Understanding Sepsis

This section will provide you with answers to some questions you may have about sepsis, including:

What is sepsis?
What is severe sepsis?
Who is at risk for severe sepsis?
What are the short-term and long-term effects of severe sepsis?

What is sepsis?

Sepsis is a complex illness involving both infection and inflammation. Normally, the body's response to an infection is targeted to the site of the infection. But with sepsis, the immune system sets off a chain reaction to fight the infection. This triggers a "systemic response," which causes symptoms to occur throughout the body.

As a result, a patient with sepsis often has a fever, and heart and breathing rates that are faster than normal. Because there may be "germs" in the blood of patients with sepsis, doctors and nurses sometimes call the condition a "blood infection" or "blood poisoning." It might not be immediately obvious that a patient is developing sepsis. But there are tests that doctors and nurses can run to detect the disease.

What is severe sepsis?

In some patients, the systemic response to infection may spin out of control, throwing off the body's state of balance and damaging one or more vital organs (heart, lungs, kidneys, or liver). This systemic response or "overreaction" to the infection and resulting organ damage is called severe sepsis and is often more dangerous than the initial infection itself. Sepsis can turn into severe sepsis very quickly, sometimes in a matter of hours. Between 28% and 50% of patients who develop severe sepsis die from the condition.

Conditions that are linked to infection and can sometimes result in severe sepsis are:

Flu and pneumonia
Urinary tract infection
Meningitis
Appendicitis
Acute respiratory distress syndrome (ARDS)
Acute lung injury
Serious cuts or burns

Who is at risk for severe sepsis?

Each year, more than 750,000 people in the U.S. develop severe sepsis — that's more than the number of people who develop lung, breast, and colon cancer combined. Any type of infection — even one that seems minor, such as flu — can lead to severe sepsis. Severe sepsis is more likely in people who:

Have been admitted to the hospital with a serious disease
Are very young or old
Have a compromised (weak) immune system
Have had a wound or injury, such as a serious cut or burn, or a gunshot wound
Have an intravenous (IV) line for infusion of medications ("IV drip")
Have a catheter to drain the bladder
Are addicted to alcohol or drugs

What are the short-term and long-term effects of severe sepsis?

Severe sepsis is a very serious, life-threatening condition. In a person with severe sepsis, one or more of the person's vital organs may not receive enough oxygen and they may fail or "shut down." And when vital organs shut down, important bodily functions shut down too. The more organs that shut down, the greater the patient's risk of death.

People who survive severe sepsis are likely to stay in an intensive care unit (ICU) until their organs begin working properly again. The amount of time spent in an ICU will vary greatly, ranging from one day to more than one month. From the ICU, a person may be sent to another area of the hospital or to another facility to recuperate. A person's condition after having severe sepsis will depend on many factors. These may include the patient's health before severe sepsis, and how serious their disease was. Someone who is recuperating from severe sepsis may notice changes in the following:

Ability to do physical activity
Ability to communicate
Energy level

Organ damage is one of the possible long-term effects of severe sepsis. Depending on several factors, this organ damage may be temporary or it may be permanent. For example, a person whose kidneys failed because of severe sepsis may need dialysis (filtering help from a machine). Early treatment of severe sepsis may minimize the amount of permanent organ damage from this condition.

Despite these challenges, many people who survive can fully recover from severe sepsis and return to their normal daily activities.

IMPORTANT SAFETY INFORMATION

Xigris is indicated for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death (eg, as determined by APACHE II*).

Xigris is not indicated in adult patients with severe sepsis and lower risk of death. Xigris is not indicated in pediatric patients with severe sepsis.

CONTRAINDICATIONS

Xigris increases the risk of bleeding. Xigris is contraindicated in patients with the following clinical situations in which bleeding could be associated with a high risk of death or significant morbidity:

Active internal bleeding
Recent (within 3 months) hemorrhagic stroke
Recent (within 2 months) intracranial or intraspinal surgery, or severe head trauma
Trauma with an increased risk of life-threatening bleeding
Presence of an epidural catheter
Intracranial neoplasm or mass lesion or evidence of cerebral herniation

Xigris is contraindicated in patients with known hypersensitivity to drotrecogin alfa (activated) or any component of this product.

WARNINGS

Bleeding

Bleeding is the most common serious adverse effect associated with Xigris therapy. Each patient being considered for therapy with Xigris should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy.

Certain conditions, many of which led to exclusion from the Phase 3 trial, are likely to increase the risk of bleeding with Xigris therapy. Therefore, for patients with severe sepsis who have one or more of the following conditions, the increased risk of bleeding should be carefully considered when deciding whether to use Xigris therapy:

Concurrent therapeutic heparin to treat an active thrombotic or embolic event
Platelet count <30,000 x 10⁶/L, even if the platelet count is increased after transfusions
Prothrombin time-INR >3.0
Recent (within 6 weeks) gastrointestinal bleeding
Recent administration (within 3 days) of thrombolytic therapy
Recent administration (within 7 days) of oral anticoagulants or glycoprotein IIb/IIIa inhibitors
Recent administration (within 7 days) of aspirin >650 mg per day or other platelet inhibitors
Recent (within 3 months) ischemic stroke
Intracranial arteriovenous malformation or aneurysm
Known bleeding diathesis
Chronic severe hepatic disease
Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location

Invasive procedures increase the risk of bleeding among patients receiving Xigris. Xigris should be discontinued prior to the performance of invasive surgical procedures or other procedures associated with special risks for bleeding.

Mortality in patients with single organ dysfunction and recent surgery

Among the small number of patients enrolled in PROWESS with single organ dysfunction and recent surgery (surgery within 30 days prior to study treatment) all-cause mortality was numerically higher in the Xigris group (28-day: 10/49; in-hospital: 14/48) compared to the placebo group (28-day: 8/49; in-hospital: 8/47).

In an analysis of the subset of patients with single organ dysfunction and recent surgery from a separate, randomized, placebo-controlled study (ADDRESS) of septic patients not at high risk of death all-cause mortality was also higher in the Xigris group (28-day: 67/323; in-hospital: 76/325) compared to the placebo group (28-day: 44/313; in-hospital: 62/314). Patients with single organ dysfunction and recent surgery may not be at high risk of death irrespective of APACHE II score and therefore not among the indicated population.

Clinicians should consider continuing prophylactic heparin when initiating Xigris therapy, unless discontinuation is considered medically necessary

In a randomized study of prophylactic heparin versus placebo in 1935 adult severe sepsis patients treated with Xigris, mortality and the rate of serious adverse events were increased in the subgroup of 434 patients whose low-dose heparin was stopped on study entry by randomization to placebo. This finding was based on prospectively defined exploratory subgroup analyses; however, the explanation for the finding is unclear.

ADVERSE REACTIONS

Bleeding is the most common adverse reaction associated with Xigris therapy. In the Phase 3 study, serious bleeding events were observed during the 28-day study period in 3.5% of Xigris-treated and 2.0% of placebo-treated patients. The difference in serious bleeding occurred primarily during infusion. The incidence of intracranial hemorrhage (ICH) was 0.2% for Xigris-treated and 0.1% for placebo-treated patients. ICH has been reported in Xigris-treated patients in non-placebo controlled trials with an incidence of approximately 1% during infusion. The risk of ICH may be increased in patients with risk factors for bleeding such as severe coagulopathy and severe thrombocytopenia. Should clinically important bleeding occur, immediately stop the Xigris infusion.

*APACHE (Acute Physiology And Chronic Health Evaluation).

Please refer to the full Prescribing Information for Xigris.