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Multiple Organ Dysfunction Syndrome (MODS) is a systemic physiological disorder affecting two or more body organs triggered after an insult complication. Beyond the systemic failure, patients who survive MODS present cognitive and neurological impairments that remain stable even several years after Intensive Care Unit (ICU) discharge. Here, we focus on the specific situation of MODS patients with no apparent brain damage (NABD), where the mechanisms driving cognitive impairment at long term are not well-understood. We recruit N 1 = 13 MODS patients with NABD at 6 months after ICU discharge, together with N 2 = 13 healthy controls (matched by age, sex and years

Pentoxifylline (PTX), a xanthine derivative used in the treatment of circulatory insufficiency, has been found to have protective effects in different models of sepsis. We hypothesized that this drug might either increase oxygen delivery (DO2) and/or increase tissue oxygen -extraction to meet oxygen demand in sepsis. We studied the effects of PTX on the oxygen uptake/oxygen delivery (VO2/DO2) relationship and tissue oxygen extraction when blood flow was reduced by Inducing cardiac tamponade in 14 anesthetized, ventilated and paralyzed dogs. Via a left thoractomy, a catheter waa inserted into the pericardial space for saline injection. Each dog was given a 2 mg/kg bolus of E.coli endotoxin and received 20 mlkg.h of normal saline•duririg the study. In 7 dogs, PTX was administered as a 20 mg/kg i.v. bolus, followed by a continuous infusion at 20 mglkg.h. V02 was derived from the expired gases. 002 was calculated by the product of the modüution cardiac index and arterial oxygen content. Oxygen extraction ratio (02ER) was defined as the ratio of V02/002. Dual-line regression was used to determine the critical 002 (DO2crit) in each animal. ANOVA was used for statistical analysis. PTX resulted in significant increases in V02 and DO2. Critical V02 was slightly higher in the PTX-treated than in the control group, but it did not reach statistical significance (6.3 ± 2.4 vs 5.4 ± 1.0 ml/kg.min, NS). D02crit which was 11.3± 4.9 ml/kg.min in the control group, was decreased to 9.6 ± 3.6 mlkg.min in the PTX-treated group (p = 0.05). Critical 02ER significantly increased from 50 ± 20% in the control to 68 ± 19% in the PTX-treated animals (p< 0.05). The V02/D02 dependency slope was steeper in the PTX-treated than in the control group (0.77 ± 0.31 vs 0.46 ± 0.18, p< 0.05). At D02c rit, PTX-treated group had lower venoarterial PCO2 difference (12.9 t. 4.3 vs 18.4 ± 7.4 mmHg, p < 0.05) and arteriovenous pH gradient (0.08 ± 0.02 vs 0.11 ± 0.06 U, p < 0.05) than in the control group. Thus, the addition of PTX and fluid therapy can increase 002 and global oxygen extraction capabilities when cardiac output is progressively reduced in the endotoxemic dog. The exact mechanisms remain to be defined.

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