Pierpaolo Terragni

RATIONALE: Tidal volume and plateau pressure limitation decreases mortality in acute respiratory distress syndrome. Computed tomography demonstrated a small, normally aerated compartment on the top of poorly aerated and nonaerated compartments that may be hyperinflated by tidal inflation. OBJECTIVES: We hypothesized that despite tidal volume and plateau pressure limitation, patients with a larger nonaerated compartment are exposed to tidal hyperinflation of the normally aerated compartment. MEASUREMENTS AND MAIN RESULTS: Pulmonary computed tomography at end-expiration and end-inspiration was obtained in 30 patients ventilated with a low tidal volume (6 ml/kg predicted body weight). Cluster analysis identified 20 patients in whom tidal inflation occurred largely in the normally aerated compartment (69.9 +/- 6.9%; "more protected"), and 10 patients in whom tidal inflation occurred largely within the hyperinflated compartments (63.0 +/- 12.7%; "less protected"). The nonaerated compartment was smaller and the normally aerated compartment was larger in the more protected patients than in the less protected patients (p = 0.01). Pulmonary cytokines were lower in the more protected patients than in the less protected patients (p < 0.05). Ventilator-free days were 7 +/- 8 and 1 +/- 2 d in the more protected and less protected patients, respectively (p = 0.01). Plateau pressure ranged between 25 and 26 cm H(2)O in the more protected patients and between 28 and 30 cm H(2)O in the less protected patients (p = 0.006). CONCLUSIONS: Limiting tidal volume to 6 ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be sufficient in patients characterized by a larger nonaerated compartment.

BACKGROUND: Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. METHODS: PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. RESULTS: Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. CONCLUSIONS: VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.

CONTEXT: Tracheotomy is used to replace endotracheal intubation in patients requiring prolonged ventilation; however, there is considerable variability in the time considered optimal for performing tracheotomy. This is of clinical importance because timing is a key criterion for performing a tracheotomy and patients who receive one require a large amount of health care resources. OBJECTIVE: To determine the effectiveness of early tracheotomy (after 6-8 days of laryngeal intubation) compared with late tracheotomy (after 13-15 days of laryngeal intubation) in reducing the incidence of pneumonia and increasing the number of ventilator-free and intensive care unit (ICU)-free days. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial performed in 12 Italian ICUs from June 2004 to June 2008 of 600 adult patients enrolled without lung infection, who had been ventilated for 24 hours, had a Simplified Acute Physiology Score II between 35 and 65, and had a sequential organ failure assessment score of 5 or greater. INTERVENTION: Patients who had worsening of respiratory conditions, unchanged or worse sequential organ failure assessment score, and no pneumonia 48 hours after inclusion were randomized to early tracheotomy (n = 209; 145 received tracheotomy) or late tracheotomy (n = 210; 119 received tracheotomy). MAIN OUTCOME MEASURES: The primary endpoint was incidence of ventilator-associated pneumonia; secondary endpoints during the 28 days immediately following randomization were number of ventilator-free days, number of ICU-free days, and number of patients in each group who were still alive. RESULTS: Ventilator-associated pneumonia was observed in 30 patients in the early tracheotomy group (14%; 95% confidence interval [CI], 10%-19%) and in 44 patients in the late tracheotomy group (21%; 95% CI, 15%-26%) (P = .07). During the 28 days immediately following randomization, the hazard ratio of developing ventilator-associated pneumonia was 0.66 (95% CI, 0.42-1.04), remaining connected to the ventilator was 0.70 (95% CI, 0.56-0.87), remaining in the ICU was 0.73 (95% CI, 0.55-0.97), and dying was 0.80 (95% CI, 0.56-1.15). CONCLUSION: Among mechanically ventilated adult ICU patients, early tracheotomy compared with late tracheotomy did not result in statistically significant improvement in incidence of ventilator-associated pneumonia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00262431.

OBJECTIVE: To evaluate whether the shape of the airway pressure-time (Paw-t) curve during constant flow inflation corresponds to radiologic evidence of tidal recruitment or tidal hyperinflation in an experimental model of acute lung injury. DESIGN: Prospective randomized laboratory animal investigation. SETTING: Department of Clinical Physiology, University of Uppsala, Sweden. SUBJECTS: Anesthetized, paralyzed, and mechanically ventilated pigs. INTERVENTIONS: Acute lung injury was induced by lung lavage. During constant inspiratory flow, the Paw-t curve was fitted to a power equation: airway pressure =a x time + c, where coefficient b (stress index) describes the shape of the curve:b = 1, straight curve; b < 1, progressive increase in slope; and b > 1, progressive decrease in slope. Tidal volume (Vt) was 6 mL/kg, and positive end-expiratory pressure was set to obtain a b value between 0.9 and 1.1 before (b = 1) and after (b = 1 after recruiting maneuver) application of a recruiting maneuver. Positive end-expiratory pressure was decreased and Vt increased to obtain 0.9 >b > 0.8 and 0.8 >b > 0.6, whereas positive end-expiratory pressure and Vt were both increased to obtain 1.3 >b > 1.1 and 1.5 >b > 1.3. Experimental conditions sequence was random. MEASUREMENTS AND MAIN RESULTS: Pulmonary computed tomography was obtained during end-expiratory and end-inspiratory occlusions. Tidal recruitment was quantified as nonaerated (between -100 and +100 Hounsfield units) lung area at end-expiration minus end-inspiration. Tidal hyperinflation was quantified as hyperinflated (between -900 and -1000 Hounsfield units) lung area at end-inspiration minus end-expiration. Computed tomography images showed that tidal recruitment and tidal hyperinflation corresponded to b < 1 and b > 1, respectively. Stress index values and tidal recruitment and tidal hyperinflation values were significantly correlated (R =.917 and R =.911, p <.0001, respectively). CONCLUSIONS: Shape of the Paw-t curve detects tidal recruitment and tidal hyperinflation.