Effect Of Low-dose Hydrocortisone Research Articles

Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets

Hospital mortality in sepsis varies between 30–45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1β maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1β. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1β form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1β processing.

Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data

IntroductionThe benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment...

Effects and safety of separate low-dose hydrocortisone use in patients with septic shock: A meta-analysis

Objective: The aim of this study was to explore the effects and safety of low-dose hydrocortisone in patients with septic shock. Methods: The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched from database inception until 1 August 2018. Two reviewers performed literature selection, data extraction, and quality evaluation independently. Results: Twelve randomized controlled trials were included in this meta-analysis. The combined results showed that low-dose hydrocortisone use had no survival benefit in patients with septic shock (relative risk = 1.09; 95% confidence interval = 0.88–1.05; P = 0.37). But low-dose hydrocortisone use was useful for shock reverse (relative risk = 1.09; 95% confidence interval = 1.00–1.19; P = 0.04) and in shortening the time of vasopressor support (weighted mean difference = −1.79, 95% confidence interval = −2.05 to −1.52; P < 0.00001). In addition, use of low-dose hydrocortisone was associated with a higher risk of hyperglycemia (relative risk = 1.21; 95% confidence interval = 1.04–1.40; P = 0.01) and hypernatremia (relative risk = 6.34; 95% confidence interval = 1.19–33.81; P = 0.03). There was no significant improvement of intensive care unit mortality (relative risk = 1.11; 95% confidence interval = 0.93–1.33; P = 0.23) or hospital mortality (relative risk = 1.08; 95% confidence interval = 0.94–1.24; P = 0.29), length of intensive care unit (weighted mean difference = −1.84; 95% confidence interval = −5.80 to 2.11; P = 0.36) or length of hospital (weighted mean difference = 0.11; 95% confidence interval = −2.06 to 2.29; P = 0.98), and time of mechanical support (weighted mean difference = −0.69; 95% confidence interval = −1.76 to −0.38; P = 0.20) with the use of low-dose hydrocortisone. There was no significant difference in secondary infection (relative risk = 1.04; 95% confidence interval = 0.91–1.18; P = 0.57), recurrence of shock (relative risk = 1.47; 95% confidence interval = 0.64–3.39; P = 0.36), and gastrointestinal bleeding (relative risk = 1.41; 95% confidence interval = 0.89–2.22; P = 0.14) with the use of low-dose hydrocortisone. Conclusion: Although there was no effect of low-dose hydrocortisone on survival of patients with septic shock, it is associated with a higher rate of shock reversal and shortening duration of vasopressor support; thus, low-dose hydrocortisone may be an alternative drug in septic shock patients who are refractory to fluid resuscitation and vasopressors.

Protective effect of early low-dose hydrocortisone on ventilator-associated pneumonia in the cancer patients: a propensity score analysis

BackgroundVentilator-associated pneumonia (VAP) is a care-related event that could be promoted by immune suppression caused by critical diseases, malignancies and cancer treatments. Low dose of hydrocortisone was proposed for modulation of immune response in the critically ill population.MethodsIn this monocentric observational study, all cancer patients mechanically ventilated for more than 48 h were included. Effect of low-dose hydrocortisone administered during the first 48 h of mechanical ventilation was evaluated applying inverse probability weighting analysis after propensity score assessment. VAP impact on 1-year mortality, ICU length of stay and mechanical ventilation duration was secondarily determined.ResultsWithin this cohort, 190 cancer patients were followed. VAP was confirmed in 22.1% of cases in the early hydrocortisone group and confirmed in 42.6% of cases in the no or late hydrocortisone group. Early hydrocortisone exhibited a protective effect on the risk of VAP (OR 0.23; 95% CI 0.12–0.44; P < 0.0001). VAP was associated with 1-year mortality (HR 1.60; 95% CI 1.10–2.34; P = 0.017) and increased ICU length of stay (mean extra length of stay: 4.2 days; 95% CI 0.6–7.8).ConclusionsImmune modulation with low-dose hydrocortisone administered in the first days of mechanical ventilation could protect from VAP occurrence in cancer patients.

Effect of low-dose hydrocortisone on gene expression profiles after severe burn injury

The systemic effect of inflammatory mediators released after severe burn is a severe cardiovascular dysfunction called burn shock. Patients need vasopressor infusion to maintain adequate delivery of oxygen but it could have deleterious effects on skin perfusion and worsen the burn depth. This shock could result from the interplay of the initial hypovolemia and the release of multiple inflammatory mediators [1]. It has been shown that a low-dose of hydrocortisone could reduce the shock duration but the mechanisms involved remain unclear. We investigated the systemic genomic response after severe burn injuries and determine whether patterns of gene expression could be associated with a low dose of glucocorticoids.

Effect of low-dose hydrocortisone on the expression of glucocorticoid receptor alpha of the septic kidney in rats and its protective effect on kidney injury

Inflammation out of control caused by sepsis can eventually lead to multiple organ dysfunction, of which the kidney is one of the most common injured organs. Sepsis-induced acute kidney injury (SI-AKI) can obviously increase the mortality of sepsis. At present, there are controversial views about the impact of exogenous glucocorticoid to SI-AKI on kidney pathological changes and glucocorticoid receptor (GR) expression. So, we want to investigate whether low-dose glucocorticoid has a protective effect on SI-AKI and what is the mechanism.

The effect of low-dose hydrocortisone on the expression of glucocorticoid receptor alpha of the septic kidney and its protective effect on kidney in rat

To investigate the protective effect and mechanism of low dose glucocorticoid(GC) on sepsis induced acute kidney injury(AKI) in rat. Eighty healthy Wistar male rats were randomly divided into sham group (n=10), AKI model group (AKI group, n=35)and hydrocortisone treatment group(HC group, n=35),according to random digital table. Septic AKI model was reproduced using cecal ligation and puncture (CLP). After the procedure hydrocortisone 6 mg/kg was injected via sublingual vein in HC group. At 24 hours after the procedure, blood was obtained and the animals were sacrificed in all groups. Pathological changes in the kidney were observed with hematoxylin eosin (HE) staining. The expressions of glucocorticoid receptor alpha (GR-α) and nuclear transcription factor-ΚB (NF-ΚB) in the kidney were assessed by immunohistochemistry. The levels of tumor necrosis factor alpha (TNF-α) and interleukins (IL-1β, IL-6,IL-10) in the plasma were determined by enzyme-linked immunosorbent assay(ELISA). ¹ The difference in survival rates in AKI group and HC group showed no statistical significance (42.8% vs. 48.6%,P>0.05). ² Renal tubular epithelial cells were swollen and exfoliated, with loss and vacuolation of tubular brush border under light microscope in AKI group. Pathological changes in renal tubules in HC group were alleviated. ³ Compared with AKI group, the expression of GR-α was increased [absorbance (A) value: 0.35 ± 0.05 vs. 0.25 ± 0.05,P<0.01] and the expression of NF-ΚB was decreased in HC group (A value: 0.23 ± 0.04 vs.0.34 ± 0.04,P<0.01). Compared with AKI group, the levels of TNF-α, IL-1β, IL-6 were lowered [TNF-α (ng/L): 94.25 ± 7.96 vs. 118.24 ± 6.63; IL-1β (ng/L): 19.14 ± 1.99 vs. 28.91 ± 6.81; IL-6 (ng/L): 66.32 ± 1.99 vs. 85.70 ± 11.54; all P <0.01] and the level of IL-10 (ng/L) was elevated (98.33 ± 6.68 vs. 88.59 ± 7.34,P<0.01) in HC group. A low dose of hydrocortisone can inhibit the activity of NF-ΚB, possibly by means of increasing the expression of renal GR-α in septic rats. Accordingly it reduces the production of pro-inflammatory factors which participate in sepsis. So it effectively inhibits inflammation in sepsis and protects the kidney in septic rats.

Use of a low-dose steroid as an adjunct in the treatment, in mice, of severe sepsis caused byBurkholderia pseudomallei

Human melioidosis caused by Burkholderia pseudomallei is a severe septic disease that is associated with high mortality, even under appropriate antibiotic treatment. The therapeutic effects of low-dose hydrocortisone plus ceftazidime, and of ceftazidime alone, have recently been investigated in the treatment of acute, severe sepsis caused by B. pseudomallei, both in normal BALB/c mice and in BALB/c mice with streptozotocin-induced diabetes. The mice were infected and then treated intravenously, from day 1 or day 2 post-infection, with saline (as a control, given twice daily for 10 days), low-dose hydrocortisone (given in twice-daily doses of 5 mg/kg, for 5 days) plus ceftazidime (given in twice-daily doses of 1200 mg/kg, for 10 days), or the same doses of ceftazidime alone. Although the infected, untreated mice all died within 14 days, almost all of the treated animals were still alive at the end of the follow-up, 30 days post-infection. The addition of the steroid appeared to have no benefit, with bacterial loads and plasma concentrations of tumour necrosis factor, aspartate aminotransferase, alanine aminotransferase and creatinine decreasing similarly in all the treated groups. The infected diabetic mice given hydrocortisone-ceftazidime from day 1 (but not those given just ceftazidime from day 1) showed an increase in their blood glucose concentrations. When infected mice were treated with the low-dose steroid and lower doses of the antibiotic (in twice-daily doses of 120-600 mg/kg), the steroid not only offered no apparent benefit but seemed to reduce survival. It therefore appears that low-dose hydrocortisone, as an adjunct to antibiotic treatment, does not provide benefit in the treatment of murine melioidosis and may have negative effects on human cases of the disease who have diabetes mellitus.

Εx-vivo effect of dexamethasone on cytokine production from whole blood of septic patients: Correlation with disease severity

Background: Controversial findings of former clinical trials on the effect of low dose hydrocortisone in patients with septic shock led to investigate the effect of corticosteroids on the production of cytokines from endotoxin (LPS)-stimulated whole blood. Methods: Whole blood from 33 septic patients was sampled within 24 h alter diagnosis. Hydrocortisone was not administered during follow-up. Whole blood was stimulated with 30 ng/ml of LPS in the presence of 0.01, 0.1, 1 and 10 μM of dexamethasone. Concentrations of cytokines and of sTREM-1 were estimated in supernatants after six hours of incubation. Results: Dexamethasone inhibited LPS-stimulated release of ΤΝFα, of IL-6, of IL-8 and of IL-10 in dose-dependent manner. A dual effect on the kinetics of release of IL-1β and of sTREM-1 was shown. Release of IL-1β was either decreased, what was connected with unfavorable outcome, or it was unaffected what was connected with a favorable outcome. Release of sTREM-1 was either increased, what was connected with unfavorable outcome, or it was decreased what was connected with a favorable outcome. Conclusions: Part of the beneficiary effect of corticosteroids in sepsis may be due to an effect on the release of IL-1β and of sTREM-1. This effect does not seem to be homogeneous for all septic patients.

Effect of low-dose hydrocortisone on early and late cytokine expression in LPS-induced septic rats

目的 研究小剂量氢化可的松(HC)对内毒素(LPS)诱导的脓毒症大鼠早、晚期炎症介质表达的影响.方法 将72只雄性Wistar大鼠随机分为3组:对照组(A组)8只、模型组(B组)32只、小剂量HC干预组(C组)32只.B组和C组设立2、8、16、24 h四个时段点,每个时段点各8只(相应的8个亚组用B2、B8、B16、B24及C2、C18、C16、C24表示).腹腔注射LPS(1 mg/kg)建立脓毒症大鼠模型,C组腹腔注射LPS后即刻尾静脉注射小剂量HC(6 mg/kg),分别在注射后2、8、16、24 h分时段采集各组大鼠血清,采用双抗体夹心酶联免疫吸附实验检测各组血清TNF-α和IL-1β含量.采集各组大鼠海马组织5 mg,制备细胞总蛋白质,进行蛋白质电泳及蛋白免疫印迹分析,检测高迁移率蛋白(HMG)B1水平.结果 各组血清TNF-α、IL-1β水平均以B2组为高,与A组比较,差异有显著性(P＜0.05),C2组与B2组比较下降明显,差异有非常显著性(P＜0.01).其余各组TNF-α、IL-1β水平与A组及同时点两两比较,差异无显著性(P＞0.05).A组海马组织可见微量HMGB1表达;B组在B8表达量始增加,以B16、B24为高(P＜0.05).B组HMGB1表达有持续增加趋势.C组HMGB1表达较B组呈减少趋势,以C16、C24组减少明显,差异有显著性(P＜0.05).结论 小剂量HC对早、晚期炎症介质TNF-α、IL-1β、HMGB1的表达有明显抑制作用。

P.8.023 Effect of low-dose hydrocortisone on serum TSH and PRL levels in female patients with chronic fatigue syndrome

P.8.023 Effect of low-dose hydrocortisone on serum TSH and PRL levels in female patients with chronic fatigue syndrome

Adrenal insufficiency in septic shock: what should one do at the present time?

In the past years many studies have demonstrated the occurrence of relative adrenal insufficiency and immunologic and hemodynamic effects of low-dose hydrocortisone in septic shock. Despite this evidence, the optimal approach to ensure the diagnoses is not yet clear.