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.

• Authors: Imane Adda, Christopher Lai, Jean-Louis Teboul, Laurent Guerin, Francesco Gavelli, Xavier Monnet
• Journal: Critical care (London, England) (Crit Care) Vol. 25 Issue 1 Pg. 302 (08 21 2021) ISSN: 1466-609X [Electronic] England
• PMID: 34419120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Plasma Substitutes
• Vasoconstrictor Agents
• Norepinephrine

Topics

• Aged
• Aged, 80 and over
• Blood Pressure (drug effects, physiology)
• Cardiac Output (drug effects)
• Female
• Hemodynamics (drug effects)
• Humans
• Male
• Middle Aged
• Norepinephrine (administration & dosage, pharmacokinetics, pharmacology)
• Plasma Substitutes (administration & dosage, pharmacokinetics, pharmacology)
• Shock, Septic (drug therapy, physiopathology)
• Treatment Outcome
• Vasoconstrictor Agents (administration & dosage, pharmacokinetics, pharmacology)