Cerebral response to norepinephrine compared with fluid resuscitation in ovine traumatic brain injury and systemic inflammation.
OBJECTIVE
Traumatic brain injury is frequently accompanied by a systemic inflammatory response. Systemic inflammation was associated with cerebral hyperperfusion uncoupled to global oxygen metabolism in ovine head trauma. The present study investigated the cerebral effects of cerebral perfusion pressure (CPP) management performed by either fluid resuscitation or vasopressor treatment of low CPP induced by systemic inflammation.


METHODS
Nonrandomized experimental study.


METHODS
University hospital laboratory.


METHODS
A total of 12 adult sheep.


RESULTS
Sheep were anesthetized and ventilated throughout the experimental period (13 hrs). After baseline measurements (hour 0), blunt head trauma was induced by a nonpenetrating stunner. After postinjury measurements (hour 2), all animals received continuous endotoxin infusion. At hour 10, one group (n = 6) was infused with hydroxyethyl starch until CPP reached 60-70 mm Hg. A second group (n = 6) received norepinephrine for CPP elevation. In the norepinephrine group, blood was isovolemically exchanged by hydroxyethyl starch to achieve comparable hematocrit levels. Head trauma increased intracranial pressure and decreased brain tissue oxygen tension. Endotoxemia induced a hyperdynamic cardiovascular response with increased internal carotid blood flow in the presence of systemic hypotension and decreased CPP. Hydroxyethyl starch infusion further increased internal carotid blood flow from (mean +/- sd) 247 +/- 26 (hour 10) to 342 +/- 42 mL/min (hour 13) and intracranial pressure from 20 +/- 4 (hour 10) to a maximum of 25 +/- 3 mm Hg (hour 12) but did not significantly affect brain tissue oxygen tension, sinus venous oxygen saturation and oxygen extraction fraction. Norepinephrine increased internal carotid blood flow from 268 +/- 19 to 342 +/- 58 mL/min and intracranial pressure from 22 +/- 11 to 24 +/- 11 mm Hg (hour 10 vs. hour 13) but significantly increased sinus venous oxygen saturation from 49 +/- 4 (hour 10) to a maximum of 59 +/- 6 mm Hg (hour 12) and decreased oxygen extraction fraction. The increase in brain tissue oxygen tension during norepinephrine treatment was not significant.


CONCLUSIONS
We conclude that despite identical carotid blood flows, only CPP management with norepinephrine reduced the cerebral oxygen deficit in this model.
Stubbe
Henning D
HD
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Germany.
Greiner
Christoph
C
Westphal
Martin
M
Rickert
Christian H
CH
Aken
Hugo Van
HV
Eichel
Vera
V
Wassmann
Hansdetlef
H
Daudel
Fritz
F
Hinder
Frank
F
D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005440:Fluid Therapy; D006439:Hemodynamics / Q000187:drug effects; D007427:Intracranial Pressure / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology / Q000627:therapeutic use*; D012756:Sheep; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000628:therapy*; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D009638:Norepinephrine