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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The hypothalamic-pituitary-adrenal (HPA) axis response in sepsis remains to be elucidated. Apart from corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol, many other neuroendocrine factors participate in the regulation of HPA stress response. The HPA response to acute and chronic illness exerts a biphasic profile. Tissue corticosteroid resistance may also play an important role. All of these add to the complexity of the concept of 'relative adrenal insufficiency' and may account for the difficulty of clinical diagnosis and for the conflicting results of corticosteroid replacement therapy in severe sepsis/septic shock. The study by Lesur and colleagues expands our understanding of the mechanism, and further study of HPA stress response is warranted.
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PMID:Sepsis-related stress response: known knowns, known unknowns, and unknown unknowns. 2061 66

Despite its widespread use in North America and many other parts of the world, the safety of etomidate as an induction agent for rapid sequence intubation in septic patients is still debated. In this article, we evaluate the current literature on etomidate, review its clinical history, and discuss the controversy regarding its use, especially in sepsis. We address eight questions: (i) When did concern over the safety of etomidate first arise? (ii) What is the mechanism by which etomidate is thought to affect the adrenal axis? (iii) How has adrenal insufficiency in relation to etomidate use been defined or identified in the literature? (iv) What is the evidence that single dose etomidate is associated with subsequent adrenal-cortisol dysfunction? (v) What is the clinical significance of adrenal insufficiency or dysfunction associated with single dose etomidate, and where are the data that support or refute the contention that single-dose etomidate is associated with increased mortality or important post emergency department (ED) clinical outcomes? (vi) How should etomidate's effects in septic patients best be measured? (vii) What are alternative induction agents and what are the advantages and disadvantages of these agents relative to etomidate? (viii) What future work is needed to further clarify the characteristics of etomidate as it is currently used in patients with sepsis? We conclude that the observational nature of almost all available data suggesting adverse outcomes from etomidate does not support abandoning its use for rapid sequence induction. However, because we see a need to balance theoretical harms and benefits in the presence of data supporting the non-inferiority of alternative agents without similar theoretical risks associated with them, we suggest that the burden of proof to support continued widespread use may rest with the proponents of etomidate. We further suggest that practitioners become familiar with the use of more than one agent while awaiting further definitive data.
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PMID:Etomidate as an induction agent in septic patients: red flags or false alarms? 2082 67


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