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

"Severe sepsis" is defined by organ dysfunction due to infection-induced hypoperfusion. "Septic shock" is defined by hypotension refractory to fluid resuscitation, associated with organ dysfunctions or hypoperfusion. Mortality from severe sepsis and from septic shock is high. Guidelines to help physicians improve the survival of patients with severe sepsis comprise one part of an international project called the Surviving Sepsis Campaign. They bring together treatment innovations based on monitoring aimed at ensuring comprehensive management of tissue oxygen levels (central venous oxygen saturation: SvcO2). They are based on the optimization of early treatment, during the first six hours of severe sepsis, and ensuring no delay in fluid resuscitation. In case of septic shock, fluid resuscitation must be rapidly accompanied by administration of vasoconstrictive catecholamines. Noradrenaline is preferred to dopamine. Dobutamine is recommended when the cardiac index is less than 2.5 L x min(-1) x m(-2). Because of the relative adrenal insufficiency that occurs during septic shock, corticoids are recommended, after a synacthen test. Activated protein C is currently the only therapy produced by biotechnology that reduces mortality from severe sepsis. Global management of septic shock must form an integral part of resuscitation guidelines and include protocols for, among other things, sedation, ventilation, strict glycemic control, and prophylaxis for deep vein thrombosis and stress ulcers.
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PMID:[Non-infective treatments for septic shock]. 1678 62

Patients with cirrhosis are susceptible to bacterial infection, which can result in circulatory dysfunction, renal failure, hepatic encephalopathy, and a decreased survival rate. Severe sepsis is frequently associated with adrenal insufficiency, which may lead to hemodynamic instability and a poor prognosis. We evaluated adrenal function using short corticotropin stimulation test (SST) in 101 critically ill patients with cirrhosis and severe sepsis. Adrenal insufficiency occurred in 51.48% of patients. The patients with adrenal insufficiency had a higher hospital mortality rate when compared with those with normal adrenal function (80.76% vs. 36.7%, P < .001). The cumulative rates of survival at 90 days were 15.3% and 63.2% for the adrenal insufficiency and normal adrenal function groups, respectively (P < .0001). The hospital survivors had a higher cortisol response to corticotropin (16.2 +/- 8.0 vs. 8.5 +/- 5.9 microg/dL, P < .001). The cortisol response to corticotropin was inversely correlated with various disease severity, Model for End-Stage Liver Disease, and Child-Pugh scores. Acute physiology, age, chronic health evaluation III score, and cortisol increment were independent factors to predict hospital mortality. Mean arterial pressure on the day of SST was lower in patients with adrenal insufficiency (60 +/- 14 vs. 74.5 +/- 13 mm Hg, P < .001), and a higher proportion of these patients required vasopressors (73% vs. 24.48%, P < .001). Mean arterial pressure, serum bilirubin, vasopressor dependency, and bacteremia were independent factors that predicted adrenal insufficiency. In conclusion, adrenal insufficiency is common in critically ill patients with cirrhosis and severe sepsis. It is related to functional liver reserve and disease severity and is associated with hemodynamic instability, renal dysfunction, and increased mortality.
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PMID:Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. 1655 38

Adrenal insufficiency during sepsis is well documented. The association between hemorrhagic shock and adrenal insufficiency is unclear and may be related to ischemia, necrosis, or resuscitation. This study was designed to determine the incidence of relative adrenal insufficiency in hemorrhagic shock. A retrospective review of a prospectively gathered database for patients admitted to the trauma intensive care unit with hemorrhagic shock was undertaken. A random serum cortisol of <25 mcg/dL defined relative adrenal insufficiency. All of the cortisol levels were drawn within the first 24 hours of admission. Data analyzed included demographics, length of stay, injury mechanism, infections, and mortality. Fifteen patients presented with hemorrhagic shock, with 14 of 15 meeting the criteria for relative adrenal insufficiency. The average serum cortisol level was 15.8 (9-26.8). The average APACHE II score was 18.3 (4-33), and the average Injury Severity Score was 22.5 (8-41). The mechanism was blunt trauma in 10 patients and penetrating trauma in 5. The average intensive care unit and hospital length of stay were 13.2 and 27.4 days, respectively. There were five urinary tract infections, four blood stream infections, and two wound infections. Two of the 15 patients died. Relative adrenal insufficiency appears to be common in hemorrhagic shock. Future research is warranted to elucidate the pathophysiology, as well as to prospectively determine which patients may benefit from steroid replacement.
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PMID:Adrenal insufficiency in hemorrhagic shock. 1680 13

Corticosteroids were proposed for the treatment of sepsis as early as 1940. Several RCTs cast serious doubts on the usefulness of high dose corticosteroids and doubt still persists regarding the efficacy of replacement therapy. Adrenal insufficiency (non-responders to the 250 microg corticotropin test: increase in cortisol < 9 microg/dl) is present in about half of patients with septic shock and is associated with higher rates of refractory hypotension and mortality. Peripheral glucocorticoid resistance, which may even occur more frequently, can be easily assessed at bedside using skin tests. Cortisol antagonizes the migration of inflammatory cells, the synthesis or action of virtually all proinflammatory mediators, promotes virtually all anti-inflammatory components and enhances humoral immunity by means of transcriptional interference between its receptor and both AP-1 and NF-kappaB. Cortisol mediates cardiovascular tolerance to endotoxin and the maintenance of vascular sensitivity to catecholamines. Low doses (about 300 mg daily for 5 days or more) of hydrocortisone increase vasoconstrictor response to catecholamines in animals, in healthy volunteers challenged with LPS and in several RCTs. Hydrocortisone also increases arterial pressure and decreases the duration of shock. A meta-analysis of all available clinical controlled studies showed a reduction in 28 days, all-cause mortality with glucocorticoids (RR = 0.88, 95% CI: 0.78 - 1.00; p = 0.04). However, there was a significant heterogeneity across the trials (p = 0.006). On the other hand, analysis of studies where low doses of glucocorticoids were given for prolonged periods showed a 24% reduction in the risk of all-cause mortality at 28 days in treated patients (RR = 0.76, 95% CI: 0.64 - 0.90; p = 0.002) without heterogeneity across the trials (p = 0.28). In conclusion, in severe sepsis, high doses of corticosteroids should not be given. Septic shock should be treated with a replacement dose of hydrocortisone.
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PMID:Glucocorticoid treatment in patients with septic shock: effects on vasopressor use and mortality. 1696 Nov 59

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.
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PMID:Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival. 1798 20

There are many noninfectious disorders in the critical care unit (CCU) that mimic sepsis. Pseudosepsis is the term applied to noninfectious disorders that mimic sepsis. Fever/leukocytosis is not diagnostic of infection but frequently accompanies a wide variety of noninfectious disorders. When fever/leukocytosis and hypotension are present, sepsis is the presumptive diagnosis until proven otherwise. After empiric therapy for sepsis is initiated, the clinician should rule out the noninfectious causes of pseudosepsis. The most common causes of pseudosepsis in the CCU setting are pulmonary embolism, myocardial infarction, gastrointestinal hemorrhage, overzealous diuretic therapy, acute pancreatitis, relative adrenal insufficiency, and (rarely) rectus sheath hematoma. Rectus sheath hematoma may occur secondary to trauma/anticoagulation therapy and may present as an acute surgical abdomen mimicking sepsis. Rectus sheath hematoma should be considered when other causes of pseudosepsis or sepsis fail to explain persistent hypotension unresponsive to fluids/pressors. The diagnosis of rectus sheath hematoma is by abdominal ultrasound or computed tomography scan. If the abdominal computed tomography scan is negative for other intra-abdominal pathology and other causes of pseudosepsis are eliminated, then the diagnosis of pseudosepsis caused by rectus sheath hematoma is confirmed by demonstrating a hematoma in the rectus sheath. Treatment of rectus sheath hematoma is surgical drainage and ligation of any bleeding vessels. Evacuation of the rectus sheath hematoma rapidly reverses the patient's hypotension and is curative. We describe a case of pseudosepsis caused by rectus sheath hematoma in an elderly man with hypotension unresponsive to fluids/pressors and mimicking septic shock. Clinicians should be aware that rectus sheath hematoma is a rare but important cause of pseudosepsis in patients in the CCU.
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PMID:Pseudosepsis: rectus sheath hematoma mimicking septic shock. 1713 47

At the beginning of the 20th century, observations of apoplectic adrenal glands in fatal meningococcemia underlined their key role in host defence against infection. Thirty years later, cortisone was discovered and rapidly proven to have numerous and diversified physiological functions in the host response to stress. Corticosteroids were introduced in the treatment of severe infection as early as in the 1940s. Several 'negative' randomized controlled trials of high-dose of glucocorticoids given for a short period of time in the early course of severe sepsis or acute respiratory distress syndrome raised serious doubts as to the benefit of this treatment. Recently, a link between septic shock and adrenal insufficiency, or systemic inflammation-induced glucocorticoid receptor resistance has been established. This finding prompted renewed interest in a replacement therapy with low doses of corticosteroids during longer periods. We will review the key role of the hypothalamic-pituitary-adrenal axis in the host response to stress.
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PMID:The hypothalamic pituitary adrenal axis in sepsis. 1738 Jul 95

Among numerous non anti-infective treatments proposed in the management of severe sepsis and septic shock, early administration of steroids and recombinant human activated protein C are the most studied and the major source of debate. Patients with functional adrenal insufficiency appear to be the best cases for early treatment with low doses of hydrocortisone. However, definition of adrenal dysfunction, interpretation of cortisol blood concentration and its appropriateness, investigation of the hypothamalo-pituitary-adrenal axis and value of corticotropin stimulation test are matter of discussion. Similarly, recombinant human activated protein C might be beneficial in patients with severe sepsis and septic shock but the results of clinical trials are controversial. Structure of the PROWESS pivotal study, post hoc analyses of numerous subgroups, use of severity scoring system for selection of the patients, unproven mechanisms of action of activated Protein C, interactions with combined treatments represent major sources of confusion and of debate in the analysis of the trials. Non anti-infective treatments should be considered in selected patients when appropriate conventional treatments have been implemented. Use of these new treatments should bring additional improvement in the prognosis in severely ill patients at high risk of death.
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PMID:[Potential benefits of non-anti-infective treatments of septic shock: a critical analysis of literature]. 1739 18

Acute hypercytokinaemia represents an imbalance of pro-inflammatory and anti-inflammatory cytokines, and is believed to be responsible for the development of acute respiratory distress syndrome and multiple organ failure in severe cases of avian (H5N1) influenza. Although neuraminidase inhibitors are effective in treating avian influenza, especially if given within 48 h of infection, it is harder to prevent the resultant hypercytokinaemia from developing if the patient does not seek timely medical assistance. Steroids have been used for many decades in a wide variety of inflammatory conditions in which hypercytokinaemia plays a role, such as sepsis and viral infections, including severe acquired respiratory syndromes and avian influenza. However, to date, the results have been mixed. Part of the reason for the discrepancies might be the lack of understanding that low doses are required to prevent mortality in cases of adrenal insufficiency. Adrenal insufficiency, as defined in the sepsis/shock literature, is a plasma cortisol rise of at least 9 microg dl(-1) following a 250 microg dose of adrenocorticotropin hormone (ACTH), or reaching a plasma cortisol concentration of >25 microg dl(-1) following a 1-2 microg dose of ACTH. In addition, in the case of hypercytokinaemia induced by potent viruses, such as H5N1, systemic inflammation-induced, acquired glucocorticoid resistance is likely to be present. Adrenal insufficiency can be overcome, however, with prolonged (7-10 or more days) supraphysiological steroid treatment at a sufficiently high dose to address the excess activation of NF-kappaB, but low enough to avoid immune suppression. This is a much lower dose than has been typically used to treat avian influenza patients. Although steroids cannot be used as a monotherapy in the treatment of avian influenza, there might be a potential role for their use as an adjunct treatment to antiviral therapy if appropriate dosages can be determined. In this paper, likely mechanisms of adrenal insufficiency are discussed, drawing from a broad background of literature sources.
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PMID:A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. 1757 50

Recently, treatment with corticosteroids in the setting of septic shock and adrenal insufficiency has been shown to decrease mortality. In septic patients, a blunted response to adrenal stimulation identifies patients with a poorer prognosis who may benefit from corticosteroid supplementation. This condition has been termed relative adrenal insufficiency (RAI). Given the similarities between septic shock and liver failure, a number of groups have now studied the incidence of RAI in various forms of liver disease. Although different definitions of RAI exist, the current literature suggests that RAI is common, being seen in 33% of acute liver failure patients and up to 65% of patients with chronic liver disease and sepsis. The finding that RAI can exist in the absence of sepsis and may be as high as 92% of patients undergoing liver transplantation using a steroid free protocol has led one group to propose the term hepatoadrenal syndrome. The purpose of this review is to summarise the existing evidence for adrenal insufficiency in liver disease, to examine the possibility that adrenal dysfunction in liver disease may have a separate pathogenesis to that observed in sepsis and to provide insight into the potential areas for further research into this condition.
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PMID:Adrenal insufficiency in liver disease - what is the evidence? 1843 15


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