Abstract
Acute Respiratory Distress Syndrome (ARDS) is a common entity in critical care medicine and associated with many diagnoses, including trauma and sepsis, which may lead to multiple organ failure and death. Pathophysiologically, increased capillary permeability is the hallmark of ARDS which is characterized by damage of the capillary endothelium and alveolar epithelium in association with impaired fluid removal from the alveolar space and the accumulation of protein-rich fluid inside the alveoli. The clinical management of patients with ARDS is even more difficult, because in the presence of capillary leakage in the lungs, adequate intravascular volume and cardiac preload are required to maintain organ perfusion. The amount of pulmonary edema fluid is, however, difficult to determine at the bedside. Pulmonary edema can be detected on physical examination and may be confirmed by chest radiography. However, it has been shown to be difficult to quantify the extent of pulmonary edema based on chest radiography or other non-invasive measures. The transpulmonary thermo-dye dilution technique has been introduced as an instrument to quantify the fluid in the pulmonary capillary bed, i.e., extravascular lung water (EVLW). This technique as shown to be potentially valuable in the management of critically ill patients and has been further developed to be clinically available nowadays as single transpulmonary thermodilution. The following review deals with the measurement of EVLW and its place in the management of critically ill patients with ARDS.
Introduction
Acute Respiratory Distress Syndrome (ARDS) which was initially described in 1967 by Ashbaugh et al. [1] is a common entity in critical care medicine. ARDS is associated with many diagnoses, including trauma and sepsis, and may lead to multiple organ failure with high mortality. Pathophysiologically, increased capillary permeability is the hallmark of ARDS which is characterized by damage of the capillary endothelium and alveolar epithelium in association with impaired fluid removal from the alveolar space and the accumulation of protein-rich fluid inside the alveoli.
The clinical management of patients with ARDS is even more difficult, because in the presence of capillary leakage in the lungs, adequate intravascular volume and cardiac preload are required to maintain organ perfusion. The amount of pulmonary edema fluid is, however, difficult to determine at the bedside. Pulmonary edema can be detected on physical examination by the presence of rales and may be confirmed by chest
radiography and the presence of bilateral pulmonary opacities. However, it has been shown to be difficult to quantify the extent of pulmonary edema based on chest radiography or other non-invasive measures [2]. In the 1980’s Sibbald et al. [3] studied the transpulmonary thermo-dye dilution technique as an instrument to quantify the fluid in the pulmonary capillary bed, i.e., extravascular lung water (EVLW). Over the following years this technique as shown to be potentially valuable in the management of critically ill patients [4,5] and has been further developed [6,7] to be clinically available nowadays as single transpulmonary thermodilution. The following review deals with the measurement of EVLW and its place in the management of critically ill patients with ARDS.
Measurement of extravascular lung water
Historically, the so-called transpulmonary double (i.e., thermo-dye) dilution technique was used for the clinical measurement of EVLW. In this technique two different indicators with specific properties and differences are simultaneously injected central venously and were then detected not prior to, but after passing through the lungs in the arterial system (transcardiopulmonary) by an appropriate sensor. In clinical practice, a bolus of cooled (0- 4°C) indocyanine green (ICG) was used and an arterial thermistor-fiberoptic catheter was used. In most cases, femoral arterial catheterization, which has been shown to be safe, was performed for measurement of the EVLW [8]. In contrast to the dye, which immediately binds to plasma proteins and remains fully in the intravascular bed, the cold equilibrates with extravascular structures. The dye (ICG) allows assessment of the intravascular compartment, i.e., the intrathoracic blood volume (ITBV). For each indicator, the concentration between both volumes is called the extravascular lung water: EVLW = ITTV - ITBV. While ITBV can be used as a cardiac preload parameter, EVLW is a marker of extravascular fluid in the lungs.
Notably, for several years now ultrasound techniques have also been suggested for assessing EVLW since Blines as vertical artifacts and arising comets were found in the presence of interstitial-alveolar imbibition [9]. These authors found a linear correlation between comet score, a sign of extravascular lung water, and radiologic lung water score (r= 0.78) while intra-patient variations showed an even stronger correlation between changes in both variables (r= 0.89). They concluded that the comet-tail is a simple, non-time-consuming, and reasonably accurate chest ultrasound which can be obtained at bedside by ultrasound. More recently, the same group compared ultrasound with EVLW in an animal model [10]. In a pig model of ALI/ARDS, B-lines assessed by lung ultrasound provided a simple, semi-quantitative, noninvasive index of lung water accumulation which
strongly correlated to invasive gravimetric assessment. Clinical data [11] supports lung ultrasound as an appropriate method with which to assess EVLW. Recently, Lichtenstein et al. [12] suggested the FALLSprotocol in the management of patients with shock where simple echocardiography is used to rule out obstructive shock (tamponade, pulmonary embolism) thereafter the lung is investigated. In fact, fluid is administered until signs of extravasation in the lungs (B-lines) occur, demanding cessation of fluid therapy.
However, this sequential approach that is combined with the usual clinical, biochemical and echocardiographic parameters is not widely accepted and must undergo validation in adequate studies. Furthermore, several other techniques (e.g., computed tomography, magnetic resonance tomography, positron emission tomography and bioimpedance) [13-16] have been used to quantify EVLW. However, the following review will focus on transpulmonary indicator dilution for measurement of EVLW.
Technology assessment
By using the double-indicator technique, Sibbald et al. [17] showed the difference between cardiac and noncardiac pulmonary edema. Patients with ARDS were shown to have a higher EVLW while their hydrostatic component (i.e., pulmonary artery occlusion pressure) was much lower (“permeability edema”) [17]. For a given hydrostatic pressure, EVLW was much higher in patients with a permeability induced lung edema (ARDS) when compared to “pure” hydrostatic pathophysiology (“cardiogenic edema”). The change in hydrostatic pressure could be demonstrated to be associated with a less steep increase in EVLW when compared to ARDS patients. Similar findings had been described before in an animal experimental setting [18]. Furthermore, for similar chest X-ray scores, EVLW in patients with ARDS was significantly higher than in cardiac patients. Consequently, EVLW cannot be estimated reliably from the hydrostatic component in ARDS this reference, only 65% of patients with fulfilled ARDS criteria had an EVLW >7 ml/kg. Consequently, about one third of patients with ARDS do not have pulmonary edema, as assessed by EVLW from the transpulmonary double indicator dilution technique.
Although effective at the bedside, the double-indicator (cooled ICG) technique is relatively time consuming, cumbersome and expensive. An approach which provides circulatory volumes and EVLW from a singleindicator technique using arterial thermodilution alone would be an advantage. Estimation of EVLW by single thermodilution is based on the assumption that, for several mixing chambers in a series with identical flow, the
decay of the dilution curve is predominantly determined by the largest compartment [20]. In an animal study, Neumann et al. [21] showed that EVLW could be reliably derived from thermodilution alone. Shortly afterwards, our group derived a correction factor for critically ill patients which was then validated in 209 other ICU patients [7]. In detail, thermodilution derived EVLW was correlated with double indicator derived EVLW
by y=0.83*x + 1.6 ml/kg, r = 0.96, P < 0.0001. Bias between both techniques was 0.2 ml/kg with a standard deviation of 1.4 ml/kg. Thermodilution EVLW systematically overestimated EVLW at low-normal values underestimated EVLW at higher values (>12 ml/kg). Changes between the first two time points of simultaneous measurements were also analyzed and revealed r=0.87.
The reliability of EVLW by transpulmonary thermodilution was studied in a swine model by FernándezMondéjar et al. [22] who reported on EVLW measurements before and immediately after intratracheal instillation of normal saline. In normal and edematous lungs EVLW increased and the transpulmonary thermodilution technique was described to accurately detect small increases in EVLW and so may permit accurate diagnosis of incipient pulmonary edema. EVLW as measured by the single thermodilution technique has been shown to be nearly identical to that measured by the double indicator technique but with a slight overestimation when EVLW is normal (<7 ml/kg) [23]. In the clinically more relevant pathological range, a close agreement between both techniques was found with high reproducibility, emphasizing that single thermodilution is accurate enough for the estimation of EVLW in clinical practice [23]. Additionally, in an experimental model of cardiogenic and non-cardiogenic pulmonary edema, thermodilution-derived EVLW was found to closely correlate with gravimetry [24].
In general, the accuracy and reproducibility of EVLW measurements by transpulmonary indicator dilution techniques per se is high [25,26,27]. Noteworthy, recent findings indicate that reliability of EVLW measurement remains preserved when the injection of room temperature saline is used [28]. Michard et al. [29] noted that the estimation of EVLW by transpulmonary thermodilution was influenced by the amount of EVLW, the PaO2/FiO2 ratio, the tidal volume, and the level of positive end-expiratory pressure. However, compared technique for the measurement of EVLW might still be influenced by changes in perfusion and ventilation. In addition, the single transpulmonary thermodilution technique, might require adjustment of the mathematical relationship to the particular condition and species subjected to the measurement.
One more recent concept is that of the pulmonary vascular permeability index (PVPI) which is the ratio between EVLW and the pulmonary blood volume (PBV), i.e. between the extravascular and the intravascular fluid compartments of the lung. The idea is that the capillary barrier in the pulmonary microcirculation is more insufficient when a low ITBV is associated with a high EVLW. In contrast, the barrier is tight and PVPI is low
in the presence of a high ITBV and low EVLW [31]. The PVPI has been studied in animals using the transpulmonary thermodilution technique. The PVPI was higher in pigs with artificial ARDS (oleic acid model) compared to animals with simulated left heart failure (left atrial balloon) [24]. Additionally, this study nicely showed that single thermodilution technique correlated well with gravimetry [24] (figure 1). Also clinical data suggest that indexes of pulmonary permeability provided by transpulmonary thermodilution may be useful for determining the mechanism of pulmonary edema in the critically ill [32]. In this study [32], patients with cardiac edema had a higher PVPI and lower left ventricular ejection fraction than ARDS patients. As such, the PVPI allows differentiation between cardiogenic and non-cardiogenic pulmonary edema, because in noncardiogenic pulmonary edema both EVLW and PBV will be high [24, 32, 33]. Chew et al. [33] showed that the ratio seemed to be a better marker of disease severity in patients with a Lung Injury Score >2.5, implying that patients with severe ARDS have greater lung edema due to greater pulmonary permeability.
Figure 1. Reliability of single transpulmonary thermodilution technique for the assessment of extravascular lung water
(EVLW) in animals with cardiogenic and non-cardiogenic pulmonary edema.
A Extravascular lung water (EVLW) to intrathoracic blood volume (ITBV) ratio in the three different groups: control group, oleic acid group (increased permeability pulmonary edema), and left atrial balloon group (hydrostatic pulmonary edema; mean ± SD).
B Correlation of extravascular lung water index (EVLWI) as measured by single transpulmonary thermodilution compared with gravimetric measurement. From [24] with permission from the authors.
In a human study, Tagami et al. [34] evaluated the correlation between pre-mortem EVLW value by single transpulmonary thermodilution and post-mortem lung weight from 30 autopsies completed within 48 hours after final clinical measurement. EVLW correlated closely with post-mortem lung weight (r= 0.90). The normal EVLW values indexed by predicted body weight were approximately 7.4 ± 3.3 mL/kg (7.5 ± 3.3 mL/kg for males and 7.3 ± 3.3 mL/kg for females). More recently Eichhorn et al. [35] published a meta-analysis in which they found that mean EVLW was 7.3 ml/kg in surgical patients and 11 ml/kg in non-surgical septic patients, respectively. In the septic group all studies except one showed EVLWI values above the limit of 7 ml/kg (20/21), whereas 9 of the 19 studies including surgical patients reported normal values of <7 ml/kg. Clinical studies show that EVLW may exceed values of up to about 40 ml/kg [35] in severe cases.
EVLW reflects the lung water that is contained in the perfused areas of the lungs (the distribution volume of the cold indicator). Thus the measured EVLW may be underestimated when significant lung areas are excluded from circulation, as in massive pulmonary embolism, a very low cardiac output, or with high PEEP [36,37]. However, these theoretical considerations have only a marginal practical value as shown by Phillips et al. [38],
seriously ill patients, and yet the EVLW was exceedingly high in spite of this high level of non-perfusion. Although surgical lung resection may constitute a limitation in the estimation of EVLW by thermodilution [39,40], changes in thermodilution-derived EVLW may be nevertheless helpful in the clinical management. Furthermore, heterogeneity in pulmonary edema and perfusion may substantially influence the accuracy of EVLW measurement using these techniques.
Notably, postmortem gravimetry used as reference technique for measurement of EVLW also has its limitations [41,42]. Furthermore, comparison of gravimetrically determined EVLW with that by other techniques may be influenced by the time elapsing from euthanasia to lung removal, and by changes in distribution of pulmonary blood following cardiac arrest. In detail, gravimetry may underestimate the real value of EVLW due to partial
re-absorption of edema fluid before excision of the lungs. In summary, single and double indicator dilution techniques may yield relevant clinical information on EVLW which make them potentially promising for their application at the bedside of critically ill patients.
Clinical considerations
Clinical examination, chest X-ray, and blood gases have been proven to be of only limited significance for quantifying pulmonary edema [43-45]. With respect to chest X-ray, scoring systems have been suggested for quantifying EVLW. Although there is a correlation with EVLW in terms of higher scoring values and extent of EVLW as measured by the double-indicator dilution technique [46], there is wide range of scatter and changes
which are obviously not always identified correctly. Furthermore, chest X-ray is not time effective, with delays of several hours for detecting EVLW [46].
An increase in EVLW is associated with reduced lung compliance, increased venous admixture, and arterial hypoxemia, causing mortality in excess of up to 40% [43, 47]. In general, positive fluid balances in critically ill patients with enhanced risk of extravasation of fluids have been found to increase mortality [48, 49]. Correspondingly, fluid restriction in order to counteract pulmonary edema, has been described as positively influencing the course of illness and improving outcomes [4,5].
Thus far EVLW has been shown to be the best pulmonary specific index of disease severity and predictor of outcome available in patients with ALI/ARDS [50,51], while all other clinical methods for quantifying lung water are either insensitive or non-specific (e.g., chest X-ray, oxygenation). In our own retrospective analysis of 373 critically ill patients, the mortality rate was 65% in patients with an EVLW>15 ml/kg and only 33% in
patients with an EVLW <10 ml/kg [26] (figure 2). In detail, the maximum EVLW was significantly higher in non-survivors (n= 186) than in survivors (n= 187) [median, 14.3 mL/kg vs. 10.2 mL/kg, respectively. In a univariate logistic regression model, the EVLW at baseline as well as SAPS II (Simplified Acute Physiology Score) and APACHE II (acute physiology and chronic health evaluation) scores were significant predictors of mortality. Correlation increased if the SAPS II and APACHE II scores were combined, but the improvement with SAPS II alone was not significant. The addition of baseline EVLW further increased the value, indicating that EVLW contributes independently to prognosis.
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Figure 2. Extravascular lung water (EVLW) and outcome in 373 critically ill patients of a mixed non-cardiosurgical
operative ICU. Box plots for different sub-populations of patients (i.e., sepsis, ARDS, all others). Bold lines
indicate medians, box plots indicate 25-75 th percentiles, and bars indicate the 1.5 fold of the whole box length.
Circles indicate values between 1.5-fold to threefold of whole length, and outliers (outside of the whole box
length) are indicated by asterisks. The bold asterisk indicates statistical significance (Mann-Whitney-U test).
From [26] with permission from the authors.
An increased EVLW value on day 1 after trauma, indexed to the predicted (instead of actual) body weight, was found to identify patients who developed sepsis later on [52]. EVLW indexed to predicted body weight (EVLWp), EVLW, and Vd/Vt, but not P/F ratio were able to discriminate between survivors and non-survivors. Three-day average EVLWp >16 mL/kg predicted in-hospital mortality with 100% specificity and 86% sensitivity [52]. Thus, increased EVLW is a feature of early ARDS and predicts survival. Indexing EVLW to the predicted body weight, instead of actual body weight was found to improve the predictive value of EVLW for survival and correlates with markers of disease severity.
Furthermore, thermodilution derived EVLW correlated with the severity of sepsis-induced acute lung injury [53]. In a prospective, observational study, Kuzkov et al. [53] described how EVLW demonstrated a moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In non-survivors, EVLWI and permeability indexes were significantly increased on day 3. Thus, EVLW may be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury. Of particular importance for the clinician, measurement of EVLW is not influenced by pleural effusion as could be shown in patients undergoing thoracocentesis [54]. Notably, drainage of largevolume effusions resulted in a statistically significant increase in thermodilution derived EVLWI. Thus, pleural effusions do not take part in single-indicator TPTD as a part of the pulmonary thermovolume and do not increase TPTD-derived EVLWI [55]. Furthermore, reliability of EVLW is preserved during running venovenous renal replacement therapy [56], i.e., the extracorporeal circuit does not need to be interrupted in order to do the measurements. As applied in patients with an ARDS and therefore of particular clinical relevance, also influence of extracorporeal lung assist systems has been studied. By principle, the higher the flow through an extracorporeal system is the higher the loss of indicator and thus cardiac output will be overestimated [57,58].
Likely, a pumpless system (PECLA) with a flow of up to 20% of cardiac output does not reduce the reliability of TPTD derived EVLW [59]. However, further data are required to confirm these preliminary findings. Although the definition of ARDS have been updated very recently [60], EVLW is still not a criterion and patients who are not diagnosed as having ARDS may have increased EVLW [19]. Notably, an increased EVLW (> 7 ml/kg) has been repeatedly suggested as one of the ARDS criteria [61,62]. However, other authors have claimed that this still has to be prospectively validated and confirmed [63]. Nevertheless, EVLW was very recently shown to predict progression to ALI in patients with risk factors on average 2.6±0.3 days before they fulfilled the conventional criteria, and that this period may represent a missed opportunity for interventions [50].
Extravascular lung water guided treatment
The fundamental question is whether an aggressive approach to reducing the amount of EVLW when guided by EVLW or other clinical parameters can reduce mortality in patients with pulmonary edema. Being an independent predictor of survival, EVLW can present a landmark in the management of critically ill patients requiring fluid and vasoactive drug support.
The measurement of EVLW may play an important role in the fluid management of critically ill patients since a positive fluid balance has been repeatedly shown to be independently associated with worst outcome [48]. Moreover, improved outcome has been shown in critically ill patients when their fluid management was guided by EVLW compared to management guided by the pulmonary artery catheter [5]. More recently it was shown that fluid loading was associated with an increase in EVLW of ≥10% in 21% of critically ill patients [64]. An early diagnosis of the pathological accumulation of EVLW during resuscitation may allow for earlier interventions and considerable changes in the therapeutic plan [64]. Finally, frequent determination of EVLW may identify the point when de-resuscitation should be started, namely, the institution of an aggressive negative fluid balance once the hemodynamic status stabilizes.
In general, patients with acute lung injury may benefit from management guided by EVLW [4,5]. In those patients, there is a need to control EVLW when developing pulmonary edema, massive fluid shifts, and severe changes in microvascular permeability. Such changes are known to occur in numerous critical care conditions, i.e., sepsis, burns, non-cardiogenic (ALI and ARDS) and cardiogenic lung edema, multiple trauma with severe
blood loss, ischemia/ reperfusion injury etc. [65,66]. Thus, in principle, any critical illness associated with shock and tissue hypoperfusion which is refractory to fluid resuscitation is a potential subject for EVLW monitoring, including in children [67]. In such a scenario, management according to the EVLW may help in diagnosing and treating pulmonary edema, especially as protocols exist which emphasize that resolution of lung edema can be hastened.
During sepsis-induced pulmonary edema, the accumulation of EVLW occurs before changes in gas exchange, chest X-ray and eventually pressure variables. Furthermore, the latter variables are non-specific tools and moreover potentially influenced by a variety of factors. Several studies have shown that in sepsis commonly used pressures such as the PAOP and right atrial pressure are poor indicators of lung edema [68]. In contrast to
central venous pressure, EVLW correlates with markers of lung injury, including the oxygenation ratio, lung compliance, roentgenogram quadrants, and lung injury score. Interestingly, the day after the onset of severe sepsis, EVLW correlated negatively with platelet count, indicating a role of platelet sequestration in the development of lung edema. Furthermore, endothelin-1 plasma concentrations which may increase pulmonary microvascular permeability and EVLW were positively correlated [53].
With respect to the prognostic properties of EVLW, as early as the 1980’s Sturm described a stepwise increase in mortality with increasing EVLW [69]. As mentioned above, own data showed that EVLW at baseline, SAPS scores, and APACHE scores were significant predictors of mortality. In particular, patients with ARDS had a significantly higher EVLW (14.9 ml/kg) than other patients. Also, subgroup analysis indicated that in patients
with sepsis, non-survivors had a significantly higher EVLW than survivors [26].
More than two decades ago, Eisenberg et al. [4] had prospectively evaluated a protocol that included EVLW instead of PAOP measurements to guide hemodynamic management of critically ill patients. Patients were randomized to receive either protocol management or routine management group. In the routine management group (RM), EVLW measurements were unknown to the primary care physicians. The 2 groups were similar
with respect to age, gender, and severity of illness. In patients with initially high EVLW, EVLW fell to a greater extent in the protocol management group (PM) than in RM patients (18 ± 5 vs. 4 ±- 8% decrease). This difference was even greater in patients with heart failure. No adverse effects on oxygenation or renal function occurred by following the protocol. Mortality for the groups as a whole were similar, but was significantly better for PM patients with initially high EVLW and normal airway pressures (predominantly patients with sepsis or ARDS). For both groups, patients with an initial EVLW > 14 ml/kg had a significantly greater mortality than those with a lesser EVLW: 13 of 15 (87%) vs. 13 of 32 (41%), p< 0.05. The authors concluded that management based on a protocol using EVLW measurements is safe, may hasten the resolution of pulmonary edema, and may lead to improved outcome in some critically ill patients.
In 1992, Mitchell et al. [5] published a randomized, prospective study to evaluate whether fluid management that emphasized diuresis and fluid restriction in patients with pulmonary edema could affect the development or resolution of EVLW and duration of mechanical ventilation and length of ICU stay in critically ill patients. Pulmonary artery catheterization was performed in 101 patients of whom 52 patients were randomized to an
EVLW management group using a protocol based on bedside indicator-dilution measurements of EVLW. The other 49 patients were randomized to a wedge pressure (WP) management group in whom fluid management decisions were guided by WP measurements. A total of 89 patients had pulmonary edema (defined as EVLW > 7 ml/kg ideal body weight). Except for a clinically unimportant difference in mean age, the two groups were
entirely comparable at baseline. The study groups were managed differently, as made obvious by the cumulative input-output of 2,239 ± 3,695 ml in the WP group vs. 142 ± 3,632 ml in the EVLW group. EVLW decreased significantly, and ventilator-days and ICU days were significantly shorter only in patients from the EVLW group. No clinically significant adverse events occurred as a result of following the EVLW group’s algorithm. Despite several limitations, this study found a lower positive fluid balance, especially in patients with pulmonary edema regardless of cause, associated with a reduced EVLW, less ventilator and ICU days.
The usefulness of EVLW may be obvious in the field of mechanical ventilation and weaning from the respirator. In pigs, the application of 10 cm H2O of PEEP reduced EVLW in a time-dependent manner and maximum protective effect was achieved if it was applied immediately after lung injury production [70]. Colmereno-Ruiz [71] showed in an animal model of ARDS that inappropriate mechanical ventilation (no PEEP, high tidal volume of 12 ml/kg) aggravated lung damage as estimated by EVLW when compared to a protective mode (PEEP 10 cmH2O, tidal volume 6 ml/kg). Zeravik et al. [72] studied patients with ALI and suggested that EVLW may be useful in deciding when to switch from controlled mechanical ventilation to assisted spontaneous breathing mode (EVLW <11 ml/kg). Thus, EVLW may be helpful in guiding fluid management and respirator treatment.
In patients undergoing cardiac surgery, Goepfert et al. [73] studied an algorithm including an EVLW maximum of 10 ml/kg as a limit for fluid treatment. While historical control and goal-directed group (each n=40) had no difference in hard criteria (length of ICU stay or mortality), duration of catecholamine and vasopressor dependence was shorter, and duration of mechanical ventilation and time to achieving status of fit for ICU
discharge was shorter in the study group. EVLW may be of value as an indicator for the prognosis and severity of illness in patients with ALI and ARDS. EVLW-guided therapy has the potential to reduce the duration of mechanical ventilation, ICU length of stay and even reduce mortality in critically ill patients. While systems for the measurement of EVLW are being introduced into the market [74], larger trials are warranted to confirm these findings in the future.
Conclusion
Particularly in patients with ARDS, inflammatory processes in the lungs may increase capillary permeability, causing the accumulation of EVLW which is associated with lung edema and a significant reduction in pulmonary function. EVLW can be safely measured at the bedside by transpulmonary indicator dilution and may be useful for clinical management. As has been shown in clinical and experimental studies, single
transpulmonary thermodilution correlates closely with gravimetry and the transpulmonary double indicator dilution technique. Dynamic changes in EVLW are of obvious clinical value allowing close monitoring of pulmonary edema at the bedside. EVLW has been demonstrated to correlate with the severity of lung damage in sepsis and ARDS and to have prognostic properties. Thus, monitoring of EVLW seems to be a promising tool
in the early goal-directed therapy of critically ill patients, with further clinical studies required to demonstrate the benefit of such a strategy.
Key messages:
The extravascular lung water as a measure of pulmonary edema can be derived accurately by single transpulmonary thermodilution. In particular, in patients with ARDS the extravascular lung water and its changes cannot be estimated by the hydrostatic component alone. The extravascular lung water is of prognostic relevance in critically ill patients and an independent factor for survival. Goal directed treatment strategies including the extravascular lung water have to potential to shorten the length of mechanical ventilation and stay in the ICU. Future studies focusing on improving outcome of critically by an EVLW guided treatment in critically ill patients are required.
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