2002 Papers - Chan


Effects of Vasopressin Infusion on Systemic Organ Perfusion in a Porcine (Sus scrofa) Model of Vasodilatory Septic Shock
Chan MM, Chung MH, Cordts PR, Sawyer MAJ, Wu J, Hashiro GM, Burghardt CA, Cheng DPY, and Uyehara CFT
Tripler Army Medical Center

Background: Septic shock leads to severe systemic hypotension and cardiovascular collapse, with a mortality rate approaching 50%. Recent studies suggest that vasopressin (VP) may maintain blood pressure when other pharmacologic vasoconstrictors fail. However, it is unclear if sustaining blood pressure actually improves survival or prevents morbidity. Defining the relationship between blood pressure and organ perfusion may assist in clarifying vasopressin's clinical utility. In this study, we investigate the effects of VP administration on hemodynamics and organ perfusion in a porcine model of septic shock.

Methods: Anesthetized, mechanically ventilated piglets were instrumented with catheters to obtain hemodynamic parameters including mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), blood gases and urine output. Regional blood flow (RBF) was measured via injection of colored microspheres. Septic shock was induced by i.v. injection of E. coli endotoxin (30 ug/kg). Measurements were obtained before endotoxin, post endotoxin and after infusion of either VP (100ng/kg/min), n=7) or normal saline (control, n=7). Ventilation settings were adjusted to keep end-tidal CO2 below 45 mmHg, and arterial saturation above 85%.

Results: Endotoxin induced a sustained hypotension (systolic blood pressure <80% of baseline) within 60 minutes of endotoxin administration (MAP 51 +/-7 and 50 +/-5 mm Hg in the control and VP groups, respectively). After infusion of VP, MAPS returned to pre-endotoxin levels (MAP 85 +/-5 mmHg), yet remained depressed in control group animals (MAP 48 +/-9 mmHg). Though the elevated blood pressure observed after VP infusion correlated with increased systemic vascular resistance, the ratio of pulmonary vascular resistance (PVR) to SVR remained constant. This was in contrast to an increased ratio in the control group, thus, suggesting a sparing of the pulmonary vasculature from the vasoconstrictive effects of VP. Overall, O2 delivery and O2 extraction were similar. Both groups developed a persistent metabolic acidosis. However, preliminary results indicate a dramatic shift in regional blood flow distribution to vital organs in the VP group. Vasopressin appears to increase perfusion to the brain, heart, kidney and liver, yet compromising flow to skin, muscle, stomach, and intestines. In addition, urine output increased remarkably by 5-fold in piglets treated with VP, implying a preservation of renal function.

Conclusions: Treatment of septic shock with VP leads to increased blood pressures, urine output, and perfusion to vital organs. These results suggest that VP may have a protective effect against multi-system organ failure in addition to maintaining systemic blood pressures.