The Effect of Fluid Pre-loading on Vital Signs and Hemodynamic Parameters in a Porcine Model of Lipopolysaccharide-Induced Endotoxemia.

Abstract

Background Animal models of distributive hypotension and resuscitation allow the assessment of hemodynamic monitoring modalities and resuscitation strategies. The fluid-first paradigm for resuscitation is currently being challenged with clinical trials. In this investigation, venous return and perfusion are assessed, and full hemodynamics are characterized, in a porcine model of endotoxemic hypotension with and without fluid pre-loading. Methods Two groups of six pigs had the induction of standardized endotoxemic hypotension("critical hypotension"). Group 1 underwent four 10 cc/kg crystalloid boluses, and Group 2 was not fluid pre-resuscitated. Both groups underwent progressive norepinephrine (NE) up-titration to 0.25 mcg/kg/minute over 30 minutes. Vital signs, central parameters, and laboratory values were obtained at baseline, "critical hypotension,"after each bolus and during NE administration. Results Endotoxemia decreased the systemic vascular resistance (SVR) in Group 1 (1031±106 dyn/s/cm-5 versus738±258 dyn/s/cm-5; P=0.03) and Group 2 (1121±196 dyn/s/cm-5 versus759±342 dyn/s/cm-5; P=0.003). In Group 1, the four fluid boluses decreased heart rate (HR), pulmonary capillary wedge pressure (PCWP), and central venous pressure (CVP) (P<0.05). No changes were observed in blood pressure, cardiac output (CO), or lactate. NE up-titration increased HR in Group 1and decreased CVP in both groups. Higher final CVP (11 {3} versus4 {4} mmHg; P=0.01) and PCWP (5 {1} versus2 {2} mmHg; P=0.005) values were observed in Group 1 relative to Group 2, reflecting increased venous return. Conclusions Porcine endotoxemic hypotension and resuscitation were robustly characterized. In this model, fluid loading improved venous return with NE, though perfusion (CO) was preserved by increased NE-induced chronotropy.