Reduction In Extravascular Lung Water Research Articles

Airway Pressure Release Ventilation Benefits in a Patient with Chronic Lymphocytic Leukemia

Background: Airway pressure release ventilation (APRV) is a novel mode of mechanical ventilation (MV) used in the treatment of acute respiratory distress syndrome (ARDS) for patients with severe hypoxemia with a strategy to prevent ventilator-induced lung injury (VILI). APRV can avert VILI because it can limit alveolar-distending pressures. This is a case report of a 45-year-old man diagnosed with chronic lymphocytic leukemia who later developed community-acquired pneumonia and ARDS. Methods: APRV was applied successfully. Initially, he was unsuccessfully managed on conventional ventilation using an “open-lung” ventilation strategy (high positive end-expiratory pressure, high respiratory rate, and low tidal volume), recruitment maneuvers, and prone positioning. Results: A change in the ventilation mode to APRV resulted in the reduction of extravascular lung water as indicated by a chest X-ray, improvement in the oxygenation indices, and successful liberation from the ventilator. Conclusion: This case report concluded that APRV is safe in patients diagnosed with ARDS if other “open-lung” MV approaches and prone positioning have failed.

Does the antisecretory peptide AF-16 reduce lung oedema in experimental ARDS?

Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS.Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained.Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange.Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.

Application of lung ultrasound surface wave elastography for assessment of extravascular lung water in patients hospitalized with congestive heart failure

Lung ultrasound (LUS) detects the presence of extravascular lung water (EVLW) through the visualization of B-Line artifacts. However, the qualitative nature of LUS limits its effectiveness in serial or longitudinal studies such as evaluating changes in EVLW at different time points in patients undergoing diuretic therapy for congestive heart failure. Lung ultrasound surface wave elastography (LUSWE) is a novel technique using a small handheld device that can measure superficial lung tissue elastic properties. We aimed to evaluate the use of LUSWE to measure quantitative changes in lung elasticity caused by acute changes in EVLW. We performed LUSWE on consecutive days in 14 patients hospitalized for acute congestive heart failure with evidence of pulmonary edema (clinical EVLW). From day#1 to day#2, the patients had an average diuresis of net negative 2.1 l associated with an average decrease in 13 B-Lines by lung ultrasound, signifying a reduction in EVLW. LUSWE analysis demonstrated a significant reduction (p < 0.05) in surface wave velocity in all interrogated intercostal spaces from day#1 to day#2. In summary, LUSWE performed at the bedside was able to demonstrate improvement in lung compliance (decreased elasticity) correlating with a reduction in EVLW in hospitalized patients being treated for congestive heart failure.

Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals

To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p < 0.05), (2) an increase in VC (53.6% ± 28.9% vs. 53.9% ± 52.3%, p < 0.05), (3) a small increase in DLCO (9.6% ± 29.3% vs. 9.9% ± 23.9%, p > 0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged.

Assessment of cardiac output with transpulmonary thermodilution during exercise in humans.

The accuracy and reproducibility of transpulmonary thermodilution (TPTd) to assess cardiac output (Q̇) in exercising men was determined using indocyanine green (ICG) dilution as a reference method. TPTd has been utilized for the assessment of Q̇ and preload indexes of global end-diastolic volume and intrathoracic blood volume, as well as extravascular lung water (EVLW) in resting humans. It remains unknown if this technique is also accurate and reproducible during exercise. Sixteen healthy men underwent catheterization of the right femoral vein (for iced saline injection), an antecubital vein (ICG injection), and femoral artery (thermistor) to determine their Q̇ by TPTd and ICG concentration during incremental one- and two-legged pedaling on a cycle ergometer and combined arm cranking with leg pedaling to exhaustion. There was a close relationship between TPTd-Q̇ and ICG-Q̇ (r = 0.95, n = 151, standard error of the estimate: 1.452 l/min, P < 0.001; mean difference of 0.06 l/min; limits of agreement -2.98 to 2.86 l/min), and TPTd-Q̇ and ICG-Q̇ increased linearly with oxygen uptake with similar intercepts and slopes. Both methods had mean coefficients of variation close to 5% for Q̇, global end-diastolic volume, and intrathoracic blood volume. The mean coefficient of variation of EVLW, assessed with both indicators (ICG and thermal) was 17% and was sensitive enough to detect a reduction in EVLW of 107 ml when changing from resting supine to upright exercise. In summary, TPTd with bolus injection into the femoral vein is an accurate and reproducible method to assess Q̇ during exercise in humans.

Extravascular Lung Water and Sepsis

Extravascular Lung Water and SepsisThe incidence of sepsis has been increasing because of the advancing age of the general population, a greater number of invasive procedures, and more immunosuppressive therapies. Nowadays, the mortality of sepsis is still high, and is still the major cause of morbidity and mortality for patients admitted to an intensive care unit. In sepsis, exaggerated responses might induce organ dysfunction including lung injury and shock, whether the focus is located in the lung or not. Extravascular lung water (EVLW) consists nearly of fluid in the pulmonary interstitial and alveolar spaces. EVLW can be measured at the bedside using the transpulmonary thermodilution technique and has a diagnostic value for the identification of patients. It is an indicator of prognosis and severity of sepsis-induced lung injury. Measurement of EVLW is useful in characterising the severity of respiratory disease, it is also beneficial in the management of patients with sepsis. Increased EVLW is associated with decreased life expectancy in patients with sepsis. Reduction of EVLW at an early stage and a negative fluid balance are associated with a more favorable outcomes.

Effect of NaCl/Hydroxyethyl Starch 200/0.5 on Lung Function and Hemodynamics in Patients Operated on under Extracorporeal Circulation

Objective: to study the effect of 7.2% NaCl/hydroxyethyl starch 200/0.5 on extravascular lung water and respiratory and cardiovascular systems in patients with coronary heart disease (CHD) after myocardial revascularization under extracorporeal circulation (EC). Subjects and methods. A prospective, randomized study was conducted in 40 patients with coronary artery disease. A study group (n=20) received 7.2% NaCl/hydroxyethyl starch 200/0.5; a control group (n=20) had 0.9% NaCl in a dose of 4 ml/kg within 30 min before EC. Extravascular lung water and central hemodynamic parameters were assessed using transpulmonary thermodilution and a Swan-Ganz catheter; respiratory function was estimated by the arterial oxygenation index, alveolar-arterial oxygen tension difference, and venous shunt fraction. Plasma osmolality and Na concentration were determined using an Osmomat 030 device. Conclusion. The intraoperative use of 7.2% NaCl/hydroxyethyl starch 200/0.5 in patients with CHD leads to a significant reduction in extravascular lung water after myocardial revascularization, thereby effectively protecting pulmonary oxygenizing function. The single administration of 7.2% NaCl/hydroxyethyl starch causes a short-term increase in cardiac index and it is a relatively safe in preventing neurological disorders and heart failure. Key words: 7.2% NaCl/hydroxyethyl starch 200/0.5; extravascular lung water, respiratory function, cardiac index, osmolarity.

Postoperative Noninvasive Ventilation

Thesemodificationsoftherespiratoryfunctionoccur early after surgery and are more often transient andcould lead to ARF. The clinical result (severity of theARF) is the product of perioperative-related ventilatoryimpairment and severity of the preoperative pulmonarycondition. Maintenance of adequate oxygenation in thepostoperative period is of major importance, especiallywhen pulmonary complications such as ARF occur. Al-though invasive endotracheal mechanical ventilation hasremained the cornerstone of ventilatory strategy for manyyearsforsevereARF,severalstudieshaveshownthatmor-tality associated with pulmonary disease is largely relatedto complications of postoperative reintubation and me-chanicalventilation.Therefore,majorobjectivesforanes-thesiologists are first to prevent the occurrence of postop-erative complications and second to ensure oxygenadministration and carbon dioxide removal while avoid-ing intubation if ARF occurs. Noninvasive ventilation(NIV) does not require an artificial airway (endotrachealtube or tracheotomy), and its use is well established toprevent ARF occurrence (prophylactic treatment) or totreat ARF to avoid reintubation (curative treatment) (fig.1). Studies show that patient-related risk factors, such aschronic obstructive pulmonary disease, age older than 60yr, American Society of Anesthesiologists class of II orhigher, obesity, functional dependence, and congestiveheart failure, increase the risk for postoperative pulmo-nary complications.

INHALED TEZOSENTAN REDUCES PULMONARY HYPERTENSION IN ENDOTOXIN-INDUCED LUNG INJURY

The vasoconstrictive and proinflammatory peptide endothelin 1 (ET-1) is highly involved in the pathogenesis of sepsis and associated lung injury. Systemic administration of ET-receptor antagonists has been beneficial in experimental pulmonary hypertension. We wanted to study the effects of inhaled tezosentan, a dual endothelin-receptor antagonist on endotoxin-induced pulmonary hypertension, deterioration of gas exchange, and edema formation. After 2 h of endotoxemia, 28 anesthetized, mechanically ventilated pigs were randomized to either inhaled tezosentan 0.5 mg x kg (TEZO(0.5), n = 7), 0.05 mg x kg (TEZO(0.05), n = 7), intravenous 0.5 mg x kg (TEZO(iv), n = 7), or control (n = 7). Cardiopulmonary hemodynamics and gas-exchange parameters were recorded as well as extravascular lung water and pulmonary capillary pressure. In addition, plasma levels of tezosentan and ET-1 were analyzed. The protocol lasted for 5 h. Endotoxin-induced pulmonary hypertension (mean pulmonary artery pressure) was efficiently reduced by all treatments (TEZO(0.5) 24 +/- 2, TEZO(0.05) 27 +/- 2, TEZO(iv) 26 +/- 1, and control 37 +/- 2 mmHg at 4 h). TEZO(0.5) and TEZO(iv) also reduced pulmonary capillary pressure. All treatments led to a modest reduction in extravascular lung water, whereas no effects were noted on oxygenation or systemic circulation. Despite similar effects on pulmonary hypertension systemic treatment resulted in significantly higher plasma levels of ET-1 (twofold) and tezosentan (10- to 100-fold). Inhalation of the dual ET-receptor antagonist tezosentan was feasible and efficiently counteracted endotoxin-induced pulmonary hypertension. These effects were obtained with only minor systemic uptake of tezosentan and without affecting circulating levels of plasma ET-1 as compared with intravenous administration.

Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by alveolar-capillary barrier damage. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of ARDS. In the Beta Agonists in Acute Lung Injury Trial, intravenous salbutamol reduced extravascular lung water (EVLW) in patients with ARDS at day 4 but not inflammatory cytokines or neutrophil recruitment. We hypothesized that salbutamol reduces MMP activity in ARDS. MMP-1/-2/-3/-7/-8/-9/-12/-13 was measured in supernatants of distal lung epithelial cells, type II alveolar cells, and bronchoalveolar lavage (BAL) fluid from patients in the Beta Agonists in Acute Lung Injury study by multiplex bead array and tissue inhibitors of metalloproteinases (TIMPs)-1/-2 by enzyme-linked immunosorbent assay. MMP-9 protein and activity levels were further measured by gelatin zymography and fluorokine assay. BAL fluid MMP-1/-2/-3 declined by day 4, whereas total MMP-9 tended to increase. Unexpectedly, salbutamol augmented MMP-9 activity. Salbutamol induced 33.7- and 13.2-fold upregulation in total and lipocalin-associated MMP-9, respectively at day 4, compared with 2.0- and 1.3-fold increase in the placebo group, p < 0.03. Salbutamol did not affect BAL fluid TIMP-1/-2. Net active MMP-9 was higher in the salbutamol group (4222 pg/mL, interquartile range: 513-7551) at day 4 compared with placebo (151 pg/mL, 124-2108), p = 0.012. Subjects with an increase in BAL fluid MMP-9 during the 4-day period had lower EVLW measurements than those in whom MMP-9 fell (10 vs. 17 mL/kg, p = 0.004): change in lung water correlated inversely with change in MMP-9, r = -.54, p = 0.0296. Salbutamol up-regulated MMP-9 and down-regulated TIMP-1/-2 secretion in vitro by distal lung epithelial cells. Inhibition of MMP-9 activity in cultures of type II alveolar epithelial cells reduced wound healing. Salbutamol specifically up-regulates MMP-9 in vitro and in vivo in patients with ARDS. Up-regulated MMP-9 is associated with a reduction in EVLW. MMP-9 activity is required for alveolar epithelial wound healing in vitro. Data suggest MMP-9 may have a previously unrecognized beneficial role in reducing pulmonary edema in ARDS by improving alveolar epithelial healing.

Measurement of extravascular lung water in patients with pulmonary edema

measurement of extravascular lung water has been a topic of major interest for more than two decades ([1][1], [5][2], [19][3]). In the recent article by Effros et al. ([2][4]), they provide a review of current and past efforts to measure extravascular lung water with thermal and osmotic dilution

Hemodynamic and respiratory changes during lung recruitment and descending optimal positive end-expiratory pressure titration in patients with acute respiratory distress syndrome*

To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration. Prospective auto-control clinical trial. Adult general intensive care unit in a university hospital. Eighteen patients with acute respiratory distress syndrome. Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cm H2O in every 4 mins. Optimal PEEP was defined at 2 cm H2O above the PEEP where Pao2 dropped by > 10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (T(end)). Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until T(end), then in 30 (T30) and 60 (T60) mins. The Pao2 increased from T0 to T(end) (203 +/- 108 vs. 322 +/- 101 mm Hg, p < .001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p < .05; ITBVI, 832 +/- 205 vs. 795 +/- 188 m/m2, p < .05). There was a positive correlation between CI and ITBVI (r = .699, p < .01), a negative correlation between CI and central venous pressure (r = -.294, p < .01), and no correlation between CI and mean arterial pressure (MAP). Following lung recruitment and descending optimal PEEP titration, the Pao2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.

The nitric oxide synthase cofactor tetrahydrobiopterin reduces allograft ischemia-reperfusion injury after lung transplantation

Objective: Exogenous nitric oxide reduces ischemia-reperfusion injury after solid organ transplantation. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthases, may restore impaired endothelium-dependent nitric oxide synthesis. We evaluated whether tetrahydrobiopterin administration to the recipient attenuates lung reperfusion injury after transplantation in swine. Methods: Unilateral left lung transplantation was performed in 15 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 L cold (1°C) low-potassium-dextran solution and preserved for 20 hours. Group I animals served as controls. Group II and III animals were treated with a bolus of tetrahydrobiopterin (20 mg/kg). In addition, in group III a continuous infusion of tetrahydrobiopterin (10 mg/kg per hour over 5 hours) was given. One hour after reperfusion, the recipient right lung was occluded. Cyclic guanosine monophosphate levels were measured in the pulmonary venous and central venous blood. Extravascular lung water index, hemodynamic variables, lipid peroxidation, and neutrophil migration to the allograft were assessed. Results: In group III a significant reduction of extravascular lung water was noted in comparison with the controls ( P = .0047). Lipid peroxidation in lung allograft tissue was significantly reduced in group II ( P = .0021) and group III ( P = .0077) in comparison with group I. Pulmonary venous levels of cyclic guanosine monophosphate increased up to 23 ± 1 pmol/mL at 5 hours in group II and up to 40 ± 1 pmol/mL in group III (group I, 4.1 ± 0.5 pmol/mL [I vs III]; P < .001), whereas central venous levels of cyclic guanosine monophosphate were unchanged in all groups. Conclusion: Tetrahydrobiopterin administration during lung allograft reperfusion may reduce posttransplantation lung edema and oxygen-derived free radical injury in the graft. This effect is mediated by local enhancement of the nitric oxide/cyclic guanosine monophosphate pathway. (J Thorac Cardiovasc Surg 1999;118: 726-32)

CRRT in the area of cost containment: Is it justified?

Intensive care accounts for at least 25% of health care costs. One third of this goes to 10% of patients who, in general, have combined respiratory and renal failure. The cost of renal replacement therapy is, therefore, of major importance. Continuous renal replacement therapy (CRRT) has many potential advantages over intermittent hemodialysis (IHD). These include better nutritional support, better volume maintenance, reduction of extravascular lung water, and potential clearance of inflammatory mediators. To date, noncomparative trials have suggested a trend toward decreased mortality. Randomized trials have suggested a CRRT mortality and morbidity benefit, but only when comparing long-term renal recovery. Acute mortality benefit has not been clearly established and, as such, cost comparison is of increased interest. Cost comparison trials are complicated, but some recent studies have led to the conclusion that costs are comparable. Others have concluded that CRRT is slightly more expensive. When comparing randomized patients in a recent prospective trial, aggregate costs for renal replacement therapy were comparable. The advantages of better nutrition, better fluid balance, easier management of hemodynamics, and more complete renal recovery, as suggested by this study, should continue to make it valuable. Physician acceptance of CRRT advantages has been established and suggests clinical benefit despite any potential increased cost.

Influence of ACE Inhibition on Fluid Metabolism in Chronic Heart Failure and Its Pathophysiologic Relevance

BACKGROUND: In congestive heart failure with water retention, subtraction of body fluid by ultrafiltration causes greater diuresis and clinical improvement in patients who are angiotensin-converting enzyme (ACE)-inhibited, suggesting an influence of ACE inhibitors on fluid metabolism. METHODS AND RESULTS: Patients with moderate congestive heart failure were subjected to ultrafiltration (around 2000 mL) and followed up for 3 months. Usual outpatient therapy, consisting of digoxin, furosemide, and ACE inhibitors (18 patients, group A) and of digoxin and furosemide only (18 patients, group B), was continued throughout the trial. Hemodynamics, renal function, body fluid and electrolytes, plasma norepinephrine, renin activity, aldosterone, and plasma volume were monitored. At 30 and 90 days after ultrafiltration, hormones, renal function, functional capacity (based on cardiopulmonary tests), and extravascular lung water (chest radiograph score) were determined. Soon after ultrafiltration, body weight, plasma volume, and diuresis were reduced (hypovolemia) and hormones were raised (reaction to hypovolemia). In the next 4 days, all these variables reverted to the pre-ultrafiltration values in group B; in group A diuresis and plasma volume recovered, body weight was still reduced, and hormones became lower than baseline. These changes persisted in the next 3 months. An early reduction of extravascular lung water continued long term in group A only, associated with increase of exercise tolerance time and oxygen uptake and decrease of the dead space/tidal volume ratio. CONCLUSIONS: In congestive heart failure, ACE inhibition persistently prevented fluid accumulation once the excess of body fluid had been withdrawn with a nonpharmacologic method, resulting in sustained improvement in functional capacity. Reduction in circulating norepinephrine, aldosterone, and renin did not seem to be the cause but the consequence of this action, whose mechanisms remain undefined.

Canine double-lung transplantation with cadaveric donors

If lungs could be retrieved from cadavers after circulatory arrest, the critical shortage of donors for lung transplantation might be alleviated. To assess gas exchange after transplantation of lungs from cadaveric donors, we performed double-lung transplantation through sequential thoracotomies in 12 dogs. Donors were sacrificed by intravenous pentobarbital injection and then ventilated with 100% oxygen. Lungs were harvested 2 hours ( n = 6) or 4 hours ( n = 6) after death and flushed with 2 L modified Euro-Collins solution. Recipients underwent sequential right and left lung transplantation; they were then monitored while under anesthesia for 8 hours, with adjustments of the fraction of inspired oxygen. Nine of 12 recipients survived the 8-hour study period. Four of six dogs with cadaveric lungs retrieved 2 hours after death survived; deaths were from pulmonary embolism at 6 hours and pulmonary edema at 2 hours. Five of six dogs with cadaveric lungs retrieved 4 hours after death survived; one died of hypoxia during implantation of the left lung, while dependent on the right lung graft. Postoperative hemodynamic and gas exchange parameters were similar in both groups. Alveolar-arterial oxygen gradient rose significantly compared with baseline 1 hour after transplantation in both groups (462 ± 60 vs 38 ± 31 mm Hg for 2-hour group, p < 0.0001, and 484 ± 63 vs 38 ± 14 mm Hg for 4-hour group, p < 0.0002). By 8 hours after operation, the gradients had significantly decreased in both groups (105 ± 37 mm Hg for 2-hour group and 146 ± 53 mm Hg for 4-hour group) and were similar to baseline values. Extravascular lung water also rose significantly 1 hour after transplantation (15.7 ± 2.8 vs 7.9 ± 0.5 ml/kg for 2-hour group, p < 0.02, and 16.9 ± 1.2 vs 6.6 ± 0.4 ml/kg for 4-hour group, p < 0.0001) and decreased gradually during the 8-hour study period. Donor lungs retrieved at 2 and 4 hours postmortem afford similar recipient outcomes. Improvement in alveolar-arterial oxygen gradient and reduction in extravascular lung water during the study period imply that the ischemia-reperfusion injury induced by this model is reversible. If this approach could be safely introduced to clinical practice, substantially more transplant procedures could be performed. (J T HORAC C ARDIOVASC S URG 1996;112:577-83)