Reduction of ventilator settings allowed by intravenous oxygenator (IVOX) in ARDS patients.

OBJECTIVE: To evaluate the possibility of reducing ventilator settings to "safe" levels by extrapulmonary gas exchange with IVOX in ARDS patients. DESIGN: Uncontrolled open clinical study. SETTING: Medical Intensive Care Unit of a University Hospital. PATIENTS: 6 patients with ARDS who entered into IVOX phase II clinical trials. INTERVENTIONS: The end-point of this study was to reduce ventilator settings from the initial values, recorded on the day of inclusion, to the following: peak inspiratory pressure < 40 cmH2O, mean airway pressure < 25 cmH2O and tidal volume < 10 ml/kg. Trials to achieve this goal were made on volume-controlled ventilation within the 24 h before and after IVOX insertion. Comparison of the results achieved during these trials used Wilcoxon test. RESULTS: Before IVOX implantation reduction of ventilator settings was not possible in the 6 patients, despite a non-significant increase in PaO2/FIO2 was achieved. IVOX permitted significant decrease in PaCO2 (from 60.5 +/- 15 to 52 +/- 11 mmHg; p = 0.02) before any modification of the ventilatory mode. After IVOX insertion, a significant decrease of the ventilator settings was performed: peak and mean airway pressures dropped from 44 +/- 10 to 36.8 +/- 6.7; p = 0.02 and from 26.3 +/- 5.6 to 22.5 +/- 3.9 cmH2O; p = 0.02, respectively. Concommitantly, PaCO2 remained unchanged and PaO2/FIO2 increased significantly from 93 +/- 28 to 117 +/- 52; p = 0.04. The interruption of oxygen flow on IVOX was associated with a slight decrease of the oxygen variables. Tolerance of IVOX was satisfactory. However, a significant decrease both in cardiac index and in pulmonary wedge pressures (from 4.5 +/- 1.2 to 3.4 +/- 9; p = 0.03 and from 16 +/- 5 to 11 +/- 2; p = 0.04, respectively) was observed. CONCLUSION: Gas exchange achieved by IVOX allowed reduction of ventilator settings in 6 ARDS patients in whom previous attempts have failed. CO2 removal by the device, may explain these results. Efficacy of IVOX on arterial oxygenation was uncertain.

[Protein-poor pleurisy and mesothelioma. Apropos of 2 cases]. / Pleurésie pauvre en protides et mésothéliome. A propos de 2 cas.

We report two cases of protein poor pleural effusions secondary to malignant mesothelioma which were proven histologically. In the absence of any extra pulmonary cause, in particular cardiac, the associated investigations carried out led to the exclusion of either a chylothorax or a mechanical effusion due to atelectasis. Pulmonary venous obstruction by the mesothelial masses which had developed on the mediastinal pleura were shown in the two cases. The high pressure in the pulmonary capillaries which resulted could be the origin of the low level of protein observed in the pleural fluid.

Activation of T cells by previously activated T cells. HLA-unrestricted alternative pathway that modifies their proliferative potential.

When cultured in the presence of previously activated T cells, up to 30% of resting T cells are activated, as indicated by lymphoblastic morphology, formation of cell aggregates, expression of activation Ags (CD25 and HLA-DR), and a proliferative response. This activation occurred in the absence of accessory cells and was not HLA restricted, and the TCR repertoire of the responding cells was extremely diverse without evidence for preferential expansion of T cells expressing certain V beta families or clonal populations. The ability of activated T cells to stimulate resting T cells was a transient phenomenon, which was first detected 24 h after activation and which peaked between 48 and 96 h; the stimulation of previously resting T cells produced more lymphostimulatory activity than restimulation of recently activated cells. Both resting CD4+ and CD8+ T cells expressing TCR-alpha beta and -gamma delta responded to previously activated cells, including cells with both the naive and memory phenotypes. When T cells were activated by this pathway and recultured in the presence of Ag and accessory cells, the strong proliferative response observed at 5 to 7 days with use of fresh T cells was almost entirely absent, and this impaired Ag-induced proliferative response could not be explained by the generation of suppressor cells or the inability of these cells to respond to growth factors. These findings are compatible with the possibility that Ag-specific activation of T cells permits the subsequent Ag-independent activation of other T cells and could explain the broad TCR repertoire and impaired Ag-induced proliferation of activated T cells at sites of immune reactions.

Permissive hypercapnia and intravascular oxygenator in the treatment of patients with ARDS.

This open clinical study was aimed at testing the hypothesis that an intravascular oxygenator (IVOX) may help to perform permissive hypoventilation in 10 patients with severe ARDS. After initial evaluation, we tried to reduce ventilator settings before and after IVOX implantation. Before IVOX, poor clinical tolerance and worsening oxygenation did not allow for a significant decrease in ventilator settings. With IVOX, peak inspiratory pressure (PIP) was reduced from 47 to 39 cm H2O (p = 0.005) and minute ventilation from 13 +/- 3.5 to 11 +/- 3 L/min. CO2 removal by IVOX allowed a significant decrease in PaCO2 from 66 +/- 15 to 59 +/- 13 mm Hg. Improvement of oxygenation with IVOX was not significant. Furthermore, interruption of oxygen flow through IVOX did not change oxygenation variables. Tolerance of the IVOX device was good, but insertion of the device was followed by a significant decrease in both cardiac index and pulmonary wedge pressure. In conclusion, IVOX improves tolerance of hypoventilation by limiting hypercapnia in ARDS patients. These preliminary results must be confirmed by a randomized controlled study.

Extracorporeal carbon dioxide removal technique improves oxygenation without causing overinflation.

Extracorporeal CO2 removal combined with low frequency positive pressure ventilation (ECCO2R-LFPPV) improves gas exchange and decreases peak pressures, respiratory rates, and tidal volumes in animals and in humans. Recent evidence suggests that pulmonary barotrauma results from lung overinflation rather than from high pressures. This study was to test the hypothesis whether ECCO2R-LFPPV could improve gas exchange without causing lung overinflation, despite the use of higher levels of PEEP, when compared with conventional mechanical ventilation. Eleven patients with severe adult respiratory distress syndrome (ARDS) who failed to respond to different modes of mechanical ventilation were treated with ECCO2R-LFPPV. Risk of pulmonary barotrauma was evaluated by static pressure-volume (P-V) curves and dynamic changes in volumes monitored by respiratory inductive plethysmography (Respitrace). ECCO2R-LFPPV PaO2/FIO2 increased from 79 +/- 21 to 207 +/- 108 (p = 0.003). Risk of barotrauma, as shown by the shape of the P-V curve, was present in all patients receiving mechanical ventilation even though most of them were treated with permissive hypoventilation. By contrast, no evidence of persistent lung overinflation could be detected by either static P-V curves or dynamic measurements in nine of 11 patients who were treated by ECCO2R-LFPPV. The two remaining patients had severe airway obstruction because of bleeding, and they remained ventilated with persistent risk of barotrauma. We conclude that ECCO2R-LFPPV improves gas exchange without causing lung overinflation in a majority of patients with ARDS.