[Intrathoracic blood volume index as an indicator of fluid management in septic shock].

OBJECTIVE: To investigate the value of intrathoracic blood volume index (ITBVI) monitoring in fluid management strategy in septic shock patients. METHODS: In a prospective study, 33 patients who were diagnosed to be suffering from septic shock in the intensive care unit (ICU) were enrolled . Seventeen patients who received pulse indicator continuous cardiac output (PiCCO) monitoring, and ITBVI was used as indicator of fluid management, were enrolled into ITBVI group; 16 patients who received traditional fluid management strategy [directed by central venous pressure (CVP)] were enrolled into control group. Acute physiology and chronic health evaluation II (APACHEII) score, sepsis related organ failure assessment (SOFA) score and vasopressor score were compared between 1 day and 3 days of treatment. The characteristics of fluid management were recorded and compared within 72 hours. RESULTS: (1)In 3 days of treatment, APACHEII, SOFA and vasopressor score were significantly lower in ITBVI group compared with that of in 1 day of treatment[21.3±6.2 vs. 25.4±7.2, 6.1±3.4 vs. 9.0±3.5, 5 (0, 8.0) vs. 20.0 (8.0, 35.0), respectively, all P<0.01], whereas there were no changes in control group. (2)Although fluid output (ml) was higher in ITBVI group during 48-72 hours period (2 421± 868 vs. 1 721±934, P=0.039), there was no difference in fluid intake, fluid output or fluid balance (ml) within 0-72 hours between two groups (fluid intake: 9 918±137 vs. 10 529±1 331, fluid output : 6 035±1 739 vs. 5 827±2 897, fluid balance: 3 882±1 889 vs. 4 703±2 813, allP>0.05). (3)Comparing the fluid volume (ml) used for fluid replacement period, except that there was no significance in fluid challenge with colloid during 0-6 hours between two groups [ml: 250 (125, 500) vs. 250 (69,250), P>0.05], more fluid intake (ml) was found in ITBVI group [0-6 hours crystalloid: 250(150,250) vs. 125 (105,125), 6-72 hours crystalloid: 125 (125, 250) vs. 100 (56, 125), 0-72 hours crystalloid: 250(125, 250) vs. 125 (75, 125), 6-72 hours colloid: 125 (106, 250) vs. 75 (50, 125), 0-72 hours colloid: 200 (125, 250) vs. 100 (50, 125),all P<0.01]. CONCLUSION: Clinical picture in patients with septic shock is improved after 3 days of treatment than 1 day of treatment under fluid management directed by ITBVI, compared with by CVP. This improvement may be attributable to accurate assessment of preload and appropriate infusion rate in fluid challenge.

Effects of a novel anticoagulant compound (TV7130) in an ovine model of septic shock.

We compared the effects of a new compound (TV7130) with those of activated protein C (APC) in a large animal model of septic shock. Thirty-two fasted, anesthetized, invasively monitored, mechanically ventilated female sheep received 1.5 g/kg body weight of feces into the abdomen to induce sepsis. Immediately after feces injection, all animals received a bolus followed by a continuous infusion of saline (n = 8, bolus 1.5 mL for 15 min, infusion 1.5 mL/[kg·h]), low-dose TV7130 (n = 8; 0.4 mg/kg bolus, 0.4 mg/[kg·h] infusion), high-dose TV7130 (n = 8; 0.8 mg/kg bolus, 0.8 mg/[kg·h] infusion), or APC (n = 8; saline bolus, APC infusion of 0.024 mg/[kg·h]). Experiments were pursued until each sheep's spontaneous death. There were no significant differences among groups in heart rate or cardiac index, but mean arterial pressure, systemic vascular resistance index, and left ventricular stroke work index decreased less in the high-dose TV7130 and APC groups than in the other groups. Gas exchange was preserved better in the high-dose TV7130 and APC groups. Interleukin 6 and lactate concentrations were lower in the high-dose TV7130 and APC groups than in the other groups. Functional capillary density and proportion of perfused vessels, evaluated in the sublingual region using sidestream dark-field videomicroscopy, were significantly higher in the TV7130 and APC groups than in the vehicle group at 16 h. Survival time was significantly longer in the high-dose TV7130 and APC groups than in the other groups (log-rank test, P = 0.0002). TV7130 has similar effects to APC and may be a promising agent for the management of severe sepsis.

[Study on the natural ligand(s) of triggering receptor expressed on myeloid cell-1 on bacteria cell wall].

OBJECTIVE: To look for the natural ligand(s) of human triggering receptor expressed on myeloid cell-1 (TREM-1), in order to provide the theoretical basis for elucidation of the pathogenesis of sepsis. METHODS: Neutrophils and monocytes isolated from human peripheral blood were treated with heat-inactivated Staphylococcus aureus, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Staphylococcus aureus L-form or Pseudomonas aeruginosa L-form respectively for 24 hours. The cell wall was extracted from Staphylococcus aureus, Pseudomonas aeruginosa and Mycobacterium tuberculosis by ultrasound. Neutrophils and monocytes were isolated and treated with the cell wall respectively for 24 hours. Neutrophils and monocytes were isolated and treated with three main components from bacterial cell wall (polysaccharides, lipids and proteins) respectively for 24 hours. The level of TREM-1 mRNA was measured with fluorescent quantitative polymerase chain reaction (PCR), and the concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: The TREM-1 mRNA level and the concentrations of TNF-alpha and IL-1 beta in cell supernatant of neutrophils and monocytes were upgraded when treated with cell, cell wall and cell wall polysaccharides of Staphylococcus aureus and Pseudomonas aeruginosa. Compared with the blank control group, the TREM-1 mRNA level of neutrophils and monocytes was upgraded to (3.86+/-0.20)-fold and (5.15+/-0.56)-fold respectively when treated with cell wall polysaccharides of Staphylococcus aureus (both P<0.05); the TREM-1 mRNA level of neutrophils and monocytes was upgraded to (4.03+/-0.15)-fold and (7.22+/-0.73)-fold respectively when treated with cell wall polysaccharides of Pseudomonas aeruginosa (both P<0.05). The effect could be attenuated by the addition of LP17 which could bind TREM-1 ligand. This attenuating effect was not found when the cells were treated with cell, cell wall or cell wall polysaccharides of Mycobacterium tuberculosis. CONCLUSION: The study provides the evidence that TREM-1 natural ligand(s) is present on cell wall of bacteria including Staphylococcus aureus and Pseudomonas aeruginosa, and it might be polysaccharides.

Effects of a selective iNOS inhibitor versus norepinephrine in the treatment of septic shock.

Inhibition of NOS is not beneficial in septic shock; selective inhibition of the inducible form (iNOS) may represent a better option. We compared the effects of the selective iNOS inhibitor BYK191023 with those of norepinephrine (NE) in a sheep model of septic shock. Twenty-four anesthetized, mechanically ventilated ewes received 1.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Animals were randomized into three groups (each n = 8): NE-only, BYK-only, and NE + BYK. The sublingual microcirculation was evaluated with sidestream dark-field videomicroscopy. MAP was higher in the NE + BYK group than in the other groups, but there were no significant differences in cardiac index or systemic vascular resistance. Mean pulmonary arterial pressure was lower in BYK-treated animals than in the NE-only group. PaO2/FiO2 was higher and lactate concentration lower in the BYK groups than in the NE-only group. Mesenteric blood flow was higher in BYK groups than in the NE-only group. Renal blood flow was higher in the NE + BYK group than in the other groups. Functional capillary density and proportion of perfused vessels were higher in the BYK groups than in the NE-only group 18 h after induction of peritonitis. Survival times were similar in the three groups. In this model of peritonitis, selective iNOS inhibition had more beneficial effects than NE on pulmonary artery pressures, gas exchange, mesenteric blood flow, microcirculation, and lactate concentration. Combination of this selective iNOS inhibitor with NE allowed a higher arterial pressure and renal blood flow to be maintained.