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To measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock.Prospective study.Medical and surgical intensive care units of a tertiary care teaching hospital.Ten patients with the diagnosis of septic shock who required pressor agents to maintain a MAP ≥ 60 mm Hg after fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) ≥ 12 mm Hg.Norepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in 10 patients with septic shock.At each level of MAP, hemodynamic parameters (heart rate, PAOP, cardiac index, left ventricular stroke work index, and systemic vascular resistance index), metabolic parameters (oxygen delivery, oxygen consumption, arterial lactate), and regional perfusion parameters (gastric mucosal Pco2, skin capillary blood flow and red blood cell velocity, urine output) were measured.Increasing the MAP from 65 to 85 mm Hg with norepinephrine resulted in increases in cardiac index from 4.7 ± 0.5 L/min/m2 to 5.5 ± 0.6 L/min/m2 (p < 0.03). Arterial lactate was 3.1 ± 0.9 mEq/L at a MAP of 65 mm Hg and 3.0 ± 0.9 mEq/L at 85 mm Hg (NS). The gradient between arterial Pco2 and gastric intramucosal Pco2 was 13 ± 3 mm Hg (1.7 ± 0.4 kPa) at a MAP of 65 mm Hg and 16 ± 3 at 85 mm Hg (2.1 ± 0.4 kPa) (NS). Urine output at 65 mm Hg was 49 ± 18 mL/hr and was 43 ± 13 mL/hr at 85 mm Hg (NS). As the MAP was raised, there were no significant changes in skin capillary blood flow or red blood cell velocity.Increasing the MAP from 65 mm Hg to 85 mm Hg with norepinephrine does not significantly affect systemic oxygen metabolism, skin microcirculatory blood flow, urine output, or splanchnic perfusion.