Early cerebral perfusion pressure augmentation with phenylephrine after traumatic brain injury may be neuroprotective in a pediatric swine model.
OBJECTIVE
Cerebral perfusion pressure<40 mm Hg following pediatric traumatic brain injury has been associated with increased mortality independent of age, and current guidelines recommend maintaining cerebral perfusion pressure between 40 mm Hg-60 mm Hg. Although adult traumatic brain injury studies have observed an increased risk of complications associated with targeting a cerebral perfusion pressure>70, we hypothesize that targeting a cerebral perfusion pressure of 70 mm Hg with the use of phenylephrine early after injury in the immature brain will be neuroprotective.


METHODS
Animals were randomly assigned to injury with a cerebral perfusion pressure of 70 mm Hg or 40 mm Hg. Diffuse traumatic brain injury was produced by a single rapid rotation of the head in the axial plane. Cerebral microdialysis, brain tissue oxygen, intracranial pressure, and cerebral blood flow were measured 30 min-6 hrs postinjury. One hour after injury, cerebral perfusion pressure was manipulated with the vasoconstrictor phenylephrine. Animals were euthanized 6 hrs posttraumatic brain injury, brains fixed, and stained to assess regions of cell injury and axonal dysfunction.


METHODS
University center.


METHODS
Twenty-one 4-wk-old female swine.


RESULTS
Augmentation of cerebral perfusion pressure to 70 mm Hg resulted in no change in axonal dysfunction, but significantly smaller cell injury volumes at 6 hrs postinjury compared to cerebral perfusion pressure 40 (1.1% vs. 7.4%, p<.05). Microdialysis lactate/pyruvate ratios were improved at cerebral perfusion pressure 70 compared to cerebral perfusion pressure 40. Cerebral blood flow was higher in the cerebral perfusion pressure 70 group but did not reach statistical significance. Phenylephrine was well tolerated and there were no observed increases in serum lactate or intracranial pressure in either group.


CONCLUSIONS
Targeting a cerebral perfusion pressure of 70 mm Hg resulted in a greater reduction in metabolic crisis and cell injury volumes compared to a cerebral perfusion pressure of 40 mm Hg in an immature swine model. Early aggressive cerebral perfusion pressure augmentation to a cerebral perfusion pressure of 70 mm Hg in pediatric traumatic brain injury before severe intracranial hypertension has the potential to be neuroprotective, and further investigations are needed.
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stuart H
SH
Friess
Colin
C
Smith
Todd J
TJ
Kilbaugh
Suzanne G
SG
Frangos
Jill
J
Ralston
Mark A
MA
Helfaer
Susan S
SS
Margulies
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D017551:Microdialysis; D008991:Monitoring, Physiologic; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010656:Phenylephrine / Q000627:therapeutic use*; D013552:Swine
D018696:Neuroprotective Agents; D010656:Phenylephrine