Purpose To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. Method Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. Results Primary outcome: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5 % in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95 % CI 0.8583–2.935). Secondary endpoints: mortality rate at day 90 was 33.6 % in PMX-HP versus 24 % in conventional groups, p = 0.10 (OR 1.6128, 95 % CI 0.9067–2.8685); reduction in SOFA score from day 0 to day 7 was −5 (−11 to 6) in PMX-HP versus −5 (−11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. Conclusion This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.

The mixed venous-to-arterial carbon dioxide (CO₂) tension difference [P (v-a) CO₂] is the difference between carbon dioxide tension (PCO₂) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO₂ in arterial blood. P (v-a) CO₂ depends on the cardiac output and the global CO₂ production, and on the complex relationship between PCO₂ and CO₂ content. Experimental and clinical studies support the evidence that P (v-a) CO₂ cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO₂ generated by the peripheral tissues. P (v-a) CO₂ can be replaced by the central venous-to-arterial CO₂ difference (ΔPCO₂), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the ΔPCO₂ during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO₂) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased ΔPCO₂ (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the ΔPCO₂ from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO₂ production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO₂ related to metabolic demand. The combination of P (v-a) CO₂ or ΔPCO₂ with oxygen-derived parameters through the calculation of the P (v-a) CO₂ or ΔPCO₂/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.

Dynamic indices, such as pulse pressure variation (PPV), are inaccurate predictors of fluid responsiveness in mechanically ventilated patients with low tidal volume. This study aimed to test whether changes in continuous cardiac index (CCI), PPV, and stroke volume variation (SVV) after a mini-fluid challenge (100 ml of fluid during 1 min) could predict fluid responsiveness in these patients. We prospectively studied 49 critically ill, deeply sedated, and mechanically ventilated patients (tidal volume <8 ml kg⁻¹ of ideal body weight) without cardiac arrhythmias, in whom a fluid challenge was indicated because of circulatory failure. The CCI, SVV (PiCCO™; Pulsion), and PPV (MP70™; Philips) were measured before and after 100 ml of colloid infusion during 1 min, and then after the additional infusion of 400 ml during 14 min. Responders were defined as subjects with a ≥15% increase in cardiac index (transpulmonary thermodilution) after the full (500 ml) fluid challenge. Areas under the receiver operating characteristic curves (AUCs) and the grey zones were determined for changes in CCI (ΔCCI₁₀₀), SVV (ΔSVV₁₀₀), and PPV (ΔPPV₁₀₀) after 100 ml fluid challenge. Twenty-two subjects were responders. The ΔCCI₁₀₀ predicted fluid responsiveness with an AUC of 0.78. The grey zone was large and included 67% of subjects. The ΔSVV₁₀₀ and ΔPPV₁₀₀ predicted fluid responsiveness with AUCs of 0.91 and 0.92, respectively. Grey zones were small, including ≤12% of subjects for both indices. The ΔSVV₁₀₀ and ΔPPV₁₀₀ predict fluid responsiveness accurately and better than ΔCCI₁₀₀ (PiCCO™; Pulsion) in patients with circulatory failure and ventilated with low volumes.

To evaluate the ability of the central venous-to-arterial CO2 content and tension differences to arteriovenous oxygen content difference ratios (∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2, respectively), blood lactate concentration, and central venous oxygen saturation (ScvO2) to detect the presence of global anaerobic metabolism through the increase in oxygen consumption (VO2) after an acute increase in oxygen supply (DO2) induced by volume expansion (VO2/DO2 dependence). We prospectively studied 98 critically ill mechanically ventilated patients in whom a fluid challenge was decided due to acute circulatory failure related to septic shock. Before and after volume expansion (500 mL of colloid solution), we measured cardiac index, VO2, DO2, ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios, lactate, and ScvO2. Fluid-responders were defined as a ≥15 % increase in cardiac index. Areas under the receiver operating characteristic curves (AUC) were determined for these variables. Fifty-one patients were fluid-responders (52 %). DO2 increased significantly (31 ± 12 %) in these patients. An increase in VO2 ≥ 15 % (“VO2-responders”) concurrently occurred in 57 % of the 51 fluid-responders (45 ± 16 %). Compared with VO2-non-responders, VO2-responders were characterized by higher lactate levels and higher ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios. At baseline, lactate predicted a fluid-induced increase in VO2 ≥ 15 % with AUC of 0.745. Baseline ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios predicted an increase of VO2 ≥ 15 % with AUCs of 0.965 and 0.962, respectively. Baseline ScvO2 was not able to predict an increase of VO2 ≥ 15 % (AUC = 0.624). ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios are more reliable markers of global anaerobic metabolism than lactate. ScvO2 failed to predict the presence of global tissue hypoxia.

Objective: To evaluate the extent to which sitting position and applied positive end-expiratory pressure improve respiratory mechanics of severely obese patients under mechanical ventilation. Design: Prospective cohort study. Settings: A 15-bed ICU of a tertiary hospital. Participants: Fifteen consecutive critically ill patients with a body mass index (the weight in kilograms divided by the square of the height in meters) above 35 were compared to 15 controls with body mass index less than 30. Interventions: Respiratory mechanics was first assessed in the supine position, at zero end-expiratory pressure, and then at positive end-expiratory pressure set at the level of auto-positive endexpiratory pressure. Second, all measures were repeated in the sitting position. Measurements and Main Results: Assessment of respiratory mechanics included plateau pressure, auto-positive end-expiratory pressure, and flow-limited volume during manual compression of the abdomen, expressed as percentage of tidal volume to evaluate expiratory flow limitation. In supine position at zero end-expiratory pressure, all critically ill obese patients demonstrated expiratory flow limitation (flow-limited volume, 59.4% [51.3–81.4%] vs 0% [0–0%] in controls; p < 0.0001) and greater auto-positive end-expiratory pressure (10 [5–12.5] vs 0.7 [0.4–1.25] cm H₂O in controls; p < 0.0001). Applied positive end-expiratory pressure reverses expiratory flow limitation (flow-limited volume, 0% [0–21%] vs 59.4% [51–81.4%] at zero end-expiratory pressure; p < 0.001) in almost all the obese patients, without increasing plateau pressure (24 [19–25] vs 22 [18–24] cm H₂O at zero end-expiratory pressure; p = 0.94). Sitting position not only reverses partially or completely expiratory flow limitation at zero end-expiratory pressure (flow-limited volume, 0% [0–58%] vs 59.4% [51–81.4%] in supine obese patients; p < 0.001) but also results in a significant drop in auto-positive end-expiratory pressure (1.2 [0.6–4] vs 10 [5–12.5] cm H₂O in supine obese patients; p < 0.001) and plateau pressure (15.6 [14–17] vs 22 [18–24] cm H₂O in supine obese patients; p < 0.001). Conclusions: In critically ill obese patients under mechanical ventilation, sitting position constantly and significantly relieved expiratory flow limitation and auto-positive end-expiratory pressure resulting in a dramatic drop in alveolar pressures. Combining sitting position and applied positive end-expiratory pressure provides the best strategy.