Hydrocortisone Reverses Refractory Septic Shock

Chawla, Kabu; Kupfer, Yizhak; Goldman, I.Ralph; Tessler, Sidney

doi:10.1097/00003246-199901001-00022

Cited by 124 publications

(92 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The values related to the levels of ␤-actin do not differ appreciably from experiment to experiment and are presented above the gel. ing levels of inflammatory mediators (3,20) and to improve organ function (1,2,5,18). This experimental work suggests that under such conditions, administration of exogenous glucocorticoids may also restore the host's ability to counteract infections.…”

Section: Discussionmentioning

confidence: 99%

Effects of Methylprednisolone on Intracellular Bacterial Growth

Meduri¹,

Kanangat²,

Bronze³

et al. 2001

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

Clinical studies have shown positive associations among sustained and intense inflammatory responses and the incidence of bacterial infections. Patients presenting with acute respiratory distress syndrome (ARDS) and high levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-␣), interleukin 1␤ (IL-1␤), and IL-6, have increased risk for developing nosocomial infections attributable to organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., compared to those patients with lower levels. Our previous in vitro studies have demonstrated that these bacterial strains exhibit enhanced growth extracellularly when supplemented with high concentrations of pure recombinant TNF-␣, IL-1␤, or IL-6. In addition, we have shown that the intracellular milieu of phagocytic cells that are exposed to supraoptimal concentrations of TNF-␣, IL-1␤, and IL-6 or lipopolysaccharide (LPS) favors survival and replication of ingested bacteria. Therefore, we hypothesized that under conditions of intense inflammation the host's micromilieu favors bacterial infections by exposing phagocytic cells to protracted high levels of inflammatory cytokines. Our clinical studies have shown that methylprednisolone is capable of reducing the levels of TNF-␣, IL-1␤, and IL-6 in ARDS patients. Hence, we designed a series of in vitro experiments to test whether human monocytic cells (U937 cells) that are activated with high concentrations of LPS, which upregulate the release of proinflammatory cytokines from these phagocytic cells, would effectively kill or restrict bacterial survival and replication after exposure to methylprednisolone. Fresh isolates of S. aureus, P. aeruginosa, and Acinetobacter were used in our studies. Our results indicate that, compared with the control, stimulation of U937 cells with 100-ng/ml, 1.0-g/ml, 5.0-g/ml, or 10.0-g/ml concentrations of LPS enhanced the intracellular survival and replication of all three species of bacteria significantly (for all, P ‫؍‬ 0.0001). Stimulation with <10.0 ng of LPS generally resulted in efficient killing of the ingested bacteria. Interestingly, when exposed to graded concentrations of methylprednisolone, U937 cells that had been stimulated with 10.0 g of LPS were able to suppress bacterial replication efficiently in a concentration-dependent manner. Significant reduction in numbers of CFU was observed at >150 g of methylprednisolone per ml (P values were 0.032, 0.008, and 0.009 for S. aureus, P. aeruginosa, and Acinetobacter, respectively). We have also shown that steady-state mRNA levels of TNF-␣, IL-1␤, and IL-6 in LPS-activated cells were reduced by treatment of such cells with methylprednisolone, in a concentration-dependent manner. The effective dose of methylprednisolone was 175 mg, a value that appeared to be independent of priming level of LPS and type of mRNA. We therefore postulate that a U-shaped relationship exists between the level of expression of TNF-␣, IL-1␤, and IL-6 within the phagocytic cells and their abilities to suppress act...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Methylprednisolone on Intracellular Bacterial Growth

Meduri¹,

Kanangat²,

Bronze³

et al. 2001

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

show abstract

“…The benefit of hydrocortisone in patients with septic shock has been evaluated in 6 randomized control trials [34,45,48,49,50,51]. A meta-analysis of these trials demonstrates greater shock reversal on day 7 with hydrocortisone, but no benefit in terms of mortality [9].…”

Section: Managementmentioning

confidence: 99%

Critical Illness-Related Corticosteroid Insufficiency in Children

Levy‐Shraga

Pinhas‐Hamiel²

2013

Horm Res Paediatr

View full text Add to dashboard Cite

Adequate adrenocortical function is essential for survival in critical illness. Most critically ill patients display elevated plasma cortisol concentrations, which reflects activation of the hypothalamic-pituitary-adrenal axis and is considered to be a homeostatic adaptation. However, many critically ill patients have ‘relative' or ‘functional' adrenal insufficiency, which is characterized by an inadequate production of cortisol in relation to an increased demand during periods of severe stress. Recently, the term ‘critical illness-related corticosteroid insufficiency' (CIRCI) was coined. CIRCI occurs as a result of a decrease in adrenal steroid production or tissue resistance to glucocorticoids. An international task force of the American College of Critical Care Medicine issued recommendations for the diagnosis and management of this condition in adult patients. We review the prevalence, diagnosis, and therapeutic approach to adrenal insufficiency in critically ill children. We found a lack of consensus within the pediatric field as to the optimal approach to CIRCI, and call for an international task force to establish unified guidelines.

show abstract

“…Additional file 1: Summary tables of included and excluded study characteristics [47][48][49][50][51][52][53][54][55][56][57][58][59][60] …”

Section: Additional Filesmentioning

confidence: 99%

Corticosteroid Treatment in Critically Ill Patients

Lee¹,

Ryu²

2017

J Neurocrit Care

View full text Add to dashboard Cite

Background: Multiple corticosteroids and treatment regimens have been used as adjuncts in the treatment of septic shock. Qualitative and quantitative differences exist at cellular and tissular levels between the different drugs and their patterns of delivery. The objective of this study was to elucidate any differences between the drugs and their treatment regimens regarding outcomes for corticosteroid use in adult patients with septic shock. Methods: Network meta-analysis of the data used for the recently conducted Cochrane review was performed. Studies that included children and were designed to assess respiratory function in pneumonia and acute respiratory distress syndrome, as well as cross-over studies, were excluded. Network plots were created for each outcome, and all analyses were conducted using a frequentist approach assuming a random-effects model. Results: Complete data from 22 studies and partial data from 1 study were included. 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.

show abstract

Hydrocortisone Reverses Refractory Septic Shock

Cited by 124 publications

References 0 publications

Effects of Methylprednisolone on Intracellular Bacterial Growth

Effects of Methylprednisolone on Intracellular Bacterial Growth

Critical Illness-Related Corticosteroid Insufficiency in Children

Corticosteroid Treatment in Critically Ill Patients

Contact Info

Product

Resources

About