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Severe sepsis is a common cause of admission to the intensive care unit and is associated with a high hospital mortality. This audit explored the current use of, and attitudes towards, recombinant activated protein C therapy across Scotland, and compared these with current guidance. Patients with severe sepsis were followed for three days. Consideration and/or usage of recombinant activated protein C were compared with two different guidelines. Ninety-seven patients were admitted to the intensive care unit over the audit period. Recombinant activated protein C was used in nine of these patients. Depending on the criteria used, between 50% and 81% of the patients who qualified for recombinant activated protein C therapy did not receive it. Subsequent to the audit, a survey was performed to study intensive care unit consultants\' attitudes to recombinant activated protein C therapy. A total of 125 consultants responded to the survey (77%). Of these, 104 (83%) stated that they used recombinant activated protein C in their clinical practice, 56 (52%) of whom prescribed it to patients with two-organ failures and an Acute Physiology and Chronic Health Evaluation II score of ≥ 25. Thirty-nine respondents (38%) stated that two-organ failures alone would be an adequate trigger for therapy. We conclude that recombinant activated protein C is potentially under-used to treat severe sepsis. Many consultants seem to reserve the drug for the most severely ill sub group of patients.

Realizing the vast medical benefits of validated protocols, recommendations and practice guidelines requires acceptance and implementation by frontline care providers. Knowledge translation is the science of accelerating the transfer of knowledge to practice by understanding and creatively addressing the barriers that prevent adoption of new professional standards. In an attempt to improve patient care and reduce mortality, the Surviving Sepsis Campaign and The Institute for Healthcare Improvement created the resuscitation and management bundles for patients with severe sepsis and septic shock. These bundles have been accepted as best practice by many clinicians since multiple clinical trials have produced similar positive results when they were implemented. However, transferring these research outcomes-based guidelines to the clinical practice arena has been associated with poor compliance due to important barriers to implementation. Delays in the adoption of sepsis bundles are not surprising since the time from validation to implementation of a new clinical practice is typically 17 years. Using sepsis bundles as a model, this article explores why guidelines are important, examines physician adherence to protocols, and reviews the literature on strategies to improve clinical compliance and enhance knowledge translation.

BACKGROUND: Bundles yield a reduction in mortality in patients with sepsis, but the majority of the data is from large academic centers. The ability of a community hospital to implement a sepsis bundle successfully, however, has not been investigated.
OBJECTIVE: To examine the effect of a collaborative 2-part sepsis bundle on clinical outcomes and mortality at a community hospital.
METHODS: The study included all patients with severe sepsis/septic shock over the age of 18 years admitted to the intensive care unit (ICU) from 2006 to 2007 who were not treated with a bundle (n = 53) and those who were treated with a bundle (n = 59). Data collected included demographics; initiation of vasopressors; days on vasopressors; blood glucose; use of drotrecogin alfa (activated), steroids, and ventilator; ICU/hospital lengths of stay; ventilator days; time to culture; time to first dose of antibiotics; time to transfer from emergency department to ICU; fluid resuscitation in the first 24 hours; percentage of patients started on dialysis; and mortality.
RESULTS: Demographics; blood glucose; use of drotrecogin alfa (activated), steroids and ventilator; ICU/hospital lengths of stay; and ventilator days were statistically similar between groups. Median time to cultures, first dose of antibiotics, and transfer to ICU were all reduced with the bundle. Percentage of non-bundle patients on vasopressors was 87% versus 66.7% of bundle patients (p = 0.011) and number of median days on vasopressors was reduced. Fewer bundle patients were initiated on dialysis (0%) versus non-bundle patients (14.8%) (p = 0.02). Median fluid administered in the first 24 hours was 2200 mL (10-13,996 mL) for non-bundle patients and 7143 mL (1000-19,104 mL) for bundle patients (p < 0.001). Mortality was 61.1% in the non-bundle group versus 20% with the bundle (p < 0.001).
CONCLUSIONS: Implementation of a 2-part sepsis bundle based on the Surviving Sepsis Campaign Guidelines can yield a positive impact on clinical outcome and mortality in a nonacademic, community hospital setting.

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Severe sepsis has a high mortality, and both incidence and mortality increases with increasing age. In recent years, several specific therapies have been recommended by guidelines to reduce mortality in severe sepsis. We review the age distribution in the key clinical trials on which these recommendations are made. Many therapeutic strategies have been evaluated, mainly in younger patients, with extrapolation of evidence toward the older population. Specific evidence of benefit in the elderly is present regarding treatment with activated protein C and ventilatory strategies. In view of the pharmacokinetic and pharmacodynamic differences in older people, and the higher incidence of comorbidity in the elderly, there is a need for clinical trials in severe sepsis to specifically include older patients.

The diagnosis of disseminated intravascular coagulation (DIC) should encompass both clinical and laboratory information. The International Society for Thrombosis and Haemostasis (ISTH) DIC scoring system provides objective measurement of DIC. Where DIC is present the scoring system correlates with key clinical observations and outcomes. It is important to repeat the tests to monitor the dynamically changing scenario based on laboratory results and clinical observations. The cornerstone of the treatment of DIC is treatment of the underlying condition. Transfusion of platelets or plasma (components) in patients with DIC should not primarily be based on laboratory results and should in general be reserved for patients who present with bleeding. In patients with DIC and bleeding or at high risk of bleeding (e.g. postoperative patients or patients due to undergo an invasive procedure) and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered. In non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless it is perceived that there is a high risk of bleeding. In bleeding patients with DIC and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful. It should not be instituted based on laboratory tests alone but should be considered in those with active bleeding and in those requiring an invasive procedure. There is no evidence that infusion of plasma stimulates the ongoing activation of coagulation. If transfusion of FFP is not possible in patients with bleeding because of fluid overload, consider using factor concentrates such as prothrombin complex concentrate, recognising that these will only partially correct the defect because they contain only selected factors, whereas in DIC there is a global deficiency of coagulation factors. Severe hypofibrinogenaemia (<1 g/l) that persists despite FFP replacement may be treated with fibrinogen concentrate or cryoprecipitate. In cases of DIC where thrombosis predominates, such as arterial or venous thromboembolism, severe purpura fulminans associated with acral ischemia or vascular skin infarction, therapeutic doses of heparin should be considered. In these patients where there is perceived to be a co-existing high risk of bleeding there may be benefits in using continuous infusion unfractionated heparin (UFH) due to its short half-life and reversibility. Weight adjusted doses (e.g. 10 mu/kg/h) may be used without the intention of prolonging the APTT ratio to 1.5-2.5 times the control. Monitoring the APTT in these cases may be complicated and clinical observation for signs of bleeding is important. In critically ill, non-bleeding patients with DIC, prophylaxis for venous thromboembolism with prophylactic doses of heparin or low molecular weight heparin is recommended. Consider treating patients with severe sepsis and DIC with recombinant human activated protein C (continuous infusion, 24 microg/kg/h for 4 d). Patients at high risk of bleeding should not be given recombinant human activated protein C. Current manufacturers guidance advises against using this product in patients with platelet counts of <30 x 10(9)/l. In the event of invasive procedures, administration of recombinant human activated protein C should be discontinued shortly before the intervention (elimination half-life approximately 20 min) and may be resumed a few hours later, dependent on the clinical situation. In the absence of further prospective evidence from randomised controlled trials confirming a beneficial effect of antithrombin concentrate on clinically relevant endpoints in patients with DIC and not receiving heparin, administration of antithrombin cannot be recommended. In general, patients with DIC should not be treated with antifibrinolytic agents. Patients with DIC that is characterised by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues, such as tranexamic acid (e.g. 1 g every 8 h).

The choice of inotropic agent, particularly in catecholamine-resistant septic shock, remains an area of debate. Here we discuss a recent trial examining the use of vasopressin in a carefully controlled trial setting. Yet more data on the use of drotrecogin alfa (activated) in septic shock are described, as are novel but as yet experimental approaches to the treatment of sepsis. Finally, it is important not to forget to read the latest surviving sepsis guidelines.