Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial.

Abstract

BACKGROUND:

Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury.

STUDY DESIGN:

Injured patients with a systolic blood pressure</=90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point.

RESULTS:

Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p=0.04) and serious adverse events (40% versus 35%; p=0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups.

CONCLUSIONS:

Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.

• Authors: Ernest E Moore, Frederick A Moore, Timothy C Fabian, Andrew C Bernard, Gerard J Fulda, David B Hoyt, Therese M Duane, Leonard J Weireter Jr, Gerardo A Gomez, Mark D Cipolle, George H Rodman Jr, Mark A Malangoni, George A Hides, Laurel A Omert, Steven A Gould, PolyHeme Study Group
• Journal: Journal of the American College of Surgeons (J Am Coll Surg) Vol. 208 Issue 1 Pg. 1-13 (Jan 2009) ISSN: 1879-1190 [Electronic] United States
• PMID: 19228496 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Blood Substitutes
• Crystalloid Solutions
• Hemoglobins
• Isotonic Solutions
• PolyHeme
• Rehydration Solutions

Topics

• Adult
• Aged
• Blood Substitutes (administration & dosage)
• Crystalloid Solutions
• Emergency Medical Services
• Erythrocyte Transfusion
• Female
• Fluid Therapy
• Hemoglobins (administration & dosage)
• Humans
• Hypotension (etiology, therapy)
• Isotonic Solutions (administration & dosage)
• Male
• Middle Aged
• Rehydration Solutions (administration & dosage)
• Shock, Hemorrhagic (etiology, therapy)
• Survival Analysis
• Trauma Centers
• United States
• Urban Population
• Wounds and Injuries (complications)