Diagnosis and Treatment

This section will give you an overview of the following topics:

How can the doctor tell if a person has severe sepsis?
What are the goals of severe sepsis therapy?
How is severe sepsis treated?
- Common treatments in addition to antibiotics
- Other types of treatment

How can the doctor tell if a person has severe sepsis?

Severe sepsis is a complex disease. It is important to know that any one of the signs discussed below does not mean a patient has severe sepsis. Patients with severe sepsis have a combination of several outward and internal symptoms. A doctor will look at all these signs before diagnosing a person with severe sepsis.

General "outward" signs of infection

Fever or abnormally low body temperature, especially in the young and old
Breathing that is faster or more shallow than normal
Heart rate that is faster than normal
Overall weakness

Infection or organ-specific "outward" signs of infection

Lungs — shallow breathing, shortness of breath, coughing up mucus ("phlegm")
Urinary tract — painful urination, cloudy urine, back pain
Brain/nervous system — confusion, severe headache, stiff neck, sensitivity of eyes to light
Abdomen or bowel — pain in the abdomen (belly)
Skin — redness, and sometimes pus forming around a wound or opening in the skin

Internal signs (detected by lab tests ordered by a doctor)

Blood count — either very high or low values of white blood cells may mean that a patient has an infection
Cultures of blood or other tissue — the blood, urine, and other body fluids may be checked for the presence of "germs"
Other blood tests — lab values to check oxygen levels, kidney and liver function
Chest x-rays — to detect problems in the lungs, such as pneumonia

What are the goals of severe sepsis therapy?

The key goals in treating severe sepsis are to keep a person alive and help him or her get better. To do this, the healthcare team has several objectives when treating patients with severe sepsis:

To fight the infection or other event that triggered severe sepsis. After getting rid of the source of the infection, some people may be able to recover from severe sepsis without having additional organ failures
To support failing organs to help them continue working. While organ support doesn't directly treat severe sepsis, it is essential for survival
To stop the body's "overreaction" to the infection
To make sure the patient is comfortable and not in pain

How is severe sepsis treated?

A patient with severe sepsis will be given antibiotics to fight infection, plus additional treatments to support failing vital organs. For example, patients with severe sepsis who have low blood pressure are usually given intravenous (IV) fluids to help correct it. If a person's blood pressure doesn't rise with this treatment, he or she may have a condition known as "septic shock." A doctor may use medications that raise blood pressure (vasopressors) to help these patients, who run an even greater risk of death than most people with severe sepsis.

Common treatments in addition to antibiotics

In addition to antibiotics, treatments commonly given include:

IV fluids — given for various reasons, including helping increase blood pressure
Vasopressors — may be given if fluids are not enough to increase blood pressure
Machines to support organ function — breathing machines (ventilators) and dialysis machines (filtering for the kidneys) are two examples
Medications specifically for the treatment of severe sepsis — a medication called Xigris* (pronounced "zy-gris") helps the body fight severe sepsis when the patient is at a high risk of dying. Xigris targets the body's systemic response or "overreaction" to infection

Other types of treatment

Other types of treatments might include:

Feeding tube — to deliver special nutrients by way of a tube inserted through the nose and into the stomach or small intestine
Pain medication/sedatives — to help patients with pain or to help them sleep
Catheters — tubes to help drain fluids from the body
IV lines — placed in veins to deliver medication to the bloodstream

*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.

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.