Increasing mean arterial pressure in patients with septic shock: Effects on oxygen variables and renal function* Aurélie Bourgoin, MD; Marc Leone, MD; Anne Delmas, MD; Franck Garnier, MD; Jacques Albanèse, MD; Claude Martin, MD, FCCM S eptic shock is a form of distrib- utive shock characterized by ar- teriolar and venous vasodilation (1). Patients generally have a high cardiac index (CI) and low systemic vascular resistance index (SVRI) in the early stage of septic shock, but CI may decrease and SVRI increase when sepsis progresses. Effective cardiovascular sup- port is of crucial importance in the man- agement of septic shock patients. Treat- ment is aimed at both maintaining oxygen delivery above a critical threshold and in- creasing mean arterial pressure (MAP) to a level that allows appropriate distribution of CI for adequate organ perfusion (2). Several factors contribute to organ dysfunction in septic patients. Hemody- namic factors such as volume depletion, low cardiac output (1), or inappropriate vasodilation resulting in systemic hypo- tension may directly produce organ hy- poperfusion through a reduction in organ perfusion pressure. Organ autoregulation, the tendency of organ blood flow to remain constant over a range of organ perfusion pressure val- ues, defines the perfusion range over which resistance can compensate for the decrease in pressure (3). The autoregula- tory threshold is the lowest pressure at which autoregulation is maintained, and it may be defined by the intercept of the autoregulated zone. Below their autoreg- ulatory thresholds, organ blood flows be- come linearly dependent on perfusion pressure (4, 5). It can therefore be spec- ulated that therapy should be aimed at providing an adequate organ perfusion pressure that is higher than commonly targeted or achieved in the treatment of septic patients (6 – 8). Although this may require the use of vasopressor cat- echolamines, with their attendant risk of organ vasoconstriction and reduction in organ blood flow, clinical studies suggest that such reactions rarely occur and that organ function usually improves when tissue perfusion pressure is augmented during sepsis and septic shock (6, 8, 9). However, the recommended end points with regard to MAP remain controversial, ranging from 60 mm Hg, which is con- sidered as the point at which open perfu- sion becomes pressure dependent, to lev- els of 80 –90 mm Hg (8 –14). Increasing blood pressure through vasoconstriction can be associated with a decrease in CI, putting some organs at risk of ischemia. Moreover, the benefit of titrating cate- cholamine infusion to higher levels has never been demonstrated. Accordingly, a prospective, randomized, controlled study was designed to examine the effects *See also p. 906. From the Department of Intensive Care Medicine and Trauma Center, Hospital Nord, Marseille Cedex 20, France. Address requests for reprints to: Claude Martin, MD, Department of Reanimation, Hopital Nord, 13915 Marseille Cedex 20, France. Copyright © 2005 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/01.CCM.0000157788.20591.23 Objective: To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock. Design: Prospective, open-label, randomized, controlled study. Setting: Medical-surgical intensive care unit of a tertiary care teaching hospital. Patients: Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure >60 mm Hg. Interventions: Patients were treated with fluid and norepineph- rine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groups: In the first group (control group, n  14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n  14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine. Measurements and Main Results: Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pres- sure, pulmonary artery occlusion pressure, cardiac index, sys- temic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic vari- ables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduc- tion of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.8 – 6.0) to 5.8 (4.3– 6.9) L·min 1 ·m 2 . Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variables: urine flow, 63 (14 –127) and 70 (15–121) mL; serum creatinine, 170 (117–333) and 153 (112–310) mol·L 1 ; and creatinine clearance, 50 (12– 77) and 67 (13– 89) mL·min 1 ·1.73 m 2 . Conclusions: Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function. (Crit Care Med 2005; 33:780 –786) KEY WORDS: septic shock; lactate; norepinephrine; renal func- tion; tissue oxygenation; tissue perfusion pressure 780 Crit Care Med 2005 Vol. 33, No. 4