Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock

Abstract

Background: Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR).

Methods: In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%.

Results: Norepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose.

Conclusions: Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.

Keywords: Cardiac preload; Fluid balance; Heart–lung interactions; Vasopressors; Venous return.

Fig. 1

Study design. Baseline_Low: baseline at the low dose of norepinephrine, Baseline_High: baseline at the high dose of norepinephrine, NE: norepinephrine, PLR_Low: passive leg raising at the low dose of norepinephrine; PLR_High: passive leg raising at the high dose of norepinephrine, Pms: mean systemic pressure, ∆Pms: changes in mean systemic pressure induced by passive leg raising

Fig. 2

Changes in mean systemic pressure during the study protocol. Baseline_Low: baseline at the low dose of norepinephrine, Baseline_High: baseline at the high dose of norepinephrine, PLR_Low: passive leg raising at the low dose of norepinephrine; PLR_High: passive leg raising at the high dose of norepinephrine, Pms: mean systemic pressure. *p < 0.05 vs. Baseline_High, **p < 0.05 vs. Baseline_Low. N = 30, mean [standard deviation]

Fig. 3

Changes in mean systemic pressure (∆Pms) induced by passive leg raising (PLR) at the highest and the lowest dose of norepinephrine (NE). N = 30, individual values and mean [standard deviation]