Association of PEEP with two different inflation volumes in ARDS patients: effects on passive lung deflation and alveolar recruitment.

OBJECTIVE: To assess the effects of the association of positive end-expiratory pressure (PEEP) with different inflation volumes (V(T)'s) on passive lung deflation and alveolar recruitment in ARDS patients. DESIGN: Clinical study using PEEP with two different V(T)'s and analyzing whether passive lung deflation and alveolar recruitment (Vrec) depend on end-inspired (EILV) or end-expired (EELV) lung volume in mechanically ventilated ARDS patients. SETTING: Medical intensive care unit in a university hospital. PATIENTS AND PARTICIPANTS: Six mechanically ventilated consecutive supine patients with ARDS. INTERVENTIONS: Time-course of thoracic volume decay during passive expiration and Vrec were investigated in six ARDS patients ventilated on PEEP with baseline V(T) (V(T),b) and 0.5V(T) (0.5V(T),b), and on zero PEEP (ZEEP) with V(T),b. Time constants of the fast (tau1) and slow (tau2) emptying compartments, as well as resistances and elastances were also determined. MEASUREMENTS AND RESULTS: (a) the biexponential model best fitted the volume decay in all instances. The fast compartment was responsible for 84+/-7 (0.5V(T),b) and 86+/-5% (V(T),b) on PEEP vs 81+/-6% (V(T),b) on ZEEP (P:ns) of the exhaled V(T), with tau1 of 0.50+/-0.13 and 0.58+/-0.17 s vs 0.35+/-0.11 s, respectively; (b) only tau1 for V(T),b on PEEP differed significantly (P < 0.02) from the one on ZEEP, suggesting a slower initial emptying; (c) for the same PEEP, Vrec was higher with a higher volume (V(T)b) than at a lesser one (0.5V(T),b), reflecting the higher V(T). CONCLUSIONS: In mechanically ventilated ARDS patients: (a) the behavior of airway resistance seems to depend on the degree of the prevailing lung distension; (b) alveolar recruitment appears to be more important when higher tidal volumes are used during mechanical ventilation on PEEP; (c) PEEP changes the mechanical properties of the respiratory system fast-emptying compartment.

Modelling of passive expiration in patients with adult respiratory distress syndrome.

The time-course of volume change during passive expiration preceded by an end-inspiratory hold was studied with a biexponential model in six adult respiratory distress syndrome (ARDS) patients. We measured the initial volumes and time constants of the fast (tau 1), and the slow (tau 2) compartments of expiration, as well as the static elastance of the respiratory system. The results were compared to those of 11 normal subjects. We observed that: 1) the biexponential model fitted closely the volume decay; 2) the fast compartment was responsible for 81 +/- 7% (ARDS) versus 84 +/- 10% (controls) of the total volume exhaled, with tau 1 = 0.35 +/- 0.11 s (ARDS) versus 0.50 +/- 0.22 s (controls); 3) the slow compartment contributed only 19 +/- 6% (ARDS) versus 16 +/- 7% (controls), with tau 2 = 4.67 +/- 2.38 s (ARDS) versus 3.27 +/- 1.54 s (controls); and 4) static elastance was higher in ARDS patients. The findings could be explained in terms of a four parameter viscoelastic model of the respiratory system.

Aspirin effect on early and late changes in acute lung injury in sheep.

OBJECTIVE: There have been several studies that have already explored the potential beneficial role of cyclo-oxygenase (CO) inhibitors on oleic acid (OA)-induced lung injury in different species. These studies report no significant effect of CO inhibition, though thromboxane B2 (TxB2) was effectively blocked. However, recent studies indicate that pre-treatment with aspirin (ASA) preserve gas exchange in OA lung injury in dogs. Aim of our study has been to evaluate the potential beneficial effects of the pre-treatment with low doses of ASA on gas exchange, hemodynamics, respiratory mechanics, prostanoids and lung histology in OA-induced lung injury in sheep. DESIGN: 0.09 ml/kg of OA was administered into the right atrium of 14 anaesthetized sheep. Six received a bolus of ASA (10 mg/kg i.v.) 30 min before OA, the others saline as placebo. MEASUREMENTS AND RESULTS: Pulmonary and tissue gas exchange, pulmonary and systematic hemodynamics, respiratory system mechanics, TxB2 and 6-keto-PGF1 alpha, leukocytes and platelets concentrations were measured throughout the subsequent 3 h and lung histology was effected at end-experiment. The principal findings of our study are: 1) ASA reduces OA-induced early pulmonary vasoconstriction and bronchoconstriction, parallelled by a suppression of TxB2 generation; 2) the late increase in pulmonary artery pressure and airway resistance due to OA is not inhibited by ASA; 3) the early disturbance in pulmonary gas exchange is reduced by ASA, whereas the late severe deterioration is exaggerated by ASA; 4) the stability of tissue exchange ratio (R) at approximately 1 in ASA-group compared to its fall to approximately 0.7 in controls. CONCLUSION: Our findings suggest that ASA: 1) is only effective to treat the very transient TxB2-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB2; 2) has a transient protective effect on the TxB2-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO2.

A single-compartment model cannot describe passive expiration in intubated, paralysed humans.

The time-course of thoracic volume changes (respiratory inductive plethysmograph) during relaxed expiration was studied in 11 intubated, paralysed, mechanically ventilated subjects. The semilog volume-time curves show that expiration is governed by two apparently separate mechanisms: one causes emptying of most of the expired volume (approximately 80%) with a time constant of 0.50 +/- 0.22 s for a baseline tidal volume of 0.44 +/- 0.12 l (mean +/- SD) and 0.37 +/- 0.14 s when the tidal volume is reduced (VTP); the other contributes a relatively small amount to the expired volume over a significantly longer time, the time constant amounting to 3.27 +/- 1.54 s for baseline VT and 2.95 +/- 1.65 s for VTp. The first mechanism probably reflects the standard elastic and flow resistive properties of the respiratory system, while the second, slower compartment, is probably an expression of the viscoelastic properties of the pulmonary and chest wall tissues.

The prominent role of thromboxane A2 formation on early pulmonary hypertension induced by oleic acid administration in sheep.

The early increase of pulmonary artery pressure observed in different models of experimentally induced lung injury have been shown to be associated with the release of vasoconstrictive agents by activated platelets. The aim of this study was to evaluate the pattern of these metabolites, in particular TxA2, and the effects of the inhibition of their production by ASA on the modifications of pulmonary hemodynamics induced by oleic acid administration in sheep. Group I (8 sheep) was infused with oleic acid (0.09 ml/kg at 0.02 ml/min) while in group II (6 sheep) ASA (10 mg/kg i.v.) was administered 30 minutes before oleic acid infusion. In group I pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were significantly higher at the end of the infusion while cardiac output (CO) significantly decreased in comparison to baseline values. A marked increase in plasma TxB2 levels paralleled pulmonary hemodynamic changes. Also plasma 6 keto PGF levels increased after OA infusion. The early increase in PAP and PVR was significantly lower in group II (p less than 0.005) while CO did not undergo any significant change. ASA pretreatment significantly blunted the rise of TxB2 concentrations and prevented the elevation of 6 keto PGFa. These results indicate that early pulmonary hypertension in oleic acid induced injury is mainly related to TxA2 released from platelets and leukocytes and that pulmonary hemodynamic changes are significantly inhibited by ASA pretreatment.

Causes of error of respiratory pressure-volume curves in paralyzed subjects.

Respiratory pressure-volume (PV) curves are commonly obtained in paralyzed patients by relating airway pressure to volume changes of a syringe (Vsyr). This is based on the implicit assumption that changes in thoracic volume (Vtho) and Vsyr are equal. We undertook to verify this assumption through simultaneous measurements of Vtho by respiratory inductive plethysmography and Vsyr in six comatose, paralyzed, intubated patients. At any constant Vsyr, Vtho fell and was smaller on deflation than on inflation during inflation-deflation (ID) cycle. The rate of fall was 110 +/- 64 (SD) ml/min. During ID cycles lasting 76 +/- 7 s, thoracic PV curves showed less hysteresis and a larger compliance on deflation than PVsyr curves (12 +/- 2 vs. 18 +/- 6% and 73 +/- 13 vs. 67 +/- 12 ml/cmH2O, P less than 0.05). With PVsyr curves, hysteresis increased and compliance on deflation decreased with increasing rate of fall of Vtho. We submit that the difference between changes in Vsyr and Vtho is best explained by gas exchange and should be taken into account when performing PV curves with a syringe in paralyzed patients.