Severe Sepsis

epsis, a complex condition that results from an infectious process, represents the body’s response to infection and involves systemic inflammatory and cellular events that result in altered circulation and coagulation, endothelial dysfunction, and impaired tissue perfusion. Severe sepsis—sepsis with malfunctioning of one or more organs—is common, affecting 750,000 Americans and causing more than 200,000 deaths annually. Sepsis is a common source of morbidity and mortality among severely ill patients, and the number of sepsis-related deaths is increasing. Mortality rates associated with severe sepsis range from 28% to 50% or more, with higher rates resulting from an increasing number of dysfunctional organs. Recently, 11 international organizations, including critical care and infectious disease associations, launched a “Surviving Sepsis Campaign” to increase awareness of severe sepsis. A disease state that impacts the health status of acutely ill patients, healthcare costs, and resource use, sepsis requires increased nurse practitioner (NP) attention regarding its identification and appropriate management. S


I Clinical Identification
Because clinical presentations may vary, identifying sepsis may prove difficult. Often, patients with sepsis exhibit signs of the systemic inflammatory response syndrome (SIRS) criteria: • alteration in temperature (most often elevation) • heart rate (>90 beats/minute) • elevated respiratory rate (PaCo 2 <32 mm Hg or >20 breaths/ minute) • altered white blood cell count (>12,000 cells/mm 3 , <4,000 cells/ mm 3 , or >10% immature (band forms). 6 Clinical definitions describing sepsis have existed since 1992 and were recently modified to reflect the current knowledge base of sepsis pathophysiology. 6,7 To promote recognition of sepsis, experts proposed to add an expanded list of signs and symptoms to the SIRS criteria, which includes clinical indices of altered tissue perfusion (such as hypotension, decreased urine output, and de creased skin perfusion) and indices of impaired coagulation (such as decreased platelets and petech iae) (see Table: "Clinical Signs of Sepsis"). 7 Sepsis should be considered when patients exhibit two or more SIRS criteria along with symptoms of a known or suspected infection. 6 Although laboratory testing can confirm the presence of infection, in 20% to 30% of patients with sepsis, a definitive source of infection goes unidentified. 8

I Pathophysiology
The pathophysiology of sepsis is complex and involves activation of the inflammatory response to infection, along with activation of coagulation and impairment of fibrinolysis. 9,10 Increased inflammation and coagulation occur as the result of mediator responses, which function as part of the immune system reaction to infection. Cytokines-or mediators released from white blood cells during phagocytosis of infectious organisms and from an activated endothelium-activate proinflammation and procoagulation responses. Concurrently, fibrinolysis is impaired, leading to decreased clot breakdown.
The imbalance of inflammation, coagulation, and

Infectious Disease
fibrinolysis results in widespread inflammation, microvascular thrombosis, endothelial injury, and systemic coagulopathy, conditions that can lead to impaired tissue perfusion and organ system dysfunction. 16,17 As a systemic response to infection, sepsis is associated with organ system dysfunction. However, once organ system dysfunction occurs, sepsis is often severe and can progress to septic shock, which is sepsis with severe hypotension. The presence of altered organ function in an acutely ill patient with sepsis indicates a compromised blood flow and threatened tissue oxygenation. 12 I Organ System Dysfunction Impaired tissue perfusion and microvascular coagulation can lead to organ system dysfunction. In severe sepsis, changes in vital signs and laboratory indices, along with clinical evidence of altered tissue perfusion, reflect acute organ system dysfunction (see Table: "Signs of Acute Organ System Failure"). 13 As sepsis progresses, multiple organ system dysfunction can re sult, and is a major cause of sepsis-related mortality. 13 While all organs are prone to failure in sepsis, pulmonary, cardiovascular, and renal dysfunction occur most commonly. As organ system failure leads to cumulative increases in sepsis mortality, early recognition and treatment of sepsis becomes essential. 8

I Management Updates
Patients with sepsis require treatment of the underlying infection causing sepsis; the administration of fluids and inotropic and vasopressor agents to increase tissue perfusion; and targeted organ system support. Antibiotics are a mainstay of treatment; appropriate antibiotic therapy decreases sepsis mortality rates. 8,9 Identification of the infection source and targeted source control (such as removal of an infected catheter or debridement of an abscess) are equally important for preventing sepsis progression.
To promote evidence-based sepsis treatment, the Surviving Sepsis Cam paign recently developed specific treatment guidelines. 5 Patients re ceive targeted organ support, including mechanical ventilation, renal re placement therapy, fluids, vasopressor or inotropic administration, and blood product administration to max imize perfusion and oxygenation.
To combat inflammatory procoagulant antifibrinolytic responses, recombinant human activated protein C (Xigris) is indicated for patients with sepsis who have at least two of the SIRS criteria and evidence of early organ system dysfunction. 14 Xigris is the first approved cogin, a new class of agents that inhibits coagulation, decreases the inflammatory response, and promotes fibrinolysis in sepsis. Xigris therapy decreases mortality rates in severe sepsis. 14 As bleeding is a risk of Xigris administration, distinct contraindications to its use exist for patients with active bleeding or who are at high risk for bleeding. 25 While risk assessment is a consideration for use of Xigris therapy, treatment is indicated for patients with sepsis-induced organ failure and respiratory distress, and septic shock. 5 Several evidence-based treatment strategies show improved outcomes for septic patients, including tight glycemic control (maintaining blood glucose <150 mg/dL) and use of steroid therapy in those with adrenal insufficiency. 5,16,17 Treatment guidelines also include prophylactic treatment measures for deep vein thrombosis and stress ulcers. While the emphasis often falls on instituting treatment measures for sepsis to promote survival of critical illness, NPs should also address communication of the likelihood of survival needs. Recent research demonstrates the impact of family communications on end-of-life decision making. 12 As sepsis is a critical illness, addressing the expected outcomes of care remain an equally important aspect of the management plan.

I Impacting Outcomes
Patients with severe sepsis tend to have a complex medical course and are at risk for an extended hospitalization and treatment course, which can result in increased costs and higher mortality rates. In conjunction with the medical plan of care, NPs play an important role in monitoring patients at risk for sepsis, promoting early detection of sepsis, and instituting treatment measures (see Table: "Measures to Improve Outcomes"). 19 Because treatment advances continually evolve, keeping up-to-date with the literature and with novel management strategies can prove challenging. Therefore, ensure continuing education for NPs and other members of the

Recognition:
Monitor vital sign changes; observe for signs of infection, presence of SIRS criteria.

Assessment:
Monitor for signs of organ system dysfunction (such as cardiovascular compromise with tachycardia and hypotension; respiratory compromise requiring mechanical ventilation, onset of acute lung injury and/or acute respiratory distress syndrome; acute renal failure with oliguria; hematologic abnormalities; skin color changes; altered neurologic status).

Comprehensive sepsis treatment:
Provide circulatory support with fluids, inotropes, and vasopressors; provide supportive treatment with oxygenation and ventilation; administer antibiotics; provide Xigris therapy; monitor and report patient response to treatment.
Patient and family comfort/care: Promote patient comfort, pain relief, sedation, turning, skin care; provide patient and family teaching; address needs of families of critically ill patients.

Sepsis prevention measures:
Take measures to prevent nosocomial infections: handwashing, oral care, proper positioning (semirecumbent position during mechanical ventilation), turning and skin care, invasive catheter care, and wound care; identify patients at risk for sepsis.

Infectious Disease
healthcare team. Promote early recognition and advocate for appropriate use of therapies to aggressively treat and prevent progression of sepsis-a fundamental strategy for achieving best outcomes.
Using quality indicators to target sepsis treatment is one successful strategy for improving sepsis care. 20 Through the use of evidence-based management principles, one healthcare system created a model to redesign care processes for septic patients. While research to test the model is ongoing, it can serve as a framework for other institutions to improve sepsis treatment. The Institute for Healthcare Improve ment, in partnership with several national organizations, recently developed another initiative that can serve as a template for improving care for patients with sepsis. Called the "Sepsis Bundle," the initiative is a group of interventions (including early diagnosis, antibiotic administration, glucose control, mechanical ventilation, and the use of drotrecogin alfa) that, when implemented together, can create better outcomes for sepsis patients. 21 Nurse practitioners can improve severe sepsis management by further testing and disseminating these initiatives (see Table: "Management Strategies").
Tracking sepsis cases and collecting unit-based and aggregate data related to the outcome of sepsis care can help identify improvement needs. Examining treatment practices and correlating clinical and economic outcomes can serve to point out evidence of performance improvements, as well as demonstrate areas needing continued emphasis.
Sepsis is a disease entity that challenges clinicians on how best to target treatment strategies for a complex condition with a high mortality rate. Nurse practitioners remain in a unique position to champion sepsis detection and treatment initiatives that enhance patient outcomes.