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Objective: To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO2 elimination in pigs at health and after ALI.Design and Setting: Randomised crossover study in the animal laboratory of Lund University Biomedical Center.Subjects and Intervention: Healthy pigs and pigs with ALI, caused by surfactant perturbation and lung-damaging ventilation were ventilated with a computer-controlled ventilator. With this device each breath could be tailored with respect to insufflation time and pause time (TI and TP) as well as flow shape (square, increasing or decreasing flow).Measurements and Results: The single-breath test for CO2 allowed analysis of the volume of expired CO2 and the volume of CO2 re-inspired from Y-piece and tubes. With a long MDT caused by long TI or TP, the expired volume of CO2 increased markedly in accordance with the MDT concept in both healthy and ALI pigs. High initial inspiratory flow caused by a short TI or decreasing flow increased the re-inspired volume of CO2. Arterial CO2 increased during a longer period of short MDT and decreased again when MDT was prolonged.Conclusions: CO2 elimination can be enhanced by a pattern of ventilation that prolongs MDT. Positive effects of prolonged MDT caused by short TI and decreasing flow were attenuated by high initial inspiratory flow. [ABSTRACT FROM AUTHOR]

Objective: High fractions of inspired oxygen (FIO(2)) used in acute lung injury (ALI) may promote resorption atelectasis. The impact of derecruitment related to high FIO(2) in ALI is debated. We evaluated derecruitment with 100% vs. 60% FIO(2) at two levels of positive end-expiratory pressure (PEEP)., Patients: Fourteen consecutive patients with ALI were studied., Interventions: Recruited volume at two PEEP levels was computed from two pressure-volume curves, recorded from PEEP and from zero end-expiratory pressure, using the sinusoidal flow modulation method. PEEP-induced recruitment was measured during prolonged expiration as the difference between the two curves at a given pressure. PaO(2)/FIO(2) was also measured. PEEP was 5 +/- 1 or 14 +/- 3 cmH(2)O and FIO(2) was 60% or 100%, yielding four combinations. We looked for differences between the beginning and end of a 30-min period with each combination., Measurement and Results: With low PEEP and 100% FIO(2), recruited volume decreased significantly from 68 +/- 53 to 39 +/- 43 ml and PaO(2)/FIO(2) from 196 +/- 104 to 153 +/- 83 mmHg. With the three other combinations (low PEEP and 60% FIO(2) or high PEEP and 60% or 100% FIO(2)) none of the parameters decreased significantly., Conclusion: In mechanically ventilated patients with ALI the breathing of pure oxygen leads to derecruitment, which is prevented by high PEEP.

Objective: Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases., Design and Setting: Prospective observational physiological study in a medical ICU., Subjects and Intervention: In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45 degrees and legs down at 45 degrees )., Measurements and Results: Vertical positioning increased PaO(2) significantly from 94+/-33 to 142+/-49 mmHg, with an increase higher than 40% in 11 responders. The volume at 20 cmH(2)O measured on the PV curve from PEEP increased using the vertical position only in responders (233+/-146 vs. -8+/-9 1ml in nonresponders); this change was correlated to oxygenation change (rho=0.55). End-expiratory lung volume variation from supine to vertical and 1 h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n=7) but not in nonresponders (n=5; 215+/-220 vs. 10+/-22 ml), suggesting a time-dependent recruitment., Conclusions: Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients.

Objective: Pressure-volume (PV) curves are recorded after induction of complete muscle paralysis, which may limit their clinical use. The feasibility of recording PV curves without paralysis has not been tested. In 19 patients with acute respiratory distress syndrome (ARDS) and no hemodynamic instability we prospectively evaluated whether PV curves can be safely and reliably recorded under deep sedation without neuromuscular blockade., Methods: After standardized sedation (continuous infusion of midazolam and fentanyl) PV curves were recorded during apneic sedation, defined as absence of respiratory effort during a 6-s expiratory pause and during paralysis induced by cis-atracurium., Measurements and Results: Agreement between PV curve parameters in the two conditions was evaluated. Curves were obtained from 10 cmH2O and from zero end-expiratory pressure in all patients under apneic sedation. In five patients propofol was given in addition to midazolam and fentanyl, and in two of them fluid resuscitation was needed. A strong agreement was found for respiratory system compliance and the lower inflection point and for chest wall compliance in the five patients whose esophageal pressure was measured. The variability of the measurements, however, should be taken into account in clinical practice., Conclusion: Neuromuscular blockade can be dispensed with when recording PV curves in many ARDS patients. Reliable PV curves can be obtained under anesthesia alone, with no serious adverse effects.

Objective: In acute respiratory distress syndrome, the relationships between changes in the elastic behavior of the respiratory system and biological markers of extra-cellular matrix or surfactant turn-over could give some insights into its pathophysiological determinants., Design and Measurements: In 17 patients with acute respiratory distress syndrome, we assessed the relationship between chord compliance measured on pressure-volume curves obtained at two levels of positive end-expiratory pressure (0 and 10[Symbol: see text]cm[Symbol: see text]H(2)O) and biological markers of collagen turn-over or surfactant degradation in bronchoalveolar lavage fluid obtained simultaneously in the early phase of the disease (first 4 days)., Main Results: The compliance of the respiratory system obtained from the pressure-volume curves was significantly correlated with markers for collagen turn-over (type III procollagen peptide and matrix metalloproteinase 2) and with markers of surfactant degradation (type-IIA secretory phospholipase A2). The correlations were stronger when the curve was traced from positive end-expiratory pressure, suggesting that this condition may improve the assessment of tissue mechanics. A logarithmic relationship best described the correlation between compliance and type III procollagen peptide, in agreement with a collagen-dependent model of maximal distension. The marker for surfactant degradation was associated with ongoing alveolar inflammation (cellularity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha concentration). Interleukin-10, an anti-inflammatory mediator, showed no correlation with compliance., Conclusion: These preliminary data suggest that a severe reduction in compliance in the early phase of acute respiratory distress syndrome is associated with both collagen deposition and surfactant degradation.

Background: The principal features of elastic pressure-volume curves of lungs or the respiratory system (P(el)/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because new knowledge can be acquired from them, and because such curves may be useful as guidelines in setting the ventilator so as to avoid ventilator-induced lung injury., Discussion: This article reviews recording methods, underlying physiology and utility of P(el)/V curves in research and clinical work.

Objective: The objective was to analyse relationships between inspiratory and expiratory static and dynamic elastic pressure-volume (P(el)/V) curves in healthy pigs., Design: The modulated low flow method was developed to allow studies also of the expiratory P(el)/V curves. Static P(el)/V (P(el,st)/V) and dynamic P(el)/V (P(el,dyn)/V) loops were studied in healthy pigs., Setting: Animal research laboratory in a university hospital., Material: Ten healthy anaesthetised and paralysed pigs., Interventions and Measurements: A computer controlled a Servo Ventilator 900C with respect to respiratory rate, inspiratory flow and expiratory pressure to achieve a sinusoidal modulation of inspiration and expiration for determination of P(el,dyn)/V loops from zero end-expiratory pressure (ZEEP) and from a positive end-expiratory pressure (PEEP) of 6 cmH(2)O to 20, 35 and 50 cmH(2)O. The same system was used for studies of P(el,st)/V loops with the flow-interruption method from ZEEP and PEEP to 35 cmH(2)O. Recordings were analysed with an iterative technique., Results: The feasibility of automated determination of P(el,dyn)/V loops was demonstrated. Differences between P(el,dyn)/V and P(el,st)/V loops were explained by viscoelastic behaviour. P(el,st)/V loops recorded from PEEP to 35 cmH(2)O showed no significant hysteresis, indicating a non-significant surface tension hysteresis. P(el,dyn)/V loops from PEEP and both P(el,st)/V and P(el,dyn)/V loops from ZEEP to 35 cmH(2)O showed hysteresis. This indicates that lung collapse/re-expansion caused P(el)/V loop hysteresis which, in P(el,dyn)/V loops, was augmented by viscoelastic behaviour., Conclusions: Viscoelasticity influences P(el,dyn)/V curves. Hysteresis caused by surface tension merits re-evaluation. Lung collapse and re-expansion may be indicated by hysteresis of P(el)/V loops.