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Objectives: To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI).Design and Setting: Prospective, controlled animal study in an animal research facility of a university hospital.Interventions: ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6).Measurement and Results: Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone.Conclusions: In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics. [ABSTRACT FROM AUTHOR]

Presents a response by M. Max, R. Kuhlen, R. Dembinski and R. Rossaint to a letter to the editor in response to their article "Inhalation of NO and PGI2," that was previously published in the journal "Intensive Care Medicine."

Background: Acute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (V(T)) strategy (V(T) ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS., Methods: Seventy-nine patients were enrolled after a 'stabilization period' (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low V(T) ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality., Results: Ventilation with very low V(T)'s was easy to implement with extracorporeal CO2-removal. VFD's within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5%) and did not differ between groups., Conclusions: The use of very low V(T) combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a 'normal' lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928).

Objective: Measurements from the pulmonary pressure-volume (PV) curve have been proposed to adjust ventilator settings. We investigated the effects of repeated construction of an inflation PV curve implemented in a standard ventilator on recruitment or derecruitment in acutely injured lungs., Design and Setting: Prospective experimental animal study in eight anesthetized and mechanically ventilated pigs., Interventions: Acute lung injury was induced by lung lavage and animals were ventilated in volume controlled mode with PEEP 10 cmH(2)O. The PV curve was constructed five times repeatedly by constant pressure rise, after which ventilation with the preset PEEP was resumed immediately. Studies of hemodynamics, lung mechanics, blood gases and computed tomography were carried out before and after maneuvers., Measurements and Results: Derecruitment was assessed as an increase in nonaerated lung volume (V(NON)), and V(PEEP) was the end-expiratory volume difference between PEEP and ZEEP. There was a significant decrease in PaO(2) from 90.4+/-33.3 to 70.9+/-36.3 mmHg and a rise in venous admixture from 47.8+/-12.7 to 59.1+/-16.6%. V(PEEP) was reduced from 244 to 202 ml. A corresponding decrease in normally aerated lung volume was observed, while regression analysis revealed increase in V(NON) depending on the amount of preexisting atelectasis., Conclusions: Repeated generation of the PV curve with a readily available tool resulted in worsened oxygenation. Derecruitment of the lungs occurred with loss of PEEP at the start of the maneuver, which could not be recovered by a maximum inflation pressure of 40 cmH(2)O. Repeated use of the investigated tool should be cautioned, and users should consider measures to preserve aerated lung volumes.

Objective: We investigated whether improvement in ventilation perfusion (.V(A)/.Q) distribution during mechanical ventilation using biphasic positive airway pressure (BIPAP) with spontaneous breathing may be attributed to an effectively increased transpulmonary pressure (P(TP)) and can also be achieved by increasing P(TP) during controlled ventilation., Design: In 12 pigs with saline lavage-induced lung injury we compared the effects of BIPAP to pressure-controlled ventilation with equal airway pressure (PCV(AW)) or equal transpulmonary pressure (PCV(TP)) on V(A)/.Q distribution assessed by the multiple inert gas elimination technique (MIGET)., Setting: Animal laboratory study., Measurements and Results: Intrapulmonary shunt was 33+/-11% during BIPAP, 36+/-10% during PCV(AW) and 33+/-15% during PCV(TP) ( p= n.s.). BIPAP resulted in higher PaO(2) than PCV(AW) (188+/-83 versus 147+/-82 mmHg, p < 0.05), but not than PCV(TP) (187+/-139 mmHg). Oxygen delivery was significantly higher during BIPAP (530+/-109 ml/min) versus 374+/-113 ml/min during PCV(AW) and 353+/-93 ml/min during PCV(TP) ( p < 0.005). Tidal volume with PCV(TP) increased to 11.9+/-2.3 ml/kg, compared to 8.5+/-0.8 with BIPAP and 7.6+/-1.4 with PCV(AW) ( p <0.001) and cardiac output decreased to 3.5+/-0.6 l/min (BIPAP 4.9+/-0.8 and PCV(AW) 3.9+/-0.8, p<0.006)., Conclusions: In experimental lung injury, BIPAP with preserved spontaneous breathing was effective in increasing regional P(TP), since pressure-controlled ventilation with the same P(TP) resulted in similar gas exchange effects. However, PCV(TP) caused increased airway pressures and tidal volumes, whereby, with BIPAP, less depression of oxygen delivery and cardiac output were observed. BIPAP could be useful in maintaining pulmonary gas exchange and slightly improving oxygenation without interfering with circulation as strongly as PCV does.

Objective: To compare ventilation-perfusion (V(A)/Q) distributions during improvement of oxygenation caused by high-frequency oscillatory ventilation (HFOV) and pressure-controlled mechanical ventilation with high PEEP levels (CMV) in experimental acute lung injury (ALI)., Design: Prospective, controlled animal study., Setting: Animal research facility of a university hospital., Interventions: Twelve pigs with oleic acid-induced ALI were randomised to HFOV ( n=6) or to CMV ( n=6) with a PEEP of 15 mbar for 1 h. The mean airway pressure was adjusted in both groups to achieve comparable improvements in arterial oxygen partial pressure (PaO(2)) and to avoid clinically relevant impairments of cardiac output, as assured by adequate mixed venous oxygen saturation and lactate levels. V(A)/Q distributions were determined by the multiple inert gas elimination technique (MIGET)., Measurements and Results: Arterial oxygen partial pressure improved during CMV with a mean airway pressure of 20 mbar ( p<0.05) whereas HFOV revealed comparable improvements with a mean airway pressure of 40 mbar ( p<0.05). Shunt decreased and blood flow to normal V(A)/Q areas increased due to CMV and HFOV ( p<0.05). The perfusion of low V(A)/Q areas remained unchanged. Statistical analysis did not reveal differences of PaO(2), shunt or blood flow to low V(A)/Q areas between the groups., Conclusions: In this model of acute lung injury CMV and HFOV improved gas exchange due to similar changes in V(A)/Q distribution. However, mean airway pressure had to be adjusted twofold higher during HFOV then during CMV to achieve comparable improvements in gas exchange.