Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in swine

Ajai K. Malhotra, John B. Schweitzer, Jeri L. Fox, Timothy Fabian, Kenneth G. Proctor

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)-a hemoglobin-based oxygen carrier with pressor activity-in the same swine model of traumatic brain injury and hemorrhagic shock. Methods: Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. Results: Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 ± 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 ± 4%) (p < 0.05 vs. baseline) and Hb1 (1 ± 5%), but was partially preserved in Hb2 (9 ± 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLhb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 ± 1 mm Hg, SAL; 42 ± mm Hg, Hb1; 45 ± 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 ± 1.6 L/min, SAL; 2.6 ± 0.1 L/min, Hb1; 2.7 ± 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. Conclusion: In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.

Original languageEnglish (US)
Pages (from-to)1049-1057
Number of pages9
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume56
Issue number5
DOIs
StatePublished - Jan 1 2004

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Cerebrovascular Circulation
Hypotension
Swine
Oxygen
Hemorrhagic Shock
Carbon Dioxide
Amyloid beta-Protein Precursor
Blood Volume
Resuscitation
Axons
diaspirin-cross-linked hemoglobin
Traumatic Brain Injury
Percussion
Brain Death
Partial Pressure
Intracranial Pressure
Vasodilation
Cardiac Output
Electroencephalography
Shock

All Science Journal Classification (ASJC) codes

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in swine. / Malhotra, Ajai K.; Schweitzer, John B.; Fox, Jeri L.; Fabian, Timothy; Proctor, Kenneth G.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 56, No. 5, 01.01.2004, p. 1049-1057.

Research output: Contribution to journalArticle

Malhotra, Ajai K. ; Schweitzer, John B. ; Fox, Jeri L. ; Fabian, Timothy ; Proctor, Kenneth G. / Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in swine. In: Journal of Trauma - Injury, Infection and Critical Care. 2004 ; Vol. 56, No. 5. pp. 1049-1057.
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abstract = "Background: Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)-a hemoglobin-based oxygen carrier with pressor activity-in the same swine model of traumatic brain injury and hemorrhagic shock. Methods: Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45{\%} blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. Results: Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5{\%} carbon dioxide evoked a 16 ± 1{\%} increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 ± 4{\%}) (p < 0.05 vs. baseline) and Hb1 (1 ± 5{\%}), but was partially preserved in Hb2 (9 ± 5{\%}). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLhb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 ± 1 mm Hg, SAL; 42 ± mm Hg, Hb1; 45 ± 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 ± 1.6 L/min, SAL; 2.6 ± 0.1 L/min, Hb1; 2.7 ± 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. Conclusion: In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.",
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TY - JOUR

T1 - Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in swine

AU - Malhotra, Ajai K.

AU - Schweitzer, John B.

AU - Fox, Jeri L.

AU - Fabian, Timothy

AU - Proctor, Kenneth G.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Background: Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)-a hemoglobin-based oxygen carrier with pressor activity-in the same swine model of traumatic brain injury and hemorrhagic shock. Methods: Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. Results: Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 ± 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 ± 4%) (p < 0.05 vs. baseline) and Hb1 (1 ± 5%), but was partially preserved in Hb2 (9 ± 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLhb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 ± 1 mm Hg, SAL; 42 ± mm Hg, Hb1; 45 ± 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 ± 1.6 L/min, SAL; 2.6 ± 0.1 L/min, Hb1; 2.7 ± 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. Conclusion: In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.

AB - Background: Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)-a hemoglobin-based oxygen carrier with pressor activity-in the same swine model of traumatic brain injury and hemorrhagic shock. Methods: Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. Results: Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 ± 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 ± 4%) (p < 0.05 vs. baseline) and Hb1 (1 ± 5%), but was partially preserved in Hb2 (9 ± 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLhb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 ± 1 mm Hg, SAL; 42 ± mm Hg, Hb1; 45 ± 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 ± 1.6 L/min, SAL; 2.6 ± 0.1 L/min, Hb1; 2.7 ± 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. Conclusion: In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.

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