Effects of vasoactive drugs on crystalloid fluid kinetics in septic sheep

Abstract

Abstract:

AIM: To explore how vasoactive drugs influence the distribution and clearance of lactated Ringer's solution(RL) in septic sheep. METHODS: This was a prospective randomized double-blinded study. Twenty-five experimental sheep were randomized into five groups: no drug (Control group), norepinephrine (Nor group), phenylephrine (Phe group), dopamine (Dop group), or esmolol (Esm group), with five animals for each group. After general anesthesia and tracheostomy tube for all sheep, septic model was established through cecal ligation puncture (CLP) method and a short infusion of lipopolysaccharide (LPS). Then a continuous intravenous administration of saline or corresponding vasoactive drugs were given to five groups respectively. 10 min later 20 mL/kg of RL solution over 30 min was given. The kinetics of RL and the effects of covariates were calculated by plasma dilution based on dilution of hemoglobin-time curve, urinary excretion by using Phoenix software for mixed effects modeling.RESULTS:Compared with Control group, Nor group and Dop group accelerated the distribution rate from plasma to peripheral tissue (k12); while decreased the distribution rate opposite direction (k21). Adrenergic α1-receprtor accelerated, while β1-receptors retarded, the distribution and elimination of the fluid. The pharmacodynamics Emax model showed that RL increased stroke volume by 13 mL/beat, α1-receptors but not β1-receptors further increased stroke volume, while both raised the mean arterial pressure, modulation of the β1-receptors limited the acidosis. CONCLUSION: The distribution and elimination of RL is slow in septic sheep. The tendency to peripheral accumulation of fluid is pronounced, in particular when phenylephrine and dopamine are given, and norepinephrine can alleviate acidosis.

Key words: Ringer's solution, volume kinetics, phenylephrine, dopamine, norepinephrine, esmolol

CLC Number:

R965.2

YI Shenghua, LI Yuhong, ZHENG Xiaozhu, AN Manli, DING Qiannan, RU Guomei, ZHANG Lin. Effects of vasoactive drugs on crystalloid fluid kinetics in septic sheep[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1081-1089.

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