Video Library

In the following video clips, you will learn more about determining the risk of mortality in critically ill patients with severe sepsis. Clinical indicators to assess the disease severity for severe sepsis patients include:

Requiring a vasopressor after adequate fluid resuscitation
2 or more sepsis-induced organ dysfunctions
APACHE II^* ≥25

Here, experts discuss these clinical indicators and how to assess severity, improve care in your institutions, and better serve your patients.

Identifying and assessing a patient with severe sepsis

Craig Lilly, MD

Professor of Medicine, Anesthesia and Surgery
University of Massachusetts, Worcester

Dr. Craig Lilly discusses the importance of recognizing sepsis early and directing therapies based on careful patient monitoring.

Running time: 01:37

Kathleen Vollman

MSN, RN, CCNS, CCRN, FCCM
Clinical Nurse Specialist

Dr. Kathleen Vollman talks about initiating routine patient assessments so that at-risk patients can be identified early and treated appropriately.

Running time: 00:45

Judith Jacobi

PharmD, FCCM, FCCP, BCPS
Critical Care Pharmacist

When assessing patients, it is important to look at the overall picture, including number of organ dysfunctions and response to therapy, as Dr. Judith Jacobi discusses here.

Running time: 01:03

Dr. Jacobi talks about how red flags, such as organ failure or need for vasopressors, are often not recognized as indicators of severe sepsis.

Running time: 01:14

The correlation between APACHE II and clinician-assessed organ dysfunction

Craig Lilly, MD

Professor of Medicine, Anesthesia and Surgery
University of Massachusetts, Worcester

The APACHE II score may have great predictive value in terms of mortality risk but, as Dr. Lilly says here, the bedside clinician plays a crucial role in assessing the patient's progress.

Running time: 01:09

Judith Jacobi

PharmD, FCCM, FCCP, BCPS
Critical Care Pharmacist

In the population of patients at Dr. Jacobi's institution, there is a correlation between the APACHE II score and number of organ dysfunctions, which suggests that organ dysfunction is an important marker for severe sepsis.

Running time: 00:48

*APACHE (Acute Physiology And Chronic Health Evaluation).

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.