Use of Hydrocortisone Based on Plasma Biomarkers in Patients with Septic Shock: Another One Bites the Dust?
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ABSTRACT:
SUBMITTER: Moller MH
PROVIDER: S-EPMC7462389 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Use of Hydrocortisone Based on Plasma Biomarkers in Patients with Septic Shock: Another One Bites the Dust?
Møller Morten Hylander MH Shankar-Hari Manu M Alhazzani Waleed W
American journal of respiratory and critical care medicine 20200901 5
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| S-EPMC2999976 | biostudies-literature
Project description:ImportancePatients with septic shock may benefit from the initiation of corticosteroids. However, the comparative effectiveness of the 2 most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs hydrocortisone alone) is unclear.ObjectiveTo compare the effectiveness of adding fludrocortisone to hydrocortisone vs hydrocortisone alone among patients with septic shock using target trial emulation.Design, setting, and participantsThis retrospective cohort study from 2016 to 2020 used the enhanced claims-based Premier Healthcare Database, which included approximately 25% of US hospitalizations. Participants were adult patients hospitalized with septic shock and receiving norepinephrine who began hydrocortisone treatment. Data analysis was performed from May 2022 to December 2022.ExposureAddition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated vs use of hydrocortisone alone.Main outcome and measuresComposite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation.ResultsAnalyses included 88 275 patients, 2280 who began treatment with hydrocortisone-fludrocortisone (median [IQR] age, 64 [54-73] years; 1041 female; 1239 male) and 85 995 (median [IQR] age, 67 [57-76] years; 42 136 female; 43 859 male) who began treatment with hydrocortisone alone. The primary composite outcome of death in hospital or discharge to hospice occurred among 1076 (47.2%) patients treated with hydrocortisone-fludrocortisone vs 43 669 (50.8%) treated with hydrocortisone alone (adjusted absolute risk difference, -3.7%; 95% CI, -4.2% to -3.1%; P < .001).Conclusions and relevanceIn this comparative effectiveness cohort study among adult patients with septic shock who began hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.
| S-EPMC10043800 | biostudies-literature
Project description:In patients with septic shock, hydrocortisone 200-400?mg/d has been shown to reverse shock compared with placebo. Lower doses of hydrocortisone have not previously been studied, and there are no previous studies comparing two different doses of hydrocortisone. At our institution, some clinicians routinely prescribe doses less than 200?mg/d. This study aims to compare the effect of lower doses of hydrocortisone to standard doses on shock reversal and adverse events in septic shock. Design:Retrospective cohort study. Setting:Single-center medical ICU. Subjects:Patients who received hydrocortisone for septic shock. Interventions:Electronic chart review. Measurements and Main Results:Patients were divided into low-dose hydrocortisone (75-150?mg/d) and standard-dose hydrocortisone (200-400?mg/d) cohorts based on initial prescribed hydrocortisone dose. Rates of shock reversal and adverse events in the two cohorts were compared. Two-hundred thirteen patients were included-41 in low-dose and 172 in standard-dose cohorts. Baseline characteristics including initial vasopressor requirement and Sequential Organ Failure Assessment scores were similar. Average rates of change in vasopressor needs, conditional hazard rate for vasopressor withdrawal, and cumulative probability for vasopressor withdrawal were all quantitatively similar for low-dose and standard-dose hydrocortisone. Insulin requirement (particularly in those with diabetes mellitus), blood glucose in those with diabetes mellitus, and frequency of secondary infections seemed to be lower in the low-dose hydrocortisone cohort. Mortality and other secondary outcomes were similar. Conclusions:In septic shock, hydrocortisone dosed 75-150 mg/d appears to reverse shock as effectively 200-400 mg/d and may cause a lower frequency of adverse events.
| S-EPMC7188423 | biostudies-literature
Project description:AimCombined hydrocortisone and fludrocortisone therapy for septic shock has not been evaluated with an independent systematic review. We aimed to elucidate the beneficial effects of a dual corticosteroid treatment regime involving both hydrocortisone and fludrocortisone for adult patients with septic shock on mortality.MethodsWe searched the Medline, Cochrane CENTRAL, and ICHUSHI databases for reports published before April 2019. We included randomized controlled trials that compared the use of both hydrocortisone and fludrocortisone with either corticosteroid-free or hydrocortisone-only treatments on adult patients with septic shock. Three researchers independently reviewed the studies. The meta-analyses were undertaken to assess primary outcome (28-day mortality) and secondary outcomes (in-hospital mortality, long-term mortality, shock reversal, and adverse events).ResultsAmong the four studies eligible for data synthesis, we included 2,050 patients from three studies for quantitative synthesis. All studies used similar regimens (hydrocortisone and fludrocortisone for 7 days without tapering). The 28-day mortality rate was reduced after dual corticosteroid treatment (risk ratio, 0.88; 95% confidence intervals [CI], 0.78-0.99). The heterogeneity between the studies was low (I 2 = 0%). Patients who underwent dual corticosteroid treatment had lower long-term mortality rates (risk ratio, 0.90; 95% CI, 0.83-0.98) and higher rate of shock reversal after 28 days (odds ratio, 1.06; 95% CI, 1.01-1.12) than control patients. Adverse events (except for hyperglycemia) were similar among the treatment groups.ConclusionsThe available evidence suggests that a combination of fludrocortisone and hydrocortisone is more effective than adjunctive therapy and could be recommended for septic shock.
| S-EPMC7507448 | biostudies-literature
Project description:The process of self-renewal in normal intestinal epithelium is characterized by a fine balance between proliferation, differentiation, migration, and cell death. When even one of these aspects escapes the normal control, cellular proliferation and differentiation are impaired, with consequent onset of tumorigenesis. In humans, colorectal cancer (CRC) is the main pathological manifestation of this derangement. Nowadays, CRC is the world's fourth most deadly cancer with a limited survival after treatment. Several conditions can predispose to CRC development, including dietary habits and pre-existing inflammatory bowel diseases. Given their extraordinary ability to interact with DNA, it is widely known that nuclear receptors play a key role in the regulation of intestinal epithelium, orchestrating the expression of a series of genes involved in developmental and homeostatic pathways. In particular, the nuclear receptor Liver Receptor Homolog-1 (LRH-1), highly expressed in the stem cells localized in the crypts, promotes intestine cell proliferation and renewal in both direct and indirect DNA-binding manner. Furthermore, LRH-1 is extensively correlated with diverse intestinal inflammatory pathways. These evidence shed a light in the dynamic intestinal microenvironment in which increased regenerative epithelial cell turnover, mutagenic insults, and chronic DNA damages triggered by factors within an inflammatory cell-rich microenvironment act synergistically to favor cancer onset and progression.
| S-EPMC7924345 | biostudies-literature
Project description:BackgroundRecent 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.MethodsWe enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 ?g/dL from baseline after stimulation with 250 ?g 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.ResultsThe 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).InterpretationRelative 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. ISRCTN99675218.).
| S-EPMC3001503 | biostudies-literature
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| S-EPMC7816555 | biostudies-literature
Project description:ObjectiveTo investigate the effects of hydrocortisone combined with vitamin C and vitamin B1 versus hydrocortisone on sublingual microcirculation in septic shock patients.MethodsThis pilot study enrolled septic shock patients admitted to the ICU of a tertiary teaching hospital from February 2019 to January 2020. We randomly assigned the enrolled patients to the treatment group (hydrocortisone combined with vitamin C and vitamin B1 added to standard care) and the control group (hydrocortisone alone added to standard care) in a 1 : 1 ratio. The primary outcome was perfused small vascular density (sPVD) monitored by a sublingual microcirculation imaging system at 24 hours after treatment.ResultsTwelve patients in the treatment group and ten in the control group completed the study. The baseline characteristics were comparable between the groups. No statistically significant difference was found in the sPVD between the groups at baseline. The sPVD in the treatment group was significantly higher than that in the control group at 4 hours after treatment (mean difference, 7.042; 95% CI, 2.227-11.857; P = 0.009) and 24 hours after treatment (mean difference, 7.075; 95% CI, 2.390-11.759; P = 0.008).ConclusionsCompared with hydrocortisone, hydrocortisone combined with vitamin C and vitamin B1 significantly improves microcirculation in septic shock patients.
| S-EPMC10357145 | biostudies-literature
Project description:This study aimed to identify septic phenotypes in patients receiving vitamin C, hydrocortisone, and thiamine using temperature and white blood cell count. Data were obtained from septic shock patients who were also treated using a vitamin C protocol in a medical intensive care unit. Patients were divided into groups according to the temperature measurements as well as white blood cell counts within 24 h before starting the vitamin C protocol. In the study, 127 patients included who met the inclusion criteria. In the cohort, four groups were identified: "Temperature ?37.1 °C, white blood cell count ?15.0 1000/mm3" (group A; n = 27), "?37.1 °C, <15.0 1000/mm3" (group B; n = 30), "<37.1 °C, ?15.0 1000/mm3" (group C; n = 35) and "<37.1 °C, <15.0 1000/mm3" (group D; n = 35). The intensive care unit mortality rates were 15% for group A, 33% for group B, 34% for group C, and 49% for group D (p = 0.051). The temporal improvement in organ dysfunction and vasopressor dose seemed more apparent in group A patients. Our results suggest that different subphenotypes exist among sepsis patients treated using a vitamin C protocol, and clinical outcomes might be better for patients with the hyperinflammatory subphenotype.
| S-EPMC6950320 | biostudies-literature