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

Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is viewed. Although complex and challenging, these therapies must be brought to the patient's bedside. We propose and describe the Multiple Urgent Sepsis Therapies (MUST) protocol as a practical way to implement a comprehensive treatment plan using available evidence-based therapies.
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PMID:A blueprint for a sepsis protocol. 1614 Oct 31

Glucocorticoids (GC) are essential for the body to maintain homeostasis. Patients with adrenal insufficiencies suffer from numerous health related problems including increased mortality due to sepsis. Here, we examine bone marrow (BM) cells from mice with adrenal insufficiency for their ability to produce nitric oxide (NO). Mice were injected with metyrapone (MR), an agent that selectively blocks glucocorticoid synthesis. BM cells were removed and tested for NO production. The stimulating agents LPS, TNF-alpha, IL-1beta, and IL-4 were all able to synergize with IFN-gamma, stimulating large concentrations of NO compared to normal mice. An important finding is that BM from injected mice produces NO in response to LPS alone, while normal BM cells do not. Experiments with anti IFN-gamma antibody demonstrate that, in MR injected mice, LPS alone stimulated sufficient quantities of IFN-gamma necessary for NO production. Our results demonstrate that reducing GCs alters regulation of NO production by BM cells at several levels.
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PMID:Decreasing endogenous glucocorticoids alters the ability of bone marrow cells to produce nitric oxide in response to stimulating agents. 1592 13

Since the publication of two case reports that are considered to represent the first clinical demonstration of iatrogenic adrenal insufficiency, it has been the generally accepted practice to cover steroid-treated patients undergoing surgery with glucocorticoids in the perioperative period. Both the inclusion criteria for the patients and the extent of the substitution pattern have been selected on an empirical rather than on a rational basis. Scientific advances over the past 50 years in the knowledge of the hypothalamic-pituitary-adrenal system's physiology and the molecular mechanism of action of its biologically active components are, for the most part, not reflected in current clinical practice and instead seem to be ignored. Clinical and experimental evidence suggests, however, that even glucocorticoid-treated patients undergoing surgery do not require maximum stress doses of hydrocortisone, which should be reserved for the treatment of sepsis. With regard to the broad spectrum of efficacy of glucocorticoids and their side effects, revision and modification of the historical regimen appear prudent.
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PMID:[Adrenal cortex and steroids. Supplementary therapy in the perioperative phase]. 1893 64

This is the first reported case of lymphoproliferative disease presenting with adrenal insufficiency after liver transplantation. A 38-year-old white man was admitted 8 months after transplantation for cryptogenic cirrhosis with fever (38-39 degrees C), chills, cough, and dyspnea. His blood pressure was 100/70 mm Hg, there was pallor of the conjunctiva, and a lymph node was palpable in the left groin. Laboratory analyses revealed the following values: serum sodium concentration (112 mmol/L), potassium (5.4 mmol/L), hemoglobin (7.8 g/L), white blood cell count (7.7 x 10(9)/L), glucose 3.9 (mmol/L), and mildly elevated liver functions. Abdominal ultrasound showed multiple hypoechoic solid-appearing lesions throughout the liver and spleen. Results of a biopsy specimen of the groin node confirmed polymorphic B-cell lymphoma. A negative Epstein- Barr virus screen before transplant became positive. The patient's fever increased to 40 degrees C. He subsequently developed sepsis and later, multiple organ failure. Autopsy confirmed extensive abdominal disease. The adrenal glands had been completely replaced by the tumor. Primary Epstein-Barr virus infection is associated with posttransplant lymphoproliferative disease. Replacement of the adrenal glands with a tumor produces a clinical picture of adrenal insufficiency.
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PMID:Posttransplant lymphoproliferative disease presenting as adrenal insufficiency: case report. 1598 81

Corticosteroids have been considered for decades for the treatment of severe sepsis and septic shock, based on their pivotal role in the stress response and their hemodynamic and antiinflammatory effects. Whereas short-term therapy with high doses of corticosteroids (up to 42 g hydrocortisone equivalent for 1-2 days) has been ineffective or potentially harmful, prolonged therapy with lower doses (200-300 mg hydrocortisone for 5-7 days or longer) in septic shock has recently revealed beneficial effects in several randomized, controlled trials. Assuming relative adrenal insufficiency (RAI) and peripheral cortisol resistance, treatment with low-dose hydrocortisone improved shock reversal, reduced inflammation, and improved outcome. Shock reversal and reduction of mortality were more effective in patients with RAI, and most significant in patients with severe shock. Diagnosis of RAI with corticotropin tests in septic shock, however, is highly dependent on cut-off values and definition of RAI. Thus, it is not clear yet which patients benefit most from low-dose hydrocortisone and if treatment should be restricted to patients with RAI. In addition the role of fludrocortisone is uncertain. Nevertheless, based on current data, low-dose hydrocortisone therapy should definitely be considered in vasopressor-dependent septic shock. This review will address some critical points.
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PMID:Corticosteroid therapy in patients with severe sepsis and septic shock. 1608 13

Adrenal insufficiency is a rare disease, but its prevalence is increasing. The most frequent cause of primary adrenal insufficiency in western countries is autoimmune adrenalitis, whereas secondary adrenal insufficiency is most often caused by pituitary tumours and their treatment (e.g., surgery). Chronic glucocorticoid replacement consists of hydrocortisone 15-25 mg/day in divided doses and dose monitoring is largely based on clinical judgement. Fludrocortisone 0.05-0.2 mg/day is given for substitution in mineralocorticoid deficiency aiming at normotension, normokalaemia and a plasma renin activity in the upper normal range. It has recently been shown that, despite adequate glucocorticoid and mineralocorticoid replacement well being in patients with adrenal insufficiency is still impaired. Several studies have demonstrated that dehydroepiandosterone 25-50 mg/day p.o. may improve mood, fatigue, well-being and, in women, also sexuality, suggesting that dehydroepiandosterone should become part of the standard treatment regime. However, large Phase III trials of dehydroepiandosterone for adrenal insufficiency are still lacking and it has not yet been approved for the treatment of this disease. Patients with adrenal insufficiency are at risk of adrenal crisis, usually precipitated by major stress, such as severe infection or surgery. Early dose adjustments are required to cover the increased glucocorticoid demand in stress. Careful and repeated education of patients and their partners is the best strategy to avoid this life-threatening emergency. Some recent studies suggest that during sepsis some patients with intact adrenal function may develop transient relative adrenal insufficiency and benefit from administration of hydrocortisone plus fludrocortisone. However, the pathophysiology and diagnosis criteria of relative adrenal insufficiency and its treatment remain unsettled issues.
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PMID:Management of adrenal insufficiency in different clinical settings. 1625 72

Septic shock occurs in 6 % of paediatric cancer patients with neutropenia and fever. The mortality of the septic shock is 40 % in BMT patients and 5 % in others. One third of paediatric ARDS cases affect immunocompromised individuals with a total mortality of 45 % and 80 % after BMT. Septic shock is caused by gram-negative bacteria in more than 75 %. ARDS is due to pneumonia in more than 50 %, sepsis in about 25 %. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for treatment of septic shock and ARDS. Therapy of septic shock includes early antibiotic therapy and volume expansion (> or = 40 ml/kg initially). Refractory shock requires vasopressors (noradrenaline), followed by a judicious circulatory management. Hydrocortisone is indicated in patients with high probability of adrenal insufficiency. Mainstay of ARDS therapy is ventilation with sufficient end-expiratory pressure (PEEP) to prevent loss of functional residual capacity and with limited tidal volumes (< or = 6 ml/kg) and limited inspiratory pressure (< 35 cm H(2)O) respectively, to minimize ventilator induced lung injury. Volume therapy consists of maintenance of sufficient preload to counteract the impaired venous return, induced by positive pressure ventilation. Diuretics and eventually veno-venous haemofiltration are used to reduce free lung water. Surfactant application may be considered in severe cases. Steroids are indicated in pneumocystis carinii pneumonia and in engraftment pneumonitis.
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PMID:[Management of septic shock and acquired respiratory distress syndrome in pediatric cancer patients]. 1628 59

The diagnosis of adrenocortical insufficiency in critically ill patients is complex. The adrenocorticotropic hormone (ACTH) stimulation test is a widely accepted method for assessing the adequacy of adrenal function in intensive care units, but it is possible that there may be wide variations in responses to the test over a short period of time. In this prospective study, we investigated the reproducibility of the ACTH stimulation test in 20 patients with sepsis, in 20 patients with septic shock, and in 20 critically ill patients without sepsis. Two consecutive ACTH stimulation tests were performed within 24 h after intensive care unit admission or at the onset of sepsis. In patients without sepsis there was good correlation between ACTH responses on days 1 and 2 (Pearson's correlation coefficient, 0.689; P = 0.001). In contrast, in patients with septic shock no correlation was observed between the two ACTH responses (Pearson's correlation coefficient, 0.401; P = 0.080). We conclude that the results of the ACTH stimulation tests are poorly reproducible in septic shock and a single ACTH stimulation test may not be the best method to diagnose adrenal insufficiency in these patients.
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PMID:A single adrenocorticotropic hormone stimulation test does not reveal adrenal insufficiency in septic shock. 1700 Aug 52

We describe an interesting case of a patient who recovered function of a previously failed kidney allograft after immunosuppressive medications were discontinued for 4 months, requiring maintenance hemodialysis. He had a split-thickness skin graft to his abdomen because of previous surgical complications. His postoperative course was complicated by sepsis and refractory hypotension. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone. At the same time, hemodialysis was stopped for possible catheter-related infection. The patient recovered function of the previously failed allograft and has not required hemodialysis.
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PMID:Recovery of allograft function after complete withdrawal of immunosuppression. 1638 25

Several lines of evidence support the use of corticosteroids as adjunctive therapy for sepsis. In human trials, high-dose, short-course corticosteroid therapy for sepsis has not shown benefit, but prolonged use of low doses has shown benefit in patients with vasopressor-dependent septic shock. The Corticosteroid Therapy of Septic Shock (CORTICUS) trial is addressing the remaining questions regarding the ideal target population for corticosteroid therapy, as well as the best definition of relative adrenal insufficiency in the critically ill.
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PMID:Use of corticosteroids in the sepsis syndrome: what do we know now? 1639 26


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