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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For more than five decades, the use of corticosteroids as an adjunctive therapy to treat severe sepsis and septic shock has incited consistent debate. Negative results of the Corticosteroid Therapy of Septic Shock (CORTICUS) study evoked a revision of Surviving Sepsis Campaign guidelines suggesting a more restricted use of low-dose hydrocortisone only in patients with severe septic shock. Hemodynamic improvement by low-dose steroids was evident and independent from adrenal insufficiency, but did not improve survival. The roles of cortisol measurement and adrenal function tests for treatment decisions have been questioned. An international task force introduced the concept of critical illness-related corticosteroid insufficiency, which challenges the predominant role of adrenal dysfunction and underscores sustained inflammation due to tissue steroid resistance. Whether moderate steroid doses induce superinfections and muscle weakness is unclear. This article reviews recent publications, actual recommendations, ongoing discussions, and future perspectives.
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PMID:Adjunctive therapies in severe sepsis and septic shock: current place of steroids. 1868 98

The role of the hypothalamic-pituitary adrenal axis in the host response to infection is crucial. The initial inflammatory response to sepsis activates the endogenous release of cortisol, which in turn modulates the synthesis and release of both pro- and anti-inflammatory mediators to restrict inflammation in infected tissues. However, a number of factors, including vascular or ischemic damage, inflammation and apoptosis within the hypothalamic-pituitary adrenal axis, as well as use of drugs that alter cortisol metabolism, may cause adrenal insufficiency. One major problem ICU physicians are faced with is the diagnosis of sepsis-induced adrenal insufficiency at the bedside. A multidisciplinary international task force has recently recommended that sepsis induced adrenal insufficiency is best recognized by basal cortisol of less than 10 microg/dl or change in cortisol of less than 9 microg/dl after administration of corticotrophin. The diagnostic value of measuring salivary free cortisol in this setting remains to be investigated. While sepsis adrenal insufficiency is undoubtedly associated with a poor prognosis, the indication and practical modalities of corticosteroids therapy remained controversial. Based on the two largest randomised, placebo-controlled trials, many investigators, myself included, contend that septic shock patients with hypotension poorly responsive to fluid replacement and vasopressors should receive a seven day treatment with the combination of hydrocortisone at a dose of 200 mg per day and fludrocortisone at the dose of 50 microg per day.
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PMID:Adrenal insufficiency in sepsis. 1869 Oct 99

Etomidate blocks the cortisol synthesis by specifically inhibiting the activity of 11 beta-hydroxylase, resulting in a primary adrenal insufficiency. Therefore, a serum accumulation of 11 beta-deoxycortisol and a low secretion of serum cortisol must be required as diagnostic criteria to assign that adrenal impairment to the drug. These requirements have been rarely fulfilled in studies exploring the contribution of etomidate to the adrenal insufficiency despite numerous causes of adrenal derangement. In critically ill patients without sepsis, a single dose of etomidate results in a wide adrenal inhibition, reversible in 48 h after etomidate administration. Although there are still uncertainties as to whether etomidate directly affects mortality and morbidity, it seems preferable to avoid the use of etomidate in patients with severe sepsis and septic shock. In patients with severe traumatic brain injury, arterial hypotension is one of major factors of poor outcome and can be prevented with the use of etomidate for facilitating tracheal intubation. Substitutive opotherapy with low doses of hydrocortisone should be assessed after a single dose of etomidate for critically ill patients.
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PMID:[Should etomidate still be used?]. 1898 Aug 26

Patients with established cirrhosis are at increased risk of sepsis. Bacterial infections are a frequent cause of morbidity and mortality in patients with advanced liver disease. Mortality for patients admitted to hospital with bacterial infection is approximately 30%, whereas the development of septic shock and multiorgan failure is associated with a mortality of 70-100%. Activation of the hypothalamic-pituitary-adrenal axis is an important feature of a patient's response to severe sepsis and major trauma. An inadequate adrenal response with suboptimal cortisol production has been recognized in patients with septic shock. Patients with septic shock and adrenal insufficiency have reduced response to vasoconstrictor agents, higher rates of refractory shock and high mortality rates. An improvement in survival with administration of hydrocortisone in patients with septic shock and an inadequate adrenal response has been demonstrated. In a more recent study, however, there was no survival benefit in septic shock though reversal of shock was faster with hydrocortisone administration. Recently, adrenal insufficiency has been demonstrated in patients with severe liver disease such as acute liver failure, acute on chronic liver failure, recent liver transplantation and cirrhosis irrespective of the presence of sepsis. Nevertheless survival benefit with administration of hydrocortisone has only been demonstrated in patients with cirrhosis and septic shock. A case report of a patient with cirrhosis and adrenal insufficiency is presented with a review of the literature.
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PMID:Relative adrenal insufficiency in a patient with liver disease. 1938 44

We report a case of a 65-year-old lady who presented with acute confusion and profound hyponatraemia (plasma sodium of 97 mmol/L). Five years earlier she had developed sepsis and was found to have hyponatraemia, thought to be due to syndrome of inappropriate antidiuretic hormone secretion. The patient was lost to follow-up. The patient was covered with steroids and investigations confirmed primary adrenal failure with flat response of cortisol to adrenocorticotropic hormone (ACTH) stimulation and very high level of ACTH. Adrenal auto-antibodies were negative and a computed tomography of the adrenals showed bilateral adrenal calcifications, suggestive of previous haemorrhage or infarction. Bilateral adrenal calcification due to haemorrhage/infarction usually does not present with severe hyponatraemia; however, adrenal insufficiency should be excluded in all cases of severe hyponatraemia. In suspected cases, patients should be treated with steroids, even when symptoms or signs are absent, while results of investigations are awaited.
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PMID:An unusual case of profound hyponatraemia and bilateral adrenal calcifications. 1979 4

Adrenal insufficiency has being reported with increased frequency in critical ill patients with sepsis and other inflammatory states. Its incidence varies widely depending on the criteria used to define it and the patient population studied. Increased glucocorticoid action is essential in the stress response to acute injury and even minor degrees of adrenal insufficiency can be fatal. Recently the so-called relative or functional adrenal insufficiency (CIRCI) has been described: in this syndrome cortisol levels may be low or high but nonetheless inadequate to meet the elevated metabolic demand. Since laboratory diagnosis of adrenal insufficiency is still controversial, the diagnosis of ICU associated adrenal insufficiency is essentially a clinical diagnosis. Whether exogenous corticosteroid support may be beneficial in critical illness is still matter of debate: most international guidelines recommend that the decision to treat patients with corticosteroids should be based on clinical criteria (low blood pressure poorly responsive to vasopressor despite adequate fluid resuscitation) rather than on tests of the hypothalamic-pituitary-adrenal axis alone. As regards specifically the role of steroids in the treatment of sepsis and septic shock, at present there are no strong evidence-based recommendations. More studies are needed to reach consensus about several issues: which is the best target population, whether a cosyntropin test should be used to guide treatment, whether fludrocortisones should be given along with hydrocortisone, and how long treatment should continue.
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PMID:Use of corticosteroids in critically ill septic patients : a review of mechanisms of adrenal insufficiency in sepsis and treatment. 1979 43

Sepsis is physiologically viewed as a proinflammatory and procoagulant response to invading pathogens. There are three recognized stages in the inflammatory response with progressively increased risk of end-organ failure and death: sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to develop sepsis, sepsis-induced organ failure, and death. There is evidence that in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response ("cytokine storm"), which converts responses that are normally beneficial for fighting infections into excessive, damaging inflammation. Molecular mechanisms for this excessive proinflammatory response are poorly understood. In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to play a role in the worsening of liver function and the development of organ/system failures such as shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In addition, these patients may have sepsis-induced hyperglycemia, defective arginine-vasopressin secretion, adrenal insufficiency, or compartmental syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), early use of antibiotics and intravenous albumin administration decreases the risk for developing renal failure and improves survival. There are no randomized studies that have been specifically performed in patients with cirrhosis and severe sepsis to evaluate treatments that have been shown to improve outcome in patients without cirrhosis who have severe sepsis or septic shock. These treatments include recombinant human activated C protein and protective-ventilation strategy for respiratory failure. Other treatments should be evaluated in the cirrhotic population with severe sepsis including the early use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone, renal-replacement therapy and liver support systems, and selective decontamination of the digestive tract or oropharynx.
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PMID:Severe sepsis in cirrhosis. 2037 75

The concept of relative adrenal insufficiency in patients with severe sepsis continues to be controversial. This arises in part from the lack of an accepted "gold standard" for the diagnosis of adrenal insufficiency in the critically ill. Historically, assessment of adrenal function in this population has relied on measurement of plasma total cortisol level, in a blood sample taken either at random or as part of a corticotropin stimulation test. However, an alternative is to focus on the site of glucocorticoid activity within the tissues as a potentially more useful index of functional adrenal status. We review the mechanisms known to affect tissue glucocorticoid activity and examine how they may be modified by critical illness. These include both free and interstitial cortisol concentrations, intracellular cortisol generation, and glucocorticoid-receptor activity and density. Changes in these factors are not reflected in plasma total cortisol concentrations, and more sophisticated techniques, including genetic transcriptional surveys, may be required to reveal the role of glucocorticoid insufficiency in critical illness.
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PMID:Assessment of tissue cortisol activity. 2000 69

Dysfunction of the hypothalamo-pituitary adrenal axis has become a central feature in descriptions of the pathophysiology of sepsis. However; despite hundreds of published articles including literature reviews and consensus statements, controversy still exists regarding the fundamental nature of the disorder and its relevance to clinical management. Often referred to as 'relative adrenal insufficiency', a recent consensus conference has proposed the alternate term 'critical illness related corticosteroid insufficiency' and suggested diagnostic criteria of a delta serum cortisol of less than 9 microg/l after adrenocorticotrophic hormone administration or a random total cortisol of under 10 microg/l. This review attempts to establish a critical reappraisal of the evidence for the existence of relative adrenal insufficiency/critical illness related corticosteroid insufficiency in patients with sepsis and examines the background, controversies and possibilities for future research into the condition.
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PMID:Relative adrenal insufficiency in the intensive care population; background and critical appraisal of the evidence. 2051 49

Patients with established cirrhosis are at increased risk of sepsis. Bacterial infections are a frequent cause of morbidity and mortality in patients with advanced liver disease. Mortality for patients admitted to hospital with bacterial infection is approximately 30%, whereas the development of septic shock and multiorgan failure is associated with a mortality of 70-100%. Activation of the hypothalamic-pituitary-adrenal axis is an important feature of a patient's response to severe sepsis and major trauma. An inadequate adrenal response with suboptimal cortisol production has been recognized in patients with septic shock. Patients with septic shock and adrenal insufficiency have reduced response to vasoconstrictor agents, higher rates of refractory shock and high mortality rates. An improvement in survival with administration of hydrocortisone in patients with septic shock and an inadequate adrenal response has been demonstrated. In a more recent study, however, there was no survival benefit in septic shock though reversal of shock was faster with hydrocortisone administration. Recently, adrenal insufficiency has been demonstrated in patients with severe liver disease such as acute liver failure, acute on chronic liver failure, recent liver transplantation and cirrhosis irrespective of the presence of sepsis. Nevertheless survival benefit with administration of hydrocortisone has only been demonstrated in patients with cirrhosis and septic shock. A case report of a patient with cirrhosis and adrenal insufficiency is presented with a review of the literature.
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PMID:Relative adrenal insufficiency in a patient with liver disease. 2061 Oct 8


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