Purpose: Sepsis affects both macro- and micro-circulatory transport of oxygen to tissues, causing regional hypoxia. However, this relationship is poorly characterized with respect to inter-organ variability, disease severity and the evolution to organ dysfunction. We hypothesized that an early circulatory insult precedes the development of organ dysfunction, and is more severe in predicted non-survivors. Consequently, we assessed temporal changes in myocardial function and regional tissue oxygenation in peripheral and deep organs in a rat model of faecal peritonitis. We also examined the utility of a dynamic oxygen challenge test to assess the microcirculation.
Methods: Awake, tethered, fluid-resuscitated male Wistar rats were randomized to receive intraperitoneal injection of faecal slurry, or to act as controls. At either 6 or 24 h post insult, rats were anaesthetized and underwent echocardiography, arterial cannulation and placement of tissue oxygen probes in peripheral (muscle, bladder) and deep (liver and renal cortex) organ beds. Measurements were repeated during fluid loading and an oxygen challenge test (administration of high oxygen concentrations).
Results: Early sepsis (6 h) was characterized by a fall in global oxygen delivery with concurrent decreases in muscle, renal cortical and, especially, liver tissue PO2. By contrast, during established sepsis (24 h), myocardial and circulatory function had largely recovered despite increasing clinical unwellness, hyperlactataemia and biochemical evidence of organ failure. O2 challenge revealed an early depression of response that, by 24 h, had improved in all organ beds bar the kidney.
Conclusions: This long-term septic model exhibited an early decline in tissue oxygenation, the degree of which related to predicted mortality. Clinical and biochemical deterioration, however, progressed despite cardiovascular recovery. Early circulatory dysfunction may thus be an important trigger for downstream processes that result in multi-organ failure. Furthermore, the utility of tissue PO2 monitoring to highlight the local oxygen supply-demand balance, and dynamic O2 challenge testing to assess microcirculatory function merit further investigation.