24 Confocal Laser Endomicroscopy to Assess Mucosal Microcirculation: A Quantitative Analysis in a Porcine Model of Septic Shock and in Patients With Severe Sepsis

Abstract

Aim Microcirculatory alterations play a central role in the pathophysiology of sepsis. Even if systemic hemodynamic parameters appear to be adequate, septic patients may suffer from significant intestinal microcirculatory alterations. It has been suggested that these changes play a central role in regard to morbidity and mortality. The present study first assessed the feasibility of In Vivo detection of mucosal microcirculation in different segments of the gastrointestinal tract in an animal model of septic shock using probe-based confocal laser endomicroscopy (pCLE) (Mauna Kea Technologies, Paris, France). Subsequently, we assessed duodenal microcirculation in patients suffering from severe sepsis in the early phase of the disease. Materials and Methods First, anesthetized and mechanically ventilated pigs were observed over 8 hrs. Septic shock was triggered by inducing fecal peritonitis (0.75 g autologous feces per kg body weight). Mucosal microcirculation was assessed simultaneously using pCLE in stomach, duodenum, terminal ileum and rectum at baseline, 4 hours after induction of septic shock as well as 2 hours after treatment of the condition. Second, six patients who presented with a severe sepsis on the intensive care unit were examined regarding their duodenal microcirculation after obtaining informed consent from their nearest relatives. These patients were compared to ten healthy controls. Four to six areas were examined for each site and images were analysed in a blinded fashion offline thereafter in both parts of the study. Mean capillary diameter, capillary length and functional capillary density (FCD) were measured quantitatively. Results Two hours after induction of sepsis in the animal model, FCD was markedly decreased in the duodenal (-20.8, p < 0.001), the ileal (-13.4, p < 0.001), the gastric (-11.9%, p < 0.001), and in the rectal mucosal beds (-5.5, p<0,01). After administration of 30 mg x kg-1 of gelatine (30 kDa) FCD increased in all mucosal compartments to 90.0% (duodenum), 94.4% (ileum), 95.4% (gastric) and 97% (rectum) of baseline values. Interestingly, mean vessel diameter was unchanged in all compartments investigated. In patients suffering from severe sepsis we found a significant decrease in mean vessel diameter (-5.0%, p<0.001) as well as in FCD (-9,4%, p<0.001) of the duodenal mucosa, as well. Conclusions During the early phase of septic shock, pCLE may be able to quantify microcirculatory alterations in the gastrointestinal mucosa. Fluid resuscitation improves but does not completely restore intestinal microcirculation in the septic shock model. pCLE may represent a useful tool in order to assess the efficacy of therapeutic interventions on mucosal microcirculation, possibly even in clinical practice.