Understanding Sepsis

Sepsis is among the top ten causes of death in the United States today. It kills 210,000 Americans each year - more than lung and breast cancer combined. Worldwide, more than 1,400 people die from severe sepsis every day. Yet it's quite likely that you know very little about it.

Sepsis has been dubbed the medical "perfect storm" because it is a medical crisis that can attack patients who are fighting off even seemingly nonfatal illnesses or injuries. Severe sepsis killed Muppets creator Jim Henson, who had been hospitalized for pneumonia, and recently took the life of actor Christopher Reeve, who was being treated for pressure sores of the skin.

With this insidious illness, the body attacks itself. Bacteria inside the body may grow out of control or invade the body from the outside through wounds or IV lines. Sepsis is not an infection; it is a systemic inflammatory response syndrome to an infection, which poses dire risk of organ damage and death.

"Sepsis is caused when severe infection over-activates the body's immune system, setting off a cascade of systemic inflammatory responses that could potentially lead to a severe drop in blood pressure and cardiovascular collapse," according to Mohammad O. Almoujahed, MD, Assistant Professor of Medicine (Infectious Diseases) at the Medical College of Wisconsin. "When this immune response and inflammation are very severe and uncontrolled, the function of many essential organs begins to deteriorate, and that may cause organ failure and possibly even death," he said.

Sepsis on the Rise
Infections leading to sepsis can be acquired outside the hospital or while in the hospital (infections acquired in the hospital are known as "nosocomial infections"). The incidence of sepsis acquired both in and outside of the hospital setting has increased by an average of 8.7% a year in the US over 22 years, according to research done at Emory University School of Medicine and the Centers for Disease Control (CDC) in 2003. Hospital-acquired infections can be more difficult to manage than those acquired in the community because patients usually are already sick and the bacteria may be resistant to common treatments due to the widespread use of antibiotics in hospitals.

According to studies, the growing number of cases of sepsis can be attributed to several factors, including the changes that have occurred in medical treatment of illness. "The Emory study showed a significant rise in sepsis in the US from 1979 through 2000. A portion of this increase is probably related to the increase in invasive procedures and medical interventions that would result in a weakened immune system like organ transplantation or chemotherapy for cancer. However, a significant portion is probably related to increased awareness of the sepsis syndrome by physicians," Dr. Almoujahed explained.

Who is at Risk?
Unfortunately, nearly everyone is at potential risk of developing sepsis from minor infections such as flu, urinary tract infections or gastroenteritis, but there are some individuals at high risk. "Patients at high risk for sepsis include hospitalized patients for any condition and patients with multiple medical problems, among others," said Dr. Almoujahed. Sepsis is most likely to develop in people who:

• Are very young (particularly premature babies)
• Are very old
• Have a weakened immune system because of chemotherapy treatments, AIDS, organ transplant, etc.
• Have wounds or injuries, such as those from burns, bullets, pressure sores, etc.
• Have addictive habits such as alcohol or drug abuse
• Are receiving treatments via intravenous catheters, wound drainage, urinary catheters, etc.

Race and Gender Differences
The Emory study also revealed racial and gender disparities in sepsis incidence are significant and are cause for additional research. In fact, nonwhite patients develop sepsis at nearly twice the rate of white patients and the greatest difference is among black men, where sepsis occurs at the youngest ages and results in the highest mortality. "This difference is very intriguing and mandates further investigation," Dr. Almoujahed noted.

Prevention and Treatment
What can be done to prevent sepsis? "Prevention can be achieved by reducing the number of invasive procedures, limiting the use of indwelling venous or urinary catheters, using antibiotics only for treating infections and following good infection control measures, especially hand hygiene for both healthcare workers and patients as well as their visitors," Dr. Almoujahed suggested.

One problem in treating sepsis in the past has been a lack of diagnosis and treatment guidelines. New consensus definitions are making diagnosing sepsis much more feasible for physicians at the bedside. In addition, critical care physicians are currently developing standard treatment guidelines for sepsis, which will help with early identification of septic patients.

New Medication
"Sepsis is managed by treating infections with appropriate antibiotics that should be started as soon as possible, as well as giving supportive care that includes maintaining adequate organ blood supply through administering IV fluids and possibly other medications as appropriate," said Dr. Almoujahed. "A recently FDA-approved drug is the recombinant form of human activated protein C called Xigris. It showed a remarkable improvement in survival in some situations in severe sepsis."

Starting appropriate antibiotics early in sepsis has also showed significant improvement in survival. "Other treatments depend on the type of infection causing it. For example, indwelling venous catheter infections may require removal of the catheter and abscesses usually require surgical drainage for optimal outcome," said Dr. Almoujahed.

New Treatments
Another dilemma in the treatment of sepsis has been that patients may die even after antibiotics have controlled the underlying bacterial infection. This leads physicians to believe the complications from the body's inflammatory response to the infection, rather than the infection itself, could be contributing to patient deaths.

Based on this premise, in 2003, physicians at the University of Virginia conducted a study on sepsis. The study, funded by the National Institutes of Health, revealed that an experimental therapy combining an antibiotic with a synthetic anti-inflammatory drug showed early promise in dramatically reducing death from sepsis in laboratory mice. Physicians are hopeful that the anti-inflammatory drug, called ATL 146e, may prove to be an effective new therapy application.

New drugs, along with new treatment guidelines and standards as well as educating the medical community, could have a major impact on sepsis, according to the Emory study. A new understanding is necessary to help physicians bring this serious illness under control.

JoAnn Petaschnick
HealthLink Contributing Writer

Each year, Medical College of Wisconsin physicians care for more than 180,000 patients, representing nearly 500,000 patient visits. Medical College physicians practice at Children's Hospital of Wisconsin, Froedtert Memorial Lutheran Hospital, the Milwaukee VA Medical Center, and many other hospitals and clinics in Milwaukee and southeastern Wisconsin.