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Objective: To investigate if prone position delays the progression of experimental ventilator-induced lung injury, possibly due to a more homogeneous distribution of strain within lung parenchyma., Design: Prospective, randomized, controlled trial., Setting: Animal laboratory of a university hospital., Subjects: Thirty-five Sprague Dawley male rats (weight 257 +/- 45 g)., Interventions: Mechanical ventilation in either supine or prone position and computed tomography scan analysis., Measurements: : Animals were ventilated in supine (n = 15) or prone (n = 15) position until a similar ventilator-induced lung injury was reached. To do so, experiments were interrupted when respiratory system elastance was 150% of baseline. Ventilator-induced lung injury was assessed as lung wet-to-dry ratio and histology. Time to reach lung injury was considered as a main outcome measure. In five additional animals, computed tomography scans (GE Light Speed QX/I, thickness 1.25 mm, interval 0.6 mm, 100 MA, 100 Kv) were randomly taken at end-expiration and end-inspiration in both positions, and quantitative analysis was performed. Data are shown as mean +/- sd., Measurements and Main Results: Similar ventilator-induced lung injury was reached (respiratory system elastance, wet-to-dry ratio, and histology). The time taken to achieve the target ventilator-induced lung injury was longer with prone position (73 +/- 37 mins vs. 112 +/- 42, supine vs. prone, p = .011). Computed tomography scan analysis performed before lung injury revealed that at end-expiration, the lung was wider in prone position (p = .004) and somewhat shorter (p = .09), despite similar lung volumes (p = .455). Lung density along the vertical axis increased significantly only in supine position (p = .002). Lung strain was greater in supine as opposed to prone position (width strain, 7.8 +/- 1.8% vs. 5.6 +/- 0.9, supine vs. prone, p = .029)., Conclusions: Prone position delays the progression of ventilator-induced lung injury. Computed tomography scan analysis suggests that a more homogeneous distribution of strain may be implicated in the protective role of prone position against ventilator-induced lung injury.

Objective: To investigate whether negative extra-abdominal pressure (NEXAP) improves respiratory function and induces a blood shift from the intrathoracic compartment and to assess whether these effects are influenced by abdominal pressure., Design and Setting: Prospective, randomized, controlled trial in the animal laboratory of a university hospital., Subjects: Eight sedated and paralyzed pigs (19.6+/-3.4 kg)., Interventions: Application of NEXAP (-20 cmH(2)O)., Measurements and Results: Airway, esophageal, gastric and central venous pressures were recorded simultaneously. Intrathoracic blood volume was assessed by PiCCO. The effects of NEXAP were assessed with and without abdominal hypertension by intraperitoneal insufflation of helium. NEXAP caused a lasting drop of gastric (1.97+/-2.26 mmHg) and esophageal (1.21+/-0.67 mmHg) pressures, while end-expiratory airway pressure was similar, hence transpulmonary pressure increased. Intrathoracic blood volume dropped from 358+/-47 to 314+/-47 ml. The fall was associated with a decrease in central venous pressure (R(2)=0.820). When peritoneal pressure was raised (24.7+/-5.5 mmHg), the effects were less marked. However, the difference between negative pressure around the abdomen and the pressure inside the abdomen (effective NEXAP) was correlated with the proportional changes in intrathoracic blood volume (R(2)=0.648), being greater with more negative effective NEXAP. NEXAP improved chest wall elastance during abdominal hypertension (from 0.067+/-0.023 to 0.056+/-0.021 cmH(2)O/ml)., Conclusions: NEXAP increases lung volume and causes a shift of blood from the intrathoracic compartment. It needs to be tailored against abdominal pressure to be effective.

Lactate measurement in the critically ill has been traditionally used to stratify patients with poor outcome. However, plasma lactate levels are the result of a finely tuned interplay of factors that affect the balance between its production and its clearance. When the oxygen supply does not match its consumption, organisms such as man who are forced to produce ATP for their integrity adapt in many different ways up to the point when energy failure occurs. Lactate, being part of the adaptive response, may then be used to assess the severity of the supply/demand imbalance. In such a scenario, the time to intervention becomes relevant: early and effective treatment may allow the cell to revert to a normal state, as long as the oxygen machinery (i.e. mitochondria) is intact. Conversely, once the mitochondria are deranged, energy failure occurs even in the presence of normoxia. The lactate increase in critically ill patients may therefore be viewed as an early marker of a potentially reversible state.

Objective: Many studies have investigated the protective role of positive end-expiratory pressure (PEEP) on ventilator-induced lung injury. Most assessed lung injury in protocols involving different ventilation strategies applied for the same length of time. This study, however, set out to investigate the protective role of PEEP with respect to the time needed to reach similar levels of lung injury., Design: Prospective, randomized laboratory animal investigation., Setting: The University Laboratory of Ospedale Maggiore, Milano, IRCCS., Subjects: Anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats., Interventions: Three groups of five Sprague-Dawley rats were ventilated using zero end-expiratory pressure ZEEP (PEEP of 0 cm H(2)O) and PEEP of 3 and 6 cm H(2)O and a similar index of lung overdistension (Paw(p)/P(100) congruent with 1.1; where Paw(p) is peak airway pressure and P(100) is the pressure corresponding to total lung capacity). To obtain this, tidal volume was reduced depending on the PEEP. To reach similar levels of lung injury, we measured respiratory system elastance while ventilating the animals and killed them when respiratory system elastance was 150% of baseline. Once target respiratory system elastance was reached, the lung wet-to-dry ratio was obtained., Results: Rats were ventilated with comparable high airway pressure (Paw(p) of 42.8 +/- 3.1, 43.5 +/- 2.6, and 46.2 +/- 4.4, respectively, for PEEP 0, 3, and 6) obtaining similar overdistension (Paw(p)/P(100) - index of overdistension: 1.17 +/- 0.2, 1.06 +/- 0.1, and 1.19 +/- 0.2). The respiratory system elastance target was reached and wet-to-dry ratio was not different in the three groups, suggesting a similar degree of lung damage. The time taken to achieve the target respiratory system elastance was three times longer with PEEP 3 and 6 (55 +/- 14 mins and 60 +/- 17) as compared with zero end-expiratory pressure (18 +/- 3 mins, p <.001)., Conclusion: These findings confirm that PEEP is protective against ventilator-induced lung injury and may enable the clinician to "buy time" in the progression of lung injury.

Objective: We hypothesized that a 50% increase in respiratory system elastance (Ers) would indicate similar degree of lung damage (equi-damage, ED), independently of ventilation strategy., Design and Setting: A prospective, randomized animal laboratory investigation at a university hospital laboratory., Subjects: 35 anesthetized, paralyzed, mechanically ventilated male Sprague-Dawley rats., Interventions: Each rat was ventilated with a different combination of tidal volume, positive end-expiratory pressure, and inspired fraction of oxygen. Ers was determined throughout the experiment; the studies were interrupted when Ers reached 150% (ED) of its baseline value, or after 5 h., Measurements and Results: Lung wet to dry weight ratio (W/D) was assessed. Morphological damage of the lung was scored on a grading of perivascular edema, hemorrhage, and breaks in the alveolar septa to obtain a total injury score. Twenty-four rats achieved an Ers of 150%: nine within 1 h (class 1), nine in 1-2 h (class 2), and six in 2-5 h (class 3). Eleven rats did not reach the target 50% increase in Ers (class 4). W/D was higher in rats that reached the target than in those that did not. W/D did not differ among rats that reached ED. Similarly, the total injury score did not differ among classes 1-3 but was higher than class 4., Conclusions: In the setting of VILI a 50% increase in Ers corresponds to an equal level of lung damage, irrespective of ventilatory setting and time of ventilation.