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Effect of norepinephrine on cardiac output and preload in septic shock patients


Norepinephrine (NE) is a first-line vasopressor used in patients with septic shock. Because of its predominant α-agonist effect, it is assumed to increase vasomotor tone and hence the mean arterial pressure (MAP) without significant effect on the cardiac index (CI). However, a potential beneficial effect on CI can be expected from its venoconstrictor α-agonist-mediated effect combined with an inotropic β1 agonist effect, provided that the increase in left ventricular afterload is not excessive (high levels of MAP). The aim of our study was to examine the cardiovascular effect of NE when it induces marked changes in MAP.


In an observational study of patients (n = 37) resuscitated for septic shock, we analysed hemodynamic PiCCO data at two consecutive time points where the MAP changed by more than 15% in response to either initiation or to change of doses of NE. Two subgroups of patients were identified. The first subgroup (MAPincr) consisted of 21 patients in whom the MAP increased by more than 15% in response to either initiation of NE infusion (n = 8) or increase in NE dose (from 1.7 ± 1.7 to 2.2 ± 1.4 mg/hour; n = 13). The second subgroup (MAPdecr) consisted of 16 patients in whom the MAP decreased by more than 15% in response to the decrease in NE doses. For both subgroups, the time between the two consecutive sets of measurements did not exceed 2 hours and no other treatments that may alter hemodynamics were administered within this period (fluids, hemofiltration, diuretics or other catecholamines).


In the MAPincr subgroup, MAP increased from 56 ± 17 to 84 ± 12 mmHg (P < 0.05) while significant increases in CI (from 3.4 ± 1.0 to 3.7 ± 0.9 l/min/m2), stroke volume index (SVi) (from 37 ± 12 to 41 ± 11 ml/m2) and global end diastolic volume index (GEDVi) (from 706 ± 203 to 767 ± 225 ml/m2) were observed. Neither the heart rate nor the global ejection fraction (GEF) significantly changed. In seven patients, the GEF markedly increased by >15% in parallel to the increase in SVi. In the MAPdecr subgroup, MAP decreased from 95 ± 12 to 70 ± 9 mmHg (P < 0.05). The CI (from 3.5 ± 1.4 to 3.0 ± 0.9 l/min/m2) and GEDVi (from 815 ± 319 to 721 ± 253 ml/m2) decreased significantly, while the heart rate, SVi (P = 0.07) and GEF did not change.


In our septic shock patients, changes in MAP resulting from increases or decreases in the doses of NE, were associated with changes in CI related to changes in GEDVi (cardiac preload) and in some patients to changes in systolic left ventricular function evaluated by GEF. These findings suggest that administration of NE in septic shock is associated not only with an increase in MAP but also with an increase in systemic blood flow.

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Hamzaoui, O., Ksouri, H., Richard, C. et al. Effect of norepinephrine on cardiac output and preload in septic shock patients. Crit Care 11 (Suppl 2), P37 (2007).

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