Hemodynamic Changes and Gut Barrier Function in Sequential Hemorrhagic and Endotoxic Shock

Abstract

Multisystem organ failure (MSOF) is the major cause of late death following trauma. The gut is hypothesized to be the source of an ongoing systemic inflammatory response that drives MSOF. It has also been suggested that while a single physiologic insult might not reliably cause MSOF, the addition of a delayed second stress will. This is known as the ``two-hit'' theory. The purpose of this study was to investigate the two-hit theory by observing the hemodynamic and bacteriologic response to a second stress in a subacute pig model of hemorrhagic and endotoxic shock. Swine (n = 18, 30-40 kg) were fed an antibiotic-free diet for 14 days. During instrumentation and experimentation on days 1 and 3, all animals were anesthetized (ketamine, isofluorane). On day 1, all animals had placement of central venous and arterial catheters, a portal venous catheter, and superior mesenteric artery flow probe. Group E (n = 6) underwent instrumentation on day 1, then infusion of endotoxin (25 mcg/kg E. coli lipopolysaccharide) on day 3. Group HE (n = 7) underwent instrumentation then hemorrhagic shock (mean arterial pressure = 40 mm Hg for 4 hours) on day 1, then infusion of endotoxin on day 3. Group H (n = 5) were instrumented and hemorrhaged on day 1, and underwent anesthesia only on Day 3. Between periods of anesthesia the animals were allowed food and water ad lib and systemic blood was sampled for culture every 12 hours. On day 5, the animals were euthanized prior to organ sampling for bacterial culture. One animal from group HE died during endotoxic shock on day 3. In response to endotoxin, group E animals showed a transient 22.9 mm Hg increase in blood pressure while group HE fell by 25.8 mm Hg (p < 0.001). Heart rate rose by 38 bpm in group E, but decreased by 2 bpm in HE animals (p < 0.01). Superior mesenteric artery flow in group E decreased to 66.4% of baseline in 30 minutes then recovered to 87.7% by 60 minutes, while that of group HE fell to 55.0% and did not recover (p < 0.001). Gut oxygen delivery showed a response similar to superior mesenteric artery flow with p values < 0.01. No pathogens were cultured from blood until after day 3. Three of six group HE animals developed positive blood cultures while 0 of 6 group E and 0 of 5 group H animals did. Tissue cultures were positive in 10 of 24 samples from group HE animals, but only 1 of 24 in group E, and 4 of 20 in group H. Group HE animals also showed a significantly higher incidence of polymicrobial infection, and infection with Enterococcus. These data suggest a difference in response to an endotoxic insult when an initial stressor (hemorrhagic shock) has been previously endured. Impaired handling of a second stress could contribute to the development of MSOF as proposed by the two-hit theory.