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Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury.
J Trauma. 2005 Sep; 59(3):553-60; discussion 560-2.JT

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Authors+Show Affiliations

Dewitt-Daughtry Family Department of Surgery, Division of Trauma, Trauma and Surgical Critical Care Research Institute, University of Miami School of Medicine, Miami, Florida 33136, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16361895

Citation

King, David R., et al. "Resuscitation With a Hemoglobin-based Oxygen Carrier After Traumatic Brain Injury." The Journal of Trauma, vol. 59, no. 3, 2005, pp. 553-60; discussion 560-2.
King DR, Cohn SM, Proctor KG. Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury. J Trauma. 2005;59(3):553-60; discussion 560-2.
King, D. R., Cohn, S. M., & Proctor, K. G. (2005). Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury. The Journal of Trauma, 59(3), 553-60; discussion 560-2.
King DR, Cohn SM, Proctor KG. Resuscitation With a Hemoglobin-based Oxygen Carrier After Traumatic Brain Injury. J Trauma. 2005;59(3):553-60; discussion 560-2. PubMed PMID: 16361895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury. AU - King,David R, AU - Cohn,Stephen M, AU - Proctor,Kenneth G, PY - 2005/12/20/pubmed PY - 2006/2/24/medline PY - 2005/12/20/entrez SP - 553-60; discussion 560-2 JF - The Journal of trauma JO - J Trauma VL - 59 IS - 3 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 0022-5282 UR - https://www.unboundmedicine.com/medline/citation/16361895/Resuscitation_with_a_hemoglobin_based_oxygen_carrier_after_traumatic_brain_injury_ L2 - https://Insights.ovid.com/pubmed?pmid=16361895 DB - PRIME DP - Unbound Medicine ER -