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Extravascular lung water.

Extravascular lung water (idQw1) is measured in vivo from the difference in mean transit times, computed by extrapolating the dilution curves, of two indicators, one freely diffusible, the other confined to the intravascular space. Using 3H2O it has been shown that idQw1 is smaller than the amount of extravascular water obtained from the difference between wet and dry lung weight (Qw1). Extrapolation allows one to use dilution curves for a short time, i.e., up to onset of obvious recirculation. Clearing the dilution curves or recirculation by deconvolution extends the observation time, which then becomes limited by sampling duration rather than onset of recirculation. This procedure entails recording recirculating tracers in the pulmonary artery (PA). Dilutions of tracers at input in PA and output in a systemic artery must be related to each other as continuous time functions. This is accomplished by means of a convolution integral. Deconvolution yields the frequency function of water molecule transit time in the extravascular lung space, l(t). In dogs and men, in both normal and edematous lungs, l(t) exhibits a knee and a fairly long tail. Extravascular lung water computed from l(t), idcQw1, agrees with Qw1 and correlates with data on the extravascular thermal volume of the lung and with radiographic findings of lung edema. A radiographic score of pulmonary edema may be used clinically to assess extravascular lung water in cardiac patients and in patients with adult respiratory distress syndrome.

Capillary Permeability↗

Bioimpedance: a novel method for the determination of extravascular lung water.

Extravascular lung water (EVLW) can be measured using the double indicator dilution technique (DD). However, because this method is highly invasive and complicated, its clinical used has been limited. In theory, changes in thoracic conductivity, or bioimpedance (BI), can reflect changes in EVLW. However, past studies were unable to directly quantitate changes in EVLW since the contribution of dynamic variables such as ventricular volumes, hematocrit (HCT), and EVLW to this impedance signal could not be discerned. Recent studies have shown that a thermodilution pulmonary artery catheter mounted with a fast response thermistor accurately measures right ventricular end-diastolic volume (RVEDV). With changes in the RVEDV and HCT known, the contribution of EVLW to the bioimpedance signal may be isolated and used to more directly measure changes in EVLW. This hypothesis was tested by creating acute sepsis in seven pigs by infusion of Pseudomonas aeruginosa. Changes in EVLW from baseline were measured using DD at 30 min and at 1, 2, and 4 hr and compared with the change in EVLW computed from a mathematical model comprising the measured changes in BI, RVEDV, and HCT at the same time points. Changes in EVLW using DD and BI were significantly correlated over the length of the study (r = 0.85, P less than 0.01). In early sepsis (30 min), BI overestimated EVLW when compared with DD (P less than 0.05). However, at 1, 2, and 4 hr there was no significant difference between the two methods. In conclusion, the use of bioimpedance and a volumetric catheter may provide a relatively simple and reliable method for continuously monitoring changes in EVLW in the intensive care setting.

Animals↗

[Bedside determination of extravascular lung water].

Extravascular lung water (EVLW) was measured at the bedside in 12 patients with the thermal-green dye double indicator dilution method using a microprocessor. The EVLW ranged from 3.3 to 17.2 ml/kg body weight; in patients without pulmonary problems we have found an average EVLW of 5.7 ml/kg body weight. The method involves easy calculations and is reproducible and accurate.

Body Water↗

Effect of cardiac output on extravascular lung water.

Extravascular lung water (EVLW) and cardiac output (CO) were determined in 21 mongrel dogs using the thermal-green dye double indicator dilution technique. In 12 of the animals the renal vessels were ligated bilaterally to increase peripheral resistance and reduce cardiac output without altering actual EVLW. Measurements before and after renal pedicle ligation revealed an average 47 per cent decrease in cardiac output with an 11 per cent increase in measured lung water. In the remaining nine animals an external arteriovenous fistula was constructed to reduce afterload and increase cardiac output. In the baseline state, opening the fistula caused a 63 per cent increase in cardiac output with a simultaneous five per cent decrease in measured EVLW. This second group of animals was then given intravenous acid sufficient to cause 30-50 per cent increases in EVLW. Measurements of EVLW and CO with the fistula open and closed were continued for three hours. The inverse relation between cardiac output and EVLW continued. The results of these experiments show that cardiac output does exert a small effect on the measurement of EVLW.

Animals↗

Effects of adenosine on extravascular lung water content in endotoxemic pigs.

OBJECTIVE: To investigate whether adenosine protects against endotoxin-induced increments in extravascular lung water content. DESIGN: Prospective, randomized, animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one anesthetized juvenile pigs. INTERVENTIONS: The animals were divided into two groups subjected to endotoxin infusion: Endotoxin alone (n = 7), or endotoxin combined with adenosine infusion (n = 7) administered during the whole experimental period. Two other groups were exposed to anesthesia alone (n = 4) or adenosine infusion alone (n = 3), respectively. MEASUREMENTS AND MAIN RESULTS: Central hemodynamic variables and extravascular lung water, as assessed by the thermal dye dilution double indicator technique, were monitored. Plasma endothelin-1 concentrations were measured hourly. Extravascular lung water increased significantly in response to endotoxemia (p <.001) along with an increase in pulmonary microvascular pressure (P(mv) [p <.01]). Although the Pmv increased less in endotoxemic animals exposed to adenosine infusion, no intergroup difference was found. From 4 through 6 hrs, adenosine-treated pigs displayed only half of the extravascular lung water content of nontreated animals (p <.01). The latter did not differ from that of anesthetized controls receiving anesthesia or adenosine alone. Adenosine administered alone had no effect on P(mv). In pigs receiving adenosine alone, extravascular lung water content reached nadir after 3 hrs. In both endotoxin groups, plasma endothelin-1 concentration increased two-fold, peaking 4-6 hrs after the start of endotoxin infusion (p <.001). CONCLUSIONS: The endotoxin-induced increase in lung extravascular water was hampered by intravenously infused adenosine in the presence of a nonsignificantly reduced microvascular pressure. This leaves reduced microvascular permeability the most likely reason for the beneficial effect of adenosine.

Adenosine↗

Extravascular lung water after extracellular fluid volume expansion in dogs.

We have compared extravascular lung water after extracellular fluid volume expansion with that predicted from lung sucrose space measured in control dogs. In control lungs mean extravascular water:dry weight ratio was 3.81 +/- 0.16 (SD) (n = 5) and extravascular sucrose space/dry weight was 1.79 +/- 0.45 (n = 4). After acute expansion of extracellular fluid volume by 10% of body weight mean extravascular water:dry lung weight was 4.17 +/- 0.27 (m = 5), less than half the predicted increase to 4.63 +/- 0.19, suggesting some degree of protection. After 20% (n = 4), 30% (n = 2), and 40% (n = 1) expansion, no protection was demonstrated and there was considerable scatter of lung water at each infusion volume. When volume expansion increased pulmonary capillary intravascular forces (due to decreased protein osmotic pressure and increased hydrostatic pressure) by more than 20 cmH2O there was a linear increase in extravascular lung water with increasing intravascular forces. Three dogs did not conform to this relationship and had disproportionately large increases in lung water, possibly due to alveolar flooding.

Animals↗

Ultrasound lung comets: a clinically useful sign of extravascular lung water.

Assessment of extravascular lung water is a challenging task for the clinical cardiologist and an elusive target for the echocardiographer. Today chest x-ray is considered the best way to assess extravascular lung water objectively, but this requires radiology facilities and specific reading expertise, uses ionizing energy, and poses a significant logistic burden. Recently, a new method was developed using echocardiography (with cardiac probes) of the lung. An increase in extravascular lung water-as assessed independently by chest computed tomography, chest x-ray, and thermodilution techniques-is mirrored by appearance of ultrasound lung comets (ULCs). ULCs consist of multiple comet tails originating from water-thickened interlobular septa and fanning out from the lung surface. The technique requires ultrasound scanning of the anterior right and left chest, from the second to the fifth intercostal space. It is simple (with a learning curve of < 10 examinations) and fast to perform (requiring < 3 minutes). ULC assessment is independent of the cardiac acoustic window, because the lung on the anterior chest is scanned. It requires very basic 2-D technology imaging, even without a second harmonic or Doppler. ULCs probably represent an ultrasonic equivalent of radiologic Kerley B-lines. On still-frame assessment, cardiogenic watery comets can be difficult to distinguish from pneumogenic fibrotic comets, although the latter are usually more localized and are not dissolved by an acute diuretic challenge. Functionally, ULCs are a sign of distress of the alveolar-capillary membrane, often associated with reduced ejection fraction and increased pulmonary wedge pressure. The ULC sign is quantitative, reproducible, and ideally suited to complement conventional echocardiography in the evaluation of heart failure patients in the emergency department (for the differential diagnosis of dyspnea), in-hospital evaluation (for tailoring diuretic therapy), home care (with portable ultrasound), and stress echocardiography lab (as a sign of acute pulmonary congestion during stress). In conclusion, ULCs represent a useful, practical, and appealingly simple way to image directly extravascular lung water.

Artifacts↗

Use of diazepam for interpreting changes in extravascular lung water.

Estimates of extravascular lung water volume (Qew) by use of the multiple indicator-dilution method with a hydrophilic indicator such as tritiated water, along with a vascular reference indicator, depend not only on tissue hydration but also on tissue perfusion. Separation of these effects might be facilitated if both hydrophilic and lipophilic indicators were used, with the assumption that the extravascular volume accessible to the lipophilic indicator would be independent of hydration. We found that in isolated perfused dog lung lobes the extravascular volume accessible to the lipophilic amine [14C]diazepam (Qed) was inversely proportional to the albumin concentration of the perfusate. This suggested that while the bolus was in the lungs, only a small fraction of the diazepam was in the aqueous phase of either lung tissue or perfusate. Changing the flow rate over a fairly wide range had little influence on the pattern of the tritiated water or [14C]diazepam effluent concentration curves when time was normalized to the lobar mean transit time. This suggests that the association of the diazepam with both the plasma albumin and the lipoid fraction of the tissue was in very rapid equilibrium on the time scale of a single pass through the lung lobe and that there was little barrier to its diffusion to and from the tissue. When the extravascular water volume was increased by either raising the hydrostatic pressure or instilling saline into the airways, both Qew and Qew/Qed increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Thermal dye measurements of extravascular lung water in critically ill patients. Intravascular Starling forces and extravascular lung water in the adult respiratory distress syndrome.

To assess the concurrent influence on extravascular lung water (EVLW) content of the intravascular Starling forces, the pulmonary capillary wedge pressure (PCWP), and the colloid osmotic pressure (COP), we measured EVLW by the thermal green dye technique in 174 patients with and without radiographically defined pulmonary edema; in the former group, patients with cardiac (CPE) and noncardiac (NCPE) causes of pulmonary edema were compared (study A). In 119 patients, EVLW was again measured one to three days later (study B). Patients with CPE demonstrated a significantly lower EVLW (9.3 +/- 3.9 ml/kg) (mean +/- SD) than patients with NCPE (14.5 +/- 4.9 ml/kg; p less than 0.05), despite a higher mean PCWP in the former group (20 +/- 7 mm Hg) than in the latter (12 +/- 6 mm Hg; p less than 0.05). In patients potentially with only a hydrostatic cause of pulmonary edema in study A, regression analysis demonstrated the following: EVLW = 3.2 + 0.30 PCWP (r2 = 0.38; p less than 0.005); and in patients with NCPE, EVLW = 10.9 + 0.304 PCWP (r2 = 0.17; p less than 0.01). In study B the change (delta) in EVLW between the two studies was described as follows: delta EVLW = 0.25 + 0.173 delta PCWP (p less than 0.01) + 0.663 group NCPE (p, not significant) + 0.236 group NCPE X delta PCWP (p less than 0.01). This latter equation indicated that the EVLW content manifested a greater change with concurrent alterations in the PCWP in patients with NCPE than was found in patients with only a hydrostatic influence to EVLW formation. Therefore, NCPE is characterized by a greater measurable thermal green dye EVLW than is observed in CPE at any given PCWP, and the PCWP synergistically influences EVLW accumulation in both CPE and NCPE.

Adult↗

In vivo validation of the thermal-green dye technique for measuring extravascular lung water.

Assessment of extravascular lung water (EVLW) is imprecise in vivo, yet of both clinical and investigative relevance in patients with cardiac disease. Recently, a double-indicator method using thermal-green dye has been proposed as a nondestructive technique for in vivo quantification of EVLW. In our 5-yr study, indocyanine green dye was used as the intravascular indicator and heat as the diffusible indicator in 44 control dogs, 74 dogs administered intravenous oleic acid, 63 dogs in whom left atrial pressure was altered with a left atrial balloon, and 31 dogs with low-output cardiac failure (electrical shock and complete heart block). In these animals, in vivo measures of EVLW correlated closely with standard gravimetric techniques (r = 0.87, p less than .001), although the indicator dilution technique tended to underestimate actual lung water at higher volumes. In an additional 26 dogs, fluid (lactated Ringer's solution) was administered directly into a distal pulmonary airway, producing alveolar rather than interstitial edema. In these animals, as the infused volume was increased, the thermal technique underestimated consistently the actual amount of infused fluid. Nonetheless, we conclude that in most clinical and experimental situations where moderate changes in lung water are anticipated, this technique can provide reasonable estimates of extravascular fluid accumulation.

Animals↗

Theoretical and practical considerations of measuring extravascular lung water.

The volume of extravascular lung water is currently measured in vivo from the difference in mean transit times of the extrapolated first-pass dilution curves of two indicators, one diffusible and the other confined to the intravascular space. To overcome the limitations of this method, one can prolong the measurement interval, introduce a highly diffusible indicator, or both. In the first case, recirculating indicators are measured and included in the computation by deconvolution of the mean transit time through the lung. In the second case, heat is used as the water indicator. In the third case, not yet explored, recirculating heat would be measured and long thermal transit times uncovered. In view of the complexity of the deconvolution method and the pitfalls of the thermal dilution method, a radiographic score of pulmonary edema may be more useful clinically to assess the volume of extravascular lung water in patients with heart disease or adult respiratory distress syndrome.

Animals↗

How important is the measurement of extravascular lung water?

PURPOSE OF REVIEW: Accurate quantification of extravascular lung water is an important issue in the management of patients with pulmonary edema. The single transpulmonary thermal indicator method has been available since the late 1990s. Its simplicity and easy application make it clinically attractive. RECENT FINDINGS: Several experimental studies have confirmed the accuracy of the single transpulmonary thermal indicator technique in comparisons with postmortem gravimetric method. Whereas changes in extravascular lung water of less than 100-200% are undetectable by other clinically applicable methods of lung injury assessment (chest radiograph and oxygenation), the single transpulmonary indicator has proven highly sensitive to small (10-20%) increases and is therefore useful to detect incipient pulmonary edema. In patients with sepsis or acute respiratory distress syndrome, extravascular lung water measurement offers information unobtainable by other means. SUMMARY: Extravascular lung water can be considered a relevant parameter that contributes to rational management of fluid and vasoactive therapy of many critically ill patients and offers a fuller picture of their overall lung function.

Acute Disease↗

Quantification of regional extravascular lung water in dogs with positron emission tomography, using constant infusion of 15O-labeled water.

Continuous infusion of 15O-labeled water allows a quantitative measurement of the total water pool in the chest region by positron emission tomography (PET). By subsequent inhalation of 11CO the intravascular space (blood pool) can be quantitated as well. After a suitable normalization of the intravascular activities the extravascular water can be determined by subtraction of the blood pool from the water pool. The regional extravascular lung water distribution can be visualized in tomographic slices. The method was validated in an animal experiment using five dogs. They were measured before and after induction of a lung edema by IV injection of oleic acid. The increase of extravascular lung water was monitored by the thermo-dye-dilution method (TDD). The correlation of extravascular lung water as measured by TDD with PET measurements is good (r = 0.94). The PET values agree also with gravimetric lung water determinations. An absolute quantitation of regional extravascular lung water is possible after absorption correction of the PET data via transmission measurements and calibration of the camera system. The uncertainty in the absolute quantification is +/- 20%. In the experiments described here the mean extravascular lung water was 0.13 g/cm3 before and 0.25 g/cm3 after induction of lung edema.

Animals↗

Accuracy and limits of transpulmonary dilution methods in estimating extravascular lung water after pneumonectomy.

STUDY OBJECTIVES: The measurement of extravascular lung water index by double indicator (EVLWIdi) or the measurement of extravascular lung water index by transpulmonary thermodilution (EVLWItt) could be useful after pneumonectomy. Since pulmonary blood flow and volume are altered after pneumonectomy, the validity of these methods is uncertain. This study has compared measurements of EVLWIdi and EVLWItt with measurement of extravascular lung water index by gravimetry (EVLWIg) in a porcine model of pulmonary edema induced after right pneumonectomy. DESIGN: Randomized laboratory study. SETTING: Animal research laboratory. SUBJECTS: Twenty-seven female pigs; mean weight, 35 +/- 5 kg (+/- SD). INTERVENTIONS: The pigs were anesthetized, placed on mechanical ventilation, and allocated to a two-lung group (n = 10) or a right pneumonectomy group (n = 17). EVLWIdi and EVLWItt were measured at baseline, 60 min after pneumonectomy, and 60 min after IV injection of oleic acid (OA). MEASUREMENTS AND RESULTS: There was a good correlation between EVLWIg and EVLWIdi values (r = 0.96, p < 0.0001 in the two-lung group; and r = 0.81, p = 0.02 in the pneumonectomy group). EVLWIdi underestimated EVLWIg in the two-lung group (- 3 mL/kg; 95% confidence interval [CI], - 7 to + 2 mL/kg) and in the pneumonectomy group (- 0.9 mL/kg; 95% CI, - 3.3 to + 1.5 mL/kg). After pneumonectomy, EVLWItt decreased in mean by 27% and increased in mean by 70% after OA acid. There was a good correlation between EVLWIg and EVLWItt values (r = 0.96, p < 0.0001 in the two-lung group; and r = 0.90, p < 0.0001 after pneumonectomy). EVLWItt slightly overestimated gravimetric value in the two-lung group (+ 1.5 mL/kg; 95% CI, - 1.5 to + 4.2 mL/kg) and largely overestimated gravimetric value after pneumonectomy (+ 5 mL/kg; 95% CI, + 3.4 to + 6.8 mL/kg). CONCLUSION: Double-indicator and transpulmonary thermodilution methods could be useful in monitoring extravascular lung water index (EVLWI) after pneumonectomy, but transpulmonary thermodilution largely overestimates EVLWI.

Animals↗

Changes in extravascular lung water during venovenous perfusion.

The accumulation of extravascular lung water was related to changes in plasma colloid osmotic pressure and pulmonary hydrostatic pressures in 12 normal dogs and 13 dogs that had venovenous perfusion for 2 hours at 45 to 70 ml. per kilogram per minute. The venovenous perfusion system included a membrane oxygenator and a roller pump. Net intravascular filtration pressure was calculated from plasma colloid osmotic pressure and pulmonary hydrostic pressures. Rapid accumulation of extravascular lung water occurred in control and bypass animals when net intravascular filtration pressure exceeded zero. At lower filtration pressures, venovenous perfusion did not affect accumulation of extravascular lung water.

Animals↗

[Determination of regional extravascular lung water in heart failure].

The measurement of regional extravascular lung water (rELW) was evaluated by two double-indicator dilution methods both in normals and in patients with congestive heart failure. 1. Time-activity curves in various regions of the lungs were recorded with a positron camera (Cycl. Corp., model 4200) following a bolus application (H2O-15 as a diffusible and CO-15-Carboxyhemoglobin as an intravascular tracer). The mean transit times were computed and the extravascular lung water per unit of plasma volume (ELW/Vp was calculated. Investigations in 4 normals (ELW/Vp = 0.10-0.37, means = 0.22) and 7 patients (ELW/Vp = 0.08-0.57, means = 0.33) showed that due to constraints in the method a clinically useful index of rELW is not yielded with this particularly technique. 2. Total lung water (constant infusion of H2O-15), blood volume (single breath inhaled C-11-O), and extravascular lung water (ELW = total lung water - blood volume) were measured with a positron camera system under steady state conditions. This study showed a relatively homogenous distribution of rELW in 2 normals (0.10-0.14 g/cm3), whereas in 2 patients with congestive heart failure (NYHA III-IV) rELW was about twice as high as in normals and showed significant regional differences (0.17-0.34 g/cm3).

Adult↗

Brain and lungs at risk after cervical spinal cord transection: intracranial pressure, brain water, blood-brain barrier permeability, cerebral blood flow, and extravascular lung water changes.

The early physiopathologic responses to transection of the cervical spinal cord (C-4) were studied in the experimental animal. After transection, increases were seen in the mean arterial pressure, pulmonary capillary wedge pressure, intracranial pressure, brain water, blood--brain barrier permeability, and extravascular lung water with a marked decrease occurring in cerebral blood flow. Pretreatment with an alpha-adrenergic blocker, phentolamine (Regitine Ciba-Geigy Corp.), followed by transection blocked the rise in mean arterial blood pressure and pulmonary capillary wedge pressure but did not affect the increases in intracranial pressure, brain water, blood--brain barrier permeability, and extravascular lung water and decreases in cerebral blood flow. Transection of the cervical spinal cord initiates a complex series of events involving intracranial compliance and pulmonary permeability, placing both brain and lungs at risk.

Animals↗