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A Safety Assessment of Diaspirin Cross-Linked Hemoglobin (DCLHb) in the Treatment of Hemorrhagic, Hypovolemic Shock

Published online by Cambridge University Press:  28 June 2012

Robert J. Przybelski ,
Elaine K. Daily ,
Jean Micheels ,
Edward Sloan ,
Pierre Mols ,
Luc Corne ,
Max D. Koenigsberg ,
William H. Bickell ,
Dan R. Thompson  and
Jay D. Harviel
...Show all authors
Robert J. Przybelski
Affiliation:
Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin USA; former Medical Vice President, Hemoglobin Therapeutics, Baxter Healthcare, Round Lake, Illinois, USA
Elaine K. Daily*
Affiliation:
Cardiovascular Research and Education Consulting, Madison, Wisconsin, USA
Jean Micheels
Affiliation:
Department of Anesthesia and Intensive Care Medicine, Centre Hospitalier Universitaire, Liége, Belgium
Edward Sloan
Affiliation:
Trauma Emergency Services, Cook County Hospital, Chicago, Illinois, USA
Pierre Mols
Affiliation:
Service des Urgences, Hopital Saint Pierre, Brussels, Belgium
Luc Corne
Affiliation:
Academisch Zeikenhuis Vrije, Universiteit Brussels, Brussels, Belgium
Max D. Koenigsberg
Affiliation:
Department of Emergency Medicine, Illinois Masonic Medical Center, Chicago, Illinois, USA
William H. Bickell
Affiliation:
Emergency Department, Saint Francis Hospital, Tulsa, Oklahoma, USA
Dan R. Thompson
Affiliation:
Intensive Care Unit and Trauma Life Support Center, The Mercy Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
Jay D. Harviel
Affiliation:
MedSTAR Trauma Unit, Washington Hospital Center, Washington, DC, USA
Stephen M. Cohn
Affiliation:
Formerly, Trauma Service, Yale University School of Medicine, New Haven, Connecticut, USA
*
FCCM 5887 Woods Edge Road Madison, Wisconsin 53711 USA
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Abstract

Objective:

To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of patients in Class II–IV hemorrhagic, hypovolemic shock.

Design:

Multicenter, randomized, normal saline-controlled, dose-escalation study.

Setting:

Eleven hospitals in the U.S. and Belgium.

Subjects:

One hundred and thirty-nine (139) hospitalized patients with Class II–IV hemorrhagic, hypovolemic shock within the previous 4 hours who still were requiring therapy for shock.

Interventions:

Beginning with the lowest dose, patients were randomized to receive 50,100, or 200 mL of either 10% DCLHb or normal saline infused intravenously over 15 minutes. Following infusion of either treatment, further fluid resuscitation could be given, as necessary, to maintain perfusion. Vital signs, laboratory assessments, blood and fluid administration, complications, and adverse events were recorded at various times from the end of infusion through 72 hours after infusion.

Results:

A total of 29 (13 DCLHb- and 16 saline-treated) patients died during the study period. Adverse events were experienced by 61% of patients in the DCLHb group and 53% of patients in the saline group; serious adverse events occurred in 28% of DCLHb-treated patients and 30% of saline-treated patients. The incidence of prospectively defined, clinical complications, including renal insufficiency and renal failure, was similar between the treatment groups except for the occurrence of dysrhythmias/conduction disorders, which occurred significantly more frequently in the saline-treated patients than the DCLHb-treated patients (p = 0.041). At the highest dose level (200 mL), statistically significant between-group differences were observed with greater increases in serum amylase, LDH, the isoenzymes LD1,2,4 and 5, and CK-MB in the DCLHb group compared to the control group; none were of clinical significance. The volume of blood administered did not differ between the groups. Overall 24- and 72-hour survival rates were similar between treatment groups, although the hospital discharge rate was slightly higher in the DCLHb-treated patients (80%) compared with the saline-treated patients (74%).

Conclusion:

Administration of 50 to 200 mL of DCLHb to patients in hemorrhagic, hypovolemic shock was not associated with evidence of end organ toxuity or significant adverse events. Further studies involving larger doses and, perhaps, earlier administration of DCLHb are warranted.

Keywords

bloodcross-linked hemoglobindiaspirinefficacyhemoglobin solutionshemophagiehypobolemic shockoxygen deliverypressorresuscitation solutionssafetytrauma
Type
Original Research
Information
Prehospital and Disaster Medicine , Volume 14 , Issue 4 , December 1999 , pp. 47 - 60
Copyright
Copyright © World Association for Disaster and Emergency Medicine 1999

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