Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow*

Abstract

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.

Immediate Fluid Bolus or Norepinephrine in Endotoxic Shock

“…T his letter is in regard to an article published by Ospina-Tascon et al (1) in a recent issue of Critical Care Medicine. In a pig model of endotoxic shock, the authors noted better splanchnic blood flow, lower resuscitation fluids, and lower extravascular lung water in the immediate norepinephrine group compared with the fluid bolus group.…”

“…Gustavo A. Ospina-Tascón, MD, PhD 1,2 José L. Aldana, MD, MSc 1,2 Alberto F. García Marín, MD, MSc 1,2 The authors reply: W e thank Jha (1) for his interest in our article about the effects of immediate start of norepinephrine (i-NE) on splanchnic regional and intestinal microcirculatory blood flow in a model of endotoxic shock, recently published in Critical Care Medicine (2).…”

Evidence for a personalized early start of norepinephrine in septic shock

“…This fluid-like effect has been demonstrated in septic shock patients [ 2 ] or after cardiac surgery [ 3 ]. This increase in Pmsf leads to a significant increase in cardiac preload [ 4 , 5 ] which, in the event of preload responsiveness, significantly increases cardiac output [ 2 ].…”

“…Only experimental data are available. In two studies in animals with endotoxic shock, early norepinephrine administration added to fluid infusion improved cardiac output, increased gut microvascular blood flow, and blunted the increase in lactate levels [ 5 , 9 ].…”