Fabienne Bregeon

Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study.

Background:Esophagectomy induces a systemic inflammatory response whose extent has been recognized as a predictive factor of postoperative respiratory morbidity. The aim of this study was to determine the effectiveness of a protective ventilatory strategy to reduce systemic inflammation in patients undergoing esophagectomy. Methods:The authors prospectively investigated 52 patients undergoing planned esophagectomy for cancer. Patients were randomly assigned to a conventional ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung and one-lung ventilation; no positive end-expiratory pressure) or a protective ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung ventilation, reduced to 5 ml/kg during one-lung ventilation; positive end-expiratory pressure 5 cm H2O throughout the operative time). Results:Plasmatic levels of interleukin (IL)-1&bgr;, IL-6, IL-8, and tumor necrosis factor &agr; were measured perioperatively and postoperatively. Pulmonary function and postoperative evolution were also evaluated. Patients who received protective strategy had lower blood levels of IL-1&bgr;, IL-6, and IL-8 at the end of one-lung ventilation (0.24 [0.15–0.40] vs. 0.56 [0.38–0.89] pg/ml, P < 0.001; 91 [61–117] vs. 189 [127–294] pg/ml, P < 0.001; and 30 [22–45] vs. 49 [29–69] pg/ml, P < 0.05, respectively) and 18 h postoperatively (0.18 [0.13–0.30] vs. 0.43 [0.34–0.54] pg/ml, P < 0.001; 54 [36–89] vs. 116 [78–208] pg/ml, P < 0.001; 16 [11–24] vs. 35 [28–53] pg/ml, P < 0.001, respectively). Protective strategy resulted in higher oxygen partial pressure to inspired oxygen fraction ratio during one-lung ventilation and 1 h postoperatively and in a reduction of postoperative mechanical ventilation duration (115 ± 38 vs. 171 ± 57 min, P < 0.001). Conclusion:A protective ventilatory strategy decreases the proinflammatory systemic response after esophagectomy, improves lung function, and results in earlier extubation.

Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise

Objectives.  Because the muscle response to incremental exercise is not well documented in patients suffering from chronic fatigue syndrome (CFS), we combined electrophysiological (compound‐evoked muscle action potential, M wave), and biochemical (lactic acid production, oxidative stress) measurements to assess any muscle dysfunction in response to a routine cycling exercise.

Open-lung Biopsy in Patients with Acute Respiratory Distress Syndrome

Background It has been suggested that fibrosis present during the fibroproliferative phase of acute respiratory distress syndrome (ARDS) can be treated by corticosteroids. However, neither clinical nor microbiologic criteria permit differentiation of this fibroproliferative phase from a nosocomial pneumonia. The aim of this observational case series was to evaluate the safety and utility of open‐lung biopsy (OLB) performed in patients receiving ventilatory support who had persistent ARDS despite negative bacterial cultures. Methods During a 4‐yr period, 37 OLBs were performed in 36 of 197 patients receiving ventilatory support who had ARDS. The severity of ARDS was assessed by a lung injury score of 3.1 +/‐ 0.4 (mean +/‐ SD) and a median ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 118 mmHg. Histologic examination; bacterial, fungal, and acid‐fast staining; and cultures of the tissue sample were performed. Results Fibrosis was present in only 41% of the lung specimens obtained by OLB. Only six patients received corticosteroids (17%). In 9 of the 15 patients with fibrosis, cytomegalovirus pneumonia precluded the use of corticosteroids. Histologic cytomegalovirus pneumonia was diagnosed in 18 cases. Histologic bacterial or mycobacterial pneumonia was diagnosed in five cases. No significant change in arterial blood gases was noted as linked to the biopsy procedure except an increase of the PaO2 /FI O2 ratio. One pneumothorax was diagnosed on a chest roentgenogram 12 h after OLB. Only one patient required blood transfusion during the 48‐h period after OLB (for an hemothorax). Five patients had moderate air leaks from operative chest tubes for 2–10 days. Conclusions Open lung biopsy appeared to be a useful and acceptably safe diagnostic technique in patients with ARDS. It permitted the diagnosis of unexpected cytomegalovirus pneumonia.

Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome*

Objective:Both prone position and high-frequency oscillatory ventilation (HFOV) have the potential to facilitate lung recruitment, and their combined use could thus be synergetic on gas exchange. Keeping the lung open could also potentially be lung protective. The aim of this study was to compare physiologic and proinflammatory effects of HFOV, prone positioning, or their combination in severe acute respiratory distress syndrome (ARDS). Design:Prospective, comparative randomized study. Setting:A medical intensive care unit. Patients:Thirty-nine ARDS patients with a Pao2/Fio2 ratio <150 mm Hg at positive end-expiratory pressure ≥5 cm H2O. Interventions:After 12 hrs on conventional lung-protective mechanical ventilation (tidal volume 6 mL/kg of ideal body weight, plateau pressure not exceeding the upper inflection point, and a maximum of 35 cm H2O; supine-CV), 39 patients were randomized to receive one of the following 12-hr periods: conventional lung-protective mechanical ventilation in prone position (prone-CV), HFOV in supine position (supine-HFOV), or HFOV in prone position (prone-HFOV). Measurements and Main Results:Prone-CV (from 138 ± 58 mm Hg to 217 ± 110 mm Hg, p < .0001) and prone-HFOV (from 126 ± 40 mm Hg to 227 ± 64 mm Hg, p < 0.0001) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio (from 134 ± 57 mm Hg to 138 ± 48 mm Hg). The oxygenation index ({mean airway pressure × Fio2 × 100}/Pao2) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group. Interleukin-8 increased significantly in the bronchoalveolar lavage fluid (BALF) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV. Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group. Conclusions:Although HFOV in the supine position does not improve oxygenation or lung inflammation, the prone position increases oxygenation and reduces lung inflammation in ARDS patients. Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation. In contrast, supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation.

Is ventilator-associated pneumonia an independent risk factor for death?

BackgroundVentilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation. MethodsDuring the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP. ResultsAnalysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia. ConclusionVentilator-associated pneumonia does not appear to be an independent risk factor for death.

High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation.

Objective: The improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ARDS) are turned supine. High‐frequency oscillatory ventilation (HFOV) aims to maintain an open lung volume by the application of a constant mean airway pressure. The aim of this study was to show that HFOV is able to prevent the impairment in oxygenation when ARDS patients are turned back from the prone to the supine position. Design: Prospective, comparative randomized study. Setting: A medical intensive care unit. Patients: Forty‐three ARDS patients with a Pao2/Fio2 ratio <150 at positive end‐expiratory pressure ≥5 cm H2O. Interventions: After an optimization period, the patients were assigned to one of three groups: a) conventional lung‐protective mechanical ventilation in the prone position (12 hrs) followed by a 12‐hr period of conventional lung‐protective mechanical ventilation in the supine position (CVprone‐CVsupine); b) conventional lung‐protective mechanical ventilation in the supine position (12 hrs) followed by HFOV in the supine position (12 hrs) (CVsupine‐HFOVsupine); or c) conventional lung‐protective mechanical ventilation in the prone position (12 hrs) followed by HFOV in the supine position (CVprone‐HFOVsupine group). Measurements and Main Results: Pao2/Fio2 ratio was higher at the end of the study period in the CVprone‐HFOVsupine group than in the CVprone‐CVsupine group (p < .02). Venous admixture at the end of the study period was lower in the CVprone‐HFOVsupine group than in the two other groups. Conclusions: HFOV maintained the improvement in oxygenation related to prone positioning when ARDS patients were returned to the supine position.

Mechanical ventilation affects lung function and cytokine production in an experimental model of endotoxemia.

Background:Mechanical ventilation using tidal volumes around 10 ml/kg and zero positive end-expiratory pressure is still commonly used in anesthesia. This strategy has been shown to aggravate lung injury and inflammation in preinjured lungs but not in healthy lungs. In this study, the authors investigated whether this strategy would result in lung injury during transient endotoxemia in the lungs of healthy animals. Methods:Volume-controlled ventilation with a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was applied in two groups of anesthetized–paralyzed rabbits receiving either intravenous injection of 5 &mgr;g/kg Escherichia coli lipopolysaccharide (n = 10) or saline (n = 10) 2 h after the start of mechanical ventilation. The third group consisted of 10 spontaneously breathing anesthetized animals receiving lipopolysaccharide. Anesthesia was then continued for 4 h in the three groups while the ventilatory modes were maintained unchanged. Lung injury was studied using blood gases, respiratory physiologic variables, analysis of the bronchoalveolar lavage cell counts, and cytokine concentrations and lung pathologic examination. Results:Significant histologic lung alterations, hypoxemia, and altered lung mechanics were observed in rabbits treated with mechanical ventilation and intravenous lipopolysaccharide but not in the mechanically ventilated animals injected with saline or in spontaneously breathing animals treated with lipopolysaccharide. Endotoxemic ventilated animals also had significantly more lung inflammation as assessed by the alveolar concentration of neutrophils, and the concentrations of the chemokines interleukin 8 and growth-related oncogen &agr;. Conclusions:These results showed that positive-pressure mechanical ventilation using a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was harmful in the setting of endotoxemia, suggesting that the use of this ventilator strategy in the operating room may predispose to lung injury when endotoxemia occurs.

Diagnosis of Ventilator-associated Pneumonia An Evaluation of Direct Examination and Presence of Intracellular Organisms

Background:Ventilator-associated pneumonia (VAP) requires early diagnosis and adequate antibiotic therapy. The aim of this prospective postmortem study was to assess the accuracy of direct examination and quantification of intracellular organisms (ICO) for the diagnosis of VAP.Methods:Total and diff

Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses.

Objectives.  As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise‐induced oxidative stress.

Conventional mechanical ventilation of healthy lungs induced pro-inflammatory cytokine gene transcription.

We investigated the potential inflammatory reaction induced by mechanical ventilation (MV) using 10 ml/kg tidal volume and no positive end-expiratory pressure (PEEP) in control (C, n = 8), spontaneously breathing (SB, n = 12) and mechanically ventilated (MV, n = 12) rabbits with normal lungs. After 6 h (MV and SB groups) or immediately (C group), lungs were removed for measurement of wet-to-dry (W/D) weight ratio and for bronchoalveolar lavage (BAL). Pulmonary mechanics were also studied. MV animals developed a modest but significant (P < 0.01) impairment of arterial blood oxygenation and had higher W/D lung weight ratio than C ones. In MV group, BAL macrophage count was greater (P < 0.05) than in SB one. MV induced an upregulation of MCP-1, TNF-alpha, and IL-1beta gene transcription (mRNAs), without significant elevation of the corresponding protein cytokines in the BAL supernatant, except for MCP-1 (P < 0.05). These data suggest that MV, even using moderate tidal volume, elicits a pro-inflammatory stimulus to the lungs.