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


METHODS
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.
Moore
Ernest E
EE
Department of Surgery, Denver Health Medical Center, University of Colorado, Denver, CO, usa.
Moore
Frederick A
FA
Fabian
Timothy C
TC
Bernard
Andrew C
AC
Fulda
Gerard J
GJ
Hoyt
David B
DB
Duane
Therese M
TM
Weireter
Leonard J
LJ
Gomez
Gerardo A
GA
Cipolle
Mark D
MD
Rodman
George H
GH
Malangoni
Mark A
MA
Hides
George A
GA
Omert
Laurel A
LA
Gould
Steven A
SA
D000328:Adult; D000368:Aged; D001802:Blood Substitutes / Q000008:administration & dosage*; D000077324:Crystalloid Solutions; D004632:Emergency Medical Services; D017707:Erythrocyte Transfusion; D005260:Female; D005440:Fluid Therapy; D006454:Hemoglobins / Q000008:administration & dosage*; D006801:Humans; D007022:Hypotension / Q000209:etiology / Q000628:therapy*; D007552:Isotonic Solutions / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015532:Rehydration Solutions / Q000008:administration & dosage; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000628:therapy*; D016019:Survival Analysis; D014193:Trauma Centers; D014481:United States; D014505:Urban Population; D014947:Wounds and Injuries / Q000150:complications*
D001802:Blood Substitutes; D000077324:Crystalloid Solutions; D006454:Hemoglobins; D007552:Isotonic Solutions; C509893:PolyHeme; D015532:Rehydration Solutions