Early cerebral perfusion pressure augmentation with phenylephrine after traumatic brain injury may be neuroprotective in a pediatric swine model*

Abstract

Objective Cerebral perfusion pressure (CPP) less than 40 mm Hg following pediatric traumatic brain injury (TBI) has been associated with increased mortality independent of age, and current guidelines recommend maintaining CPP between 40–60 mm Hg. Although adult TBI studies have observed an increased risk of complications associated with targeting a CPP > 70, we hypothesize that targeting a CPP 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 CPP = 70 mm Hg (CPP70) or CPP = 40 mm Hg (CPP40). Diffuse TBI 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 (CBF) were measured 30 min – 6 h post-injury. One hour after injury, CPP was manipulated with the vasoconstrictor phenylephrine. Animals were euthanized 6 h post-TBI, brains fixed, and stained to assess regions of cell injury and axonal dysfunction. Setting University center. Subject 21 four week-old female swine. Measurements and Main Results Augmentation of CPP to 70 mm Hg resulted in no change in axonal dysfunction, but significantly smaller cell injury volumes at 6 hours post injury compared to CPP40 (1.1% vs. 7.4%, p < 0.05). Microdialysis lactate/pyruvate ratios were improved at CPP70 compared to CPP40. CBF was higher in the CPP70 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 CPP of 70 mm Hg resulted in a greater reduction in metabolic crisis and cell injury volumes compared to a CPP of 40 mm Hg in an immature swine model. Early aggressive CPP augmentation to a CPP of 70 mm Hg in pediatric TBI before severe intracranial hypertension has the potential to be neuroprotective, and further investigations are needed.

Differing Effects when Using Phenylephrine and Norepinephrine To Augment Cerebral Blood Flow after Traumatic Brain Injury in the Immature Brain

“…CPP augmentation with NE did not reduce microdialysate LPR similar to findings in adult patients with TBI 30 . However, vasopressor support with PE did result in a reduction in LPR, similar to our previous results 12 . Most likely, PbtO 2 reflects the accumulation of oxygen in the brain extracellular space, which is directly influenced by three factors: oxygen delivery, oxygen diffusion characteristics of the region of interest, and oxygen utilization by the brain tissue.…”

“…pediatric neurocritical care 12 . However, several other vasopressors are commonly utilized clinically to augment CPP and the conclusions in our previous study were limited by the use of volatile anesthetics during the post-injury period.…”

“…We have previously reported that early CPP support to 70 mm Hg with phenylephrine resulted in a greater reduction in metabolic crisis and cell injury volumes compared with targeting a CPP of 5 5 40 mm Hg 12 . The goal of this study was to compare the efficacy of phenylephrine with norepinephrine to target a CPP of 70 mm Hg early after non-impact inertial head injury.…”

Neuroprotection with phenylephrine in traumatic brain injury

“…The large doses of phenylephrine required to achieve the higher CPP by Friess et al (6) appear to be well-tolerated in this series without any evidence of systemic tissue hypoperfusion or pulmonary congestion (suggested by stable Pao2 and unchanged Fio2 requirements). Importantly, phenylephrine was used only for 5 hrs in this study and implications on safety of longer durations of use may not be drawn.…”

“…They observed greater reduction in metabolic crisis (evidenced by improvement in microdialysis lactate/pyruvate ratios) and lower cell injury volumes by maintaining a CPP of 70 mm Hg compared to a CPP of 40 mm Hg in the 6 hrs following experimental TBI induced by rapid axial head rotations without impact (6). Their results suggest that aggressive augmentation of CPP to 70 mm Hg in pediatric TBI before severe intracranial hypertension may be neuroprotective (6).…”