• Fishman N, Fuchs B, Manaker S, Hanson W, Sarani B, Taichman D, Christie J, Kahn J, Kinniry P, Umscheid CA, Williams K. Drotrecogin alfa (activated protein C) use for adult patients with sepsis: recommendation statement. Philadelphia (PA): University of Pennsylvania Health System; 2007 Jan 30. 17 p. [13 references]

This is the current release of the guideline.

The rating schemes for the quality of the evidence (very low, low, moderate, high) and the strength of the recommendations (weak, strong) are defined at the end of the "Major Recommendations" field.

1. The task force supports the targeted use of Activated protein C in adult patients with sepsis who are judged to be at high risk of death and opposes its use in patients who are not at high risk of death. (Strong Recommendation, Moderate Quality Evidence)
2. An assessment of patients' risk of death should consider, but should not be limited to, the patients' APACHE (Acute Physiology and Chronic Health Evaluation) scores or number of dysfunctional organs. (Strong Recommendation, Low Quality Evidence)
   • Patients who do not have either multi-organ dysfunction or APACHE scores >25 should not receive Activated protein C as there is certain harm and unclear benefit in this population.
   • Patients who are judged to be at "low risk of death" by an experienced clinician should not receive Activated protein C.
   • In patients who do have multi-organ dysfunction or an APACHE score >25, Activated protein C can then be used if an experienced clinician additionally judges the patient to be at "high risk of death".

3. The task force supports the current policy at the Hospital of the University of Pennsylvania (HUP) that the treating physician, the Pharmacy and Therapeutics (P&T) physician representative, and the intensive care unit (ICU) director must all agree that a patient is at a "high risk of death" before Activated protein C is administered. The task force encourages all hospitals in the health system to adopt a policy that incorporates a similar multi-tiered approval process involving at least the ICU director and the treating physician. (Strong Recommendation, Very Low Quality Evidence)

Definitions:

GRADE* rating scheme for quality of evidence:

Type of evidence
Randomized trial = high
Quasi-randomized trial = moderate
Observational study = low
Any other evidence = very low

Decrease grade if:

Serious (-1) or very serious (-2) limitation to study quality
Important inconsistency (-1)
Some (-1) or major (-2) uncertainty about directness
Sparse data (-1)
High probability of reporting bias (-1)

Increase grade if:

Strong evidence of association-significant relative risk of >2 (<0.5) based on consistent evidence from two or more observational studies, with no plausible confounders (+1)
Very strong evidence of association-significant relative risk of >5 (<0.2) based on direct evidence with no major threats to validity (+2)
Evidence of a dose response gradient (+1)
All plausible confounders would have reduced the effect (+1)

GRADE* rating scheme for strength of recommendation:

• Strong conclusion: Based on the balance of benefits and harms, the evidence clearly favors using or not using the intervention.
• Weak conclusion: Based on the balance of benefits and harms, the evidence probably favors using or not using the intervention, or is equivocal.

*GRADE (Grading of Recommendations, Assessment, Development, and Evaluation)

None provided

The type of evidence supporting each recommendation was not specifically stated.

• Fishman N, Fuchs B, Manaker S, Hanson W, Sarani B, Taichman D, Christie J, Kahn J, Kinniry P, Umscheid CA, Williams K. Drotrecogin alfa (activated protein C) use for adult patients with sepsis: recommendation statement. Philadelphia (PA): University of Pennsylvania Health System; 2007 Jan 30. 17 p. [13 references]

Not applicable: The guideline was not adapted from another source.

2007 Jan 30

University of Pennsylvania Health System - Academic Institution

The University of Pennsylvania Health System Office of the Chief Medical Officer provided support for the development of this guideline.

University of Pennsylvania Health System (UPHS) Activated Protein C Task Force

Neil Fishman MD; Barry Fuchs MD; Scott Manaker MD; William Hanson MD; Babak Sarani MD; Darren Taichman MD; Jason Christie MD, MSCE; Jeremy Kahn MD MSc; Paul Kinniry MD; Craig A. Umscheid MD, MSCE; and Kendal Williams MD, MPH

JC reports having received unrestricted grant support from Eli Lilly, the manufacturer of aprotinin, and abstained from voting on the final guideline. No other potential conflict of interest relevant to this guideline was reported.

This is the current release of the guideline.

None available

None available

This NGC summary was completed by ECRI Institute on October 3, 2007. The information was verified by the guideline developer on October 31, 2007.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.