Effects of norepinephrine on mean systemic pressure and venous return in human septic shock

Objectives: Norepinephrine exerts venoconstriction that could increase both the mean systemic pressure and the resistance to venous return, but this has not yet been investigated in human septic shock. We examined the relative importance of both effects and the resulting effect on venous return when decreasing the dose of norepinephrine. Setting: Intensive care unit. Patients: Sixteen septic shock patients. Measurements: For estimating the venous return curve, we constructed the regression line between the pairs of cardiac index (pulse contour analysis) and central venous pressure values. These values were measured during 15-sec end-inspiratory and end-expiratory ventilatory occlusions performed at two levels of positive end-expiratory pressure, in view of widening the range of cardiac index: central venous pressure measurements and increasing the accuracy of the regression line. The x-axis intercept of the regression line was used to estimate the mean systemic pressure and the inverse of the slope of the regression line to quantify resistance to venous return. These measurements were obtained before and after decreasing the dose of norepinephrine. Passive leg raising was performed before and after decreasing the dose of norepinephrine. Main Results: Decreasing the dose of norepinephrine from 0.30 (0.10-1.40) to 0.19 (0.08-1.15) mu g/kg/min decreased the mean systemic pressure from 33 +/- 12 mm Hg to 26 +/- 10 mm Hg (p = .0003). The slope of the multipoint cardiac index: central venous pressure relationship increased (p = .02). The resistance to venous return decreased, i.e., 1/slope decreased. Simultaneously, cardiac index decreased from 3.47 +/- 0.86 L/min/m(2) to 3.28 +/- 0.76 L/min/m(2) (p = .04), - indicating a decrease in venous return. Passive leg raising increased cardiac index to a larger extent after (8% +/- 4%) than before (1% +/- 4%) decreasing norepinephrine (p = .001), suggesting an increase in unstressed blood volume at the lowest dose of norepinephrine. Conclusions: In septic shock patients, decreasing the dose of norepinephrine decreased the mean systemic pressure and, to a lesser extent, the resistance to venous return. As a result, venous return decreased. (Crit Care Med 2012; 40:3146-3153)