Decrease In Extravascular Lung Water Research Articles

High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS.

The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium. Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated. No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR. HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

The relationship between extravascular lung water and oxygenation in three patients with influenza A (H1N1)-induced respiratory failure

SummaryThis case series reports the correlation between extravascular lung water (EVLW) and the partial arterial oxygen pressure/fractional inspiratory oxygen (PaO2/FiO2) ratio in three patients with severe influenza A (H1N1)-induced respiratory failure. All patients suffered from grave hypoxia (PaO2, 26–42 mmHg) and were mechanically ventilated using biphasic airway pressure (PEEP, 12–15 mmHg; FiO2, 0.8–1) in combination with prone positioning at 12 hourly intervals. All patients were monitored using the PICCO® system for 8–11 days. During mechanical ventilation, a total of 62 simultaneous determinations of the PaO2/FiO2 ratio and EVLW were performed. A significant correlation between EVLW and the PaO2/FiO2 ratio (Spearman-rho correlation coefficient, –0.852; p < 0.001) was observed. In all patients, a decrease in EVLW was accompanied by an improvement in oxygenation. Serum lactate dehydrogenase levels were elevated in all patients and significantly correlated with EVLW during the intensive care unit stay (Spearman-rho correlation coefficient, 0.786; p < 0.001). In conclusion, EVLW seems increased in patients with severe H1N1-induced respiratory failure and appears to be closely correlated with impairments of oxygenatory function.

High fluid volume removal with continuous renal replacement therapy as a therapeutic option for early posttraumatic acute respiratory distress syndrome

The increase in vascular permeability, due to capillary leakage, seems to be responsible for high density on CT lung examination and worsening of gas exchange in acute respiratory distress syndrome (ARDS) patients. An improvement of the PaO2/FiO2 ratio and ARDS reversal following lung water removal has been shown. The aim of our study was to investigate whether hourly depletion of high fluid volume through continuous renal replacement therapy (CRRT) could reverse posttraumatic ARDS. The body water redistribution in different compartments can lead to a rapid decrease in extravascular lung water (EVLW).

Lung Fluid Balance During Development

After completing this article, readers should be able to: 1. Describe the major driving forces for liquid formation in and liquid removal from the lumen of the fetal lung. 2. Delineate the role of a normal volume of liquid within the lumen of the fetal lung for normal lung growth during development. 3. Describe the effects of labor on Na,K-ATPase activity in lung epithelial cells and clearance of lung liquid after birth. 4. Explain the route by which most residual liquid drains from the lung. 5. List the conditions associated with preterm birth that may contribute to delayed removal of fetal lung liquid. Curious students of mammalian development recognized more than a century ago that the lungs are filled with liquid during fetal life, (1) but the origin of that liquid remained obscure until 1948, when an unexpected discovery by two French scientists dispelled the prevailing view that fetal lung liquid derived from intrauterine inhalation of amniotic fluid. In studies designed to explore the ontogeny of the pituitary-adrenal axis, tracheal ligation of fetal rabbits for 9 days resulted in fluid distention of the lungs. (2) This serendipitous finding, subsequently confirmed and embellished by others, (3)(4)(5) established that the fetal lung itself, rather than the amniotic sac, is the source of the liquid that fills the lung during development. This liquid forms a slowly expanding structural template that prevents collapse and promotes growth of the fetal lung. Subsequent studies, conducted mostly with sheep, showed that liquid in the lumen of the fetal lung forms as a result of chloride secretion in the respiratory epithelium, (6)(7) a process that can be inhibited by diuretics that block Na,K-2Cl cotransport. (8)(9) In vitro experiments using cultured explants of lung tissue and monolayers of epithelial cells harvested from human fetal lung have …

Surfactant reduces extravascular lung water and invasion of polymorphonuclear leukocytes into the lung in a piglet model of airway lavage

Acute respiratory distress syndrome (ARDS) in newborns and young infants is linked with an inflammatory response of the lungs which affects the capillary-alveolar permeability, epithelial integrity and type I and II pneumocyte function. Abundant extravascular lung water with a high protein content inactivates surfactant together with the enzymatic action of polymorphonuclear leukocytes (PMNL). We asked if a decrease in extravascular lung water and a reduction in lung infiltration with PMNL could be achieved by surfactant administration (Curosurf®) within 6h of mechanical ventilation when given in a newborn piglet model of repeated airway lavage. Improvements in gas exchange and lung mechanics were predominantly caused by resorption of extravascular lung water rather than by the reopening of alveolar atelectases. PMNL were significantly reduced in the bronchoalveolar lavage fluid after 6h of mechanical ventilation. However, acute phase cytokines (IL-6, TNF-α) remained unchanged, except for IL-8 which increased after administration of surfactant. We conclude that the decrease in extravascular lung water and in infiltration with PMNL following surfactant administration is accomplished within 6h through mechanisms different from attenuation of pro-inflammatory cytokines. Surfactant treatment for newborn and infant ARDS might therefore improve fluid overload and atelectasis and reduce PMNL infiltration.

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

Effects of inhaled nitric oxide and surfactant treatment on lung function and pulmonary hemodynamics in bronchoalveolar-lavage-induced respiratory failure.

Our aim was to study whether inhaled nitric oxide (iNO) moderates respiratory failure induced by bronchoalveolar lavage (BAL) without severe pulmonary hypertension. The following successive treatments, interrupted by 20-30-min rest periods, were given to piglets: iNO (20 ppm for 20 min), exogenous surfactant, iNO, Nomega-nitro-L-arginine methyl ester (L-NAME), and iNO. The controls inhaled NO first after L-NAME. Lung mechanics and hemodynamics were measured serially. The pulmonary to systemic arterial pressure ratio decreased during iNO and tended to increase after its discontinuation. In contrast, the iNO-induced decreases in severity of respiratory failure were not reversible during the rest periods. In a second experiment, iNO/placebo and surfactant containing (3)H-labeled dipalmitoyl phosphatidylcholine were given to rabbits. The surfactant aggregates and the surface activity from postmortem BAL, and extravascular lung water, were studied. Inhaled NO improved the surface activity and increased the large surfactant aggregates. There was no detectable decrease in extravascular lung water. The results suggest that a low dose of iNO has a beneficial effect on the gas exchange that is in part unrelated to its effect on the pulmonary vasculature.

Acute affect of mitral calve replacement on extravascular lung water in patients receiving colloid or crystalloid priming of cardiopulmonary bypass

Despite numerous studies on extravascular lung water (EVLW) in patients undergoing coronary artery bypass surgery, few data are available on the perioperative time course of EVLW in patients undergoing mitral valve replacement for mitral valve insufficiency (MVI). We have investigated 26 patients undergoing elective mitral valve replacement in order to determine the influence of the preoperative degree of mitral valve insufficiency (degree III or IV) and the effect of different priming solutions for cardiopulmonary bypass. Crystalloid priming with Ringer's lactate was compared with human albumin priming solution. Measurement of EVLW was performed using the thermo-dye dilution technique, before and 1, 6 and 24 h after surgery. Before operation, EVLW is increased significantly in patients with MVI degree IV (MVI-degree IV) compared with patients with degree III (MVI-degree III) and patients undergoing coronary artery bypass surgery. During the postoperative time course a significant decrease in EVLW was observed in patients with MVI-degree IV whereas in patients with MVI-degree III the amount of EVLW did not change. However, compared with patients undergoing coronary artery bypass surgery, EVLW remained above normal in both groups. There was no interaction between the type of priming solution and the postoperative time course of EVLW, and no differences in respiratory variables or duration of mechanical ventilation were observed between groups.

Interest of a Therapeutic Optimization Strategy in Severe ARDS

Evaluate the interest of the response to a therapeutic optimization as a predictor of prognosis in ARDS. Prospective study. ICU of a University Hospital. Thirty-six consecutive patients with severe ARDS addressed for extracorporeal carbon dioxide removal (ECCO2R). We studied the response during the first 2 days after arrival to the therapeutic optimization strategy consisting in a combination of the following: (1) decrease in extravascular lung water (diuretics or hemofiltration); (2) selection of the best ventilatory mode; (3) permissive hypercarbia; and (4) correction of hypoxemia by alveolar recruitment, additional continuous oxygen insufflation, body position changes (prone position), inhaled nitric oxide, enhancement of hypoxic pulmonary vasoconstriction with almitrine, and drainage of pleural or mediastinal effusions. In patients remaining severely hypoxemic despite these modalities, ECCO2R was then proposed. Thirty-six patients were addressed after 8.3+/-5.5 days of mechanical ventilation. On arrival, mean simplified acute physiologic score was 46.8+/-14.2, multiple system organ failure score was 1.8+/-1.6, Murray score was 3.4+/-0.4, PaO2 was 75.3+/-31.3 (fraction of inspired oxygen [FIO2]=1) for a positive end-expiratory pressure level of 12.3+/-3.4 cm H2O. Nineteen of 36 patients improved their gas exchange within 2 days and their mortality was 21%. The seventeen remaining patients did not improve PaO2/FIO2; PaCO2 and airway pressures remained high and their mortality was 88%. This different response to therapeutic optimization appeared using stepwise logistic regression as the most predictive factor for mortality (p<0.05). In patients with severe ARDS, the response to an early performed therapeutic optimization used to improve hypoxemia appeared to be a highly discriminant factor distinguishing deceased from surviving patients.

Microemboli reduce phase III slopes of CO 2 and invert phase III slopes of infused SF 6

We investigated the effect of increasing doses of intravenously infused glass microspheres (mean diameter 125 μm) on gas exchange in anesthetized, heparinized, mechanically ventilated goats ( Vt= 16–18ml/kg). Breath-by-breath CO 2 expirograms were collected using a computerized system (Study A) during the infusion of a total of 15 g of microspheres. We found a 50% decrease in extravascular lung water by indicator dilution with a corresponding doubling of alveolar dead space ( Vdalv). Airways deadspace ( Vdaw) decreased by 13 ml (10%) and mean normalized phase III slope for CO 2 decreased from 0.23 to −0.08 L − becoming negative in 3 of 5 animals. In a second study (Study B), simultaneous breath-by-breath CO 2 and infused SF 6 expirograms were collected using a infrared CO 2 analyzer and a mass spectrometer. Under baseline conditions Vdaw for CO 2 was smaller than for SF 6 and the ratio of the phase III slope for SF 6 to the phase III slope for CO 2 was 1.39. Following embolization there were no differences in Vdaw between the two gases, however, the phase III slope for CO 2 became either slightly negative or extremely flat, while the phase III slope for SF 6 became negative in 73% of the breaths (−0.17 L −1, P < 0.05). Negative phase III slopes have been predicted by a single path model when blood flow is confined to the most mouthward generations of the acinus (Schwardt et al., Ann. Biomed. Engin, 19: 679–697, 1991). The agreement between the numerical model and the experimental data is consistent with a serial distribution of blood flow within the acinus.

Videodensitometry and chest radiography in the evaluation of pulmonary blood flow and pulmonary oedema in a porcine model of early adult respiratory distress syndrome.

The adult respiratory distress syndrome was induced in pigs (n = 11) by a continuous infusion of E. coli endotoxin in order to evaluate the use of radiographic videodensitometry and chest radiography for assessment of pulmonary circulation and pulmonary oedema. A further aim was to determine the effect of an ionic contrast medium, Urografin 60%, on extravascular lung water (EVLW). The infusion resulted in a decline in arterial oxygen tension. Mean pulmonary arterial pressure increased, and cardiac output decreased, resulting in a marked rise in pulmonary vascular resistance. EVLW increased moderately. The corresponding variables in control animals (saline infusion; n = 5) changed very little. Good correlations were found (r = 0.87-1.0) between absolute flows as measured by the thermodilution technique and relative flows as determined by videodensitometry in animals with pulmonary damage. In the endotoxin group there was a significant correlation (r = 0.75) between the change in EVLW from baseline to the final measurement (at 6 hours) and the corresponding change in radiographic density. Radiographic signs of pulmonary damage were sparse. Only 3 of 11 animals displayed increased radiographic density of the lung parenchyma indicative of pulmonary oedema. Pleural effusion developed in 4 animals. Injection of Urografin 60%, 1 ml X kg-1, caused a slight but significant decrease in EVLW. We propose that at this concentration and dosage the contrast medium acts mainly as an osmotic diuretic.

Ultrafiltration During Cardiopulmonary Bypass: Laboratory Evaluation and Initial Clinical Experience

Ultrafiltration during crystalloid hemodilution cardiopulmonary bypass (CPB) was evaluated in two groups of mongrel dogs: in one group during 2 hours of CPB with the heart empty and beating and in the other during 90 minutes of cold cardioplegic arrest followed by 30 minutes of recovery. In both groups, the accumulation of extravascular lung water was less in the dogs undergoing ultrafiltration than in control animals. In 10 patients with clinical evidence of severe fluid overload, ultrafiltration was employed during CPB. The amount of fluid removed ranged from 1,700 to 6,100 ml (mean, 3,240 ± 1,481 ml [standard deviation]) and resulted in an average intraoperative fluid balance of − 901 ± 2,537 ml, a weight gain of 1.9 ± 2.5 kg, and a decrease in extravascular lung water from 1,132 ± 183 ml to 919 ± 267 ml ( p = 0.209). Ultrafiltration is a safe, effective means of removing body water and of preventing further accumulation of such water during hemodilution CPB.

Dynamics of pulmonary water before and after birth.

In fetal life an electrochemical gradient across the pulmonary epithelium causes liquid to flow from the microcirculation of the lungs through the interstitium into potential air spaces. That liquid is rich in chloride (greater than 150 meq/l) and almost free of protein (less than 0.03 g/dl). At birth rapid reversal of the direction of liquid flow is essential for a smooth transition from placental to pulmonary gas exchange. Removal of liquid from the lungs begins even before birth. In fetal rabbits and lambs, a substantial decrease in extravascular lung water occurs late in gestation and during labor. When breathing begins, transpulmonary pressure inflates the lungs and displaces residual liquid from terminal respiratory units into the interstitium. Fluid accumulates in connective tissue spaces surrounding large pulmonary blood vessels, distant from sites of gas exchange. The concentration of protein in the interstitium decreases, thereby increasing the transvascular gradient of protein osmotic pressure. Air entry into the lungs also decreases hydraulic pressure in the pulmonary microcirculation and increases pulmonary blood flow, which expands microvascular surface area for fluid exchange in the lungs. These developments facilitate reabsorption of water into the pulmonary vascular bed. In lambs, the postnatal increase in lung lymph flow is small and transient, accounting for only 10-15% of the total amount of liquid drained from the lungs after birth. Normally, the pulmonary microcirculation directly absorbs most of the fetal lung liquid that is present at birth.

1628 REMOVAL OF LIQUID FROM THE LUNGS OF LAMBS BEFORE AND AFTER BIRTH

Labor decreases lung water in fetal rabbits (Bland et al, Am J Obstet Gynec 135:364, 1979). To see if labor would have the same effect in lambs, we measured the amount of blood and extravascular water in the lungs of 15 late-term lambs (term=147d) killed either without prior labor (n=6), late in labor (n = 4), or 6 h after spontaneous vaginal birth (n=5). Summary (X± sx):Labor was associated with a 53% increase in lung blood and a 36% decrease in extravascular lung water. These results indicate that the lungs shed 11.6 ± 1.5 ml water/kg body weight before birth, and 6.0±0.5 ml water/kg body weight after birth. In the 5 lambs killed after birth, we measured lung lymph flow before and during labor, and for 6 h after breathing began. Lymph flow was unaffected by labor, but increased transiently after birth, as liquid entered the interstitium from air spaces. The postnatal increase in lymph flow accounted for 13-18% of the liquid removed from the lungs after birth. We conclude that in lambs (1) lung blood increases and lung water decreases before birth, and (2) the pulmonary circulation directly absorbs more than 80% of the liquid expelled from the lungs after birth.