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BJA Advance Access originally published online on November 25, 2005
British Journal of Anaesthesia 2006 96(1):21-30; doi:10.1093/bja/aei286
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

CARDIOVASCULAR

Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery

J. Verheij1,{dagger}, A. van Lingen2, P. G. H. M. Raijmakers2, E. R. Rijnsburger3, D. P. Veerman3, W. Wisselink4, A. R. J. Girbes1 and A. B. J. Groeneveld1,*

1 Department of Intensive Care, 2 Department of Nuclear Medicine, 3 Department of Anaesthesiology and 4 Department of Vascular Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands

* Corresponding author. E-mail: johan.groeneveld{at}vumc.nl

Accepted for publication October 19, 2005.


   Abstract
Top
 Footnotes
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. The optimal type of fluid for treating hypovolaemia without evoking pulmonary oedema is still unclear, particularly in the presence of pulmonary vascular injury, as may occur after cardiac and major vascular surgery.

Methods. In a single-centre, prospective, single-blinded clinical trial 67 mechanically ventilated patients were randomly assigned to receive saline, gelatin 4%, HES 6% or albumin 5%, according to a 90 min fluid loading protocol with target central venous pressure of 13 and pulmonary capillary wedge pressure of 15 mm Hg, within 3 h after cardiac or major vascular surgery. Before and after the protocol, we recorded haemodynamics and ventilatory variables and took chest radiographs. The pulmonary vascular injury was evaluated using the 67Ga-transferrin pulmonary leak index (PLI) and extravascular lung water (EVLW). Plasma colloid osmotic pressure (COP) was determined and the lung injury score (LIS) was calculated.

Results. More saline was infused than colloid solutions (P<0.005). The COP increased in the colloid groups and decreased in patients receiving saline. Cardiac output increased more in the colloid groups. At baseline, PLI and EVLW were above normal in 60 and 30% of the patients, with no changes after fluid loading, except for a greater PLI decrease in HES than in gelatin-loaded patients. The oxygenation ratio improved in all groups. In the colloid groups, the LIS increased, because of a decrease in total respiratory compliance, probably associated with an increase in intrathoracic plasma volume.

Conclusions. Provided that fluid overloading is prevented, the type of fluid used for volume loading does not affect pulmonary permeability and oedema, in patients with acute lung injury after cardiac or major vascular surgery, except for HES that may ameliorate increased permeability. During fluid loading, changes in LIS (and respiratory compliance) do not represent changes in pulmonary permeability or oedema.

Keywords: fluids, i.v.; heart, cardiopulmonary bypass; lung, damage; surgery, vascular


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
Hypovolaemia is common in the critically ill and crystalloid and colloid fluids are available for treatment.1 Crystalloids may promote fluid extravasation in the lungs and formation of pulmonary oedema since they tend to lower colloid osmotic pressure (COP). In contrast, colloids may decrease pulmonary fluid extravasation and the formation of pulmonary oedema because of their capacity to increase COP. The so-called colloid–crystalloid controversy includes the relative propensity of fluid types to evoke pulmonary oedema, which is not yet settled in the absence of direct permeability and oedema measurements in most studies.1 Indeed, the controversy is complicated by the fact that the potentially protective role of COP may diminish when permeability is increased, while the propensity for oedema formation may increase, unless hydrostatic pressure is kept low, as demonstrated in experimental and human studies.2 –4 In the recent SAFE study, resuscitation of critically ill (non-cardiac surgery) patients with albumin or saline proved almost equally safe without differing mortality rates, although pulmonary oedema was not studied specifically.5

Cardiac and major vascular surgery are often complicated by hypovolaemic hypotension, necessitating fluid therapy, but the optimal type of fluid for this purpose is hotly debated.1 6 –13 Cardiac and major vascular surgery, involving ischaemia and reperfusion, are well known risk factors for a systemic inflammatory response and for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), associated with increased capillary permeability in the lungs in some patients, as measured by a non-invasive double radionuclide technique to detect pulmonary 67Ga-transferrin extravasation.14 –18 This could thus affect the contribution of infusion fluids to pulmonary oedema formation. Indeed, studies documented an increase in extravascular lung water (EVLW) after cardiac or major vascular surgery and fluid loading, at least transiently in some patients.9 –11 19 –22

Finally, experimental studies suggest that middle and large molecular solutions of starches may ‘plug’ the leaks during increased permeability after ischaemia/reperfusion, endotoxaemia, toxic injury or extracorporeal bypass.23 –27 They may even improve pulmonary function after aortic surgery in humans.28 Moreover, albumin solutions may have anti-inflammatory antioxidant effects, thereby ameliorating endothelium–neutrophil interactions in the lungs and increased permeability in experimental studies.29 Infusion fluids may thus affect capillary permeability in human lungs.

We hypothesized that colloid fluid loading would aggravate less oedema formation in the lungs than saline loading in the treatment of presumed hypovolaemia after major surgery, even if complicated by increased pulmonary permeability. We also hypothesized that hydroxyethyl starch (HES) or albumin loading would attenuate pulmonary oedema attributable to increased permeability as compared with gelatin loading. We therefore compared filling pressure-guided fluid challenges30 with saline and with the colloids gelatin, HES and albumin on their effects on pulmonary capillary permeability, EVLW, COP, and the lung injury score (LIS) in 67 presumably hypovolaemic patients after cardiac or major vascular surgery.


   Patients and methods
Top
 Footnotes
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
This study is a prospective, stratified, randomized, single-blinded and single-centre clinical trial. The study was approved by the Ethical Committee of the Vrije Universiteit Medical Centre. Written informed consent was obtained in each of the 89 eligible patients, on the day before the scheduled surgery. The hospital pharmacy assigned the patients randomly, via the sealed envelope method, to various groups, after stratification between cardiac (n=40) or major vascular surgery (n=28). A total of 68 patients fulfilled the study criteria on arrival at the intensive care unit (ICU) after the operation. One cardiac patient assigned to saline, however, was excluded because of technical failures and one patient assigned to the gelatin group inadvertedly received albumin. Hence, 67 consecutive patients were included in the study. The inclusion criteria, judged when the patients arrived at the ICU, were presumed hypovolaemia, defined as a systolic blood pressure <110 mm Hg and reduced filling pressures: a pulmonary capillary wedge pressure (PCWP) at or below 10 mm Hg in the presence of a pulmonary artery catheter (n=49) and proper wedging (n=36) or a central venous pressure (CVP) at or below 8 mm Hg (n=31). Patients were thus only included if they had or needed, on clinical grounds, arterial and pulmonary artery or central venous catheters. Exclusion criteria were: age >75 yr and known anaphylactoid reactions to colloids or iodide.

On the day of surgery, anaesthesia was induced by sufentanil, pancuronium and midazolam and maintained by a continuous infusion of propofol with supplemental bolus doses of sufentanil. Radial artery, central venous and, if indicated on clinical grounds, pulmonary artery catheters were inserted for haemodynamic measurements and blood sampling. After tracheal intubation, the lungs were volume-controlled ventilated with a tidal volume of 8–10 ml kg–1 resulting in an end-tidal carbon dioxide concentration between 4 and 5%, using an oxygen–air mixture with an inspiratory oxygen concentration of 40%. A PEEP of 5 cm H2O was applied. Cardiac surgery patients received 50–100 mg dexamethasone at induction. Thirty-one cardiac surgery patients and five major vascular surgery patients underwent surgery adopting a cardiopulmonary bypass (CPB) or a left-left shunt, respectively (Stockert-Sorin S3, Sorin Biomedica, Mirandola, Modena, Italy). The extracorporeal bypass was primed with Ringer's lactate, gelatin 4%, mannitol, sodium bicarbonate, aprotinin and heparin.

After systemic heparinization, extracorporeal blood flow was started, provided that the activated clotting time was prolonged. Non-pulsatile flow rate was maintained at 2–3 litre min–1 m–2. Cardiac surgery patients were cooled to 32°C nasopharyngeal temperature. Mean arterial pressure (MAP) was maintained at 50–80 mm Hg and if the MAP declined to <50 mm Hg, the blood flow rate was increased and vasoactive drugs were given. After aortic cross-clamping, all cardiac surgery patients received crystalloid cardioplegia for myocardial protection (in total, 2000 ml, potassium 16 mmol litre–1, 4°C). Patients were weaned from the CPB/left-left shunt, using inotropic support, if necessary and heparin was neutralized using an equivalent dose of protamine sulphate (3 or 1 mg kg–1). Autologous blood and residual volume from the extracorporeal circuit were infused as first-choice fluid administration. Guided by low systemic and filling pressures, saline or colloids were infused additionally. If the haemoglobin (Hb) concentration was <6 mmol litre–1, packed red blood cell concentrates were infused. Preoperative use of aspirin, excessive bleeding and a long pump-time prompted for administration of donor platelets. At the end of the surgery, a 4F introducing sheath (Arrow, Reading, USA) was inserted into the femoral artery, for use in the study protocol, in 33 cardiac and 21 major vascular surgery patients.

Measurements
For the measurement of the pulmonary leak index (PLI), as done in previous studies,14 –16 autologous red blood cells were labelled with 99mTechnetium (Tc, 11 MBq, physical half-life 6 h; Mallinckrodt Diagnostica, Petten, The Netherlands). Transferrin was labelled in vivo, after i.v. injection of 67Gallium (Ga)-citrate, 4.5 MBq for the pre-infusion study and 9 MBq for the post-infusion study (physical half-life 78 h; Mallinckrodt Diagnostica, Petten, The Netherlands). Patients were in the supine position and two scintillation detection probes (Eurorad C.T.T., Strasburg, France) were positioned over the right and left lung apices. Starting at the time of the i.v. injection of 67Ga, radioactivity was detected during 30 min. The 99mTc and 67Ga counts were corrected for background radioactivity, physical half-life, spillover of 67Ga into the 99mTc window, obtained by in vitro measurement of 67Ga, and expressed as cpm per lung field. At 1, 5, 8, 12, 16, 20, 25 and 30 min after 67Ga injection, blood samples (2 ml aliquots) were taken. Each blood sample was weighed and radioactivity was determined with a single-well well-counter (LKB Wallac 1480 WIZARD, Perkin Elmer, Life Science, Zaventem, Belgium), taking background, spillover of 67Ga into 99mTc and decay into account. Results were expressed as cpm g–1. For each blood sample, a time-matched cpm over each lung was taken. A radioactivity ratio was calculated, (67Galung/99mTclung)/(67Gablood/99mTcblood), and plotted against time. The PLI was calculated from the slope of increase of the radioactivity ratio divided by the intercept, to correct for physical factors in radioactivity detection. The PLI represents the transport rate of 67Ga-transferrin from the intravascular to the extravascular space of the lungs and is therefore a measure of pulmonary vascular permeability. The values for both lung fields were averaged. The upper limit normal for the PLI is 14.7x10–3 min–1 and the measurement error is ~10%.14 16

For the measurement of cardiac output (CO), intrathoracic blood volume (ITBV) and EVLW, the transpulmonary thermal/dye dilution technique was used.22 31 This involves a central venous injection of a dye and thermal bolus, 15 ml of 1 mg ml–1 indocyanine green in an ice-cold dextrose 5% solution and concomitant registration of the dye dilution and thermal shift in the femoral artery, using a 3F catheter equipped with a thermistor and fiberoptic (PV 2024, Pulsion Medical Systems, Munich, Germany) connected to a bedside computer (COLD Z-021, Pulsion Medical Systems, Munich, Germany). The catheter was introduced via the introducing sheath. Measurements were done in duplicate, irrespective of the ventilatory cycle, and average values were taken. The technique yields the transpulmonary thermodilution CO, and a transit time of the dye in the thorax and thereby the ITBV. From the differences in transit time of the thermal and dye signal, the EVLW is computed.31 The upper limit of normal for the EVLW is 7 ml kg–1 and the measurement error is ~10%. In overt pulmonary oedema, the EVLW is usually doubled. In the absence of a thermal-dye dilution femoral artery catheter, CO was measured by thermodilution via the pulmonary artery catheter as this is almost interchangeable with transpulmonary measurements.31 32 We calculated plasma volume changes from (Hb0/Hb90) – [(1 – Hct90)/(1 – Hct0)], in which Hct is haematocrit, measured at 0 and 90 min.33

Protocol
After surgery, the patients were admitted to the ICU, and connected to the ventilator (Evita 3, Dräger, Lübeck, Germany) and volume-controlled ventilation was started with similar settings as during surgery. The study protocol was started within 3 h after arrival. Patient characteristics were recorded, including variables of the acute physiology and chronic health evaluation (APACHE-II) score and baseline measurements of the 67Ga-transferrin PLI (t=–30 to t=0 min) and haemodynamics were performed and an anteroposterior chest radiograph was taken. Pulmonary and systemic haemodynamic variables were measured after calibration and zeroing to atmospheric pressure at mid-chest level (TramscopeR, Marquette, WI, USA). Mean pulmonary artery pressure (MPAP), CVP and, after balloon inflation, the PCWP were taken at end-expiration, with patients in the supine position. Arterial and pulmonary artery (n=49) or central venous blood samples (n=18) were obtained for determinations of Hb/Hct (Sysmex SE-9000, Sysmex Corporation, Kobe, Japan) and partial oxygen pressure/saturation (Rapidlab 865, Bayer Diagnostics, Tarrytown, NY, USA). The COP was measured by a membrane osmometer (Osmomat 050, Gonotex, Berlin, molecular cut-off at 20 kDa). Venous admixture was calculated from arterial, mixed (or central) venous and capillary oxygen contents, calculated from Hb, oxygen pressures and saturations, according to standard formulae. The inspiratory oxygen fraction (), PEEP (cm H2O), tidal volume and inspiratory plateau pressure were taken from the ventilator. The total respiratory compliance was calculated from tidal volume/(plateau pressure-PEEP), ml cm–1 H2O. The chest x-ray was scored by a consultant radiologist, blinded to the study, who evaluated the number of quadrants with alveolar consolidations, ranging from 0 to 4. To further document the severity of the pulmonary abnormalities, a LIS was calculated, taking into account the level of PEEP, the arterial ratio, to total respiratory compliance and the number of quadrants with alveolar consolidations on the chest radiograph.34 The score ranges from 0 to 4, with values <2.5 denoting ALI and >2.5 ARDS.

Patients had been randomly assigned to NaCl 0.9%, GelofusineR (gelatin 40 g litre–1, B. Braun Melsungen AG, Germany, in 154/120 mmol litre–1 NaCl), HES 6% (MW 200,000, substitution 0.45–0.55, HemohesR, B. Braun Melsungen AG, Germany, in saline) or albumin 5% (100 ml Cealb 20%, Sanquin, CLB, Amsterdam, The Netherlands, diluted in 300 ml of saline). After baseline measurements, fluids were given during 90 min on the basis of the response within predefined pressure limits, on the basis of the PCWP after appropriate wedging (n=36) or the central venous pressure (n=31), according to a fluid challenge protocol described in the literature30 (Fig. 1) and targeting to a maximum PCWP of 15 mm Hg and a CVP of 13 mm Hg. Boluses of maximum 200 ml were given per 10 min, so that the maximum fluid challenge was 1800 ml in 90 min. Concomitant treatment, including ventilatory settings and administration of vasoactive and sedative drugs was unchanged. The measurements were repeated immediately after completing the fluid challenge (t=90 min). Diuresis was recorded.



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  		Fig 1 Fluid challenge protocol (modified data from ref. 30).

 
Statistical analysis
The CO and ITBV were indexed to body surface area, yielding cardiac index (CI) and ITBV index (ITBVI), respectively. EVLW was expressed as EVLW kg–1 body weight. As we were primarily interested in the effect of colloid and the intrinsic effects of HES and albumin, we evaluated using the non-parametric Mann–Whitney U-test if there were statistically significant differences between saline and (pooled) colloid fluid loading, and between HES or albumin vs gelatin loading. Baseline and changes from baseline were evaluated, after studying changes in the whole group using the paired non-parametric Wilcoxon signed rank test. We have indicated four levels of significance, P<0.05, 0.01, 0.005 and 0.001 to account for multiple testing. Spearman rank correlation coefficients were used to express relations. Data are presented as median and range. The study was powered to detect a PLI and EVLW difference between saline (n=14) and colloid fluid resuscitation (n=40) of 22% (at a SD of 25%), at two-sided {alpha}=0.05 and ß=0.80.


   Results
Top
 Footnotes
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
Patient characteristics
Patient characteristics are listed in Table 1. Patients had an uneventful recovery except for one cardiac surgery patient in the gelatin group, who eventually died from postoperative complications (cerebral infarction), and one vascular surgery patient in the saline group, who died 1 day after operation from re-bleeding. Both events were judged not to relate to fluid loading. Groups were comparable, except for sex distribution. Except for one patient with ARDS (LIS>2.5, in the saline group) all patients had ALI. More saline than colloid fluid was administered.


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  		Table 1 Patient characteristics.

 
Haemodynamic and biochemical variables
There were no baseline differences. Fluid loading increased CVP, MPAP (n=49) and PCWP (n=36) (P-values in Table 2). CVP and PCWP changes interrelated (rs=0.61, P<0.001). CI increased more in the colloid than in the saline groups. Saline loading decreased COP and colloid loading increased COP. Hct decreased in the colloid groups and remained unchanged in the saline group, so that plasma volume increased more in the former (Table 2).


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  		Table 2 Haemodynamic and biochemical changes. Median (ranges) or number (N) where appropriate.

 
PLI and EVLW
Technical problems precluded PLI measurements in three patients. EVLW (and ITBV) measurements were available in 14 patients in the saline, 10 patients in the gelatin, 14 patients in the HES and 16 patients in the albumin group. Baseline PLI and EVLW were above normal in 9 (56%) and 5 (31%) patients in the saline group, 7 (44%) and 2 (13%) patients in the gelatin group, 13 (76%) and 5 (29%) patients in the HES group and 11 (61%) and 8 (44%) patients in the albumin group, and cardiac and major vascular surgery patient groups did not differ. The baseline PLI was thus above normal (>14.7x10–3 min–1) in 40 of 67 (60%) patients and the baseline EVLW in 20 of 67 (30%) patients, without significant group differences. The PLI decrease in the HES group was greater than in the gelatin group (Fig. 2). Whereas EVLW declined for all groups together (P<0.05), the change did not differ between saline and colloid fluid resuscitation, whether the PLI was elevated or not (Fig. 3). The changes in EVLW directly correlated with changes in PCWP (rs=0.43, P<0.05).



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  		Fig 2 Box and whisker plots of changes in PLI (PLIt=90 – PLIt=0,x10–3.min–1) in the various resuscitation fluid groups within cardiac surgery patients and vascular surgery patients. There was no difference among groups, except for a greater decrease in the HES than the gelatin group (P<0.05). Values in boxes are at 25th percentile, median and 75th percentile (= interquartile range, IQR); whiskers are values <1.5 IQR and extremes (*, at >3 IQR), where appropriate.

 


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  		Fig 3 Box and whisker plots of changes in EVLW (EVLWt=90 – EVLWt=0) in the various resuscitation fluid groups within cardiac and vascular surgery patients. There was no difference between groups, while for all patients together EVLW decreased (P<0.05). Values are at 25th percentile, median and 75th percentile (IQR); whiskers are values <1.5 IQR and outliers [1.5 < outlier ({circ}) < 3 IQR], where appropriate.

 
Respiratory variables (Table 3)
At baseline, the in the saline group was 50 (39–62), in the gelatin group 41 (37–61), in the HES group 41 (39–60) and in the albumin group 40 (38–60)% (NS). The PEEP at baseline was 6 (5–15), 7 (5–12), 5 (4–10) and 7 (5–16) cm H2O and the tidal volumes were 600 (500–730), 580 (450–740), 571 (400–730) and 566 (395–1110) ml, in the saline, gelatin, HES and albumin groups, respectively (NS). During fluid loading, the , and oxygenation ratio increased in all groups, while the (not shown) did not change. In the patients receiving colloids, a small elevation in LIS was associated with a decrease in total respiratory compliance. The decrease in compliance correlated with the increase in ITBVI (rs=0.28, P<0.05).


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  		Table 3 Respiratory variables.

 

   Discussion
Top
 Footnotes
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
Many patients after cardiac or major vascular surgery had some degree of ALI, associated with increased permeability, oedema, and ventilatory and radiographic abnormalities in the lungs. While fluid overloading was prevented, the changes observed as a result of a filling pressure-guided loading protocol were not affected by the type of fluid be it saline, gelatin, HES or albumin. However, HES attenuated the increased permeability. Nevertheless, the LIS slightly increased in the colloid groups, associated with a decrease in total respiratory compliance.

In our study, 60% of patients had an increase in the PLI directly after surgery, confirming that cardiac and major vascular surgery are risk factors for capillary injury and ALI.14 –18 Indeed, 30% of patients had an EVLW of >7 ml kg–1 directly after surgery, agreeing with the literature, showing a moderate and transient increase in EVLW in some patients after cardiac or major vascular surgery.9 10 19 –22 31

As diuresis was similar in both groups, the EVLW did not change in either group and plasma volume increased less in the saline than in the colloid groups, the extrapulmonary extravascular fluid volume must have been higher in the saline than in the colloid groups. Hence, the plasma COP increase in colloid-treated patients was effective in keeping colloid fluids, at least temporarily within the plasma volume compartment with less extravasation into the extrapulmonary extravascular space, as compared with saline loading. The increase in systemic venous pressure was apparently able to increase fluid extravasation in the systemic circulation during fluid loading, which was limited by a concomitant increase in COP in the patients receiving colloids. Apparently, COP remained operative, even though it is widely accepted that cardiac surgery evokes a systemic inflammatory response and cardiac and vascular surgery are accompanied by ischaemia–reperfusion, contributing to an increase in capillary permeability.14 15 18 Increased extravascular accumulation of saline as compared with colloid fluids apparently did not include the lungs.

The lack of effect of COP on PLI and EVLW in our study agrees with the findings by Sibbald and co-workers,2 describing transvascular small and large molecular tracer flux in ALI/ARDS patients, loaded with albumin, and the predominant effect of hydrostatic pressure rather than of COP on these fluxes, at least when permeability was severely increased, as in the experimental oleic acid model.4 The fact that the transvascular albumin transport increased with albumin loading in their study but not in ours can be explained as the PLI method in our study takes intravascular albumin mass and surface area into account and is a specific measure of permeability independent of bulk flow.14 Our results do not agree with experimental studies showing a benefit of colloid vs saline fluid loading regarding oedema formation in injured lungs.3 In contrast to those studies, the increase in permeability may have been more severe in our patients, or hydrostatic pressures promoting oedema formation may have been lower than in the experiments, or both. Otherwise, the unchanged PLI during an increase in CI may agree with the literature showing that an increase in CI does not increase protein permeability in the isolated dog lung.35 Although lung water may increase with increased CI and surface area available for exchange in the isolated dog lung,35 lung oedema is CI-independent when evaluated in the in vivo lung injured by oleic acid or in humans after cardiac surgery.32 36 In our study, a maximum PCWP of 10–15 mm Hg, at a PEEP of 4–16 cm H2O, was well tolerated, even though the changes in EVLW between t=0 and 90 min directly correlated with changes in PCWP rather than with changes in PLI or COP. The latter indeed suggests an important role of hydrostatic pressure in the formation of pulmonary oedema in ALI after major surgery and the protective role of avoiding high filling pressures on the formation of oedema, even when permeability is increased and COP lowered. Conversely, our results show the safety of the fluid challenge protocol,30 whether CVP or PCWP are used. Indeed, the fair interrelation between CVP and PCWP changes in our patients agrees with the literature.37

In spite of an increased oxygenation ratio, the LIS slightly but significantly increased, but more in colloid than in saline groups, because of a greater decline in total respiratory compliance in the colloid group. As changes in compliance were associated with changes in ITBVI that includes pulmonary blood volume, a decrease in compliance may relate to greater pulmonary intravascular filling with colloids. Indeed, volume loading in pigs decreased total respiratory compliance, and exsanguination of dogs/pigs increased pulmonary compliance because of a loss of pulmonary blood volume.38 39 Finally, the greater increase in CI in colloid vs saline groups can be explained by greater expansion of the plasma volume tending to elevate the ITBVI, determining the preload of the heart,22 31 with colloids than with crystalloids. These disparate haemodynamic effects agree with the literature, showing that crystalloids were less effective expanders of plasma volume and in boosting CO after cardiac or major vascular surgery, than colloids.6 8 9 11 13 22 40 The increase in arterial can be explained by an increase in venous , concomitantly with an increase in CI and tissue oxygenation, at constant venous admixture, and to the concomitant slight reduction in EVLW with time.41 Alternatively, the increase in may be associated with opening up of increased atelectatic areas after the operation, with increasing airway pressures.

Finally, there is evidence in our study that HES favourably affects pulmonary permeability, independent of COP, in ALI after cardiac surgery or major vascular surgery. This agrees with experimental studies, suggesting that middle and high molecular weight starch molecules may ameliorate lung injury and permeability oedema under a variety of circumstances, including ischaemia/reperfusion, endotoxaemia, toxic injury and extracorporeal bypass.23 –27 Rittoo and co-workers 28 described better pulmonary function after aortic surgery in patients treated with HES than with gelatins, but did not study permeability nor oedema directly. Some caution is warranted, however, as some patients underwent thoracic procedures in the HES group and baseline PLI tended to be somewhat higher than in the gelatin group. We could not confirm the experimental observations that albumin solutions have antioxidant properties and may ameliorate endothelial–neutrophil interactions in the lungs and permeability oedema.29 Since our study was primarily powered to detect a difference between saline and colloid fluid loading, the number of patients studied may have been too small to demonstrate a small specific effect of albumin.

Although our study has the advantage of a multiple comparison among fluids in a relatively large patient group and independent measurements of permeability and oedema, it carries some limitations. The study was not investigator-blinded. Fluid resuscitation was guided by filling pressures, which is common practice since hydrostatic pressures are important determinants of EVLW. However, we believe that the conclusion that EVLW does not depend on the type of fluid given within this range of hydrostatic pressures is clinically relevant. We cannot exclude however, that more saline would have been needed and more EVLW had developed, as compared with colloid fluid, if fluid loading had been guided by filling volumes (ITBV) rather than pressures. Thermal-dye EVLW may be underestimated when focal lung injury is accompanied by regional hypoperfusion.42 However, the underestimation and CI-dependency of EVLW in hypoperfused areas may be minimal in less severe, indirect, lung injury in humans as opposed to animal models of ARDS.32 42 There are only few studies utilizing direct measurements of EVLW, often adopting old techniques and ex vivo dye concentration measurements, and their response to multiple fluids after cardiac or major vascular surgery.9 –11 19 20 22 31 In other studies, only surrogate indicators of pulmonary oedema have been used.6 –8 12 13 28 40 The number of fluids evaluated in the studies has often been limited to two or three, so that the potential intrinsic properties of fluids could not be easily separated from effects caused by COP changes. Gallagher and colleagues10 compared saline, HES and albumin (n=5 in each group) after operation and did not find differences in EVLW (elevations). Karanko and colleagues compared dextran11 (n=14) with Ringer's acetate (n=18) for fluid loading after cardiac surgery and found that EVLW did not increase in both groups, while gas exchange transiently deteriorated in the dextran group. Wahba and colleagues22 found that gelatin loading (n=11) increased ITBVI and thus CI more than Ringer's solution (n=11) after cardiac surgery, without affecting EVLW, as in our study. Studying aortic surgery patients, Shires and colleagues9 compared Ringer's lactate with a colloid (plasmanate) in 18 patients during surgery, and despite differences in COP, EVLW after surgery did not differ. As in our study, this can be explained by the relatively low filling pressure attained.9 Our study thus extends some of these previous studies and may confirm the conclusion from meta-analyses that the type of fluid used for treating hypovolaemia does not affect pulmonary oedema formation, provided that fluid overloading is avoided.

In conclusion, saline or colloids do not affect permeability oedema in ALI after cardiac or major vascular surgery, provided that fluid overloading is avoided, and except for HES which may ameliorate increased permeability. The LIS, however, may slightly increase after colloid vs saline loading, because of greater intrathoracic plasma volume expansion decreasing total respiratory compliance, thus indicating that changes in LIS (and respiratory compliance) during fluid loading do not represent changes in permeability oedema.


   Footnotes
Top
 Footnotes
Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
{dagger} Declaration of interest. Dr Verheij was supported by an unrestricted research grant from B. Braun Medical, Melsungen, Germany. Back


   References
Top
 Footnotes
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
1 Roberts I, Alderson P, Bunn F, Chinnock P, Ker K, Schierhout G. Colloid versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2004; 4: CD000567.

2 Sibbald WJ, Driedger AA, Wells GA, Myers ML, Lefcoe M. The short-term effects of increasing plasma colloid osmotic pressure in patients with non-cardiac pulmonary edema. Surgery 1983; 93: 620–36[Medline]

3 Finch JS, Reid C, Bandy K, Fickle D. Compared effects of selected colloids on extravascular lung water in dogs after oleic acid-induced lung injury and severe hemorrhage. Crit Care Med 1983; 11: 267–70[Medline]

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