Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin*

Abstract

Phenylephrine is often used for management of cerebral perfusion pressure after traumatic brain injury, but can have undesirable actions. Few studies have evaluated alternatives. The hypothesis was that arginine vasopressin was as effective as phenylephrine for maintaining tissue oxygenation during cerebral perfusion pressure management. Prospective randomized, blinded animal study. University laboratory. Thirty-five anesthetized swine (46 +/- 1 kg). Blunt trauma to the head and bilateral chests (estimated injury severity score was 25-32) was followed by hypoventilation. Resuscitation was divided into phases to simulate treatment in a typical prehospital, emergency room, and intensive care unit. For 30-45 mins postinjury, 1 L of normal saline was administered. For 45-120 mins, normal saline maintained systolic blood pressure >100 mm Hg plus mannitol for intracranial hypertension. After 120 mins, phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure >70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure >12 mm Hg plus glucose to maintain normoglycemia. Mortality rate was 37% (13 of 35) within 2 hrs. Before resuscitation, mean arterial pressure was 61 +/- 5 mm Hg, heart rate was 110 +/- 6 beats/min, PaO2 was 46 +/- 2 mm Hg, and lactate was 5.0 +/- 0.4 mM. Intracranial pressure increased from 8 +/- 1 mm Hg to 20 +/- 1 mm Hg and brain tissue PO2 decreased from 19 +/- 1 mm Hg to 8 +/- 1 mm Hg. Resuscitation corrected most variables, as well as mixed venous, renal, portal, and muscle oxygen saturations, but 90% (20 of 22) required pressor support. After 6 hrs with either pressor, hemodynamics were stable. However, with phenylephrine vs. arginine vasopressin, intracranial pressure averaged >10 mm Hg higher and brain tissue PO2 was 6 mm Hg lower, whereas tissue oxygen saturations were >10% higher in the shoulder and hindlimb muscles (all p < 0.05). Arginine vasopressin was as effective as phenylephrine for maintaining cerebral perfusion pressure, but intracranial pressure and brain tissue oxygenation were improved at the expense of the periphery.