A Guide To Severe Sepsis

Every year, more than 750,000 people in the United States develop severe sepsis (sepsis with associated acute organ failure), a syndrome characterized by an overwhelming systemic response to infection, which can rapidly lead to organ dysfunction and ultimately death. Severe sepsis strikes hard and takes lives quickly. Each year, approximately 215,000 people in the United States die from severe sepsis, more than breast, colon/rectal, pancreatic, and prostate cancer combined.

Sepsis can strike anyone, but often develops from infections of any type associated with pneumonia, trauma, surgery, burns, or cancer. In fact, deaths that are attributed to "complications" from cancer or pneumonia often are actually caused by severe sepsis. Sepsis frequently occurs among hospitalized patients, infants and children, and the elderly. In the United States, sepsis is the leading cause of death in non-coronary intensive care units. According to the Centers for Disease Control and Prevention, septicemia, a form of sepsis, is the tenth leading cause of death overall. And more people die from sepsis each year than from septicemia.

Until recently, sepsis was poorly understood. Medical professionals even disagreed on terminology to describe the condition in its various stages. But increasing knowledge about the human immune system and the biochemistry of sepsis has created the hope of discovering potentially useful forms of therapy.

What are the symptoms of sepsis?
Sepsis refers to the presence of an infection, plus any two of these four criteria:

• Heart rate greater than 90 beats per minute
  
• Increased respiratory rate
  
• High or low white blood cell count
  
• Fever or low body temperature

Visible symptoms of sepsis include reduced mental alertness, confusion, shaking, chills, fever, nausea, vomiting, and diarrhea in the presence of an infection. The most frequent sites of infection leading to sepsis are the lung, urinary tract, abdomen, and pelvis. In up to 30 percent of patients, however, a definite source of infection cannot be identified. The course of the disease is unpredictable. Some patients quickly deteriorate, while others suffer from varying degrees of organ dysfunction or begin to recover.

Severe sepsis is a condition in which sepsis is accompanied by associated acute dysfunction in one or more of the organs. Septic shock refers to a severe sepsis case in which the cardiovascular system begins to fail, blood pressure drops, and vital organs are deprived of adequate blood supply.

The course of sepsis
While the event that triggers an infection to develop into sepsis is unknown, increasing evidence suggests that sepsis is associated with widespread inflammation, coagulation, and suppression of fibrinolysis (the body's clot-busting system), which is thought to occur when chemical signals in the immune system go awry.

Under normal circumstances, substances called immune modulators that affect the endothelium, or lining, of the blood vessels and cause inflammation and coagulation, or blood clotting are released to help the body fight infection and heal itself. In a healthy person, the body is able to control this process.

In a person with sepsis, this process breaks down and the immune modulators go into overdrive. Triggered by an insult to the body, like a burn, trauma or infection, bacteria and other toxic stimuli provoke the release of too many immunomodulators. These immunomodulators inflame the endothelium and activate the coagulation process, which then triggers another wave of immunomodulators. This inflammation prompts the release of a substance called tissue factor, which in turn generates thrombin, a key stimulus for blood clots to form. Thrombin forms fibrin, the protein building block of blood clots.

Ordinarily, the body regulates inflammation and coagulation. It keeps blood clot formation from going dangerously out of control by breaking down fibrin in a process called fibrinolysis, sometimes called "clot-busting." But in the vicious cascade of sepsis, fibrinolysis is suppressed. In addition, endogenous Activated Protein C, which modulates coagulation, controls inflammation and supports fibrinolysis, is decreased.

As a result of the coagulation and weakened clot-busting associated with sepsis, microscopic blood clots begin to form in vital organs and extremities, limiting blood flow and causing tissue damage, which can lead to organ failure and the loss of limbs, fingers or toes. If the inflammation, coagulation, and impaired fibrinolysis continue, the patient's condition may deteriorate rapidly. As the tissue damage progresses, more organs may begin to fail, ultimately leading to death.

Current diagnosis and treatment
Diagnosing sepsis can be tricky. Some of its symptoms, such as fever, rapid pulse, and respiratory difficulty, are very general, and can mimic many other disorders. The first line of treatment is to identify and eliminate the underlying infection with anti-infection agents. However, some believe certain antibiotics may even worsen sepsis, by increasing the breakdown of bacteria and the release of toxins into the bloodstream. Depending on the patient's clinical status, other supportive care methods are used, such as mechanical ventilation and kidney dialysis.

Mounting cost in lives and dollars
The physical and economic costs of severe sepsis are enormous. In 1995, in the United States alone, the annual cost of treating patients with severe sepsis was estimated to be about $17 billion. Expenditures for each patient are high and largely due to:

• Intensive care unit charges
  
• Physicians and nursing care
  
• Mechanical ventilation
  
• Drug therapy

The death rate for patients with severe sepsis has dipped slightly since the 1960s, probably due to improved general medical care. But the incidence of severe sepsis is expected to rise from 750,000 to 1 million by the end of the decade due to an aging population, improved supportive care for the most medically fragile patients, and the widening use of aggressive and invasive medical procedures.

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