- Email: [email protected]
Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung density distribution: randomized controlled study of experimental lung injury
British Journal of Anaesthesia 94 (5): 671–4 (2005)
doi:10.1093/bja/aei090
Advance Access publication February 18, 2005
RESPIRATION AND THE AIRWAY Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung density distribution: randomized controlled study of experimental lung injury K. P. Kelly1*, B. J. Stenson2 and G. B. Drummond3 1
*Corresponding author. E-mail: [email protected] Background. Perfluorocarbon (PFC) liquid can improve gas exchange in acute lung injury. How PFC aerosol is distributed in the lung is unknown. Methods. We induced lung injury in rabbits with saline lavage, followed by mechanical ventilation in the supine position. The animals were divided into three groups: a control group, a group treated with partial liquid ventilation and a group given nebulized perfluorocarbon (PF 5080). We made CT image slices of the excised lungs. In the apical, middle and caudal slices we defined three regions of interest, from anterior to posterior, and noted the mean attenuation of each area. We also studied two rabbits which had not received lung injury or mechanical ventilation. Results. Group means were different between the normal rabbits and all three study groups. There was a difference between the control and partial liquid ventilation groups, and between the partial liquid ventilation and nebulized groups, but no difference between the nebulized and control groups. Within each treatment group, there was no regional difference in the distribution of density. Conclusions. PF 5080 is not deposited in large amounts by aerosol. Less PFC was found in the lungs after partial liquid ventilation than expected. Within treatment groups, lung densities indicate less gravitational and regional differences than found in other studies. Br J Anaesth 2005; 94: 671–4 Keywords: lung, lavage; measurement techniques, computed tomography; model, rabbit; ventilation, partial liquid, perfluorocarbon Accepted for publication: December 12, 2004
Partial liquid ventilation with perfluorocarbon (PFC) is a promising novel means of respiratory support in acute lung injury (ALI). PFCs are dense and may enter the dependent regions of the lung, distending collapsed lung by acting as ‘liquid PEEP’. CT scanning is used to assess and investigate the lungs in adult respiratory distress syndrome (ARDS),1 but rarely to study the effects and distribution of PFC during liquid ventilation in experimental ARDS.2 In partial liquid ventilation, PFC is usually poured into the airway. Aerosols are used to introduce drugs into the respiratory tract, but PFCs have rarely been given in this way. PFC has been given by jet nebulizer into the endotracheal tube, with promising results.3 Until the present study, CT
had not been used to study nebulized PFC used for treatment of lung injury.
Methods and results We studied 26 young adult female New Zealand white rabbits (10 control rabbits, six treated with PLV and 10 treated with nebulized PFC). Procedures were conducted according to the UK Animal Act (Home Office Project Licence PPL 60/2181). We induced and maintained anaesthesia with urethane, and neuromuscular blockade with pancuronium. We placed a 4 French gauge catheter in a carotid artery and another 4 French gauge catheter in an internal jugular vein,
# The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: [email protected]
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
Department of Anaesthesia, Critical Care and Pain Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. 2Department of Reproductive and Developmental Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, EH16 4HA, UK. 3Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, EH16 4HA, UK
Kelly et al.
(1) Control (10 animals). (2) Partial liquid ventilation (PLV) (six animals). Warmed PFC PF 5080 (3 M Chemicals, Bracknell, Berks, UK), was poured into the endotracheal tube (20 ml kg1, or until a meniscus was seen in the endotracheal tube at the level of the sternum when PEEP was temporarily switched off). Further PF 5080 was added through a side arm of the endotracheal tube so that the meniscus remained at this level, checked intermittently at zero PEEP. (3) ‘Nebulized PFC’ (10 animals). We administered 20 ml kg1 PF 5080 using an ultrasonic nebulizer (Devilbiss Ultra-Neb 2000, Sunrise Medical, UK) set at maximum output (1.63 MHz). We estimated the hourly requirement to be 13 ml kg1 h1 according to the formula used by Salman and colleagues.6 After randomization we ventilated the animals’ lungs with an inspiratory tidal volume of 10 ml kg1 (maximum inspiratory pressure 45 cm H2O) for 15 min before starting treatment. We checked respiratory, cardiovascular and gas exchange values hourly as previously described.4 After 12 h, surviving animals were killed with an overdose of urethane. After death we clamped the lungs at end-expiration whilst maintaining 4 cm H2O PEEP, removed the lungs en bloc, immersed them in liquid nitrogen and stored them at 70 C until CT scanning. For comparison, the lungs of two healthy rabbits which had not received lung injury or mechanical ventilation were also excised, frozen and scanned. We used an IGE Medical Systems Hi-Speed Advantage Rapid Processing CT Scanner (IGE Medical Systems, Milwaukee, USA) with the following settings: 100 kV; 100 mA; pixel size 0.64·0.64 mm; 1 mm slice thickness (thus the voxel size was 0.64·0.64·1 mm); 5 mm gaps; 1 s exposure with a bone algorithm (high resolution) axial acquisition. The lungs were placed in crushed ice and scanned after blinding to treatment group. Three transverse images from cranial to caudal were made for each lung to give an
Caudal slice Middle slice
Posterior zone
Cranial slice
Middle zone Anterior zone
Region of interest from each zone without large airways or vessels
Fig 1 Representation of the ‘image slices’ showing three zones for each slice together with a typical region of interest. Table 1 Summary values of CT densities (Hounsfield units) for the four groups
Minimum Lower quartile Median Upper quartile Maximum
Control (n=81)
PLV (n=54)
Nebulized (n=81)
Normal (n=18)
228 71 57 46 24
80.0 14.5 8 71.50 449
118 65 57 47 55
326 274 201 156.5 103
apical, middle and caudal slice. In each slice we defined an anterior, middle and posterior region of interest (ROI) that consisted of lung parenchyma and did not include large vessels or airways (Fig. 1). The mean attenuation (Hounsfield units [HU]) was calculated for each ROI. We also measured the attenuation of pure PF 5080 with the same CT settings. One control group specimen and one nebulized group specimen were unsuitable for measurement because of fractures. The groups were compared using the Kruskal–Wallis test, with Dunn’s correction for multiple comparison. Withingroup comparisons for each lung area were also made for the three study groups. Suitable samples were obtained from nine control, six PLV, nine nebulized and two normal animals, with CT densities measured in nine fields in each animal. Data are shown in Table 1. There was a highly statistically significant difference in CT densities between control and PLV and between control and normal rabbits (P<0.001). Comparisons between PLV and nebulized groups, and between PLV and normal groups, were also significant (P<0.001). There was a difference between the nebulized and normal groups (P<0.001), but not between the nebulized and control groups. We found no difference in the distribution of densities within groups, in either the craniocaudal or anterioposterior direction, for any of the three study groups.
Discussion As expected, the injured lungs were denser than those from healthy animals. Lung density after nebulized PFC was similar to the lung density in the control group, indicating that nebulization deposited little PFC in the lungs. We have
672
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
using methods reported previously.4 The animals were supine. After tracheostomy, the lungs were ventilated with an inspired oxygen fraction Fio2 of 1.0 and inspiratory duration of 1 s using an SLE 250 paediatric pressurecontrolled time-cycled ventilator (Specialised Laboratory Equipment, Croydon, Surrey, UK). The ventilator was first set with a pressure limit to obtain a tidal volume of 10 ml kg1, measured with a Ventrak 1550 Respiratory Mechanics Monitoring System (Novametrix Medical Systems, Wallingford, CT, USA), a respiratory rate of 30 bpm and 4 cm H2O PEEP. We induced lung injury by repeated lavage with warmed 0.9% saline5 until the arterial oxygen partial pressure (Pao2 ) was <13.3 kPa in two arterial blood samples taken 15 min apart, with a peak inspiratory pressure of 24 cm H2O and 4 cm H2O PEEP.4 Animals were allocated randomly to one of the following treatment groups.
Nebulized perfluorocarbon in acute lung injury
CT number¼Kð½m-mw Þ=mw where K is a constant (usually 1000), m is the linear attenuation coefficient of the sample and mw is the linear attenuation coefficient of water.8 For PF 5080 with a density of 606 and a density of water of 1, the formula yields
Other CT studies of ARDS and PLV found that lung density varied with gravity.10 These studies were of adults with ARDS. We did not find gravity-related differences, but in small animals the weight of the overlying lung is less likely to cause collapse because the thorax is smaller than in larger animals11 or humans. Studies using CT scanning on lung-injured animals receiving PLV have been performed in vivo.2 11 Practical and financial reasons prevented us from scanning the lungs in vivo, and so we froze them in liquid nitrogen and scanned them later. This may introduce an artefact. Freezing caused fissuring of some of the lungs and damaged two specimens so much that they were unsuitable for examination. In summary, lung density in control animals and animals receiving nebulized PF 5080 was similar, and so this appears to be an ineffective method for PFC administration. CT attenuation was greater in animals treated with PLV than in control animals and animals treated with nebulized PFC, but was less than predicted for the alveoli being completely filled with PFC.
Acknowledgements We acknowledge the help of our colleagues in the Department of Clinical Radiology, Royal Infirmary of Edinburgh, for their assistance with the CT imaging. This project was funded by an Intavent Fellowship from the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland. We also thank The Mason Medical Foundation and The Sir Stanley and Lady Davidson Medical Research Fund for additional equipment grants. This work represented part of KPK’s MD thesis.
References
m¼606=1000þ1¼1:6: For a median density of 8, the lung tissue could consist mainly of oedema fluid alone or 37% air and 63% PF 5080. A small amount of material with high attenuation such as PF 5080 would substantially increase the density of the measured tissue. We found values in lungs treated with PLV that were not much greater than those in the untreated lungs, suggesting that either less PFC is present than expected or that more space is occupied by low-attenuation material such as gas or fluid. Studying the effects of PEEP added to PLV, Kaisers and colleagues2 found a combination of PFC with oedema and lavage fluid in the airways. Airway obstruction would prevent PF 5080 from moving into the alveoli. Lung tissue beyond this obstruction would have the radiographic density of collapsed lung (1 HU) rather than that of PF 5080. Another reason why alveoli may not completely fill with PFC is because gas is trapped in them at end-expiration.9 The exact distribution of gas in the alveoli is unclear. The trachea was clamped in end-expiration to maintain PEEP, but the lungs had been filled to functional residual capacity with PF 5080, which may explain some gas trapping.
673
1 Pelosi P, Crotti S, Brazzi L, Gattinoni L. Computed tomography in adult respiratory distress syndrome: what has it taught us? Eur Respir J 1999; 9: 1055–62 2 Kaisers U, Kuhlen R, Sommerer A, Mohnhaupt A, Falke KJ, Rossaint R. Superimposing positive end-expiratory pressure during partial liquid ventilation in experimental lung injury. Eur Respir J 1998; 11: 1035–42 3 Kandler MA, von der Hardt K, Schoof E, Dotsch J, Rascher W. Persistent improvement of gas exchange and lung mechanics by aerosolized perfluorocarbon. Am J Respir Crit Care Med 2001; 164: 31–5 4 Kelly KP, Stenson BJ, Drummond GB. Randomised comparison of partial liquid ventilation, nebulised perfluorocarbon, porcine surfactant, artificial surfactant and combined treatments on oxygenation, lung mechanics, and survival in rabbits after saline lung lavage. Intensive Care Med 2000; 26: 1523–30 5 Lachmann B, Jonson B, Lindroth M, Robertson B. Modes of artificial ventilation in severe respiratory distress syndrome: lung function and morphology in rabbits after wash out of alveolar surfactant. Crit Care Med 1982; 10: 724–32 6 Salman NH, Fuhrman BP, Steinhorn DM, et al. Prolonged studies of perfluorocarbon associated gas exchange and the resumption of conventional mechanical ventilation. Crit Care Med 1995; 23: 919–24 7 Bleyl JU, Ragaller M, Tscho U, et al. Vaporized perfluorocarbon improves oxygenation and pulmonary function in an ovine model of acute respiratory distress syndrome. Anesthesiology 1999; 91: 461–9 8 Mull RT. Mass estimates by computed tomography: physical densities from CT numbers. Am J Radiol 1984; 143: 1101–4
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
shown that nebulized PFC does not affect lung mechanics or gas exchange.4 In contrast, using an intratracheal jet nebulizer to give FC 77 (which has similar physical properties to PF 5080) improved oxygenation substantially in piglets with lavage injury.3 PFC is probably better deposited in the lungs by intratracheal administration. Our continuous-flow ventilator had the nebulizer in the circuit and the inspired gas was a small percentage of the total circuit flow, so that much of the nebulized PFC would not have been in the inspired gas. When PFC vapour was given with a rebreathing circuit, gas exchange was improved.7 The lungs of animals treated with instilled PLV were denser than the lungs of animals in other groups. These animals had a substantial sustained improvement in oxygenation compared with control animals and those given nebulized PFC.4 PFC will increase tissue density, but the increase was less than expected from the density of PF 5080. Radiographic density reflects all the tissue components and is affected by aeration and by interstitial and alveolar fluid, and so we cannot estimate exactly how much PFC was in the lung. The CT density of pure PF 5080 is 606 HU. The radiographic density is determined by both physical density and electron density8 and differs slightly from the physical density which is 1.76 g ml1 for PF 5080. An approximation value of the physical density of a substance can be calculated from the radiographic density values using the following formula:
Kelly et al.
9 Fuhrman BP, Paczan PR, DeFrancis M. Perfluorocarbon associated gas exchange. Crit Care Med 1991; 19: 712–22 10 Meaney JFM, Kazerooni EA, Garver KA, Hirschl RB. Acute respiratory distress syndrome: CT findings during partial liquid ventilation. Radiology 1997; 202: 570–3
11 Quintel M, Hirschl RB, Roth H, Loose R, van Ackern K. Computer tomographic assessment of perfluorocarbon and gas distribution during partial liquid ventilation of acute respiratory failure. Am J Respir Crit Care Med 1998; 158: 249–55
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
674
doi:10.1093/bja/aei090
Advance Access publication February 18, 2005
RESPIRATION AND THE AIRWAY Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung density distribution: randomized controlled study of experimental lung injury K. P. Kelly1*, B. J. Stenson2 and G. B. Drummond3 1
*Corresponding author. E-mail: [email protected] Background. Perfluorocarbon (PFC) liquid can improve gas exchange in acute lung injury. How PFC aerosol is distributed in the lung is unknown. Methods. We induced lung injury in rabbits with saline lavage, followed by mechanical ventilation in the supine position. The animals were divided into three groups: a control group, a group treated with partial liquid ventilation and a group given nebulized perfluorocarbon (PF 5080). We made CT image slices of the excised lungs. In the apical, middle and caudal slices we defined three regions of interest, from anterior to posterior, and noted the mean attenuation of each area. We also studied two rabbits which had not received lung injury or mechanical ventilation. Results. Group means were different between the normal rabbits and all three study groups. There was a difference between the control and partial liquid ventilation groups, and between the partial liquid ventilation and nebulized groups, but no difference between the nebulized and control groups. Within each treatment group, there was no regional difference in the distribution of density. Conclusions. PF 5080 is not deposited in large amounts by aerosol. Less PFC was found in the lungs after partial liquid ventilation than expected. Within treatment groups, lung densities indicate less gravitational and regional differences than found in other studies. Br J Anaesth 2005; 94: 671–4 Keywords: lung, lavage; measurement techniques, computed tomography; model, rabbit; ventilation, partial liquid, perfluorocarbon Accepted for publication: December 12, 2004
Partial liquid ventilation with perfluorocarbon (PFC) is a promising novel means of respiratory support in acute lung injury (ALI). PFCs are dense and may enter the dependent regions of the lung, distending collapsed lung by acting as ‘liquid PEEP’. CT scanning is used to assess and investigate the lungs in adult respiratory distress syndrome (ARDS),1 but rarely to study the effects and distribution of PFC during liquid ventilation in experimental ARDS.2 In partial liquid ventilation, PFC is usually poured into the airway. Aerosols are used to introduce drugs into the respiratory tract, but PFCs have rarely been given in this way. PFC has been given by jet nebulizer into the endotracheal tube, with promising results.3 Until the present study, CT
had not been used to study nebulized PFC used for treatment of lung injury.
Methods and results We studied 26 young adult female New Zealand white rabbits (10 control rabbits, six treated with PLV and 10 treated with nebulized PFC). Procedures were conducted according to the UK Animal Act (Home Office Project Licence PPL 60/2181). We induced and maintained anaesthesia with urethane, and neuromuscular blockade with pancuronium. We placed a 4 French gauge catheter in a carotid artery and another 4 French gauge catheter in an internal jugular vein,
# The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: [email protected]
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
Department of Anaesthesia, Critical Care and Pain Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. 2Department of Reproductive and Developmental Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, EH16 4HA, UK. 3Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, EH16 4HA, UK
Kelly et al.
(1) Control (10 animals). (2) Partial liquid ventilation (PLV) (six animals). Warmed PFC PF 5080 (3 M Chemicals, Bracknell, Berks, UK), was poured into the endotracheal tube (20 ml kg1, or until a meniscus was seen in the endotracheal tube at the level of the sternum when PEEP was temporarily switched off). Further PF 5080 was added through a side arm of the endotracheal tube so that the meniscus remained at this level, checked intermittently at zero PEEP. (3) ‘Nebulized PFC’ (10 animals). We administered 20 ml kg1 PF 5080 using an ultrasonic nebulizer (Devilbiss Ultra-Neb 2000, Sunrise Medical, UK) set at maximum output (1.63 MHz). We estimated the hourly requirement to be 13 ml kg1 h1 according to the formula used by Salman and colleagues.6 After randomization we ventilated the animals’ lungs with an inspiratory tidal volume of 10 ml kg1 (maximum inspiratory pressure 45 cm H2O) for 15 min before starting treatment. We checked respiratory, cardiovascular and gas exchange values hourly as previously described.4 After 12 h, surviving animals were killed with an overdose of urethane. After death we clamped the lungs at end-expiration whilst maintaining 4 cm H2O PEEP, removed the lungs en bloc, immersed them in liquid nitrogen and stored them at 70 C until CT scanning. For comparison, the lungs of two healthy rabbits which had not received lung injury or mechanical ventilation were also excised, frozen and scanned. We used an IGE Medical Systems Hi-Speed Advantage Rapid Processing CT Scanner (IGE Medical Systems, Milwaukee, USA) with the following settings: 100 kV; 100 mA; pixel size 0.64·0.64 mm; 1 mm slice thickness (thus the voxel size was 0.64·0.64·1 mm); 5 mm gaps; 1 s exposure with a bone algorithm (high resolution) axial acquisition. The lungs were placed in crushed ice and scanned after blinding to treatment group. Three transverse images from cranial to caudal were made for each lung to give an
Caudal slice Middle slice
Posterior zone
Cranial slice
Middle zone Anterior zone
Region of interest from each zone without large airways or vessels
Fig 1 Representation of the ‘image slices’ showing three zones for each slice together with a typical region of interest. Table 1 Summary values of CT densities (Hounsfield units) for the four groups
Minimum Lower quartile Median Upper quartile Maximum
Control (n=81)
PLV (n=54)
Nebulized (n=81)
Normal (n=18)
228 71 57 46 24
80.0 14.5 8 71.50 449
118 65 57 47 55
326 274 201 156.5 103
apical, middle and caudal slice. In each slice we defined an anterior, middle and posterior region of interest (ROI) that consisted of lung parenchyma and did not include large vessels or airways (Fig. 1). The mean attenuation (Hounsfield units [HU]) was calculated for each ROI. We also measured the attenuation of pure PF 5080 with the same CT settings. One control group specimen and one nebulized group specimen were unsuitable for measurement because of fractures. The groups were compared using the Kruskal–Wallis test, with Dunn’s correction for multiple comparison. Withingroup comparisons for each lung area were also made for the three study groups. Suitable samples were obtained from nine control, six PLV, nine nebulized and two normal animals, with CT densities measured in nine fields in each animal. Data are shown in Table 1. There was a highly statistically significant difference in CT densities between control and PLV and between control and normal rabbits (P<0.001). Comparisons between PLV and nebulized groups, and between PLV and normal groups, were also significant (P<0.001). There was a difference between the nebulized and normal groups (P<0.001), but not between the nebulized and control groups. We found no difference in the distribution of densities within groups, in either the craniocaudal or anterioposterior direction, for any of the three study groups.
Discussion As expected, the injured lungs were denser than those from healthy animals. Lung density after nebulized PFC was similar to the lung density in the control group, indicating that nebulization deposited little PFC in the lungs. We have
672
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
using methods reported previously.4 The animals were supine. After tracheostomy, the lungs were ventilated with an inspired oxygen fraction Fio2 of 1.0 and inspiratory duration of 1 s using an SLE 250 paediatric pressurecontrolled time-cycled ventilator (Specialised Laboratory Equipment, Croydon, Surrey, UK). The ventilator was first set with a pressure limit to obtain a tidal volume of 10 ml kg1, measured with a Ventrak 1550 Respiratory Mechanics Monitoring System (Novametrix Medical Systems, Wallingford, CT, USA), a respiratory rate of 30 bpm and 4 cm H2O PEEP. We induced lung injury by repeated lavage with warmed 0.9% saline5 until the arterial oxygen partial pressure (Pao2 ) was <13.3 kPa in two arterial blood samples taken 15 min apart, with a peak inspiratory pressure of 24 cm H2O and 4 cm H2O PEEP.4 Animals were allocated randomly to one of the following treatment groups.
Nebulized perfluorocarbon in acute lung injury
CT number¼Kð½m-mw Þ=mw where K is a constant (usually 1000), m is the linear attenuation coefficient of the sample and mw is the linear attenuation coefficient of water.8 For PF 5080 with a density of 606 and a density of water of 1, the formula yields
Other CT studies of ARDS and PLV found that lung density varied with gravity.10 These studies were of adults with ARDS. We did not find gravity-related differences, but in small animals the weight of the overlying lung is less likely to cause collapse because the thorax is smaller than in larger animals11 or humans. Studies using CT scanning on lung-injured animals receiving PLV have been performed in vivo.2 11 Practical and financial reasons prevented us from scanning the lungs in vivo, and so we froze them in liquid nitrogen and scanned them later. This may introduce an artefact. Freezing caused fissuring of some of the lungs and damaged two specimens so much that they were unsuitable for examination. In summary, lung density in control animals and animals receiving nebulized PF 5080 was similar, and so this appears to be an ineffective method for PFC administration. CT attenuation was greater in animals treated with PLV than in control animals and animals treated with nebulized PFC, but was less than predicted for the alveoli being completely filled with PFC.
Acknowledgements We acknowledge the help of our colleagues in the Department of Clinical Radiology, Royal Infirmary of Edinburgh, for their assistance with the CT imaging. This project was funded by an Intavent Fellowship from the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland. We also thank The Mason Medical Foundation and The Sir Stanley and Lady Davidson Medical Research Fund for additional equipment grants. This work represented part of KPK’s MD thesis.
References
m¼606=1000þ1¼1:6: For a median density of 8, the lung tissue could consist mainly of oedema fluid alone or 37% air and 63% PF 5080. A small amount of material with high attenuation such as PF 5080 would substantially increase the density of the measured tissue. We found values in lungs treated with PLV that were not much greater than those in the untreated lungs, suggesting that either less PFC is present than expected or that more space is occupied by low-attenuation material such as gas or fluid. Studying the effects of PEEP added to PLV, Kaisers and colleagues2 found a combination of PFC with oedema and lavage fluid in the airways. Airway obstruction would prevent PF 5080 from moving into the alveoli. Lung tissue beyond this obstruction would have the radiographic density of collapsed lung (1 HU) rather than that of PF 5080. Another reason why alveoli may not completely fill with PFC is because gas is trapped in them at end-expiration.9 The exact distribution of gas in the alveoli is unclear. The trachea was clamped in end-expiration to maintain PEEP, but the lungs had been filled to functional residual capacity with PF 5080, which may explain some gas trapping.
673
1 Pelosi P, Crotti S, Brazzi L, Gattinoni L. Computed tomography in adult respiratory distress syndrome: what has it taught us? Eur Respir J 1999; 9: 1055–62 2 Kaisers U, Kuhlen R, Sommerer A, Mohnhaupt A, Falke KJ, Rossaint R. Superimposing positive end-expiratory pressure during partial liquid ventilation in experimental lung injury. Eur Respir J 1998; 11: 1035–42 3 Kandler MA, von der Hardt K, Schoof E, Dotsch J, Rascher W. Persistent improvement of gas exchange and lung mechanics by aerosolized perfluorocarbon. Am J Respir Crit Care Med 2001; 164: 31–5 4 Kelly KP, Stenson BJ, Drummond GB. Randomised comparison of partial liquid ventilation, nebulised perfluorocarbon, porcine surfactant, artificial surfactant and combined treatments on oxygenation, lung mechanics, and survival in rabbits after saline lung lavage. Intensive Care Med 2000; 26: 1523–30 5 Lachmann B, Jonson B, Lindroth M, Robertson B. Modes of artificial ventilation in severe respiratory distress syndrome: lung function and morphology in rabbits after wash out of alveolar surfactant. Crit Care Med 1982; 10: 724–32 6 Salman NH, Fuhrman BP, Steinhorn DM, et al. Prolonged studies of perfluorocarbon associated gas exchange and the resumption of conventional mechanical ventilation. Crit Care Med 1995; 23: 919–24 7 Bleyl JU, Ragaller M, Tscho U, et al. Vaporized perfluorocarbon improves oxygenation and pulmonary function in an ovine model of acute respiratory distress syndrome. Anesthesiology 1999; 91: 461–9 8 Mull RT. Mass estimates by computed tomography: physical densities from CT numbers. Am J Radiol 1984; 143: 1101–4
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
shown that nebulized PFC does not affect lung mechanics or gas exchange.4 In contrast, using an intratracheal jet nebulizer to give FC 77 (which has similar physical properties to PF 5080) improved oxygenation substantially in piglets with lavage injury.3 PFC is probably better deposited in the lungs by intratracheal administration. Our continuous-flow ventilator had the nebulizer in the circuit and the inspired gas was a small percentage of the total circuit flow, so that much of the nebulized PFC would not have been in the inspired gas. When PFC vapour was given with a rebreathing circuit, gas exchange was improved.7 The lungs of animals treated with instilled PLV were denser than the lungs of animals in other groups. These animals had a substantial sustained improvement in oxygenation compared with control animals and those given nebulized PFC.4 PFC will increase tissue density, but the increase was less than expected from the density of PF 5080. Radiographic density reflects all the tissue components and is affected by aeration and by interstitial and alveolar fluid, and so we cannot estimate exactly how much PFC was in the lung. The CT density of pure PF 5080 is 606 HU. The radiographic density is determined by both physical density and electron density8 and differs slightly from the physical density which is 1.76 g ml1 for PF 5080. An approximation value of the physical density of a substance can be calculated from the radiographic density values using the following formula:
Kelly et al.
9 Fuhrman BP, Paczan PR, DeFrancis M. Perfluorocarbon associated gas exchange. Crit Care Med 1991; 19: 712–22 10 Meaney JFM, Kazerooni EA, Garver KA, Hirschl RB. Acute respiratory distress syndrome: CT findings during partial liquid ventilation. Radiology 1997; 202: 570–3
11 Quintel M, Hirschl RB, Roth H, Loose R, van Ackern K. Computer tomographic assessment of perfluorocarbon and gas distribution during partial liquid ventilation of acute respiratory failure. Am J Respir Crit Care Med 1998; 158: 249–55
Downloaded from http://bja.oxfordjournals.org/ at University of Strathclyde on March 19, 2015
674