1776: A Reproducible Swine Model of Endotoxemia-Induced Septic Shock for Critical Care Investigations

Introduction: Preclinical septic shock models are vital for translational evaluation of emerging therapies, yet current swine models vary in shock definitions, sampling, and hemodynamic thresholds—limiting reproducibility. We developed a rigorously controlled swine endotoxemia-induced model with four distinct phases reflecting septic shock: baseline, endotoxemia induction, shock with vasopressor initiation, and vasopressor steady state. Methods: Four Yorkshire pigs (22±3 kg) were anesthetized, intubated, and monitored via arterial, central venous, and pulmonary artery catheters. Continuous mean arterial pressure (MAP), systolic/diastolic pressure (SBP/DBP), central venous (CVP), heart rate (HR), and ECG—were recorded at 30-second intervals. Baseline was defined as MAP ≥65 mmHg for 20 minutes. Endotoxemia was induced with peripheral intravenous lipopolysaccharide (E.coli O111:B4) infusion at 2.5 µg/kg/hr, titrated up every 6 minutes until SBP dropped ≥20% and MAP ≤65mmHg. A 30cc/kg crystalloid bolus was given and norepinephrine (0.01–0.30 µg/kg/min) initiated to restore MAP ≥65 mmHg. Steady state was defined after 15 minutes of stable vasopressor dosing and maintained for 2.5 hours. ABGs and lactate were sampled serially. Data were cleaned and aggregated into 10-minute means for analysis using linear mixed-effects models. Results: Endotoxemia developed over 23.5±7.4 minutes. MAP fell from baseline 81.2±5.8 to 50±2.5 mmHg (Δ-38%) and SBP from 97.8±4.4 to 62.8±2.5 mmHg (Δ–36%) with shock onset. After norepinephrine, MAP and SBP improved to 61±4 and 82±6.5 mmHg at steady state. HR rose from baseline 107±9 bpm to 116±10 bpm during endotoxemia and peaked at 147±8.1 bpm after 2.5 hours. Lactate increased from baseline 2.9±1.2 to 3.8±2.5 mmol/L after endotoxemia and reached 4.5±1.4 mmol/L by 2.5 hours. Across all variables, inter-pig SEM remained ≤6% of the mean, confirming low variability supporting reproducibility of the model. Total endotoxin dosed averaged 7.4± 5.9 µg/kg with pigs receiving 54±18 µg/kg of norepinephrine in aggregate. Conclusions: This novel four-phase swine model provides a reproducible, low-variance septic shock model using vasopressor therapy. It offers a robust control condition to test adjunctive interventions in septic shock and serves as a translational reference for preclinical research.