Does the timing of instrumentation under anaesthesia impact upon mortality and organ function in a rodent model of fecal peritonitis?

INTRODUCTION. Rodent models of sepsis are commonly used to explore pathophysiology and treatment strategies, yet considerable heterogeneity exists [1]. We anecdotally observed different outcomes when the onset of sepsis was delayed after vascular instrumentation. OBJECTIVES. To determine whether the timing of instrumentation under anaesthesia impacts upon mortality and organ function in a rodent model of fecal peritonitis. METHODS. 26 male Wistar rats (296 ± 30 g) were instrumented with tunnelled internal jugular and carotid artery catheters under a brief period of isoflurane anesthesia. Animals were connected via a tethered swivel to allow free movement within the cage and randomized to receive intra-peritoneal injection of faecal slurry (3 ll slurry/g), either at the same time (SD n = 13) or 24 h post-instrumentation (AD n = 13). Half were placed in a metabolic cart for continuous monitoring of oxygen consumption (VO2). Blood pressure (BP) was continuously monitored. Animals received a continuous infusion of hydroxyethyl starch and glucose at 10 ml/kg/h, halving at 24 h intervals. Blood samples were taken at 6 and 24 h post-slurry for blood gases, cytokines and markers of organ function. Data are presented as mean ± SEM. RESULTS.Median survival was significantly prolonged in the AD group (52 vs. 18 h, p = 0.0004). At post-mortem all animals but one (SD group, excluded from analysis) had evidence of peritoneal inflammation. During the observation period BP was not different between groups. At 24 h post-slurry lactate (5.0 ± 1.5 vs. 2.3 ± 0.3 mmol/l, p = 0.02) and IL-6 levels (40,312 ± 5,838 vs. 11,086 ± 4,699 pg/ml, p = 0.008) were significantly higher in the SD group. No significant differences were seen in urea, bilirubin, alanine aminotransferase and troponin levels. At the median survival timepoint, SD animals showed significant decreases in VO2 (1,237 ± 315 vs. 1,750 ± 92 ml/kg/h, p = 0.02). CONCLUSIONS. Despite an identical septic insult in similar animals receiving equivalent instrumentation and resuscitation those receiving fecal slurry at the time of anaesthesia and instrumentation had a more severe inflammatory response with worse clinical outcomes. However, no clear difference was seen in tested clinically relevant organ function markers. While the mechanisms for this altered phenotype remain to be elucidated, this study highlights the need for caution in attempting to reproduce findings in different experimental models of sepsis. REFERENCE. 1. Dyson A. Crit Care Med 2009;37:S30-7.