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Published on: May 16, 2015
Early cerebral perfusion pressure augmentation with phenylephrine after traumatic brain injury may be neuroprotective
Stuart H Friess1, Colin Smith, Todd J Kilbaugh
1Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Insights
Targeting higher cerebral perfusion pressure (CPP) of 70 mm Hg in pediatric traumatic brain injury (TBI) reduced cell injury and metabolic crisis. Early CPP augmentation may be neuroprotective in immature brains.
Area of Science:
- Neuroscience
- Pediatric Traumatic Brain Injury Research
- Vascular Physiology
Background:
- Pediatric traumatic brain injury (TBI) with cerebral perfusion pressure (CPP) < 40 mm Hg is linked to higher mortality.
- Current guidelines recommend maintaining CPP between 40-60 mm Hg.
- Adult TBI studies suggest risks with CPP > 70 mm Hg, but pediatric data is limited.
Purpose of the Study:
- To investigate the neuroprotective potential of targeting a CPP of 70 mm Hg using phenylephrine in an immature brain model following TBI.
- To evaluate the effects of early CPP augmentation on cellular injury and metabolic crisis.
Main Methods:
- Twenty-one 4-week-old female swine underwent diffuse TBI.
- Animals were randomized to injury with CPP maintained at 70 mm Hg or 40 mm Hg.
- Phenylephrine was used to augment CPP 1 hour post-injury; measurements included microdialysis, brain tissue oxygen, ICP, and cerebral blood flow up to 6 hours post-TBI.
Main Results:
- Targeting CPP of 70 mm Hg significantly reduced cell injury volumes (1.1% vs. 7.4%, p<.05) and improved lactate/pyruvate ratios compared to CPP of 40 mm Hg.
- No significant changes in axonal dysfunction were observed.
- Phenylephrine was well-tolerated, with no increase in serum lactate or intracranial pressure.
Conclusions:
- Maintaining CPP at 70 mm Hg in immature swine models reduced metabolic crisis and cell injury volumes post-TBI.
- Early, aggressive CPP augmentation to 70 mm Hg prior to severe intracranial hypertension shows potential neuroprotective effects in pediatric TBI.
- Further research is warranted to confirm these findings in clinical settings.
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.
Design:
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.
Setting:
University center.
Subject:
Twenty-one 4-wk-old female swine.
Measurements And Main 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.
