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Multiple organ dysfunction syndrome: the scapegoat? Assessment of organ dysfunction between surviving and dying mice in the acute phase of polymicrobial sepsis
Critical Care volume 13, Article number: P48 (2009)
Multiple organ dysfunction syndrome (MODS) frequently complicates sepsis contributing to poor outcome. Yet the evolution of MODS in the early septic mortality (ESM) is unclear. To delineate the ESM-MODS relationship, we compared the development and magnitude of organ injury between dying and surviving mice in the acute phase (days 1 to 5) of polymicrobial sepsis.
Female OF-1 mice were subjected to cecal ligation and puncture (CLP). In the first mouse subset, 20 μl blood was collected daily for 5 days or until death (mice followed for 28 days). To define the pre-lethal changes in circulating parameters, mice were retrospectively divided into two groups based on outcome in the acute sepsis: DEAD (all died within 5 days, n = 39) and survivors (SUR; alive at day 28, n = 40). In the second subset, mice were sacrificed within 24 hours of projected death (based on the body T <28°C, 100% specificity, n = 7) and matched with SUR (body T >35°C, 100% sensitivity) from the same post-CLP day and controls.
In the first subset, significant difference was observed between SUR and DIED in the circulating urea, ALT, LDH and glucose during the 1-day to 5-day time course but the magnitude of these changes varied among post-CLP days. Therefore, we used the day of death as a reference point clustering all pre-lethal parameter values as the 72, 48 and 24 hours prior-to-death (on any 1 to 5 post-CLP day) time points for comparison with the SUR values. A significant separation between SUR and DIED occurred generally at 24 hours prior to death: pre-lethal urea increased to 78 (vs. 40 mg/dl in SUR), ALT to 173 (vs. 106 U/l) and LDH to 798 (vs. 445 U/l), while pre-lethal glucose declined to 41 (vs. 74 mg/dl). In the second subset (only 24 hours prior-to-death time point), acute deaths were not preceded by a significant rise in creatinine (DIED 6.8 vs. 4.3 μM/l in SUR) and troponin I (239 vs. 119 pg/ml). Similarly, respiratory function of mitochondria in the liver and kidney was not impaired in either DIED and SUR compared with controls. Injury scores in the liver, kidney, heart and lung showed no apparent morphological disparity between moribund, surviving or control mice. Incidence of cell apoptosis (TUNEL) in organs was not increased in either of the groups.
The increase of selected organ function/metabolic markers was manifested at least 24 hours prior to death. Despite statistical significance, the relatively small magnitude of these changes questions organ failure as a direct cause of death in the early phase of CLP sepsis.
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Osuchowski, M., Weixelbaumer, K., Raeven, P. et al. Multiple organ dysfunction syndrome: the scapegoat? Assessment of organ dysfunction between surviving and dying mice in the acute phase of polymicrobial sepsis. Crit Care 13, P48 (2009). https://doi.org/10.1186/cc8104
- Acute Phase
- Respiratory Function
- Organ Injury
- Multiple Organ Dysfunction Syndrome
- Injury Score