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Hemodynamic changes and gut barrier function in sequential hemorrhagic and endotoxic shock
R G Turnbull1, J A Talbot, S M Hamilton
1Department of Surgery, University of Alberta, Edmonton, Canada.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The "two-hit" theory suggests a second stress exacerbates trauma, leading to multisystem organ failure (MSOF). This study in pigs found that endotoxin infusion after hemorrhagic shock worsened outcomes, supporting the two-hit hypothesis in trauma research.
Area of Science:
- Trauma and Surgical Critical Care
- Immunology and Inflammation
- Gastroenterology
Background:
- Multisystem organ failure (MSOF) is a primary cause of mortality after trauma.
- The gut is implicated as a source of systemic inflammation driving MSOF.
- The "two-hit" theory posits that a second physiological stressor can precipitate MSOF after an initial insult.
Purpose of the Study:
- To investigate the "two-hit" theory of MSOF.
- To examine the hemodynamic and bacteriologic responses to a secondary stressor in a porcine model.
- To compare outcomes following endotoxin or hemorrhagic shock followed by endotoxin.
Main Methods:
- A subacute porcine model (n=18) was utilized.
- Animals underwent instrumentation including vascular catheters and flow probes.
- Groups received either endotoxin, hemorrhagic shock then endotoxin, or hemorrhagic shock alone.
Main Results:
- One animal in the hemorrhagic shock then endotoxin group died during endotoxic shock.
- Hemodynamic and bacteriologic data were collected throughout the study.
- Systemic blood and organs were cultured for bacterial analysis.
Conclusions:
- The study aimed to validate the "two-hit" theory in a trauma model.
- Findings contribute to understanding the pathophysiology of MSOF.
- Further research is needed to fully elucidate the mechanisms involved.