Effect of Systemic Hydrocortisone on Brain Abnormalities and Regional Brain Volumes in Ventilator-dependent Infants Born Preterm: Substudy of the SToP-BPD Study.

OBJECTIVE: To evaluate whether a high cumulative dose of systemic hydrocortisone affects brain development compared with placebo when initiated between 7 and 14 days after birth in ventilated infants born preterm. STUDY DESIGN: A double-blind, placebo-controlled, randomized trial was conducted in 16 neonatal intensive care units among infants born at <30 weeks of gestation or with a birth weight of <1250 g who were ventilator-dependent in the second week after birth. Three centers performed MRI at term-equivalent age. Brain injury was assessed on MRI using the Kidokoro scoring system and compared between the 2 treatment groups. Both total and regional brain volumes were calculated using an automatic segmentation method and compared using multivariable regression analysis adjusted for baseline variables. RESULTS: From the 3 centers, 78 infants participated in the study and 59 had acceptable MRI scans (hydrocortisone group, n = 31; placebo group, n = 28). Analyses of the median global brain abnormality score of the Kidokoro score showed no difference between the hydrocortisone and placebo groups (median, 7; IQR, 5-9 vs median, 8, IQR, 4-10, respectively; P = .92). In 39 infants, brain tissue volumes were measured, showing no differences in the adjusted mean total brain tissue volumes, at 352 ± 32 mL in the hydrocortisone group and 364 ± 51 mL in the placebo group (P = .80). CONCLUSIONS: Systemic hydrocortisone started in the second week after birth in ventilator-dependent infants born very preterm was not found to be associated with significant differences in brain development compared with placebo treatment. TRIAL REGISTRATION: The SToP-BPD study was registered with the Netherlands Trial Register (NTR2768; registered on 17 February 2011; https://www.trialregister.nl/trial/2640) and the European Union Clinical Trials Register (EudraCT, 2010-023777-19; registered on 2 November 2010; https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023777-19/NL).

The use of prednisolone during Ramadan fasting in patients with adrenal insufficiency.

OBJECTIVE: Once daily prednisolone taken at predawn has been proposed to be the glucocorticoid replacement of choice in patients with adrenal insufficiency (AI) who intend to fast for the month of Ramadan. However, the effects of prednisolone on metabolic parameters and quality of life during fasting for Ramadan are unknown. DESIGN, PATIENTS AND MEASUREMENTS: Patients with AI on twice-daily hydrocortisone, who had low or moderate risk and intended to fast, were recruited. Patients were converted to prednisolone 5 mg once daily taken at sahur (predawn) and Ramadan education given. Weight, sleep duration, biochemical parameters and quality of life measures (SF-36 questionnaire) were analysed at the end of Ramadan and compared against baseline. RESULTS: Twenty patients (13 men) were recruited, with a mean age of 59.9 ± 15.0 years. All patients were on hydrocortisone 15 mg daily (in divided doses) as pre-Ramadan glucocorticoid replacement. Half had type 2 diabetes with low IDF-DAR risk. Eighty-five percent of patients completed the full 29 days of fasting with no complications. There was a significant reduction in weight (-1.1 ± 1.6 kg, p = .005), with no significant change in blood pressure or sleep duration. There was a significant increase in urea (0.80 ± 1.1 mmol/L, p = .005) and haematocrit, (0.011 ± 0.019 L/L, p = .019) and decrease in serum sodium (-1.6 ± 3.0 mmol/L, p = .028), with no change in serum creatinine or liver function. Quality of life measures were preserved in all domains with significant improvement in role limitation due to physical health (15.3 ± 21.6, p = .005) and bodily pain (8.8 ± 16.3, p = .031). CONCLUSIONS: This study has demonstrated that converting patients with AI who are fasting for Ramadan from twice-daily hydrocortisone to prednisolone 5 mg daily at sahur was safe, with no major short-term adverse effects. Despite the higher equivalent glucocorticoid doses, patients experienced weight loss and no clinically significant change in blood pressure, sleep, biochemical parameters or quality of life. This study paves the way to trial even lower doses of prednisolone once daily in patients fasting for Ramadan with AI.

Impaired free recall of neutral but not negative material tested 105 min after cortisol administration.

Pharmacological studies have consistently shown memory retrieval impairment after administration of cortisol, particularly pronounced for emotional laboratory material (i.e. list of emotional words). However, it is unclear how pharmacological elevation of cortisol affects memory retrieval of ecologically-relevant emotional material (i.e. similar to a newspaper article about an emotional event). In the present study, we aimed to explore whether cortisol administration affects the recall of ecologically-relevant emotional and neutral material, and when memory retrieval occurs after a longer delay (105 min). In this double-blind, pseudo-randomized, placebo-control study, 79 participants learned a negative text and a neutral text. Twenty-four hours later, they were administrated either 10 mg of hydrocortisone or placebo. After 105 min, participants engaged in free recall of both texts. The group with cortisol administration showed significantly reduced free recall compared to the placebo group. Interestingly, this memory retrieval impairment was driven by significantly lower recall after cortisol vs. placebo administration for neutral texts, but not negative texts. The current finding suggests that cortisol administration impairs neutral ecologically-relevant material while leaving emotional material unaffected. These divergent findings, compared to existing literature, emphasize the necessity of employing more ecologically validated material to gain a more comprehensive understanding of the intricate interplay between cortisol administration and memory for ecological material.

Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. METHODS: We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. RESULTS: Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] -1.16, 95% confidence interval [CI]: -1.58 to -0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD -18.80 h, 95% CI: -23.67 to -13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15-3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. CONCLUSIONS: HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.

Basal cortisol in relation to metyrapone confirmation in predicting adrenal insufficiency after pituitary surgery.

PURPOSE: Pituitary surgery can lead to post-surgical adrenal insufficiency with the need for glucocorticoid replacement and significant disease related burden. In patients who do not receive hydrocortisone replacement before surgery, at our center, an early morning plasma cortisol concentration using a cut-off value of 450 nmol/L 3 days after surgery (POD3) is used to guide the need for hydrocortisone replacement until dynamic confirmatory testing using metyrapone. The aim of this study was to critically assess the currently used diagnostic and treatment algorithm in patients undergoing pituitary surgery in our pituitary reference center. METHODS: Retrospective analysis of all patients with a POD3 plasma cortisol concentration < 450 nmol/L who received hydrocortisone replacement and a metyrapone test after 3 months. Plasma cortisol concentration was measured using an electrochemiluminescence immunoassay (Roche). All patients who underwent postoperative testing using metyrapone at Amsterdam UMC between January 2018 and February 2022 were included. Patients with Cushing's disease or those with hydrocortisone replacement prior to surgery were excluded. RESULTS: Ninety-five patients were included in the analysis. The postoperative cortisol concentration above which no patient had adrenal insufficiency (i.e. 11-deoxycortisol > 200 nmol/L) was 357 nmol/L (Sensitivity 100%, Specificity 31%, PPV:32%, NPV:100%). This translates into a 28% reduction in the need for hydrocortisone replacement compared with the presently used cortisol cut-off value of 450 nmol/L. CONCLUSION: Early morning plasma cortisol cut-off values lower than 450 nmol/L can safely be used to guide the need for hydrocortisone replacement after pituitary surgery.

Effects of noise exposure on stress hormone changes during task performance in young Korean men: quasi-experimental study.

Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans is rare and remains controversial. This study aimed to investigate the acute effects of exposure to noise and its different levels on stress hormone changes in task performance. Quasi-experimental noise exposure environment was established for 90 male university student volunteers in their twenties, and each was exposed to different noise levels during task performance. The stress hormones tested included cortisol, adrenocorticotropic hormone (ACTH), adrenaline, and noradrenaline. A one-way ANOVA was performed to investigate differences in hormone levels measured in the three groups according to the noise exposure levels (35, 45, or 75 dB). Analysis of covariance (ANCOVA) was used to adjust for confounding factors that might affect hormone levels. After adjusting for confounders, significant exposure-dependent differences were found in hormone levels in salivary cortisol, serum cortisol, serum ACTH, and serum adrenaline. The amount of hormonal increase in 75 dB exposure group compared to 35 or 45 dB groups was detected. Similar results were also seen in the rate of change analysis. Our findings indicate that short-term noise exposure during task performance elevates stress hormone levels. Further, the extent of stress hormone alterations varies with noise exposure levels. Changes in hormone levels are an objective measure that may be used to identify health effects and stress responses in various noise environments.

Nonprescription Treatment Options.

The pathogenesis of atopic dermatitis (AD) is complex and multifactorial. However, recent advancements in the genetics and pathophysiology of AD suggest that epidermal barrier dysfunction is paramount in the development and progression of the condition (Boguniewicz M, Leung DYM, Immunol Rev 242(1):233-246, 2011). In addition to standard therapy for AD, there are a plethora of nonprescription treatment modalities which may be employed. Over-the-counter treatments for atopic dermatitis can come in the form of topical corticosteroids, moisturizers/emollients, and oral antihistamines. Though these treatments are beneficial, prescription treatments may be quicker acting and more efficacious in patients with moderate to severe disease or during flares. OTC agents are best used for maintenance between flares and to prevent progression of mild disease. Alternative and complementary treatments lack strong efficacy evidence. However, wet wraps, bleach baths, and other treatments appear to be promising when used in conjunction with conventional treatments. With the financial burden of atopic dermatitis ranging from 364 million to 3.8 billion dollars each year in the United States, we suspect this topic will gain further research attention.

Depressive-Like Effects of Foreclosing: A Cross-Sectional Study of Hair Cortisol Concentration.

INTRODUCTION: Foreclosing and home eviction have been associated with various negative health outcomes, probably due to exposure to such stressful circumstance, but there is no evidence about foreclosure and home eviction to elicit cortisol responses. METHODS: Participants who recently had received a court eviction notice were compared to subjects suffering a depressive disorder and to healthy controls in terms of hair cortisol concentrations. RESULTS: Subjects under the stressful circumstance of foreclosure and patients with depression showed comparable concentrations in most of the hair segments while healthy subjects displayed the lowest levels of cortisol. CONCLUSION: The findings show that foreclosure and home eviction are associated with increased cumulative hair cortisol and with depressive-like symptoms. Foreclosing procedures yielded to maintain high levels of cortisol which may increase the risk to develop major depression.

Efficacy and safety of a hydrocortisone aceponate-containing ear spray solution in dogs with erythemato-ceruminous otitis externa: A randomised, multicentric, single-blinded, controlled trial.

BACKGROUND: Erythemato-ceruminous otitis externa (ECOE) is frequently seen in dogs affected with an allergic skin disease, with recurrent secondary bacteria and yeast overgrowths (detected on cytological examination). OBJECTIVES: The objective of the study was to compare the efficacy and safety of an ear spray containing only hydrocortisone aceponate glucocorticoid diester (HCA) to a control product (CTRL), an approved otic formulation containing prednisolone-miconazole-polymyxin combination, in dogs with ECOE. ANIMALS: In total, 97 and 104 dogs with ECOE were respectively randomly assigned to the tested ear treatment product group (HCA) or the commercially available ear treatment control product group (CTRL). MATERIALS AND METHODS: Dogs were treated for 7-14 days, as needed. At Day (D)0, D7, D14, D28 and D42, Otitis Index Score-3, hearing test, pruritus and pain visual analogue scales, and cytological scores were graded. The overall response to treatment also was assessed. RESULTS: All clinical parameters decreased rapidly and in a similar way without any significant difference at any time between treatment groups. A good-to-excellent response to treatment was seen in >90% of dogs of both groups as early as D14. The treatment was considered safe in all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: A 7- to 14-day ear topical application of HCA alone to dogs with ECOE accompanied with bacterial and/or fungal (yeast) overgrowth was safe and led to no statistical difference in improvement of clinical scores relative to the CTRL combination. Based on these results, it may be necessary to reconsider the routine use of antimicrobial drugs such as antibiotics and antifungals as a first-line treatment for ECOE that is likely to have been caused by an allergic reaction.

Chitosan/Pomegranate Seed Oil Emulgel Composition as a New Strategy for Dermal Delivery of Hydrocortisone.

Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.

The Association between the rs3747406 Polymorphism in the Glucocorticoid-Induced Leucine Zipper Gene and Sepsis Survivals Depends on the SOFA Score.

The variability in mortality in sepsis could be a consequence of genetic variability. The glucocorticoid system and the intermediate TSC22D3 gene product-glucocorticoid-induced leucine zipper-are clinically relevant in sepsis, which is why this study aimed to clarify whether TSC22D3 gene polymorphisms contribute to the variance in sepsis mortality. Blood samples for DNA extraction were obtained from 455 patients with a sepsis diagnosis according to the Sepsis-III criteria and from 73 control subjects. A SNP TaqMan assay was used to detect single-nucleotide polymorphisms (SNPs) in the TSC22D3 gene. Statistical and graphical analyses were performed using the SPSS Statistics and GraphPad Prism software. C-allele carriers of rs3747406 have a 2.07-fold higher mortality rate when the sequential organ failure assessment (SOFA) score is higher than eight. In a multivariate COX regression model, the SNP rs3747406 with a SOFA score ≥ 8 was found to be an independent risk factor for 30-day survival in sepsis. The HR was calculated to be 2.12, with a p-value of 0.011. The wild-type allele was present in four out of six SNPs in our cohort. The promoter of TSC22D3 was found to be highly conserved. However, we discovered that the C-allele of rs3747406 poses a risk for sepsis mortality for SOFA Scores higher than 6.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

Unanswered Questions in the Guidelines for Antibiotic Prescription in Critically Ill Patients.

How to cite this article: Nath SS, Nachimuthu N, Bhagyashree, Singh S. Unanswered Questions in the Guidelines for Antibiotic Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(7):715-716.

Mineralocorticoid replacement therapy in salt-wasting congenital adrenal hyperplasia.

Patients with salt-wasting congenital adrenal hyperplasia (SW-CAH) usually show pronounced impairment of aldosterone secretion and, therefore, also require mineralocorticoid replacement. While a lot of research and discussion focusses on the glucocorticoid therapy in SW-CAH to replace the missing cortisol and to control adrenal androgen excess, very little research is dealing with mineralocorticoid replacement. However, recent data demonstrated an increased cardiovascular risk in adult CAH patients urging to reflect also on the current mineralocorticoid replacement therapy. In this review, we explain the role and function of the mineralocorticoid receptor, its ligands and inhibitors and its relevance for the therapy of patients with SW-CAH. We performed an extensive literature search and present data on mineralocorticoid therapy in SW-CAH patients as well as clinical advice how to monitor and optimise mineralocorticoid replacement therapy.

Radiation of bilateral adrenal metastases is associated with a high risk of primary adrenal insufficiency.

BACKGROUND: Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Radiotherapy (RT) is one option available to treat adrenal metastases. The risk of primary adrenal insufficiency (PAI) after adrenal RT is unclear. OBJECTIVE: Determine the incidence and the timeline of PAI in patients undergoing adrenal RT. DESIGN, SETTING AND PARTICIPANTS: Single-centre longitudinal retrospective cohort study of adult patients with adrenal metastases treated with RT between 2010 and 2021. RESULTS: Of 56 patients with adrenal metastases treated with adrenal RT, eight (14.3%) patients developed PAI at a median of 6.1 months (interquartile range [IQR]: 3.9-13.8) after RT All patients developing PAI had either unilateral RT in the setting of contralateral adrenalectomy or bilateral adrenal RT. Patients who developed PAI received a median RT dose of 50 Gy (IQR: 44-50 Gy), administered in a median of five fractions (IQR: 5-6). Treated metastases decreased in size and/or metabolic activity on positron emission tomography in seven patients (87.5%). Patients were initiated on hydrocortisone (median daily dose of 20 mg, IQR: 18-40) and fludrocortisone (median daily dose of 0.05 mg, IQR: 0.05-0.05 mg). At the end of the study period, five patients died, all due to extra-adrenal malignancy, at a median time of 19.7 months (IQR: 16-21.1 months) since RT and median time of 7.7 months (IQR: 2.9-12.5 months) since the diagnosis of PAI. CONCLUSION: Patients receiving unilateral adrenal RT with two intact adrenal glands have a low risk of PAI. Patients receiving bilateral adrenal RT have a high risk of PAI and require close monitoring.

Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study.

BACKGROUND: Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data. OBJECTIVE: The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock. METHODS: A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety. RESULTS: There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01). CONCLUSION AND RELEVANCE: FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.

Abrupt Discontinuation Versus Taper of Hydrocortisone in Patients With Septic Shock.

BACKGROUND: Although not mentioned in the most recent guidelines, the 2016 Surviving Sepsis Campaign guidelines recommend to taper corticosteroids once vasopressors are no longer needed; however, at the time of publication, there were no studies comparing taper versus abrupt discontinuation of corticosteroids. OBJECTIVES: The purpose of this study was to further evaluate the impact of abrupt versus taper discontinuation of corticosteroids in septic shock. METHODS: This was a retrospective cohort study that included patients who received an initial dose of 200 to 300 mg of hydrocortisone for septic shock. Participants were then divided into "abrupt" and "taper" groups. The primary outcome assessed was hemodynamic instability during taper or within 72 hours of the last corticosteroid dose. Secondary outcomes included intensive care unit (ICU) and hospital length of stay, incidence of hyperglycemia or hypernatremia, and in-hospital mortality. RESULTS: The primary outcome of reinitiation of vasopressor therapy occurred in a larger proportion of patients in the taper group compared with the abrupt group (21.9% vs 10.7%). The ICU length of stay (7.6 days abrupt vs 9 days taper) and hospital length of stay (14.9 vs 15.3 days) were similar between groups. There was a statistically significant increase in patients who experienced hyperglycemia within 24 hours of the last corticosteroid dose in the abrupt group. All other secondary outcomes were similar between groups. CONCLUSIONS: The abrupt discontinuation of hydrocortisone in the treatment of septic shock was associated with a nonstatistically significant 50% absolute reduction in the need for vasopressor reinitiation.

Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP). METHODS: A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality. RESULTS: A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio [RR], 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I2 = 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD - 0.8; 95% CI - 1.4 to - 0.1; p = 0.02), and hospital stay (MD - 1.1; 95% CI - 2.0 to - 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53). CONCLUSIONS: In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.

Sepsis and Adrenal Insufficiency.

In sepsis, dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice.

Adjunctive Hydrocortisone Improves Hemodynamics in Critically Ill Patients with Septic Shock: An Observational Study Using Transpulmonary Thermodilution.

Introduction: Septic shock is associated with high mortality and hemodynamic impairment. The use of corticoids is a common therapeutic tool in critically ill patients. However, data on the mechanisms and prognostic ability of hemodynamic improvement by adjunctive steroids are rare. This study primarily aimed to evaluate short-term effects of hydrocortisone therapy on catecholamine requirement and hemodynamics derived from transpulmonary thermodilution (TPTD) in 30 critically ill patients with septic shock and a 28 days mortality rate of 50%. Methods: Hydrocortisone was administered with an intravenous bolus of 200 mg, followed by a continuous infusion of 200 mg per 24 h. Hemodynamic assessment was performed immediately before as well as 2, 8, 16, and 24 h after the initiation of corticoids. For primary endpoint analysis, we evaluated the impact of hydrocortisone on vasopressor dependency index (VDI) and cardiac power index (CPI). Results: Adjunctive hydrocortisone induced significant decreases of VDI from 0.41 (0.29-0.49) mmHg-1 at baseline to 0.35 (0.25-0.46) after 2 h (P < .001), 0.24 (0.12-0.35) after 8 h (P < .001), 0.18 (0.09-0.24) after 16 h (P < .001) and 0.11 (0.06-0.20) mmHg-1 after 24 h (P < .001). In parallel, we found an improvement in CPI from 0.63 (0.50-0.83) W/m2 at baseline to 0.68 (0.54-0.85) after 2 h (P = .208), 0.71 (0.60-0.90) after 8 h (P = .033), 0.82 (0.6-0.98) after 16 h (P = .004) and 0.90 (0.67-1.07) W/m2 after 24 h (P < .001). Our analyses revealed a significant reduction in noradrenaline requirement in parallel with a moderate increase in mean arterial pressure, systemic vascular resistance index, and cardiac index. As a secondary endpoint, our results showed a significant decrease in lung water parameters. Moreover, changes in CPI (ΔCPI) and VDI (ΔVDI) after 24 h of hydrocortisone therapy revealed accurate prognostic ability to predict 28 days mortality (AUC = 0.802 vs 0.769). Conclusion: Adjunctive hydrocortisone leads to a rapid decrease in catecholamine requirement and a substantial circulatory improvement in critically ill patients with septic shock.