+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Resuscitation with a novel hemoglobin-based oxygen carrier in a Swine model of uncontrolled perioperative hemorrhage



Resuscitation with a novel hemoglobin-based oxygen carrier in a Swine model of uncontrolled perioperative hemorrhage



Journal of Trauma 54(5): 915-924



Systemic and pulmonary hypertension, possibly related to nitric oxide scavenging by free hemoglobin (Hb), is often seen during resuscitation with hemoglobin-based oxygen carriers (HBOCs). Recently, a second-generation HBOC, rHb2.0 for Injection (rHb), has been developed using recombinant human Hb that has reduced reactivity with nitric oxide. The current study evaluates the efficacy of this novel compound for resuscitation in a swine model of uncontrolled perioperative hemorrhage. After instrumentation, animals underwent splenectomy and rapid hemorrhage to a systolic blood pressure of 35 mm Hg and isoelectric electroencephalography. 15 minutes of shock was followed by resuscitation over 30 minutes. In phase I, 18 animals were randomized into three resuscitation groups: (1) lactated Ringer's (LR) equal to three times the shed blood, the negative control group; (2) heterologous blood (BL) equal to Hb 2 g/kg, the positive control group; and (3) rHb equal to 2 g/kg, the treatment group. In phase II, six animals underwent the same experiment with a first-generation HBOC, diaspirin cross-linked Hb (DCLHb) equal to 2 g/kg, an additional control group. On day 0 after 2 hours of observation, spontaneously breathing animals were returned to their cages. Surviving animals were redosed on days 1, 2, and 3 (rHb/DCLHb 1 g/kg; LR/BL-LR 500 mL). Survivors were killed on day 5 and organs harvested for histologic examination. Group comparisons were performed using Student's t test, repeated-measures analysis of variance, and chi2 test. Significance was set at 95% confidence intervals. After resuscitation, systemic mean arterial pressure (MAP) (baseline = 107 +/- 15 mm Hg) was 128 +/- 34 and 108 +/- 15 mm Hg in rHb and BL animals, respectively, and remained stable. In LR and DCLHb animals, after normalization, MAP declined to 67 +/- 13 and 84 +/- 34 mm Hg, respectively. The rHb group maintained higher MAP than the LR and BL groups (p < 0.05 vs. both). With resuscitation, mean pulmonary arterial pressure (PAP) (baseline = 25 +/- 5 mm Hg) increased in rHb (40 +/- 4 mm Hg), BL (34 +/- 3 mm Hg), and DCLHb (40 +/- 3 mm Hg) groups, but stayed elevated only in the DCLHb group (36 +/- 3 mm Hg). PAP in the rHb group was similar to the BL group (p > 0.05), and both rHb and BL groups showed a higher PAP than the LR group (p < 0.05 vs. both). PAP was highest in the DCLHb group (p < 0.05 vs. rHb). Cardiac output of rHb and BL groups was similar (p > 0.05) throughout the observation period. Arterial lactate increased to 5.6 +/- 2.5 mmol/L with shock and then normalized to < 2.0 mmol/L in the rHb, BL, and LR groups within 30 minutes of resuscitation. It remained elevated to > 3.5 mmol/L and showed a delayed increase in the DCLHb group (p < 0.05). Causes and number of deaths were as follows: rHb, zero of six; BL-transfusion reaction, one of six; LR-irreversible shock, four of six; and DCLHb-ventricular failure, six of six. There was no significant increase in plasma methemoglobin (rHb) and no difference in liver or cardiac enzymes (rHb vs. BL). No histologic abnormalities were seen in the rHb group except for cytoplasmic vacuolation, a process thought to be related to metabolism of the test article. rHb2.0 for Injection, a second-generation recombinant human HBOC, performs as well as heterologous blood for resuscitation after perioperative blood loss, does not cause sustained pulmonary hypertension, maintains adequate cardiac output and oxygen delivery, and is superior to either LR or DCLHb.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011296077

Download citation: RISBibTeXText

PMID: 12777904

DOI: 10.1097/01.ta.0000061000.74343.e1


Related references

Resuscitation with the hemoglobin-based oxygen carrier, HBOC-201, in a swine model of severe uncontrolled hemorrhage and traumatic brain injury. Shock 31(1): 64-79, 2009

Hemoglobin-based oxygen carrier (HBOC-201) and escalating doses of recombinant factor VIIa (rFVIIa) as a novel pre-hospital resuscitation fluid in a swine model of severe uncontrolled hemorrhage. Artificial Cells Blood Substitutes and Immobilization Biotechnology 39(2): 59-68, 2011

Hematologic effects of recombinant factor VIIa combined with hemoglobin-based oxygen carrier-201 for prehospital resuscitation of swine with severe uncontrolled hemorrhage due to liver injury. Blood Coagulation and Fibrinolysis 19(7): 669-677, 2008

Innate immune response after resuscitation with hemoglobin-based oxygen carrier and recombinant factor VIIA in uncontrolled hemorrhagic shock in a swine model. Journal of Trauma 64(6): 1498-1510, 2008

Bovine hemoglobin-based oxygen carrier (HBOC-201) for resuscitation of uncontrolled, exsanguinating liver injury in swine. Carolina Resuscitation Research Group. Shock 13(2): 152-159, 2000

Fluid resuscitation of uncontrolled hemorrhage using a hemoglobin-based oxygen carrier: effect of traumatic brain injury. Shock 39(2): 210-219, 2013

Bovine Hemoglobin-Based Oxygen Carrier (Hboc-201) For Resuscitation Of Uncontrolled, Exsanguinating Liver Injury In Swine. Shock 13(2): 152-159, 2000

Prolonged Hypotensive Resuscitation With Lactated Ringers Solution (Lr), Hextend, Or Hemoglobin-Based Oxygen Carrier (Hboc) In A Conscious, Sedated Swine Hemorrhage Model. Shock 21: 25-26, 2004

Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine. Journal of Laboratory & Clinical Medicine 132(5): 421-431, 1998

Resuscitation following severe, controlled hemorrhage associated with a 24 h delay to surgical intervention in swine using a hemoglobin based oxygen carrier as an oxygen bridge to definitive care. Resuscitation 74(2): 332-343, 2007

A hemoglobin based oxygen carrier, bovine polymerized hemoglobin (HBOC-201) versus hetastarch (HEX) in an uncontrolled liver injury hemorrhagic shock swine model with delayed evacuation. Journal of Trauma Injury Infection and Critical Care 57(4): 726-738, 2004

Immune effects of resuscitation with HBOC-201, a hemoglobin-based oxygen carrier, in swine with moderately severe hemorrhagic shock from controlled hemorrhage. Shock 25(1): 50-55, 2006

Immune Effects Of Resuscitation With Hboc-201, A Hemoglobin-Based Oxygen Carrier, In Swine With Moderately Severe Hemorrhagic Shock From Controlled Hemorrhage. Shock 25(1): 50-55, 2006

Validity of arterial and mixed venous oxygen saturation measurements in a canine hemorrhage model after resuscitation with varying concentrations of hemoglobin-based oxygen carrier. Anesthesia and Analgesia 96(1): 46-50 Table of Contents, 2003

Validity of arterial and mixed venous oxygen saturation measurements in a canine hemorrhage model after resuscitation with varying concentrations of hemoglobin-based oxygen carrier. Anesthesia & Analgesia 96(1): 46-50, 2003