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

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.

DCL-Hb for trauma patients with severe hemorrhagic shock: the European "On-Scene" Multicenter Study

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Extracellular Methemoglobin Mediated Early ROS Spike Triggers Osmotic Fragility and RBC Destruction: An Insight into the Enhanced Hemolysis During Malaria

“…Development of oxidative stress and down-stream events prime the RBC to get lysed. Infusion of hemoglobin solution in healthy volunteers as well as a variety of acquired and iatrogenic hemolytic disorders suggest links between hemolysis and hemoglobenia [23][24][25].…”

Redox cycling of diaspirin cross-linked hemoglobin induces G2/M arrest and apoptosis in cultured endothelial cells

“…Although heme-mediated vascular injury and dysfunction have been ongoing concerns with the use of hemoglobin-based oxygen carriers, traditional measures of cytotoxicity (eg, LDH or liver enzyme tests) have mainly suggested mild toxicities. 53,54 In this regard, it may be important to consider that G2/M-arrested cells maintain plasma membrane integrity and that arrested cells that become apoptotic would be cleared by phagocytes in vivo, minimizing the leakage of intracellular contents. Thus, the occurrence of G2/M arrest and apoptosis in vivo may elude some of the more traditional measures of cytotoxicity.…”