Immediate Norepinephrine in Endotoxic Shock: Effects on Regi... : Critical Care Medicine

Ospina-Tascón, Gustavo A. MD, PhD1,2; Aldana, José L. MD, MSc1,2; García Marín, Alberto F. MD, MSc1,2; Calderón-Tapia, Luis E. MD1,2; Marulanda, Angela MD1,2; Escobar, Elena P. MD1,2; García-Gallardo, Gustavo MD1,2; Orozco, Nicolás MD1,2; Velasco, María I. MSN1,2; Ríos, Edwin MSN1,2; De Backer, Daniel MD, PhD3; Hernández, Glenn MD, PhD4; Bakker, Jan MD, PhD4–7

1 Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia.

2 Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia.

3 Intensive Care Department, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium.

4 Departamento de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile.

5 Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

6 Department of Pulmonary and Critical Care, New York University, New York, NY.

7 Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY.

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This project received financial support from the Universidad Icesi, Cali, Colombia (COL0099642-989) and the Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia (FVL-2020-004).

Dr. Ospina-Tascón disclosed that this study received funding from the Universidad Icesi, Cali, Colombia (COL0099642-989) and Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia (FVL-2020-004). The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: [email protected]; [email protected]

To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock.

Animal experimental study.

University translational research laboratory.

Fifteen Landrace pigs.

Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) (n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) (n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) (n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.

Hypotension was significantly shorter in i-NE group (7.5 min [5.5–22.0 min] vs 49.3 min [29.5–60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy (p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group (p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels (p = 0.01) and venous-to-arterial carbon dioxide differences (p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes (p = 0.015) and required significantly less resuscitation fluids (p < 0.001) and lower doses of norepinephrine (p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group (p = 0.021 and p = 0.004, respectively).

In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.