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Small dose of exogenous surfactant combined with partial liquid ventilation in experimental acute lung injury: effects on gas exchange, haemodynamics, lung mechanics, and lung pathology

2001; Elsevier BV; Volume: 87; Issue: 4 Linguagem: Inglês

10.1093/bja/87.4.593

1471-6771

Steffen Wolf, H. Lohbrunner, Thilo Busch, Anja Sterner‐Kock, Maria Deja, A. Sarrafzadeh, Ulf Neumann, Udo Kaisers,

Cardiac Arrest and Resuscitation

A combination of exogenous surfactant and partial liquid ventilation (PLV) with perfluorocarbons should enhance gas exchange, improve respiratory mechanics and reduce tissue damage of the lung in acute lung injury (ALI). We used a small dose of exogenous surfactant with and without PLV in an experimental model of ALI and studied the effects on gas exchange, haemodynamics, lung mechanics, and lung pathology. ALI was induced by repeated lavages (PaO2/FiO2 less than 13 kPa) in 24 anaesthesized, tracheotomized and mechanically ventilated (FiO2 1.0) juvenile pigs. They were treated randomly with either a single intratracheal dose of surfactant (50 mg kg–1, Curosurf®, Serono AG, München, Germany) (SURF‐group, n=8), a single intratracheal dose of surfactant (50 mg kg–1, Curosurf®) followed by PLV with 30 ml kg–1 of perfluorocarbon (PF 5080, 3M, Germany) (SURF‐PLV‐group, n=8) or no further intervention (controls, n=8). Pulmonary gas exchange, respiratory mechanics, and haemodynamics were measured hourly for a 6 h period. In the SURF‐group, the intrapulmonary right‐to‐left shunt (Q˙s/Q˙t) decreased significantly from mean 51 (sem 5)% after lavage to 12 (2)%, and PaO2 increased significantly from 8.1 (0.7) to 61.2 (4.7) kPa compared with controls and compared with the SURF‐PLV‐group (P<0.05). In the SURF‐PLV‐group, Q˙s/Q˙t decreased significantly from 54 (3)% after induction of ALI to 26 (3)% and PaO2 increased significantly from 7.2 (0.5) to 30.8 (5.0) kPa compared with controls (P<0.05). Static compliance of the respiratory system (CRS), significantly improved in the SURF‐PLV‐group compared with controls (P<0.05). Upon histological examination, the SURF‐group revealed the lowest total injury score compared with controls and the SURF‐PLV‐group (P<0.05). We conclude that in this experimental model of ALI, treatment with a small dose of exogenous surfactant improves pulmonary gas exchange and reduces the lung injury more effectively than the combined treatment of a small dose of exogenous surfactant and PLV. A combination of exogenous surfactant and partial liquid ventilation (PLV) with perfluorocarbons should enhance gas exchange, improve respiratory mechanics and reduce tissue damage of the lung in acute lung injury (ALI). We used a small dose of exogenous surfactant with and without PLV in an experimental model of ALI and studied the effects on gas exchange, haemodynamics, lung mechanics, and lung pathology. ALI was induced by repeated lavages (PaO2/FiO2 less than 13 kPa) in 24 anaesthesized, tracheotomized and mechanically ventilated (FiO2 1.0) juvenile pigs. They were treated randomly with either a single intratracheal dose of surfactant (50 mg kg–1, Curosurf®, Serono AG, München, Germany) (SURF‐group, n=8), a single intratracheal dose of surfactant (50 mg kg–1, Curosurf®) followed by PLV with 30 ml kg–1 of perfluorocarbon (PF 5080, 3M, Germany) (SURF‐PLV‐group, n=8) or no further intervention (controls, n=8). Pulmonary gas exchange, respiratory mechanics, and haemodynamics were measured hourly for a 6 h period. In the SURF‐group, the intrapulmonary right‐to‐left shunt (Q˙s/Q˙t) decreased significantly from mean 51 (sem 5)% after lavage to 12 (2)%, and PaO2 increased significantly from 8.1 (0.7) to 61.2 (4.7) kPa compared with controls and compared with the SURF‐PLV‐group (P<0.05). In the SURF‐PLV‐group, Q˙s/Q˙t decreased significantly from 54 (3)% after induction of ALI to 26 (3)% and PaO2 increased significantly from 7.2 (0.5) to 30.8 (5.0) kPa compared with controls (P<0.05). Static compliance of the respiratory system (CRS), significantly improved in the SURF‐PLV‐group compared with controls (P<0.05). Upon histological examination, the SURF‐group revealed the lowest total injury score compared with controls and the SURF‐PLV‐group (P<0.05). We conclude that in this experimental model of ALI, treatment with a small dose of exogenous surfactant improves pulmonary gas exchange and reduces the lung injury more effectively than the combined treatment of a small dose of exogenous surfactant and PLV. Deficiency of alveolar surfactant, pulmonary hyperten sion, intrapulmonary right‐to‐left shunting, and poor arterial oxygenation are features of both experimental acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). 1Lewis JF Jobe AH. 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Effect of artificial surfactant on pulmonary function in preterm and full‐term lambs.J Appl Physiol. 1990; 69: 465-472PubMed Google Scholar partial liquid ventilation (PLV), 12Fuhrmann BP Paczan PR DeFrancisis M. Perfluorocarbon associated gas exchange.Crit Care Med. 1991; 19: 712-722Crossref PubMed Scopus (333) Google Scholar, 13Tu¨tu¨ncu¨ AS Faithfull NS Lachmann B. Comparison of ventilatory support with intratracheal perfluorocarbon administration and conventional mechanical ventilation in animals with acute respiratory failure.Am Rev Respir Dis. 1993; 148: 785-792Crossref PubMed Scopus (150) Google Scholar, 14Papo MC Paczan PR Fuhrmann BP et al.Perfluorocarbon‐associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome.Crit Care Med. 1996; 24: 466-474Crossref PubMed Scopus (94) Google Scholar, 15Zobel G Rodl S Urlesberger B Dacar D Trafojer U Trantina A. The effect of positive end‐expiratory pressure during partial liquid ventilation in acute lung injury in piglets.Crit Care Med. 1999; 27: 1934-1939Crossref PubMed Scopus (22) Google Scholar, 16Kirmse M Fujino Y Hess D Kacmarek RM. Positive end‐expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation.Am J Respir Crit Care Med. 1998; 158: 1550-1556Crossref PubMed Scopus (63) Google Scholar, 17Kaisers U Kuhlen R Keske U et al.Superimposing positive end‐expiratory pressure during partial liquid ventilation in experimental lung injury.Eur Respir J. 1998; 11: 1035-1042Crossref PubMed Scopus (40) Google Scholar and extracorporal membrane oxygenation (ECMO). 18Lewandowski K Rossaint R Pappert D et al.High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.Intensive Care Med. 1997; 23: 819-835Crossref PubMed Scopus (242) Google Scholar Giving surfactant may reduce surface tension, improve gas exchange and lung mechanics. 7Goldsmith LS Greenspan JS Rubenstein DS Wolson MR Shaffer TH. Immediate improvement in lung volume after exogenous surfactant: alveolar recruitment versus increased distension.J Pediatr. 1991; 119: 424-428Abstract Full Text PDF PubMed Scopus (132) Google Scholar, 8Lewis JF Goffin J Yue P McCaig LA Bjarneson D Veldhuizen RA. Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.J Appl Physiol. 1996; 80: 1156-1164Crossref PubMed Scopus (17) Google Scholar, 9Gregory TJ Steinberg P Spragg R et al.Bovine surfactant therapy for patients with acute respiratory distress syndrome.Am J Respir Crit Care Med. 1997; 155: 1309-1315Crossref PubMed Scopus (347) Google Scholar, 10Walmrath D Gu¨nther A Ghofrani HA et al.Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis.Am J Respir Crit Care Med. 1996; 154: 57-62Crossref PubMed Scopus (182) Google Scholar, 11Gladstone IM Ray AO Salafia CM Perez‐Fontan J Mercurio MR Jacobs HC. Effect of artificial surfactant on pulmonary function in preterm and full‐term lambs.J Appl Physiol. 1990; 69: 465-472PubMed Google Scholar In PLV the lung is partially filled with a perfluorocarbon and conventional mechanical ventilation is resumed. PLV can improve gas exchange and lung mechanics without significantly affecting systemic circulation. 12Fuhrmann BP Paczan PR DeFrancisis M. Perfluorocarbon associated gas exchange.Crit Care Med. 1991; 19: 712-722Crossref PubMed Scopus (333) Google Scholar, 13Tu¨tu¨ncu¨ AS Faithfull NS Lachmann B. Comparison of ventilatory support with intratracheal perfluorocarbon administration and conventional mechanical ventilation in animals with acute respiratory failure.Am Rev Respir Dis. 1993; 148: 785-792Crossref PubMed Scopus (150) Google Scholar, 14Papo MC Paczan PR Fuhrmann BP et al.Perfluorocarbon‐associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome.Crit Care Med. 1996; 24: 466-474Crossref PubMed Scopus (94) Google Scholar, 15Zobel G Rodl S Urlesberger B Dacar D Trafojer U Trantina A. The effect of positive end‐expiratory pressure during partial liquid ventilation in acute lung injury in piglets.Crit Care Med. 1999; 27: 1934-1939Crossref PubMed Scopus (22) Google Scholar, 16Kirmse M Fujino Y Hess D Kacmarek RM. Positive end‐expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation.Am J Respir Crit Care Med. 1998; 158: 1550-1556Crossref PubMed Scopus (63) Google Scholar, 17Kaisers U Kuhlen R Keske U et al.Superimposing positive end‐expiratory pressure during partial liquid ventilation in experimental lung injury.Eur Respir J. 1998; 11: 1035-1042Crossref PubMed Scopus (40) Google Scholar Exogenous surfactant and PLV have been investigated using different doses and different experimental models of ALI. 19Go¨thberg S Parker TA Abman SH Kinsella JP. High‐frequency oscillatory ventilation and partial liquid ventilation after acute lung injury in premature lambs with respiratory distress syndrome.Crit Care Med. 2000; 28: 2450-2456Crossref PubMed Scopus (31) Google Scholar, 20Kelly KP Stenson BJ Drummond GB. Randomised comparison of partial liquid ventilation, nebulised perfluorocarbon, porcine surfactant, and combined treatments on oxygenation, lung mechanics, and survival in rabbits after saline lung lavage.Intensive Care Med. 2000; 26: 1523-1530Crossref PubMed Scopus (22) Google Scholar, 21Merz U Kellinghaus M Ha¨usler M Pakrawan N Klosterhalfen B Ho¨rnchen H. Partial liquid ventilation with surfactant: effects on gas exchange and lung pathology in surfactant‐depleted piglets.Intensive Care Med. 2000; 26: 109-116Crossref PubMed Scopus (19) Google Scholar, 22Hartog A Vazquez de Anda GF Gommers D et al.Comparison of exogenous surfactant therapy, mechanical ventilation, with high end‐expiratory pressure and partial liquid ventilation in a model of acute lung injury.Br J Anaesth. 1999; 82: 81-86Crossref PubMed Scopus (24) Google Scholar, 23Tarczy‐Hornoch P Hildebrandt J Standaert TA Jackon JC. Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ.J Appl Physiol. 1998; 84: 1316-1322Crossref PubMed Scopus (60) Google Scholar, 24Wolfson MR Kechner NE Roache RF et al.Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency.J Appl Physiol. 1998; 84: 624-640PubMed Google Scholar, 25Mrozek JD Bing DR. Meyers PA Connett JE Mammel MC. High‐frequency oscillation versus conventional ventilation following surfactant administration and partial liquid ventilation.Pediatr Pulmonol. 1998; 26: 21-29Crossref PubMed Scopus (19) Google Scholar, 26Davidson A Heckmann JL Donner RM Miller TF Shaffer TH Wolfson MR. Cardiopulmonary interaction during partial liquid ventilation in surfactant‐treated preterm lambs.Eur J Pediatr. 1998; 157: 138-145Crossref PubMed Scopus (15) Google Scholar, 27Mrozek JD Smith KM Bing DR et al.Exogenous surfactant and partial liquid ventilation: physiologic and pathologic effects.Am J Respir Crit Care Med. 1997; 156: 1058-1065Crossref PubMed Scopus (103) Google Scholar, 28Tarczy‐Hornoch P Hildebrandt J Mates EA et al.Effects of exogenous surfactant on lung pressure‐volume characteristics during liquid ventilation.J Appl Physiol. 1996; 80: 1764-1771PubMed Google Scholar, 29Leach CL Holm B Morin FC et al.Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant.J Pediatr. 1995; 126: 412-420Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar The effects on gas exchange, haemodynamics, lung mechanics, and lung damage were variable. A combination of 100 mg kg–1 of surfactant with PLV, restored pulmonary gas exchange more efficiently in an experimental model of neonatal ALI than surfactant therapy alone. However, a combination of PLV with only 5 mg kg–1 of surfactant failed to give additional benefit compared with PLV alone. 27Mrozek JD Smith KM Bing DR et al.Exogenous surfactant and partial liquid ventilation: physiologic and pathologic effects.Am J Respir Crit Care Med. 1997; 156: 1058-1065Crossref PubMed Scopus (103) Google Scholar, 29Leach CL Holm B Morin FC et al.Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant.J Pediatr. 1995; 126: 412-420Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar We compared a single dose of 50 mg kg–1 surfactant alone vs 50 mg kg–1 surfactant combined with PLV in a pig model of ALI, with measurements of gas exchange, haemodynamics, respiratory mechanics, and progression of lung injury. This study was approved by the Berlin Animal Protection Committee in accordance with German Animal Protection Law, and conforms with the Guide for the Care and Use of Laboratory Animals (DHHS, PHS, NIH Publication No. 85‐23). We studied 24 piglets (weight 23–27 kg), aged between 6 and 8 weeks. Anesthesia was induced with thiopental (10 mg kg–1 i.v.) and fentanyl (10 µg kg–1 i.v. followed by an infusion of 0.05–0.08 µg kg–1 min–1). Muscle relaxation was obtained with pancuronium bromide (0.15 mg kg–1 i.v. bolus, followed by a continuous infusion of 2.5 µg kg–1 min–1). Immediately after induction, the pigs were tracheotomized and intubated with a 9.0 mm outer diameter tracheal tube, fitted with a heat and moisture exchanger. The animals were placed supine and ventilated in a volume controlled mode (tidal volume 10–12 ml kg–1, respiratory rate 16 min–1, FiO2 1.0, I:E ratio 1:1, PEEP 5 cm H2O) with an EVITA 2 model 76 ventilator (Dräger, Lübeck, Germany). Core temperature was maintained within ±0.5°C of the pre‐study value using a heating pad. No drugs were used to support the circulation. We placed a pulmonary artery catheter (model 93A‐431‐7.5 Fr, Baxter Healthcare Corporation, Irvine, CA, USA) percutaneously via the femoral vein, and an arterial cannula (18 G; Vygon, Ecouen, France) into the femoral artery, for blood sampling and haemodynamic measurements. Heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), and pulmonary artery wedge pressure (PCWP) were recorded using a Hewlett‐Packard monitoring system (Model 66 S, Böblingen, Germany). Measurements were taken with pigs in the supine position with zero at the level of the midaxilla. Vascular pressures were the average taken at end‐expiration of three successive respiratory cycles. Cardiac output (CO) was determined by thermodilution using the mean of four measurements (10 ml saline at 1–5°C) arbitrarily performed during different phases of the respiratory cycle. Intrapulmonary shunt (Q˙s/Q˙t), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated using standard formulae. All blood samples (arterial and mixed venous) were collected anaerobically, and analysed within 5 min (ABL 520, Radiometer, Copenhagen, Denmark). Arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SvO2) were measured by spectrophotometry with the analyser calibrated with pig blood (OSM 3 Hemoximeter, Radiometer). Static compliance of the respiratory system (CRS) was determined using automated inspiratory, repetitive occlusions (1 s) at single volume steps (SCASS). 30Sydow M Burchardi H Zinserling J Ische H Crozier TA Weyland W. Improved determination of static compliance by automated single volume steps in ventilated patients.Intensive Care Med. 1991; 17: 108-114Crossref PubMed Scopus (42) Google Scholar Measurements started with 10 ml Vt up to a maximum Vt of 10–12 ml kg–1, using volume steps of 10 ml each. CRS was calculated as mean of all generated pressure–volume curves from the inspiratory limb. Lung tissue from all animals was examined histologically. After killing the animals, the tracheal tube was clamped at end‐expiration (PEEP 5 cm H2O) and the lungs were removed. Perfluorocarbon was left in situ in animals treated with PLV. Tissues were fixed in 5% formalin. Specimens from the cranial ventral (non‐dependent) and caudal dorsal (dependent) lobes were stained with haematoxylin and eosin and then scored using a semiquantitative scoring system by an experienced veterinary pathologist (A. S‐K.), blinded to treatment, for interstitial infiltration, interstitial oedema, emphysema, and atelectasis. Each variable was scored using a 0–4‐point scale, with no injury scored 0, injury in 25% of the field scored 1, injury in 50% of the field scored 2, injury in 75% of the field scored 3, and injury throughout the field scored 4. The total score maximum was 16. Repeated lavage with warmed isotonic saline (37°C) was done to produce lung surfactant depletion as reported by Lachmann and co‐workers, and described in detail elsewhere. 31Kaisers U Max M Walter J et al.Partial liquid ventilation with small volumes of FC 3280 increases survival time in experimental ARDS.Eur Respir J. 1997; 10: 1955-1961Crossref PubMed Scopus (34) Google Scholar, 32Lachmann B Robertson B Vogel J. In‐vivo lavage as an experimental model of the respiratory distress syndrome.Acta Anaesthesiol Scand. 1980; 24: 231-236Crossref PubMed Scopus (517) Google Scholar Induction of ALI was assumed when the PaO2/FiO2 ratio was persistently less than 13 kPa for 1 h. After induction of ALI, the animals were randomly assigned to receive a single intratracheal dose of surfactant alone (50 mg kg–1, Curosurf®) (SURF‐group, n=8), or a single intratracheal dose of surfactant (50 mg kg–1), followed after 30 min by 30 ml kg–1 of perfluorocarbon (PF 5080, 3M, Germany) (SURF‐PLV‐group, n=8), or no further intervention (controls, n=8). Evaporative losses of PF 5080 were replaced at a dose of 4 (3) ml kg–1 every hour as previously found by our group. 33Kaisers U Max M Schnabel R et al.Partial liquid ventilation with FC 3280 in experimental lung injury: dose‐dependent improvement of gas exchange and lung mechanics.Appl Cardiopulm Pathophysiol. 1996; 6: 163-170Google Scholar PF 5080 (C8F18) is a non‐ozone‐depleting PFC with boiling point 102°C, density (at 25°C) 1.76 g ml–1, viscosity (at 25°C) 1.4 cp, vapour pressure (at 37°C) 6.8 kPa, solubility of oxygen (at 37°C) 49 ml 100 ml–1, solubility of carbon dioxide (at 37°C) 176 ml 100 ml–1, and surface tension (at 25°C) of 15 dyn s cm–1 (information taken from 3M data sheet). Curosurf® is isolated from minced pig lungs and contains 99% lipids, mainly phospholipids, and 1% low molecular weight hydrophobic apoproteins SP‐B and SP‐C. 16Kirmse M Fujino Y Hess D Kacmarek RM. Positive end‐expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation.Am J Respir Crit Care Med. 1998; 158: 1550-1556Crossref PubMed Scopus (63) Google Scholar Results are expressed as mean (sem). The data were obtained at baseline (pre‐lavage), immediately after the induction of ALI (post‐lavage) and at hourly intervals for 6 h thereafter. Statistical analysis was performed using SPSS for Windows 8.0 and Sigmastat (SPSS Inc., Chicago, IL, USA). Differences between groups were evaluated using Kruskal–Wallis anova followed by post hoc comparisons with Dunn's test (intergroup comparison). The Friedman test was used to compare the data after induction of ALI with the data measured during the subsequent 6 h (intragroup comparison). For post hoc testing, Dunn's test also was applied. Statistical significance was assumed at P<0.05. All animals were comparable with regard to body weight and pre‐study conditions. Pre‐lavage data of pulmonary gas exchange, lung compliance, and haemodynamics did not differ significantly between groups (Tables 1 and 2).Table 1Time course of HR, MABP, MPAP, CO, SVR, and PVR during baseline (pre‐lavage), after induction of ALI (post‐lavage), and for 6 h thereafter, in controls (n=8 at ALI; four pigs died before 6 h after ALI), in pigs treated with a single intratracheal dose of 50 mg kg–1 of surfactant (Curosurf®) after induction of ALI (SURF‐group) (n=8 pigs, none died), and in pigs treated with a single intratracheal dose of 50 mg kg–1 of surfactant (Curosurf®) followed by PLV with 30 ml kg–1 of perfluorocarbon (PF 5080) after induction of ALI (SURF‐PLV‐group) (n=8 pigs, none died). Data are mean (sem). Intergroup comparison: controls vs SURF‐PLV‐group and controls vs SURF‐group: *P<0.05, and SURF‐PLV‐group vs SURF‐group: †P<0.05 (Kruskal–Wallis ANOVA and post hoc Dunn's test). Intragroup comparison: data measured after induction of ALI vs data obtained at hourly intervals thereafter: ‡P<0.05 (Friedman test and post hoc Dunn's test)GroupHR (beats min–1)MABP (mm Hg)MPAP (mm Hg)CO (litre min–1)SVR (dyn s cm–5)PVR (dyn s cm–5)MeansemMeansemMeansemMeansemMeansemMeansemBaselineSURF77410252013.60.2208111914930SURF‐PLV9559952313.80.5202628524152Controls9598852013.60.3182720116525ALISURF102119442514.40.6165021026649SURF‐PLV10269452824.40.4159319126828Controls9368962823.80.21718227301531 hSURF92109142723.703176915033563SURF‐PLV10069263224.003161416036638Controls9358773023.9041688243329492 hSURF8899262823.40.3193016339260SURF‐PLV89594534‡23.50.3194422946676Controls9378373523.40.21697194466333 hSURF8699863022.8‡0.32573186525‡73SURF‐PLV88693236‡13.1‡0.32145192578‡79Controls100108783623.80.41767279486504 hSURF77599530*22.6‡0.22723176592‡79SURF‐PLV90591438†‡12.9‡0.32278258667‡69Controls971089939‡23.70.31845326563705 hSURF79899529*22.6‡0.32831207581‡98SURF‐PLV931188639†‡13.2‡0.42009290663‡104Controls102981941‡33.50.41742323596‡1006 hSURF80897530*32.6‡0.22662188560‡83SURF‐PLV95882740†‡13.1‡0.31857337659‡82Controls109774‡1141‡33.50.51601427627110 Open table in a new tab Table 2Time course of intrapulmonary shunting (Q˙s/Q˙t), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), arterial pH (pHa), oxygen delivery (DO2), oxygen consumption (V˙O2), static compliance of the respiratory system (CRS), and survivors during baseline (pre‐lavage), after induction of ALI (post‐lavage), and for 6 h thereafter, in controls (n=8 at ALI; four pigs died before 6 h after ALI), in pigs treated with a single intratracheal dose of 50 mg kg–1 of surfactant (Curosurf®) after induction of ALI (SURF‐group) (n=8 pigs, none died), and in pigs treated with a single intratracheal dose of 50 mg kg–1 of surfactant (Curosurf®) followed by PLV with 30 ml kg–1 of perfluorocarbon (PF 5080) after induction of ALI (SURF‐PLV‐group) (n=8 pigs, none died). Data are mean (sem). Intergroup comparison: controls vs SURF‐PLV‐group and controls vs SURF‐group: *P<0.05, and SURF‐PLV‐group vs SURF‐group: †P<0.05 (Kruskal–Wallis ANOVA and post hoc Dunn's test). Intragroup comparison: data measured after induction of ALI vs data obtained at hourly intervals thereafter: ‡P<0.05 (Friedman test and post hoc Dunn's test)GroupQ˙s/Q˙t(%)PaO2 (kPa)PaCO2 (kPa)pHaDO2 (ml min–1)V˙O2 (ml min–1)CRS (ml mbar–1)Survivors (n)MeansemMeansemMeansemMeansemMeansemMeansemMeansemBaselineSURF12175.73.24.70.57.560.034232814214221.08SURF‐PLV16368.03.85.50.47.480.024185014321211.88Controls16372.73.66.10.77.430.043962611010231.08ALISURF5158.10.76.10.67.420.04361341341690.68SURF‐PLV5437.20.57.30.67.370.02338331501491.08Controls5647.60.77.50.57.330.03257201221491.081 hSURF38*419.2*4.86.60.47.410.03363271301590.38SURF‐PLV44‡411.03.17.60.77.370.02349291521012*0.98Controls5737.30.47.10.67.360.04277251181180.482 hSURF25*‡336.8*6.75.7*0.37.460.03365*311361190.38SURF‐PLV28‡223.5*3.68.4†0.37.320.02362381521514*1.78Controls5248.00.58.00.87.330.04249171111091.083 hSURF20*‡248.3*‡6.65.7*0.47.480.043243112816100.38SURF‐PLV24*‡231.6*‡3.38.4†0.47.340.01331251391213*1.38Controls5358.10.68.50.87.300.04282321261980.584 hSURF13*‡164.5*‡2.65.7*0.37.470.04321281321390.28SURF‐PLV22*‡234.0‡3.48.5†0.67.340.02308271361613*0.48Controls5237.70.58.20.47.320.03296251311160.975 hSURF12*‡264.9*‡3.75.9*0.57.460.04312281251290.18SURF‐PLV24‡335.1‡4.69.2†0.87.310.033483914614141.28Controls5667.20.79.10.87.290.0327846121360.456 hSURF12*‡261.2*‡4.77.01.07.450.04326231331490.28SURF‐PLV26‡330.8†‡5.010.0‡1.07.290.03338381391315*0.48Controls5647.00.49.9‡0.77.270.03291571371970.54 Open table in a new tab In all animals, induction of ALI increased Q˙s/Q˙t concomitant with a decrease in PaO2. Cardiac output (CO), mean pulmonary artery pressure (MPAP), and pulmonary vascular pressure (PVR) increased while mean arterial blood pressure (MABP), and systemic vascular resistance (SVR) decreased (Tables 1 and 2). Surfactant alone improved PaO2 from 8.1 (0.7) kPa after onset of ALI to 61.2 (4.7) kPa after 6 h of treatment (P<0.05 vs controls; Fig. 1, Table 2). The increase of PaO2 in the SURF‐group was greater than the increase in the SURF‐PLV‐group after 6 h of treatment (P<0.05 vs SURF‐PLV; Fig. 1, Table 2). In the PLV‐SURF‐group the increase of PaO2 from 7.2 (0.5) kPa after onset of ALI to 30.8 (5.0) kPa after 6 h of treatment was greater than in controls (P<0.05 vs controls; Fig. 1, Table 2). In the SURF group Q˙s/Q˙t decreased significantly compared with controls (51 (5)% at onset of ALI to 12 (2)% 6 h after treatment, P<0.05 vs controls; Fig. 2, Table 2). In the SURF‐PLV‐group Q˙s/Q˙t was significantly decreased compared with controls (54 (4)% at onset of ALI to 26 (3)% after 6 h of treatment, P<0.05 vs controls; Fig. 2, Table 2). There were no significant changes between groups in HR, MABP, and SVR. In the SURF‐group the MPAP increased from 25 (1) mm Hg at onset of ALI to 30 (3) mm Hg after 6 h of treatment, and was significantly less than in controls and in the SURF‐PLV‐group (P<0.05 vs controls and vs SURF‐PLV; Fig. 3, Table 1). In the SURF‐group, PVR increased significantly from 266 (49) dyn s cm–5 at onset of ALI to 560 (83) dyn s cm–5 at 6 h of treatment (P<0.05 vs ALI‐values; Table 1). In the SURF‐PLV‐group, PVR increased significantly from 268 (28) to 659 (82) dyn s cm–5 (P<0.05 vs ALI‐values, Table 1). In the SURF‐group and in the SURF‐PLV‐group, CO decreased significantly during the treatment period compared with ALI‐values (P<0.05 vs ALI‐values; Table 1). In controls there were no significant changes in PVR and CO. After induction of ALI, static compliance of the respiratory system decreased from 22 (2) ml cm H2O–1 in all groups to 9 (1) ml cm H2O–1. No further changes of CRS occurred in the SURF‐group. In the SURF‐PLV‐group, CRS improved significantly compared with controls from 9 (1) to 15 (0.4) ml cm H2O–1 at 6 h of treatment (P<0.05 vs controls; Fig. 4, Table 2). The non‐dependent lobes in the SURF‐group had a significantly smaller injury score for interstitial oedema and emphysema compared with controls and the SURF‐PLV‐group (P<0.05, Table 3). In the SURF‐PLV‐