Corticosteroids in Sepsis: From Bench to Bedside?

Annane, Djillali; Cavaillon, Jean‐Marc

doi:10.1097/01.shk.0000079423.72656.2f

Cited by 113 publications

(65 citation statements)

References 113 publications

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“…It is a powerful immunosuppressive hormone and modulates the inflammatory response and cytokine production. 13,[37][38][39] By this mechanism it inhibits the production of nitric oxide and other mediators of septic shock. 39 A direct inhibitory effect of cortisol on the inducible form of nitric oxide synthase has also been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

et al. 2006

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Relative adrenal insufficiency is frequent in patients with severe sepsis and is associated with hemodynamic instability, renal failure, and increased mortality. This study prospectively evaluated the effects of steroids on shock resolution and hospital survival in a series of 25 consecutive patients with cirrhosis and septic shock (group 1). Adrenal function was evaluated by the short corticotropin test within the first 24 hours of admission. Patients with adrenal insufficiency were treated with stress doses of intravenous hydrocortisone (50 mg/6 h). Data were compared to those obtained from the last 50 consecutive patients with cirrhosis and septic shock admitted to the same intensive care unit in whom adrenal function was not investigated and who did not receive treatment with steroids (group 2). Incidence of adrenal insufficiency in group 1 was 68% (17 patients). Adrenal dysfunction was frequent in patients with advanced cirrhosis (Child C: 76% vs. Child B: 25%, P ‫؍‬ .08). Resolution of septic shock (96% vs. 58%, P ‫؍‬ .001), survival in the intensive care unit (68% vs. 38%, P ‫؍‬ .03), and hospital survival (64% vs. 32%, P ‫؍‬ .003) were significantly higher in group 1. The main causes of death in group 1 were hepatorenal syndrome or liver failure (7 of 9 patients). In contrast, refractory shock caused most of the deaths in group 2 (20 of 34 patients). In conclusion, relative adrenal insufficiency is very frequent in patients with advanced cirrhosis and septic shock. Hydrocortisone administration in these patients is associated with a high frequency of shock resolution and high survival rate. (HEPATOLOGY 2006;44:1288-1295 B acterial infections are a frequent complication and an important cause of death in patients with advanced cirrhosis. 1-3 The mortality rate for patients admitted to the hospital with severe bacterial infections but without septic shock is approximately 30%, 4-6 although it may decrease to 10% if circulatory support with intravenous albumin is given at infection diagnosis. 7 The development of a complex syndrome characterized by acute deterioration of circulatory, hepatic, and renal function and hepatic encephalopathy is the main cause of death in these patients. 6,7 Prognosis of patients with cirrhosis admitted with septic shock is even worse. Hospital mortality in these patients ranges between 60% and 100%, 8,9 which is higher than that reported in the general population of patients with septic shock (25%-70%). [10][11][12] In our experience, survival of patients with cirrhosis in septic shock has not improved greatly during the past decades despite important advances in antibiotic treatment and general supportive measures.During the last few years, several studies have shown that septic shock is frequently associated with relative adrenal insufficiency, a condition characterized by an inadequate production of cortisol with respect to the peripheral demands. [11][12][13][14][15][16][17][18] It also has been reported that patients with septic shock and relative adrenal insufficiency sho...

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Section: Discussionmentioning

confidence: 99%

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

et al. 2006

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“…The beneficial effects of low-dose steroids in vasopressor-dependent patients in septic shock is likely mediated by attenuation of the systemic inflammatory response as well as direct effects on vasomotor tone and an increased responsiveness to vasopressors [19]. The antiinflammatory effects of corticosteroids have been when established, the full extent of which is beyond the scope of this review.…”

Section: Introductionmentioning

confidence: 99%

The Apoptotic Pathway as a Therapeutic Target in Sepsis

Wesche-Soldato¹,

Swan²,

Chung³

et al. 2007

CDT

139

114

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Recent research has yielded many interesting and potentially important therapeutic targets in sepsis. Specifically, the effects of antagonistic anti-cytokine therapies (tumor necrosis factor-alpha [TNF-α], interleukin-1 [IL-1]) and anti-endotoxin strategies utilizing antibodies against endotoxin or endotoxin receptor/carrier molecules (anti-CD14 or anti-LPS-binding protein) have been studied. Unfortunately, these approaches often failed clinically, and in many cases, the efficacy of these treatments was dependent on the severity of sepsis. Recently, clinical trials using insulin to lock blood glucose levels and activated protein C treatment have showed that while they provided some survival benefit, their efficacy does not appear to be predicated solely upon anti-inflammatory effects. Here, we will review work done in animal models of polymicrobial sepsis and clinical findings that support the hypothesis that apoptosis in the immune system is a pathologic event in sepsis that can be a therapeutic target. In this respect, experimental studies looking at the septic animal suggest that loss of lymphocytes during sepsis may be due to dysregulated apoptosis and that this appears to be brought on by a variety of mediators effecting 'intrinsic' as well as 'extrinsic' cell death pathways. From a therapeutic perspective this has provided a number of novel targets for clinically successful current, as well as future therapies, such as caspases (caspase inhibition/protease inhibition), pro-apoptotic protein-expression (via administration and/or over-expression of Bcl-2) and the death receptor family Fas-FasL (via. FasFP [fas fusion protein] and the application of siRNA against a number proapoptotic factors).

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“…These soluble mediators include eicosanoids, leukotrienes, complement, cytokines, chemokines, coagulation factors, and other potentially important small peptides and vasogenic substances. Multiple unsuccessful attempts have been made to block the inflammatory response; however, recent successes in patients with severe sepsis have come from broad-spectrum immunomodulation, such as APC (84) and low-dosage corticosteroids (95,96), rather than specific blockers of inflammation. Moreover, growing evidence suggests that the anti-inflammatory response to sepsis induces immunoparalysis and may be just as dangerous or even more deleterious compared with the proinflammatory response.…”

Section: Restoration Of Immune Homeostasismentioning

confidence: 99%

Potential Interventions in Sepsis-Related Acute Kidney Injury

Ronco¹,

Kellum²,

Bellomo³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Sepsis is an important cause of morbidity and mortality. Acute kidney injury often complicates sepsis, leading to greater complexity, cost of care, and worsening prognosis. In recent years, a consensus definition of acute kidney injury has been developed, facilitating research into the pathophysiology and epidemiology of this disorder. New and emerging biomarkers to recognize kidney injury before functional abnormalities are manifest may allow early recognition and facilitate prevention or treatment. Furthermore, advances in the clinical management of sepsis may have secondary benefits with respect to renal outcomes. Existing and hybrid extracorporeal therapies are being investigated not only as means to replace lost kidney function but also to modulate the immune response to sepsis. For those who have more advanced forms of kidney injury, strategies to promote renal recovery are being sought to minimize the long-term consequences of impaired kidney function. This review provides an update on the current state of the science and a glimpse toward the future of intervention in sepsis-related acute kidney injury.

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Corticosteroids in Sepsis: From Bench to Bedside?

Cited by 113 publications

References 113 publications

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

The Apoptotic Pathway as a Therapeutic Target in Sepsis

Potential Interventions in Sepsis-Related Acute Kidney Injury

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