Evaluation of the association between extravascular lung water and prognosis of sepsis: A protocol of systematic review.

BACKGROUND: The purpose of this study is to explore the association between extravascular lung water (EVLW) and prognosis of sepsis (PS). METHODS: We will carry out comprehensive literature search in electronic databases (PUBMED/MEDLINE, EMBASE, CENTRAL, WorldSciNet, PsycINFO, Allied and Complementary Medicine Database, CBM, and CNKI) and additional sources. All electronic databases will be searched from their initial to the present without language restrictions. Case-controlled studies reporting the association between EVLW and PS will be evaluated for inclusion. Outcomes of interest will include mortality rate, extravascular lung water index, pulmonary vascular permeability index, blood lactate clearance, oxygenation index, blood gas analysis, PaO2/FiO2, cardiac output index, global end diastolic volume index, intrathoracic blood volume index, systemic resistance index, acute physiology and chronic health scoring system II, and infection-related organ failure scoring system. Study quality will be evaluated using Newcastle-Ottawa Tool, and statistical analysis will be performed utilizing RevMan 5.4 software. RESULTS: This study will summarize the most recent evidence to investigate the association between EVLW and PS. CONCLUSIONS: The results of this study will provide an exhaustive view of the association between EVLW and PS. STUDY REGISTRATION OSF: osf.io/vhnxw.

Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, Placebo-Controlled Trial.

OBJECTIVES: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether preoperative administration of oral high-dose cholecalciferol ameliorates early acute lung injury postoperatively in adults undergoing elective esophagectomy. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Three large U.K. university hospitals. PATIENTS: Seventy-nine adult patients undergoing elective esophagectomy were randomized. INTERVENTIONS: A single oral preoperative (3-14 d) dose of 7.5 mg (300,000 IU; 15 mL) cholecalciferol or matched placebo. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in extravascular lung water index at the end of esophagectomy. Secondary outcomes included PaO2:FIO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D, and vitamin D-binding protein), pulmonary vascular permeability index, and extravascular lung water index day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in extravascular lung water index at the end of the operation between treatment groups (placebo median 1.0 [interquartile range, 0.4-1.8] vs cholecalciferol median 0.4 mL/kg [interquartile range, 0.4-1.2 mL/kg]; p = 0.059). Median pulmonary vascular permeability index values were significantly lower in the cholecalciferol treatment group (placebo 0.4 [interquartile range, 0-0.7] vs cholecalciferol 0.1 [interquartile range, -0.15 to -0.35]; p = 0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations, but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. CONCLUSIONS: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations and reduced changes in postoperative pulmonary vascular permeability index, but not extravascular lung water index.

Omega-3 polyunsaturated fatty acids improve host response in chronic Pseudomonas aeruginosa lung infection in mice.

Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.

[A case of idiopathic ARDS treated by sivelestat sodium and fluid management based on extravascular lung water index].

A 65-year-old woman was given emergency admission with fever, cough and dyspnea. Chest computed tomography (CT) findings showed bilateral ground-glass opacity, consolidation, and this case were fulfilled the criteria for acute respiratory distress syndrome (ARDS). We clinically diagnosed the patient as suffering from idiopathic ARDS including acute interstitial pneumonia (AIP) based on the absence of any known causes of ARDS and systemic immunologic diseases. We started treatment with sivelestat sodium and strictly managed fluid balance under mechanical ventilation. We found this treatment quite effective because there were significant improvements in the extravascular lung water index (EVLWI) measured by the PiCCO system and neutrophile elastase value and in oxygenation and the chest radiograph. This is apparently the first case report in the literature that clearly shows the treatment with sivelestat sodium and strict fluid management ended in a favorable outcome, as reducing EVLWI measured by the PiCCO system in an idiopathic ARDS patient.

Hyperbaric oxygen therapy attenuates pancreatic microcirculatory derangement and lung edema in an acute experimental pancreatitis model in rats.

This study was designed to investigate hyperbaric oxygen (HBO) therapy as a treatment for managing animals with induced acute pancreatitis. Forty-five anesthetized male Sprague-Dawley rats were studied. A severe acute pancreatitis model was established by combining an intravenous infusion of cerulein (15 microg/kg/h) and an intraductal injection of 0.1 ml of glycodeoxycholic acid (5 mM). Pathology, serum amylase level, pancreatic malondiadehyde levels and water content of the lungs and the pancreas were used to evaluate the severity of disease. Moreover, an in vivo microscopic technique was used to investigate microcirculatory derangement in the pancreas, i.e., flow velocity and leukocytes sticking in postcapillary venules. HBO was delivered in three regimens, i.e., 100% oxygen at 2.5 absolute atmospheric pressure (AAP), 40% oxygen at 2.5 AAP, and 100% oxygen at 1 AAP, 6 h after the initiation of induction of acute pancreatitis. All animals survived until the end of the experiments. HBO significantly improved the pathologic conditions and pancreatic malondiadehyde levels. Concomitantly, it also significantly lessened the severity of lung edema and improved the microcirculatory environment in the pancreas. Our results support the findings that HBO therapy has a beneficial effect on pancreatic microcirculation and lung edema during acute pancreatitis in rats.

[Study on extravascular lung water and polymorphonuclear leukocyte elastase during acute phase following radical treatment of lung cancer: effect of ulinastatin on respiratory functions].

We studied respiratory functions, extravascular lung water (EVLW) as measured by a thermodilution method using double Na indicators, and variations in polymorphonuclear leukocyte elastase (PMNE) during the acute phase following radical treatment of lung cancer, as well as to investigate clinical effect of ulinastatin. Using 16 patients with lung cancer who had undergone surgery of R 2 a or more, 10 patients without ulinastatin therapy were compared with six patients given 300,000 U/day of this drug by drip infusion from Day 0 and 4 of disease. It was found that EVLW value decreased most on Day 1, and gradually increased thereafter but did not return to the preoperative level. PMNE value increased from immediately after surgery and peaked on Day 3, but returned nearly to the preoperative level by Day 5. Although this was different from the variations in EVLW value, there was a correlation between these two parameters on Day 3 when PMNE peaked. Further, ulinastatin tended to inhibit PMNE and improve oxygenation index. Respiratory and circulatory parameters vary in complex manners during the acute phase following radical treatment of lung cancer, and could not be accurately evaluated by means of thermodilution using Na. PMNE is considered a contributing factor to pulmonary tissue disorders following radical treatment of lung cancer, and ulinastatin appeared to be effective in the postoperative management of patients undergoing radical treatment of lung cancer.

Furosemide, when used in combination with positive end-expiratory pressure, facilitates the resorption of extravascular lung water in experimental hydrostatic pulmonary oedema.

The study aimed to establish whether furosemide given intravenously improved resorption of hydrostatic pulmonary oedema in 14 dogs mechanically ventilated with positive end-expiratory pressure (PEEP). Hydrostatic pulmonary oedema was created by simultaneous inflation of a left atrial balloon and rapid intravenous infusion of isotonic saline. The hydrostatic process was terminated by deflating the balloon and reducing the infusion rate. A PEEP of 10 cmH2O (1.0 kPa) was applied in all animals; in seven, furosemide was administered (diuretic group), 1 mg/kg intravenously as a bolus followed by an infusion of 0.5 mg/kg per hour, while the remaining seven dogs served as a control group. All dogs were studied for a period of 4 h. The extravascular lung water measured with the double indicator dilution technique was 28.3 +/- 3.8 (diuretic group) and 28.2 +/- 6.8 ml/kg (control group) during maximum oedema. It was reduced to 16.4 +/- 2.2 (diuretic group) vs 19.8 +/- 3.7 ml/kg (control group) after 4 h of resorption, P less than 0.05. Postmortem gravimetric values of extravascular lung water were 9.1 +/- 3.4 (diuretic group) vs 12.6 +/- 5.0 g/kg (control group). In the diuretic group the urinary output increased threefold, and haemoglobin and serum protein concentrations were higher than in the control group. There was a significantly greater decrease in cardiac output and central blood volume in the diuretic group. In conclusion, furosemide given intravenously improved lung fluid resorption in hydrostatic pulmonary oedema, probably by increasing the plasma colloid osmotic pressure.

Tolerance of the isolated perfused lung to hyperthermia.

With the use of in vivo isolated lung perfusion for targeting antitumor therapy in the treatment of lung cancer, tolerance of normal lung tissue to the tumoricidal conditions becomes the limiting factor. This study was performed to determine the short-term tolerance of the lung to hyperthermia. Isolated dog lung lobes were perfused with autologous blood or an artificial salt solution at constant flow. Measurements of lung weight, extravascular water, vascular volume, serotonin uptake, urea permeability surface area product, perfusion pressure, and lung compliance were made with the temperature at about 37 degrees C. The temperature was then set at between 37 degrees and 45 degrees C, and at the end of the subsequent 2 hours the measurements were repeated. When the temperature was less than about 44.4 degrees C, hyperthermia had no detectable influence on the measured variables. Thus on the time frame consistent with in vivo perfusion therapy the normal lung appears to tolerate a fairly severe hyperthermia.