensive insulin , 117 ( 45.9 % ) , and 109 of 254 ( 42.9 % ) treated with conventional insulin therapy died ( relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 0.88 - 1.30 ; P = .50 ) . Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia ( < 40 mg/dL ) than those in the conventional-treatment group , with a difference in mean number of episodes per patient of 0.15 ( 95 % CI , 0.02 - 0.28 ; P = .003 ) . At hospital discharge , 105 of 245 patients treated with fludrocortisone ( 42.9 % ) died and 121 of 264 ( 45.8 % ) in the control group died ( RR , 0.94 ; 95 % CI , 0.77 - 1.14 ; P = .50 ) . CONCLUSIONS Compared with conventional insulin therapy , intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock . The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00320099 Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis . However , the effect of corticosteroid replacement on mortality in this high-risk group remains unclear . We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock . Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a r and omized double-blind placebo-controlled trial . Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin . Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved , followed by steroid tapering over eight days . The primary outcome was 28-day all-cause mortality . Results The trial was stopped for futility at interim analysis after 75 patients were enrolled . Relative adrenal insufficiency was diagnosed in 76 % of patients . Compared with the placebo group ( n = 36 ) , patients in the hydrocortisone group ( n = 39 ) had a significant reduction in vasopressor doses and higher rates of shock reversal ( relative risk [ RR ] 1.58 , 95 % confidence interval [ CI ] 0.98–2.55 , p = 0.05 ) . Hydrocortisone use was not associated with a reduction in 28-day mortality ( RR 1.17 , 95 % CI 0.92–1.49 , p = 0.19 ) but was associated with an increase in shock relapse ( RR 2.58 , 95 % CI 1.04–6.45 , p = 0.03 ) and gastrointestinal bleeding ( RR 3.00 , 95 % CI 1.08–8.36 , p = 0.02 ) . Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock . Despite initial favourable effects on hemodynamic  parameters , hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects . ( Current Controlled Trials registry no. IS RCT N99675218 . Abstract . Objective : To study the time course of corticosteroid binding-globulin ( CBG ) level and the free cortisol index ( FCI ) in comparison with total cortisol and ACTH concentrations during acute and prolonged critical illness . Design : Prospect i ve observational clinical study . Setting : Twenty-bed medical/surgical intensive care unit . Patients and participants : Thirty patients with septic shock , eight patients with multitrauma , and forty healthy control subjects . Measurements and results : During 14 days or until discharge/death , we serially measured serum concentrations of CBG , cortisol , TNF-α , IL-6 , plasma ACTH immunoreactivity , and the FCI  ( = cortisol/CBG × 100 ) . We also recorded haemodynamic parameters , APACHE II , ISS , SOFA scores , shock duration , inotrope use , and ICU mortality . In both groups we found markedly decreased CBG levels in the early phase ( septic shock : 17.5±5.9 , and trauma : 16.1±2.3 mg/l ) in comparison with controls ( 37.3±5.3 mg/l ) . The FCI was high in this early phase ( septic shock : 7.2±2.7 ; trauma : 6.5±1.3 ; controls : 1.25±0.76 ) . During follow-up , CBG levels significantly increased , reaching normal levels from day 7 on . The FCI showed an opposite biphasic pattern , with near-normalising FCI values during the second phase . Regression analysis showed a negative correlation between CBG and IL-6 levels ( rs=–0.63 ; P<0.05 ) , but no relation between CBG concentrations and disease severity , shock duration or death was found . Conclusions : We found extremely low CBG levels in early stage septic shock and multitrauma . These dramatic changes are reflected in a concomitant higher FCI , indicating a higher free cortisol level . A second phase displays increasing and normalising CBG levels , independent from clinical parameters . We believe that CBG plays an active role in the glucocorticoid response to severe stress and in the regulation of cortisol availability to target tissues Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin , and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis . Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients . One group ( 20 patients ) received st and ard therapy for sepsis and physiological-dose steroid therapy for 10 days ; the other group ( 20 patients ) received only st and ard therapy for sepsis .  Basal cortisol level was measured on the 14th day in patients who recovered . The outcome of sepsis was compared . Results Only Sequential Organ Failure Assessment ( SOFA ) score was found related to mortality , independent from other factors in multivariate analysis . No significant difference was found between the changes in the percentage of SOFA scores of the  steroid therapy group and the st and ard therapy group in survivors , nor between the groups in basal and peak cortisol levels , cortisol response to corticotropin test and mortality . The mortality rates among patients with occult adrenal insufficiencies were 40 % in the steroid therapy group and 55.6 % in the st and ard therapy group . Discussion There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy . In the advancing process from sepsis to septic shock , adrenal insufficiency was not frequent as supposed . There was a trend ( that did not reach significance ) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy Objective : To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients . Participants : A multidisciplinary , multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine . In addition , international experts in endocrinology were invited to participate . Design / Methods : The task force members review ed published literature and provided expert opinion from which the consensus was derived . The consensus statements were developed using a modified Delphi methodology . The strength of each recommendation was quantified using the Modified GRADE system , which classifies recommendations as strong ( grade 1 ) or weak ( grade 2 ) and the quality of evidence as high ( grade A ) , moderate ( grade B ) , or low ( grade C ) based on factors that include the study design , the consistency of the results , and the directness of the evidence . Results : The task force coined the term critical illness – related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness . Critical illness – related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response . Critical illness – related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents , particularly in the setting of sepsis . At this time , the diagnosis of tissue corticosteroid resistance remains problematic . Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 & mgr;g/dL after adrenocorticotrophic hormone ( 250 & mgr;g ) administration or a r and om total cortisol of < 10 & mgr;g/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome ( Pao2/Fio2 of < 200 and within 14 days of onset ) . The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids . Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day ( 10 mg/hr ) for ≥7 days is recommended for septic shock . Methylprednisolone in a dose of 1 mg·kg−1·day−1 for ≥14 days is recommended in patients with severe early acute respiratory distress syndrome . Glucocorticoids should be weaned and not stopped abruptly . Reinstitution of treatment should be considered with recurrence of signs of sepsis , hypotension , or worsening oxygenation .  D 
    Output:
    
Network meta- analysis provided no clear evidence that any intervention or treatment regimen is better than any other across the spectrum of outcomes .
There was strong evidence of differential efficacy in only one area : shock reversal .
Hydrocortisone boluses and infusions were more likely than methylprednisolone boluses and placebo to result in shock reversal .
Conclusions There was no clear evidence that any one corticosteroid drug or treatment regimen is more likely to be effective in reducing mortality or reducing the incidence of gastrointestinal bleeding or superinfection in septic shock .
Hydrocortisone delivered as a bolus or as an infusion was more likely than placebo and methylprednisolone to result in shock reversal