Prolonged hypervolemic hemodilution decreases functional capillary density of ileal mucosa in pigs revealed by sidestream dark-field imaging*

Objective: Hemodilution changes the physical properties of blood by reducing its hematocrit and blood viscosity. We tested whether prolonged hypervolemic hemodilution (HHD) impairs functional capillary density (FCD) of ileal mucosa in healthy mechanically-ventilated pigs and if there is any correlation between changes in FCD of ileal and sublingual mucosas during HHD. Methods: Sixteen domestic female pigs were anesthetized, mechanically-ventilated, and randomly assigned to the HHD (20 ml/(kg∙h) Hartmann’s solution for 3 h) or fluid restrictive (5 ml/(kg∙h) Hartmann’s solution for 3 h) group. Microcirculations of sublingual and ileal mucosas via ileostomy were visualized using sidestream dark-field (SDF) imaging at baseline conditions (t=0 h) and at selected time intervals of fluid therapy (t=1, 2, and 3 h). Results: A significant decrease of ileal FCD (285 (278–292) cm/cm2) in the HHD group was observed after the third hour of HHD when compared to the baseline (360 (350–370) cm/cm2) (P<0.01). This trend was not observed in the restrictive group, where the ileal mucosa FCD was significantly higher after the third hour of fluid therapy as compared to the HHD group (P<0.01). No correlation between microhemodynamic parameters obtained from sublingual and ileal mucosas was found throughout the study. Conclusions: Prolonged HHD established by crystalloid solution significantly decreased ileal villus FCD when compared to restrictive fluid regimen. An inappropriate degree of HHD can be harmful during uncomplicated abdominal surgery

Drotrecogin alfa (Activated) in adults with septic shock

There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.)