Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury.

Traumatic brain injury (TBI) remains an exclusionary criterion in nearly every clinical trial involving hemoglobin-based oxygen carriers (HBOCs) for traumatic hemorrhage. Furthermore, most HBOCs are vasoactive, and use of pressors in the setting of hemorrhagic shock is generally contraindicated. The purpose of this investigation was to test the hypothesis that low-volume resuscitation with a vasoactive HBOC (hemoglobin glutamer-200 [bovine], HBOC-301; Oxyglobin, BioPure, Inc., Cambridge, MA) would improve outcomes after severe TBI and hemorrhagic shock.
In Part 1, anesthetized swine received TBI and hemorrhage (30 +/- 2 mL/kg, n = 15). After 30 minutes, lactated Ringer's (LR) solution (n = 5), HBOC (n = 5), or 10 mL/kg of LR + HBOC (n = 5) was titrated to restore systolic blood pressure to > or = 100 mm Hg and heart rate (HR) to < or = 100 beats/min. After 60 minutes, fluid was given to maintain mean arterial pressure (MAP) at > or = 70 mm Hg and heterologous whole blood (red blood cells [RBCs], 10 mL/kg) was transfused for hemoglobin at < or = 5 g/dL. After 90 minutes, mannitol (MAN, 1 g/kg) was given for intracranial pressure > or = 20 mm Hg, LR solution was given to maintain cerebral perfusion pressure at > or = 70 mm Hg, and RBCs were given for hemoglobin of < or = 5 g/dL. In Part 2, after similar TBI and resuscitation with either LR + MAN + RBCs (n = 3) or HBOC alone (n = 3), animals underwent attempted weaning, extubation, and monitoring for 72 hours.
In Part 1, relative to resuscitation with LR + MAN + RBCs, LR + HBOC attenuated intracranial pressure (12 +/- 1 mm Hg vs. 33 +/- 6 mm Hg), improved cerebral perfusion pressure in the initial 4 hours (89 +/- 6 mm Hg vs. 60 +/- 3 mm Hg), and improved brain tissue PO2 (34.2 +/- 3.6 mm Hg vs. 16.1 +/- 1.6 mm Hg; all p < 0.05). Cerebrovascular reactivity and intracranial compliance were improved with LR + HBOC (p < 0.05) and fluid requirements were reduced (30 +/- 12 vs. 280 +/- 40 mL/kg; p < 0.05). Lactate and base excess corrected faster with LR + HBOC despite a 40% reduction in cardiac index. With HBOC alone and LR + HBOC, MAP and HR rapidly corrected and remained normal during observation; however, with HBOC alone, lactate clearance was slower and systemic oxygen extraction was transiently increased. In Part 2, resuscitation with HBOC alone allowed all animals to wean and extubate, whereas none in the LR + MAN + RBCs group was able to wean and extubate. At 72 hours, no HBOC animal had detectable neurologic deficits and all had normal hemodynamics.
The use of HBOC-301 supplemented by a crystalloid bolus was clearly superior to the standard of care (LR + MAN + RBCs) after TBI. This may represent a new indication for HBOCs. Use of HBOC eliminated the need for RBC transfusions and mannitol. The inherent vasopressor effect of HBOCs, especially when used alone, may misguide initial resuscitation, leading to transient poor global tissue perfusion despite restoration of MAP and HR. This suggests that MAP and HR are inadequate endpoints with HBOC resuscitation. HBOC use alone after TBI permitted early extubation and excellent 72-hour outcomes.
AuthorsDavid R King, Stephen M Cohn, Kenneth G Proctor
JournalThe Journal of trauma (J Trauma) Vol. 59 Issue 3 Pg. 553-60; discussion 560-2 (Sep 2005) ISSN: 0022-5282 [Print] United States
PMID16361895 (Publication Type: Evaluation Studies, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Hemoglobins
  • hemoglobin glutamer-200
  • Analysis of Variance
  • Animals
  • Brain (blood supply)
  • Brain Injuries (therapy)
  • Female
  • Hemodynamics
  • Hemoglobins (therapeutic use)
  • Intracranial Hypertension (prevention & control)
  • Male
  • Random Allocation
  • Resuscitation (methods)
  • Shock, Hemorrhagic (therapy)
  • Statistics, Nonparametric
  • Swine

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: