Changes In Extravascular Lung Water Research Articles

In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury

Background: Acute lung injury is an important cause of respiratory failure in the critically ill patient. It is caused by damage to the alveolar barrier with subsequent alveolar flooding leading...

Extravascular lung water after pneumonectomy and one-lung ventilation in sheep

To compare the single thermodilution and the thermal-dye dilution techniques with postmortem gravimetry for assessment of changes in extravascular lung water after pneumonectomy and to explore the evolution of edema after injurious ventilation of the left lung. Experimental study. University laboratory. A total of 30 sheep weighing 35.6 +/- 4.6 kg. The study included two parts: a pneumonectomy study (n = 18) and an injurious ventilation study (n = 12). Sheep were anesthetized and mechanically ventilated with an FiO2 of 0.5, tidal volume of 6 mL/kg, and positive end-expiratory pressure of 2 cm H2O. In the pneumonectomy study, sheep were assigned to right-sided pneumonectomy (n = 7), left-sided pneumonectomy (n = 7), or lateral thoracotomy only (sham operation, n = 4). In the injurious ventilation study, right-sided pneumonectomy was followed by ventilation with a tidal volume of 12 mL/kg and positive end-expiratory pressure of 0 cm H2O (n = 6) or by ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure of 2 cm H2O for 4 hrs (n = 6). Volumetric variables, including extravascular lung water index (EVLWI), were measured with single thermodilution (STD; EVLWI(STD)) and thermal-dye dilution (TDD; EVLWI(TDD)) techniques. We monitored pulmonary hemodynamics and respiratory variables. After the sheep were killed, EVLWI was determined for each lung by gravimetry (EVLWI(G)). In total, the study yielded strong correlations of EVLWI(STD) and EVLWI(TDD) with EVLWI(G) (n = 30; r = .83 and .94, respectively; p < .0001). After pneumonectomy, both the left- and the right-sided pneumonectomy groups displayed significant decreases in EVLWI(STD) and EVLWI(TDD). The injuriously ventilated sheep demonstrated significant increases in EVLWI that were detected by both techniques. The mean biases (+/-2 SD) compared with EVLWI(G) were 3.0 +/- 2.6 mL/kg for EVLWI(STD) and 0.4 +/- 1.6 mL/kg for EVLWI(TDD). After pneumonectomy and injurious ventilation of the left lung, TDD and STD displayed changes in extravascular lung water with acceptable accuracy when compared with postmortem gravimetry. Ventilator-induced lung injury seems to be a crucial mechanism of pulmonary edema after pneumonectomy.

Changes in extravascular lung water determined with single transpulmonary thermodilution after pneumonectomy and lung resection

Changes in extravascular lung water determined with single transpulmonary thermodilution after pneumonectomy and lung resection

Chest Ultrasonography for the Diagnosis and Monitoring of High-Altitude Pulmonary Edema

The comet-tail technique of chest ultrasonography has been described for the diagnosis of cardiogenic pulmonary edema. This is the first report describing its use for the diagnosis and monitoring of high-altitude pulmonary edema (HAPE), the leading cause of death from altitude illness. Eleven consecutive patients presenting to the Himalayan Rescue Association clinic in Pheriche, Nepal (4,240 m) with a clinical diagnosis of HAPE underwent one to three chest ultrasound examinations using the comet-tail technique to determine the presence of extravascular lung water (EVLW). Seven patients with no evidence of HAPE or other altitude illness served as control subjects. All examinations were read by a blinded observer. HAPE patients had higher comet-tail score (CTS) [mean +/- SD, 31 +/- 11 vs 0.86 +/- 0.83] and lower oxygen saturation (O(2)Sat) [61 +/- 9.2% vs 87 +/- 2.8%] than control subjects (p < 0.001 for both). Mean CTS was higher (35 +/- 11 vs 12 +/- 6.8, p < 0.001) and O(2)Sat was lower (60 +/- 11% vs 84 +/- 1.6%, p = 0.002) at hospital admission than at discharge for the HAPE patients with follow-up ultrasound examinations. Regression analysis showed CTS was predictive of O(2)Sat (p < 0.001), and for every 1-point increase in CTS O(2)Sat fell by 0.67% (95% confidence interval, 0.41 to 0.93%, p < 0.001). The comet-tail technique effectively recognizes and monitors the degree of pulmonary edema in HAPE. Reduction in CTS parallels improved oxygenation and clinical status in HAPE. The feasibility of this technique in remote locations and rapid correlation with changes in EVLW make it a valuable research tool.

How important is the measurement of extravascular lung water?

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. 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. 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.

Pulmonary Oedema following Exercise in Humans

Pulmonary physiologists have documented many transient changes in the lung and the respiratory system during and following exercise, including the incomplete oxygen saturation of arterial blood in some subjects, possibly due to transient pulmonary oedema. The large increase in pulmonary arterial pressure during exercise, leading to either increased pulmonary capillary leakage and/or pulmonary capillary stress failure, is likely to be responsible for any increase in extravascular lung water during exercise. The purpose of this article is to summarise the studies to date that have specifically examined lung water following exercise. A limited number of studies have been completed with the specific purpose of identifying pulmonary oedema following exercise or a similar intervention. Of these, approximately 50% have observed a positive change and the remaining have provided results that are either inconclusive or show no change in extravascular lung water. While it is difficult to draw a firm conclusion from these studies, we believe that pulmonary oedema does occur in some humans following exercise. As such, this is a phenomenon of significance to pulmonary and exercise physiologists. This possibility warrants further study in the area with more precise measurement tools than has previously been undertaken.

Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange.

Sepsis-induced acute lung injury is still associated with high morbidity and mortality. The pathophysiology is complex, and markers of injury include increased extravascular lung water. To evaluate the effects of the novel dual endothelin receptor antagonist tezosentan on endotoxin-induced changes in extravascular lung water and gas exchange, 16 pigs were anaesthetized and catheterized. Twelve animals were subjected to 5 h of endotoxemia. After 2 h, six of these animals received a bolus of tezosentan 1 mg kg(-1) followed by a continuous infusion of 1 mg kg(-1) h(-1) to the end of the experiment at 5 h. Conventional pulmonary and hemodynamic parameters were measured. Extravascular lung water was determined in these pigs after 5 h of endotoxemia, as well as in the four additional nonendotoxemic sham animals. Tezosentan in the current dosage counteracted the deterioration of lung function caused by endotoxin, as measured by dead space, venous admixture, and compliance. In addition, pulmonary hypertension was attenuated. Tezosentan had a marked effect on the endotoxin-induced increase in extravascular lung water that was reduced to levels observed in nonendotoxemic sham animals. These results suggest that endothelin is involved in endotoxin-induced lung injury and the development of pulmonary edema. Dual endothelin receptor antagonism may be of value in the treatment of sepsis-related acute lung injury.

Quantification of lung water by transpulmonary thermodilution in normal and edematous lung

Purpose: To analyze the accuracy of the transpulmonary thermodilution method in the determination of extravascular lung water (EVLW). Material and Methods: Acute lung injury was produced in eight adolescent pigs weighing 28 to 35 kg by bronchoalveolar lung lavage. EVLW was measured by transpulmonary thermodilution method before and after the intratracheal introduction of 250 or 500 mL of saline solution in different lung injury conditions. No corrections for anatomic dead space were made. Results: When 250 mL was introduced, 195 ± 17 mL was detected in normal (uninjured) lungs versus 74 ± 57 mL in edematous (injured) lungs ( P < .05). When 500 mL was introduced, 343 ± 67 mL was detected in normal lungs versus 160 ± 51 mL in edematous lungs ( P < .001). Considering all determinations together, there was a very high negative correlation between the baseline EVLW and the percentage of EVLW detected (r = -0.92, P < .001). Conclusion: The transpulmonary thermodilution method is very accurate to detect changes in EVLW in normal lungs. In edematous lung, this method may underestimate the EVLW.

PEEP decreases atelectasis and extravascular lung water but not lung tissue volume in surfactant-washout lung injury.

To examine the effects of positive end-expiratory pressure (PEEP) on extravascular lung water (EVLW), lung tissue, and lung volume. Experimental animal study at a university research facility. Fifteen adult sheep. All animals were studied before and after saline washout-induced lung injury while ventilated with sequentially increasing PEEP (0, 7, 14, or 21 cmH(2)O). Lung volume was determined by computed tomography and EVLW by the thermal dye dilution technique. Saline washout significantly increased lung tissue volume (21+/-3 to 37+/-5 ml/kg) and EVLW (9+/-2 to 36+/-9 ml/kg). While increasing levels of PEEP reduced EVLW (30+/-7, 24+/-8, and 18+/-4 ml/kg), lung tissue volume remained constant. Total lung volume significantly increased (50+/-8 ml/kg at PEEP 0 to 77+/-12 ml/kg at PEEP 21). Nonaerated lung volume significantly decreased and was closely correlated with the changes in EVLW ( r=0.67). In addition, a highly significant correlation was found between PEEP-induced decrease in nonaerated lung volume and decrease in transpulmonary shunt ( r=0.83). The main findings are as follows: (a) PEEP effectively decreases EVLW. (b) The decrease in EVLW is closely correlated with the PEEP-induced decrease in nonaerated lung volume, making EVLW a valuable bedside parameter indicating alveolar recruitment, similar to measurements of transpulmonary shunt. (c) As excess tissue volume remained constant, however, EVLW may not be suitable to reflect overall severity of lung disease

Electrical Impedance Tomography in the Assessment of Extravascular Lung Water in Noncardiogenic Acute Respiratory Failure

To establish the value of electrical impedance tomography (EIT) in assessing pulmonary edema in noncardiogenic acute respiratory failure (ARF), as compared to the thermal dye double indicator dilution technique (TDD). Prospective clinical study. ICU of a general hospital. Fourteen ARF patients. In order to use the TDD to determine the amount of extravascular lung water (EVLW), a fiberoptic catheter was placed in the femoral artery. Fourteen consecutive ARF patients receiving mechanical ventilation were measured by EIT and TDD. EIT visualizes the impedance changes caused by the ventilation in two-dimensional image planes. An impedance ratio (IR) of the ventilation-induced impedance changes of a posterior and an anterior part of the lungs was used to indicate the amount of EVLW. For the 29 measurements in 14 patients, a significant correlation between EIT and TDD (r = 0. 85; p < 0.001) was found. The EIT reproducibility was good. The diagnostic value of the method was tested by receiver operator characteristic analysis, with 10 mL/kg of EVLW considered as the upper limit of normal. At a cutoff level of the IR of 0.64, the IR had a sensitivity of 93%, a specificity of 87%, and a positive predictive value of 87% for a supranormal amount of EVLW. Follow-up measurements were performed in 11 patients. A significant correlation was found between the changes in EVLW measured with EIT and TDD (r = 0.85; p < 0.005). We conclude that EIT is a noninvasive technique for reasonably estimating the amount of EVLW in noncardiogenic ARF.

Edema development and recovery in neurogenic pulmonary edema

We determined the time course of changes in extravascular lung water (EVLW) that occur after massive sympathetic activation produced by intracisternal veratrine administration in chloralose-anesthetized dogs. Three groups of dogs were studied. In the first group (n = 9), acute increases in EVLW (occurring within minutes) were determined both by measuring extravascular thermal volume and by gravimetric analysis. In the second (n = 6) and third (n = 7) groups, changes in EVLW were followed for 2-3 h after veratrine administration. Extravascular thermal volume was measured in the second group. In the third group, right atrial injections of a vascular indicator (125I-labeled serum albumin) and an extravascular indicator (3HOH) were made while blood was sampled from the pulmonary artery (PA) and left atrium, and EVLW was determined by deconvolution of the left atrial and PA concentration-time curves. Indicator-dilution and gravimetric EVLW increased acutely only in dogs in which PA pressure exceeded 60 Torr, with two- to four-fold increases in EVLW being observed in dogs that developed the highest PA pressures (maximum 94 Torr). Thus, severe edema can develop rapidly after massive sympathetic nervous system activation but requires extreme degrees of pulmonary hypertension. In several dogs after the acute increase in EVLW associated with the pulmonary hypertension, the indicator-dilution EVLW decreased with time. These decreases appear to effect clearance of edema fluid rather than alterations in perfusion.

Effect of indomethacin on increases in leukotriene B 4 and pulmonary edema in response to phorbol ester administration in dogs

The administration of leukotrienes (LTs) into the pulmonary circulation results in edema formation and increased vascular permeability. We reported previously that the administration of phorbol myristate acetate (PMA, 20 μg/kg) to intact anesthetized dogs results in a reduction in circulating white blood cells as well as the development of pulmonary edema concomitant with the appearance of LTs in the lungs. In contrast, when a smaller dose of PMA (10 μg/kg) was administered, neither extravascular lung water nor LTs increased, although there was a similar reduction in circulating white blood cells. In the present study, we used a property of indomethacin, namely, its capacity to augment the formation of LTs, to examine further the relationship between LT generation and pulmonary edema formation in response to PMA administration. In intact pentobarbital-anesthetized dogs pretreated with saline (N = 9), the administration of PMA at a dose of 10 μg/kg, i.v., did not result in any change in extravascular lung water or in LTB 4 present in bronchoalveolar lavage fluid (BALF). In contrast, in six animals pretreated with indomethacin (5 mg/kg), the administration of this dose of PMA resulted in increases in both extravascular lung water (P < 0.05) and LTB 4 (P < 0.05) in BALF. These results provide support for the hypothesis that leukotrienes are requisite for PMA-induced increases in extravascular lung water.

Fluid Balance during Pulmonary Edema: Is Fluid Gain a Marker or a Cause of Poor Outcome?

To evaluate the importance of fluid balance and changes in extravascular lung water (EVLW) on survival in the ICU and short-term outcome in patients with pulmonary edema.Retrospective analysis of data (sorting by survival and "treatment received") from a recent randomized controlled trial of fluid restriction in this population.Medical ICU of a university-affiliated, tertiary-care medical center.Eighty-nine patients (from the previously mentioned study) requiring pulmonary artery catheterization with abnormally high EVLW (greater than 7 ml/kg).When analyzed by survival, the survivors had no significant fluid gain or change in EVLW but decreased wedge pressure and body weight, compared to nonsurvivors. When analyzed by fluid balance, patients who gained less than 1 L of fluid by 36 hours into the study had a better rate of survival (74 percent) than the rest (50 percent; p less than 0.05). Also, the median duration of days on the ventilator, ICU days, and days of hospitalization was approximately half as long for each variable in the group with less than 1 L of fluid gain. Even accounting for baseline differences in the severity of illness, fluid balance was an independent predictor of survival (p less than 0.05). When analyzed by whether or not EVLW decreased by more than 15 percent between the first and last measurement, only patients with ARDS or sepsis had decreased days on the ventilator and ICU days.These data support the concept that positive fluid balance per se is at least partially responsible for poor outcome in patients with pulmonary edema and defend the strategy of attempting to achieve a negative fluid balance if tolerated hemodynamically.

Measurement of extravascular lung water — methods and clinical implications

The estimation of changes in extravascular lung water during different experimental and clinical conditions forms an intriguing field of research. Present methods for the measurement of lung water are difficult to apply in day-to-day clinical practice. Most methods are not only low in accuracy and sensitivity but are also invasive. A new indicator-dilution technique using heavy water and indocyanine green as diffusible and nondiffusible indicators, respectively, may provide us with a new investigative method for longterm bedside estimation of lung water.

Net fluid leakage (LN) in experimental pulmonary oedema in the dog

Net fluid leakage (LN) from the intravascular to the extravascular pulmonary space was estimated in anaesthetised dogs after injection of oleic acid (OA) (n = 8), or after hydrostatic pressure elevation by inflation of a left atrial balloon (n = 5). LN was calculated as the sum of: (i) rate of change in extravascular lung water (delta EVLW), (ii) thoracic lymph flow, and (iii) pleural fluid formation per time unit. Pleural fluid formation was measured in five dogs with hydrostatic or OA induced pulmonary oedema and was 1.8 +/- 0.9 ml/kg/h. In OA-induced pulmonary oedema, LN increased to a peak of 9.2 ml/kg/h within 2 h after OA injection. Thereafter LN fell and was 2-4 ml/kg/h during the succeeding 2-4 h. During hydrostatic pulmonary oedema LN was increased to as much as 13 ml/kg/h, but it became negative, -5 to -8 ml/kg/h (reabsorption of extravascular fluid) as soon as pulmonary vascular pressures returned to normal following deflation of the left atrial balloon. We conclude that in both forms of oedema there is an initial rapid leakage. In OA-induced oedema this leakage continues, although at a slower rate, whereas in hydrostatic oedema there is a considerable net fluid absorption from the pulmonary extravascular to the intravascular space as soon as vascular pressures are brought to normal levels.

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 use 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 < 0.01). In early sepsis (30 min), BI overestimated EVLW when compared with DD ( P < 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.

Five percent human albumin in lactated Ringerʼs solution for resuscitation from hemorrhagic shock

Using an ovine model of acute hemorrhagic shock, we evaluated the utility of 5% albumin in lactated Ringer's (5% ALR) solution as a resuscitation solution. After instrumentation and obtaining baseline values for BP, mean arterial pressure (MAP), pulmonary capillary wedge pressure (WP), CVP, cardiac output, extravascular lung water (EVLW), and blood gases (mixed venous and arterial), animals were rapidly exsanguinated to an MAP of 50 mm Hg. After 30 min at this pressure, measurements were repeated and 5% ALR was administered until two of three variables (WP, MAP, cardiac output) were restored to baseline values. The administration of 5% ALR was continued as needed to maintain baseline values of these variables. Sixty minutes later, data were again recorded. For induction of shock, 15.7 +/- 5.2 ml of blood/kg body weight was removed. Pulmonary artery pressure, WP, MAP, and cardiac output all significantly decreased with shock. After resuscitation, all values except MAP returned to baseline. The resuscitation volume of 5% ALR was 25.2 +/- 18.4 ml/kg. There were no changes in EVLW or intrapulmonary shunt. Oxygen delivery was significantly compromised during shock but returned to baseline after resuscitation. We conclude that in a model such as ours, 5% ALR can reverse the hemodynamic effects of acute hemorrhagic shock.

Lung management during cardiopulmonary bypass: Influence on extravascular lung water

Progressive respiratory insufficiency secondary to cardiopulmonary bypass (CPB) is still a hazard after cardiac surgery. Pathophysiologically, impaired capillary endothelial integrity seems to be the fundamental lesion, followed by increased interstitial fluid accumulation. The reasons for this pulmonary damage age controversial; however, management of the nonperfused lungs during CPB has been widely neglected and may be partly responsible. In this study, 90 patients undergoing coronary artery bypass grafting were randomly divided into six groups (15 patients each) with different management of the lungs during CPB: group 1, lungs collapsed (0/0); group 2, static inflation with +5 cm H 2O and F 1O 2 1.0 (+5/1.0); group 3, static inflation with +5 cm H 2O and F 1O 2 0.21 (+5/0.21); group 4, static inflation with +15 cm H 2O and F 1O 2 1.0 (+15/1.0); group 5, static inflation with +15 cm H 2O and F 1O 2 0.21 (+15/0.21); and group 6, controlled mechanical ventilation as before start of CPB (positive end-expiratory pressure [PEEP +5 cm H 2O; F 1O 2 1.0) (ventilation). In addition to hemodynamic monitoring, extravascular lung water (EVLW) was measured by means of a double-indicator dilution technique with heat and indocyanine green. Measurements were performed after induction of anesthesia, before onset of CPB, and immediately after weaning from bypass, as well as 60 minutes and 5 hours after termination of CPB. Pulmonary gas exchange (PaO 2) and intrapulmonary shunting (Q̇s/Q̇t) were also measured. Starting from comparable, normal baseline values, EVLW was increased in all groups after weaning from CPB, with the most pronounced increase in group 4 (maximum, +35%) and group 5 (+40%). Five hours after CPB, lung water content had normalized, except in groups 4 and 5, which still had values higher than those prior to CPB. (PaO 2) decreased most in these groups (group 4, −109 mm Hg; group 5, −130 mm Hg), and Q̇s/Q̇t increased significantly (group 4, +6.7%; group 5, +6.9%) after bypass. It is concluded that the handling of the lungs during CPB significantly influenced changes in EVLW after bypass. Static inflation with high levels of PEEP, particularly in combination with 100% oxygen, should be avoided due to the risk of an increase in lung water content. Static inflation with moderate PEEP and air seems to be the best way to optimize postbypass pulmonary function.

Pringle法急性肝流入血行遮断の肺血管外水分量におよぼす影響

Pringle法急性肝流入血行遮断の肺血管外水分量におよぼす影響

Noninvasive estimation of extravascular lung water using bioimpedance

Currently, accurate measurements of extravascular lung water (EVLW) are obtained using the double dye dilution technique (DD). However, this method is invasive and complicated and has limited its clinical use. The purpose of this study was to develop a noninvasive method for determining changes in EVLW using bioimpedance (BI) and compare these measurements with DD in a model of acute pulmonary injury. Nine adult dogs were anesthetized and instrumented with a pulmonary artery and an EVLW arterial catheter with EVLW-DD and cardiac output calculated from the dye and thermal dilution curves. Eight external electrodes were placed on the thorax and impedance changes were measured by computer. Changes in EVLW-BI were computed as a function of the thoracic volume and impedance. Cardiac output (CO) from BI was obtained by electronically differentiating the bioimpedance signal. EVLW and CO were measured using DD and BI at 0, 15, 30, and 60 min following injection of oleic acid (0.1 cc/kg). Changes in EVLW were correlated over all time periods using DD and BI ( r = 0.70, P < 0.05); however, several impedance EVLW estimates varied greatly from double dilution methods. There was no difference in computed EVLW using DD and BI at 15, 30, and 60 min following oleic acid infusion ( P > 0.35). CO was significantly correlated using DD and BI ( r = 0.81, P < 0.05). In summary, bioimpedance may hold promise as a noninvasive and continuous means for estimation of EVLW in the critical care setting.