TY - JOUR
T1 - Immediate Norepinephrine in Endotoxic Shock
T2 - Effects on Regional and Microcirculatory Flow∗
AU - Ospina-Tascón, Gustavo A.
AU - Aldana, José L.
AU - García Marín, Alberto F.
AU - Calderón-Tapia, Luis E.
AU - Marulanda, Angela
AU - Escobar, Elena P.
AU - García-Gallardo, Gustavo
AU - Orozco, Nicolás
AU - Velasco, María I.
AU - Ríos, Edwin
AU - De Backer, Daniel
AU - Hernández, Glenn
AU - Bakker, Jan
N1 - Funding Information:
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).
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - OBJECTIVES: 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. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.
AB - OBJECTIVES: 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. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.
UR - http://www.scopus.com/inward/record.url?scp=85164845560&partnerID=8YFLogxK
U2 - 10.1097/CCM.0000000000005885
DO - 10.1097/CCM.0000000000005885
M3 - Article
C2 - 37255347
AN - SCOPUS:85164845560
SN - 0090-3493
VL - 51
SP - E157-E168
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 8
ER -