The effects of diaspirin cross-linked hemoglobin on hemodynamics, metabolic acidosis, and survival in burned rats.
OBJECTIVE
Diaspirin cross-linked hemoglobin (DCLHb) is a vasoactive hemoglobin-based oxygen carrier or "blood substitute" that has been shown to improve base deficit in several experimental studies of hemorrhagic shock. Our objective was to determine if the addition of DCLHb to the resuscitation regimen would improve hemodynamic parameters, metabolic acidosis, and survival in our rat burn shock model compared with currently used resuscitation therapy.


METHODS
This was a randomized, controlled, experimental rat study. Male Wistar rats, weighing 200 to 250 g, were surgically prepared for an acute study. After placement of indwelling catheters, baseline hemodynamic values (mean arterial pressure, cardiac output, systemic vascular resistance, stroke volume, and base excess) were obtained. Thirty-two rats were used in the study, and they were either subjected to a 30% scald burn (experimental group) or sham burned (control group). The experimental animals were immediately intravenously resuscitated and followed for 6 hours. The resuscitation was based on the Parkland formula (4 mL/kg for each 1% of total body surface area [TBSA] burn), with 50% of the calculated fluid amount to be administered at a constant rate during the first 8 hours after burn. The animals were resuscitated for 6 hours and received between 9.00 and 11.25 mL of fluid depending on weight. The experimental animals were randomly assigned to one of three treatment groups: group I, lactated Ringer's solution; group II, lactated Ringer's solution-human serum albumin; group III, lactated Ringer's solution-DCLHb. Group I (n = 8) received 4 mL/kg lactated Ringer's solution for each 1% of TBSA burn. Group II (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg human serum albumin for each 1% of TBSA burn. Group III (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg DCLHb for each 1% of TBSA burn. The sham group (n = 8) was not burned and was not resuscitated. Animals that survived up to 6 six hours were killed.


RESULTS
We found that mean arterial pressure, cardiac output, stroke volume, and base excess were all improved in the DCLHb-lactated Ringer's solution-treated animals compared with the other experimental treatment groups. The 6-hour mortality rates were zero of eight (lactated Ringer's solution-DCLHb group), zero of eight (sham group), three of eight (lactated Ringer's solution-human serum albumin group), and six of eight (lactated Ringer's solution only group).


CONCLUSIONS
Early resuscitation with DCLHb is superior to non-oxygen-carrying resuscitative fluids in improving hemodynamics and survival in this model of burn shock. DCLHb might improve general tissue perfusion in the acute postburn period, and it could be useful in the early management of patients with severe burns.
Department of Surgery, University of California San Diego Medical Center, 92103, USA.
R G
RG
Soltero
J F
JF
Hansbrough
D000138:Acidosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002056:Burns / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000627:therapeutic use*; D006801:Humans; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012709:Serum Albumin / Q000627:therapeutic use; D012769:Shock / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D016019:Survival Analysis; D013997:Time Factors
D006454:Hemoglobins; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D012709:Serum Albumin; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin