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Anesth Analg 2004;98:782-789
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000096261.89531.90

CRITICAL CARE AND TRAUMA

Functional Residual Capacity and Respiratory Mechanics as Indicators of Aeration and Collapse in Experimental Lung Injury

Christian Rylander, MD*,{dagger}, Marieann Högman, PhD{ddagger}, Gaetano Perchiazzi, MD{dagger},§, Anders Magnusson, PhD||, and Göran Hedenstierna, PhD{dagger}

*Department of Anesthesia, Sahlgrenska University Hospital, Gothenburg, Sweden, the {dagger}Department of Medical Sciences, Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden, the {ddagger}Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, Sweden, the §Department of Emergency and Transplantation, Bari University Hospital, Bari, Italy, and the ||Department of Radiology, Uppsala University Hospital, Uppsala, Sweden

Address correspondence and reprint requests to Göran Hedenstierna, MD, PhD, Department of Medical Sciences, Clinical Physiology, Uppsala University Hospital, S-751 85 Uppsala, Sweden. Address email to goran.hedenstierna{at}thorax.uas.lul.se


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Increased functional residual capacity (FRC) and compliance are two desirable, but seldom measured, effects of positive end-expiratory pressure (PEEP) in mechanically ventilated patients. To assess how these variables reflect the morphological lung perturbations during the evolution of acute lung injury and the morphological changes from altered PEEP, we correlated measurements of FRC and respiratory system mechanics to the degree of lung aeration and consolidation on computed tomography (CT). We used a porcine oleic acid model with FRC determinations by sulfur hexafluoride washin-washout and respiratory system mechanics measured during an inspiratory hold maneuver. Within the first hour, during constant volume-controlled ventilation with PEEP 5 cm H2O, FRC decreased by 45% ± 15% (P = 0.005) and compliance decreased by 35% ± 12% (P = 0.005). Resistance increased by 60% ± 62% (P = 0.005). Only the FRC changes correlated significantly to the decreased aeration (R2 = 0.56; P = 0.01) and the increased consolidation (R2 = 0.43; P = 0.04) on CT. When the PEEP was changed to either 10 or 0 cm H2O, there were larger changes in FRC than in compliance. We conclude that, in our model, FRC was a more sensitive indicator of PEEP-induced aeration and recruitment of lung tissue and that FRC may be a useful adjunct to PaO2 monitoring.

IMPLICATIONS: Lung injury was quantified on computed tomography and related to monitored values of functional residual capacity and mechanical properties of the respiratory system. We found the functional residual capacity to be a more sensitive marker of the lung perturbations than the compliance. It might be of value to include functional residual capacity in the monitoring of acute lung injury.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Lung collapse and consolidation are morphological hallmarks of the acute respiratory distress syndrome (ARDS). The lung tissue collapse causes shunting of blood with hypoxemia (1), and the arterial oxygen tension (PaO2) is a commonly used variable for monitoring of the degree of lung injury in ARDS patients. The morphology of the lung changes has been extensively described in both experimental and clinical studies using computed tomography (CT) (2). In clinical CT studies, functional residual capacity (FRC) (3) and static lung compliance (4) have each been found to be directly correlated to the lung perturbations seen on CT in late ARDS. However, the value of these physiological variables for the detection of an evolving acute lung injury has not been established. The main purpose of this study was to assess to what extent "bedside" measurements of FRC and respiratory system mechanics detect the changes in aerated and consolidated lung volumes as assessed by CT (5). Considering that the early phase of ARDS is characterized by edema formation rather than fibrosis (6), it is possible that a reduction of air space volume occurs before a deterioration of the mechanical properties of the lung. It was thus hypothesized that a reduction in FRC is a more sensitive indicator of the airway collapse and lung consolidation in evolving lung injury than changes in respiratory system compliance (CRS) or resistance (RRS) and that the morphological effects induced by a positive end-expiratory pressure (PEEP) change are more closely reflected by FRC than by lung mechanics changes. These hypotheses were tested in a porcine oleic acid (OA) model of the early, exudative phase of ARDS, in which FRC was determined using an open circuit multiple breath washin-washout method and respiratory system mechanics were measured during an inspiratory hold maneuver.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The experimental protocol (Fig. 1) was approved by the local animal ethics committee and the study was performed according to the National Research Council guide for "Principles of laboratory animal care." All procedures were performed in the supine position. Ten healthy pigs of mixed gender (mean weight, 30.7 kg; range, 25–41 kg) were fasted with free access to water overnight before they were premedicated with an IM dose of azaperonum (40 mg, Stresnil; Janssen, Vienna, Austria). General anesthesia was induced by injections of atropine (0.04 mg/kg), tiletamin-zolazepam (5 mg/kg, Zoletil; Boeringer Ingelheim, Copenhagen, Denmark) and medetomin (5 µg/kg, Dormitor vet; Orion Pharma, Sollentuna, Sweden) IM in the neck. Fentanyl (5 µg/kg) was given IV after peripheral venous cannulation, and the trachea was intubated with a cuffed tube (6.0 Hi-Contour; Mallinckrodt Medical, Athlone, Ireland). Anesthesia was maintained by IV infusion of ketamine (20 mg · kg-1 · h-1, Ketaminol; Vetpharma, Zurich, Switzerland), fentanyl (5 µg · kg-1 · h-1, Pharmalink, Spånga, Sweden) and pancuronium (0.24 mg · kg-1 · h-1, Pavulon; Organon Teknika, Gothenburg, Sweden) in buffered glucose 2.5% (Rehydrex; Fresenius Kabi, Uppsala, Sweden) at a volume rate of 7 mL · kg-1 · h-1. For blood pressure recording, an 18-gauge, 20-cm catheter was inserted into the right carotid artery. A floating tip pulmonary artery (PA) catheter (Swan-Ganz thermodilution SP5107H, 7F, 110 cm; Baxter, Irvine, CA) was introduced into the right internal jugular vein. Its proper positioning was guided by pressure recordings and later confirmed on the CT topogram. Another 18-gauge catheter was placed in the internal jugular vein for injections and blood sampling. The bladder was exposed through an incision in the left groin, and a rubber catheter was inserted via a cystostomy and fixed with sutures. Core temperature was monitored by the PA catheter thermistor and maintained in the normal range by means of heating blankets.



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  		Figure 1. Experimental protocol. After baseline registrations (T0) and the first computed tomography (CT) scan, oleic acid injury was induced. Measurements of hemodynamics, respiratory mechanics (Mech.), and functional residual capacity (FRC) were performed in repeated cycles every 15 min (T15, T30, T45, T60) during the first hour with positive end-expiratory pressure (PEEP) at 5 cm H2O (10 animals). After a CT scan (T60), PEEP was either increased to 10 cm H2O (5 animals) or reduced to 0 cm H2O (5 animals) in randomized order. Next set of measurements and CT exposure were performed 30 min later (T90). PEEP was then set to 5 cm H2O again, and a final series of data was obtained after another 30 min (T120), then the protocol was ended 2 h after the first oleic acid injection.

 
A Servo 900 C ventilator (Siemens-Elema AB, Solna, Sweden) was used with the following settings fixed during the experiment: constant flow, volume-controlled mode, inspiratory/expiratory ratio 1:2 without inspiratory pause, respiratory rate 20 breaths/min, and inspiratory oxygen fraction (FIO2) 0.50. Tidal volume (VT) was initially set to 15 mL/kg at the induction of anesthesia and then fixed to a level giving a stable baseline of end-tidal CO2 (AS/3; Datex-Ohmeda, Helsinki, Finland) between 35 and 45 mm Hg. Sixty minutes after the completion of surgery, the animals were transported to the CT lab. A baseline registration was made at time zero (T0) during MV with PEEP 5 cm H2O. Lung injury was then induced by slow injection of 0.1 mL/kg OA (Apoteksbolaget, Gothenburg, Sweden) into a rapid flow of high-pressure driven fluid into the central venous catheter. Hypotension was counteracted by titrated IV adrenaline. Measurements of hemodynamics, respiratory mechanics, and FRC were performed in repeated cycles every 15 min (ending at T15, T30, T45, and T60) during the first hour of lung injury, after which another CT scan was taken (T60). PEEP was then either increased to 10 or reduced to 0 cm H2O (ZEEP) in randomized order. The next CT exposure was made 30 min after the PEEP change (T90). Then, the PEEP was again set to 5 cm H2O again and a final series of data was obtained 30 min later, 2 h after the first oleic acid injection (T120). After the experiment, the lungs were excised and inspected for the extent and distribution of macroscopic injury. Representative 2 x 2 cm samples of affected tissue from the middle and lower lobes were weighed before and after being dried completely in a heating box at 50°C. Their wet/dry weight ratio was used as an arbitrary measure of the degree of edema (7).

Using a Somatom Plus 4 (Siemens, Erlangen, Germany), the lung injury was quantified as decreased aeration and increased collapse/consolidation of the lung parenchyma. All scans were taken in expiratory hold lasting 20 s without ventilator circuit disconnection. Initial topograms defined the limits of the lungs for helical exposures from the apex to the base including the dorsal sinuses. Scanning parameters were 120 Kv and 180 mA, rotation time 0.75 s, collimation 5 mm, pitch 1.5, and the procedure lasted approximately 20 s. Images were reconstructed with a 512 x 512 matrix and an increment of 5 mm, yielding 38–44 slices covering the entire lung, depending on its dimensions. Within each slice, the lateral, frontal, and dorsal limits of the lungs including the mediastinum were manually traced, excluding abdominal structures in caudal slices. The accumulated areas of all pixels within specified attenuation intervals were automatically calculated by the software provided with the CT scanner (Sienet Magic View, version VA 30A; Siemens, Erlangen, Germany) and the volume of voxels within the slice was obtained by multiplying with its thickness. For the quantification of aerated tissue, we used the attenuation interval from -1000 to -100 Hounsfield units (HU) (CTAER), which includes well-aerated and poorly aerated tissue according to Gattinoni et al. (1). For calculation of the volume of collapsed/consolidated tissue (in the following called consolidated tissue for simplicity), we used the -100 to +100 HU interval (CTCONS) (1,8).

Blood pressures were recorded with reference to atmospheric pressure at midthoracic level. Cardiac output (CO) was determined by standard thermodilution, using the mean of triplicate injections of 10 mL iced saline. Arterial and mixed venous blood gas samples were analyzed at 37°C on an instrument with the dissociation curve adjusted for pig blood (ABL 300; Radiometer, Copenhagen, Denmark). Oxyhemoglobin saturation (SaO2) was monitored by infrared spectrometry (AS/3, Datex-Ohmeda). RRS and CRS of the total respiratory system were determined during an inspiratory hold maneuver using a differential pressure transducer (Sensym, SensorTechnics, Pucheim, Germany). The transducer had been calibrated for flow and static pressure at the beginning of each experimental session using a constant flow through a serially connected precision flowmeter (Calibration Analyzer TS4121/P; Timeter Instrument Corporation, St. Louis, MO) and a water column, respectively. Airway peak pressure (PawPeak) and plateau pressures (P1, just after the inspiratory flow was stopped; P2, after 2 s of inspiratory hold) were obtained during a rapid occlusion of a constant-flow inflation (9) with correction for the closing time of the ventilator valves (10). RRS was defined as the decrease in pressure between PawPeak and P1, divided by the instantaneous flow (VI) at peak airway pressure: RRS = (PawPeak - P1)/V. CRS was calculated as VT divided by the difference between P2 and end-expiratory airway pressure (PawExp): CRS = VT/(P2 - PawExp). FRC was measured from multiple breath washin/washout of sulfur hexafluoride (SF6): FRC = 1.09 x VSF6/CSF6 - VAPP, where VSF6 is the total amount of SF6 washed out, CSF6 is the alveolar concentration of SF6 at the end of washin, VAPP is the dead space of the system, and 1.09 is a conversion factor to body temperature and pressure saturated conditions (11,12). The tracer gas was added to the inspiratory flow until a steady-state expiratory concentration of 0.5% SF6 was established. Washout SF6 concentrations were analyzed by a quadrupole mass spectrometer (M-100 lab gas analyzer system; Marquette, Milwaukee, WI), which was calibrated to a known concentration of SF6 in a precision calibration gas before the experiment and to zero reference before each measurement. Raw signals were stored on a personal computer, where calculations of respiratory mechanics and FRC were performed in a purposely written program (C-O Sjöberg Engineering AB, Upplands-Väsby, Sweden) in the LabView system (Lab View 4.0.1; National Instruments, Austin, TX). The reproducibility, expressed as the mean coefficient of variation of paired measurements, was 5.0% for RRS, 1.6% for CRS, and 3.0% for FRC. The means of duplicate measurements were used for statistical evaluation.

Data are presented as means ± SD, and P < 0.05 was chosen as the level of significance. Repeated measures within groups were tested with Friedman’s analysis of variance, and if significant differences were detected, Wilcoxon’s signed-rank test was applied. For calculation of linear regression and correlation, the least square method and the product moment correlation were used, respectively. The residuals were checked for normal distribution in each analysis. The differences between the ß coefficients of two regression equations with the same independent variable were tested using a two-sided Student’s t-test. The coefficient of variation (CV) for paired measurements was calculated as the error standard deviation divided by the mean (13). Calculations were performed with Statistica 5.5 A (StatSoft Inc, Tulsa, OK) on a personal computer.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Evolution of Lung Injury
On OA exposure, the animals were hemodynamically stable except for increasing arterial pressure, pulmonary artery pressure, and CO. A gradual effect on gas exchange appeared during the first hour. There was a progressive and uniform decrease of FRC, CRS, and RRS present in all animals at the time of the first measurement after 15 min. Data are shown in Table 1. Compared with baseline, FRC decreased by 45% ± 15% (P = 0.005) and CRS decreased by 35% ± 12% (P = 0.005) during the first hour (Fig. 2). RRS increased by 60% ± 62% (P = 0.005). CTAER decreased by 25% ± 12% from 33.9 ± 4.1 mL/kg at T0 to 25.6 ± 6.0 mL/kg at T60. CTCONS increased by 57% ± 23% from 19.3 ± 2.1 mL/kg to 30.3 ± 5.3 mL/kg. The decreased FRC correlated significantly to the decrease in CTAER (P = 0.01) and to the decrease in CTCONS (P = 0.04), but the decreased CRS did not clearly correlate to the CT changes (Fig. 3). The RRS changes did not correlate to the CT changes at all (CTAER; R2 = 0.04 and CTCONS; R2 = 0.04). The decrease in oxygenation correlated to increased consolidation ({Delta}PaO2 [%] = -0.55 ± 0.10 x {Delta}CTCONS [%] -31 ± 6.2) (R2 = 0.78; P = 0.0007) but not to the decreased aeration (R2 = 0.30). Thus, the decrease in FRC well detected the loss of aeration, and the decrease in PaO2 well detected the increased consolidation on CT.


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  		Table 1. FRC, Respiratory Mechanics, and Cardiorespiratory Variables During the Evolution of Lung Injury with Constant Ventilation and Positive End-Expiratory Pressure 5 cm H2O
 


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  		Figure 2. Proportional changes of functional residual capacity (FRC) and compliance (CRS) in all 10 animals during the first hour of lung injury on constant ventilation with positive end-expiratory pressure 5 cm H2O. Means and SD are displayed. *Significant (P < 0.05) change at T60 compared with baseline T0.

 


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  		Figure 3. Functional residual capacity (FRC) and compliance (CRS) changes in all 10 animals correlated to changes in volume of aerated (CT aeration) and consolidated tissue (CT consolidation) during the first hour of oleic acid injury with constant positive end-expiratory pressure of 5 cm H2O. *Significant (P < 0.05) correlation.

 
Effect of the PEEP Intervention
While still on PEEP 5 cm H2O at T60, there were no significant differences in study variables between the two groups obtained after randomization to PEEP of either 10 or 0 cm H2O for 30 min. Data appear in Tables 2 and 3. Application of PEEP 10 cm H2O increased FRC by 64% ± 21% (P = 0.043), whereas the CRS and RRS were not significantly altered (Fig. 4). CTAER increased by 57% ± 28% (P = 0.043), from 23.4 ± 6.3 mL/kg at T60 to 35.6 ± 4.2 mL/kg at T90, and CTCONS decreased by 13% ± 12% (P = 0.043), from 31.1 ± 5.5 mL/kg to 26.9 ± 5.0 mL/kg. Application of ZEEP in the other 5 animals induced opposite changes. FRC decreased by 26% ± 19% (P = 0.043) and CRS decreased by 19% ± 3.8% (P = 0.043) (Fig. 4). RRS did not change. CTAER decreased by 34% ± 15% (P = 0.043), from 27.8 ± 5.5 mL/kg to 18.7 ± 7.5 mL/kg, and CTCONS increased by 19% ± 6.9% (P = 0.043), from 29.5 ± 5.6 mL/kg to 34.8 ± 5.4 mL/kg. Reinstitution of PEEP 5 cm H2O returned hemodynamic and respiratory variables, as well as respiratory mechanics and FRC, in all animals to levels similar to those preceding the intervention. At T120, CTAER was 24.5 ± 5.3 mL/kg and CTCONS was 32.4 ± 5.8 mL/kg.


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  		Table 2. FRC, Respiratory Mechanics, and Cardiorespiratory Variables When Positive End-Expiratory Pressure was Changed From 5 to 10 cm H2O for 30 Minutes
 

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  		Table 3. FRC, Respiratory Mechanics, and Cardiorespiratory Variables When Positive End-Expiratory Pressure was Changed From 5 to 0 cm H2O for 30 Minutes
 


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  		Figure 4. Proportional changes of functional residual capacity (FRC) and compliance (CRS) in the two groups of five animals during the intervention where positive end-expiratory pressure (PEEP) was changed from 5 cm H2O to 10 cm H2O or 0 cm H2O (ZEEP) between T60 and T90, then set back to 5 cm H2O between T90 and T120. Means and SD are displayed. *Significant (P < 0.05) change at T90 compared with T60.

 
A correlation analysis on pooled data from the PEEP:10 group and the ZEEP group showed that both the FRC changes (R2 = 0.93; P = 0.000006) and the CRS changes (R2 = 0.77; P = 0.0008) correlated positively to increased CTAER. The FRC (R2 = 0.87; P = 0.00007) and the CRS (R2 = 0.73; P = 0.002) changes correlated negatively to increased CTCONS. The ß regression constant was significantly higher (P < 0.001) for FRC than for CRS when CTAER was used as predictor. When CTCONS was used as predictor, the negative ß regression constant was significantly lower (P < 0.01) for FRC than for CRS (Fig. 5). PaO2 increased with increased PEEP and it decreased when ZEEP was instituted. These PaO2 changes correlated positively to CTAER ({Delta}PaO2 [%] = 0.74 ± 0.13 x {Delta}CTAER [%] -9.6 ± 6.6) (R2 = 0.80; P = 0.0004) and negatively to CTCONS ({Delta}PaO2 [%] = -2.1 ± 0.34 x {Delta}CTCONS [%] 4.8 ± 6.2) (R2 = 0.82; P = 0.0003).



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  		Figure 5. Functional residual capacity (FRC) and compliance (CRS) changes in all ten animals correlated to changes in volume of aerated (CT aeration) and consolidated tissue (CT consolidation) during the intervention where positive end-expiratory pressure was changed from 5 cm H2O to 10 cm H2O or 0 cm H2O. *Significant (P < 0.05) correlation.

 
At ex vivo inspection, the lung lobes showed a typical pattern of more injury to the dorsal parts in all pigs. The lobes were equally affected with no difference between the wet to dry ratios of the excised samples. The ratios were 3.8 ± 0.7 (Mid right), 3.8 ± 0.7 (Mid left), 3.8 ± 1.1 (Lower right), and 3.6 ± 1.2 (Lower left).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Our intention was to assess the capacity of FRC and respiratory mechanics measurements in predicting morphological lung tissue changes in acute lung injury. During one hour of constant, volume-controlled ventilation with PEEP 5 cm H2O, we found that decreased FRC and compliance equally well reflected the evolution of OA injury without any temporal or magnitude difference. The binding of OA to capillary cell membranes causes cell death, resulting in lesions with hemorrhagic edema and diffuse alveolar damage (14). There is a well-known deterioration of compliance (15) and an expected loss of end-expiratory air space (16) in such an edematous lung. Having combined measurements of both phenomena, we can conclude that there is no temporal difference in their appearance. However, only FRC was found weakly correlated to the changes in aeration and consolidation during the first hour of lung injury, whereas compliance was not.

These findings were paralleled by a decrease in arterial oxygenation during the initial course of the lung injury. The strongest correlation to the consolidation process was found for PaO2, compatible with the presence of shunt. Then, when PEEP was changed, FRC was more sensitive than compliance to the morphological effects seen on CT, which indicates a potential use for FRC measurements when mechanical ventilation is titrated for better lung aeration. However, it should be noted that when PEEP was increased and recruitment was induced both by increasing aeration and decreasing consolidation, a positive PaO2 effect was linked to both CT variables. The decrease in oxygenation under ZEEP conditions was well correlated to the loss of aeration and increased consolidation. Thus, our results also indirectly support the traditional use of PaO2 as a simple monitoring variable of progressing acute lung injury and PEEP effects.

We chose the OA injury because it has been extensively studied and used to represent the early, exudative phase of ARDS in several species (14). Lung injury evolves progressively, and most investigators allow a period of stabilization before their experimental interventions. Sum-Ping et al. (17) reported no further deterioration of cardiopulmonary variables after 30 minutes in a porcine model, and we allowed 60 minutes before the PEEP intervention. As we investigated intraindividual changes during a controlled manipulation, we did not use any control group. The different measurement principles of the study methods influenced the design of the experiment, in which hemodynamic and respiratory data had to be linked to variables calculated from a subsequent CT scan in expiratory hold. The reproducibility of the FRC and lung mechanics measurements was well within limits of the recommendations for even better controlled conditions (13).

For FRC determination in mechanically ventilated patients, a number of methods have been reported, all based on tracer gas dilution. Nitrogen breath-by-breath washout with 100% oxygen generally carries a limited accuracy when the FIO2 is more than 0.6 (18), and a continuous correction for the dynamic gas viscosity changes during washout is needed (19). Helium rebreathing in a closed circuit with a CO2 absorber and compensation for O2 consumption is a slower procedure than open-circuit dilution (20), and both are sensible to small leaks because of the high diffusivity of this gas. Open circuit multiple breath washin-washout of SF6 can be performed during mechanical ventilation and has been proven precise (11,12). This study did not compare these different methods of FRC determination, but the choice of SF6 carries the advantage of a very small inert gas concentration (<1%), leaving the inspired oxygen concentration almost unaffected during the recording of FRC.

For compliance measurements, we chose the two-point technique because of its simplicity and bedside readiness. It has been shown to agree with static lung compliance measurements if a low inspiratory flow is used (21), and when tested as a tool for "best" PEEP adjustment in patients, it has been found comparable to the static pressure-volume (P-V) curve (22). However, compliance may not be linear within the tidal breath, as found in a lavage model (23), and different relations between altered inspiratory airway pressure and the resulting recruitment of lung tissue have been demonstrated in different animal models (24–26). This illustrates the difficulties in experimental research when simulating disease conditions in human patients, and our results must be interpreted cautiously.

The CT technique has become a reference tool for the evaluation of aeration and collapse of the lung parenchyma (27), but it is not suitable for bedside monitoring. The use of attenuation of electromagnetic radiation, measured on the Hounsfield scale, is accurate for volume determination of homogenous tissue, well delineated from surrounding structures (28). As used in this study with heterogeneously injured lungs, the volume of voxels within a chosen HU interval does not correspond to anatomically defined lung regions, but rather to scattered tissue with similar density. The term "consolidation" was used for the dynamic and potentially reversible density that might be caused by collapse, flooding, or both. The CT technique cannot separate fluid-filled terminal airways from collapsed and empty alveoli or fibrotic, physically stiff lung tissue. The assumption of the consolidations being dynamic had thus to be made out of the properties of the lung injury model, where fibrosis is not expected at such an early point. This also implies a likelihood that some of the tissue that was found devoid of gas at end-expiration became aerated during inspiration and participated in the gas exchange. This recruitment, which is by definition an inspiratory process, was not measured in this study, in which FRC and mechanics measurements were correlated to the morphology at end-expiration. Another consideration is that the amount of density detected by CT is influenced by the thoracic fluid content, whether in the vessels as blood or in the alveoli as edema, which in turn is related to the hemodynamic situation. This is an inherent problem in CT studies where the airway pressure is manipulated and it was the reason why the PEEP change was limited in the present protocol (29).

Although no evidence exists for its prophylactic effect against the development of ARDS (30), early PEEP adjusted to blood gases remains common practice to support oxygenation and the mechanical properties of the failing lung. As recruitment of collapsed tissue is an inspiratory process, clinical management also includes inflation maneuvers with large VT to be combined with simultaneous increase of the PEEP (31). The point of using surrogate variables for the end-expiratory consolidation is to use them as markers of the initial edema formation and of the response to a clinically relevant increase of PEEP (32), which is commonly set to 5 cm H2O in clinical practice (33). Our finding, that the early consolidation of lung tissue was better correlated to FRC changes than to compliance changes during constant PEEP, indicate a relevance of FRC as a straightforward monitoring variable in early acute lung injury. We found this true for the comparison between compliance and FRC, but with deteriorating mechanical properties, we also saw a simultaneous decrease in PaO2 that remains a simple marker of collapse/consolidation and shunt. For further titration of PEEP, the use of advanced respiratory mechanics measurements might be of value, but although sophisticated methods to obtain these are emerging (21,34,35), esophageal balloon data for the calculation of lung compliance are seldom available and they are difficult to interpret. In addition, the detection of an optimal compliance interval on the dynamic P-V curve remains an indirect estimate of the underlying increase of aerated lung volume (4).

In conclusion, FRC reflected the loss of aeration during the evolution of lung injury, and it was a better indicator than compliance of the recruitment and derecruitment caused by the PEEP manipulations in this study. Arterial oxygenation best reflected the progressive consolidation in the evolving lung injury and well detected the effects induced by changed PEEP. An easily available bedside FRC method might thus be of clinical value as a complement to PaO2 when judging acute lung injury in progress and the effects of PEEP changes.


   Acknowledgments
 
Supported, in part, by grants from Swedish Medical Research Council (no 5315), the Swedish Heart-Lung Foundation, AGA AB Medical Research Fund, the Gothenburg Medical Association and the LUA grant S02711 at Sahlgrenska University Hospital.

We are indebted to Karin Fagerbrink, Eva-Maria Hedin, and Agneta Ronéus for invaluable assistance in the animal laboratory and to Marianne Almgren, Ann Eriksson, Ewa Larsson, and Monica Segelsjö for skillful CT scan handling.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication September 4, 2003.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press