Effects of Reversal of Hypotension on Cerebral Microcirculation and Metabolism in Experimental Sepsis

The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < 65 mmHg, unresponsive to fluid challenge), a norepinephrine infusion was titrated in eight sheep to restore a MAP >= 75 mmHg; the other four sheep were kept hypotensive. The microcirculation of the cerebral cortex was evaluated using side-stream dark-field video-microscopy. Brain partial pressure of oxygen (PbtO(2)) was measured, and cerebral metabolism was assessed using microdialysis. All animals developed septic shock after a median of 15 (14-19) h. When MAP was raised using norepinephrine, the PbtO(2) increased significantly (from 41 +/- 4 to 55 +/- 5 mmHg), and the cerebral lactate/pyruvate ratio decreased (from 47 +/- 13 to 28 +/- 4) compared with values at shock onset. Changes in the microcirculation were unchanged with restoration of MAP and the glutamate increased further (from 17 +/- 11 to 23 +/- 16 mu M), as it did in the untreated animals. In septic shock, the correction of hypotension with vasopressors may improve cerebral oxygenation but does not reverse the alterations in brain microcirculation or cerebral metabolism.