Extravascular Lung Water Index Research Articles

Utility of lung ultrasound for extravascular lung water volume estimation during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Background and Aims:Rising extravascular lung-water index (ELWI) following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), if not timely intervened, can progress to pulmonary oedema. Transpulmonary thermodilution (TPTDL) is a standard technique to estimate ELWI (T-ELWI score), and track ongoing changes. Lung ultrasound (LUS) is another technique for ELWI (L-ELWI score) estimation. However, reproducibility and reliability of LUS for tracking serial L-ELWI changes during CRS + HIPEC remains to be validated.Methods:This prospective observational study included 360 L-ELWI and T-ELWI measurements at 12 peri-operative time-points. Cohen's Kappa test was used to assess reproducibility, Inter-rater agreement (between the anaesthetist and radiologist), and agreement between LUS and TPTDL for classifying the severity of pulmonary oedema. Reliability of LUS for 'tracking serial changes' in ELWI over time in individual patients was assessed by determining the repeated measures correlation (z-rrm) between weighted L-ELWI and T-ELWI scores. The ability of both techniques to discriminate pulmonary oedema was compared by analysing the area under ROC curves.Results:Excellent inter-rater agreement for assigned L-ELWI scores was observed (linear weighted κ = 0.95 for both). Both techniques had a good agreement in classifying the severity of pulmonary oedema (linear weighted κ = 0.63, 95% CI 0.51–0.79). T-ELWI and weighted L-ELWI scores correlated strongly (z-rrm = 0.88, 95% CI 0.80–0.92, P < 0.0001). Both techniques had comparable ability to discriminate pulmonary oedema (difference in area under ROC curve = 0.0014, 95%CI –0.0027 to 0.0055, P = 0.5043).Conclusion:We found the utility of LUS as a reliable and reproducible technique for ELWI estimation and tracking its changes over time in CRS + HIPEC.

Blunt Pulmonary Injury Induces Profound Pulmonary Hypertension in a Porcine Polytrauma Model

Traumatic blunt pulmonary injuries, while typically appearing mild on initial exam, notoriously progress into cases of pulmonary hypertension (PHT) and pulmonary edema often worsened with the fluid resuscitation necessitated by such injuries. Increased hypoxemia in acute lung injury is believed to cause pulmonary vasoconstriction which further increases pulmonary arterial pressure, and worsens hypoxemia in a vicious cycle of persistent PHT. The relationship between pulmonary hemodynamics and pulmonary edema, however is not well understood. We hypothesize that the initial increase in pulmonary vasoconstriction occurs to isolate damaged lung tissue and prevent pulmonary infiltration due to traumatic disruption of the alveolar air-liquid interface. In this study, we tested this hypothesis by examining the development of extravascular lung water in relation to pulmonary vasoconstriction in a porcine polytrauma model of acute lung injury. Pulmonary function and hemodynamics were examined before and after localized blunt right chest injury trauma in anesthetized, mechanically ventilated Yorkshire cross pigs (26+/- 1 kg, n=9). Acute grade II-III lung injury was verified at the end of the experiment. Cardiac output was measured via thermodilution with a SwanGanz catheter and extravascular lung water index (ELWI) and pulmonary capillary permeability were assessed in real time using the Pulse Ion Contour Cardiac Output (PiCCO) method (Getinge). Pulmonary arterial pressure increased within 60 minutes of initial lung injury (19 +/- 1 mm Hg at baseline vs 23 +/- 2 mm Hg) despite a drop in mean arterial pressure (60 +/- 1 mm Hg at baseline to 48 +/- 4 mm Hg after trauma). The ratio of pulmonary vascular resistance to systemic vascular resistance (PVR/SVR), indicated a selective pulmonary vasoconstriction(0.23 +/- 0.01 to 0.41 +/- 0.05, p = 0.054). ELWI was negatively correlated with the PVR/SVR ratio (r=0.44, p=0.010). Central venous pressure was lowest (6 +/- 0.6 mm Hg) right after trauma and increased (8 +/- 0.4 mm Hg) 2 hours after trauma along with the increase in PVR/SVR post trauma. Results suggests that traumatic pulmonary edema was limited via autoregulatory vasoconstriction. While effective in preventing pulmonary fluid extravasation, pulmonary hypertension resulted in a marked increase in heart afterload and accumulation of fluid in the right heart. The magnitude of this effect was such that even a moderate degree of fluid resuscitation risked precipitating florid congestive heart failure. Our data suggest that great caution must be exercised during fluid resuscitation of the blunt pulmonary trauma patient. The views expressed are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.

Extravascular Lung Water and Intrathoracic Blood Volume Index Are Associated With Liver Function in Brain Dead Donors for Organ Transplant.

Hemodynamic measurements during organ transplant procedures are essential. In this observational study, we measured clinical and hemodynamic parameters in 11 patients with advanced pulse indicator continuous cardiac output monitoring. Normally distributed clinical data were calculated as means ± standard deviation; hemodynamic, metabolic, and respiratory parameters related to liver and renal function were compared by linear regression analysis using Pearson correlation. Compared with the normal range, systemic vascular resistance was high (2278.02 ± 719.6 dyne·s/cm²/m²) and intrathoracic blood volume was low (787.37 ± 224.01 mL/m²) in our patient group. C-reactive protein and interleukin 6 levels were 96.26 ± 68.10 mg/mL and 246.24 ± 355.74 mmol/L, respectively. Liver and renal function parameters were in normal ranges. Extravascular lung water was correlated with total, conjugated, and unconjugated bilirubin and albumin (r = 0.342/P = .005; r = 0.338/ P = .005; r = 0.394/P = .001, and r = 0.358/P = .003) but not with aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Intrathoracic blood volume index was correlated with total bilirubin, unconjugated bilirubin, and albumin (r = 0.324/P = .007; r = 0.394/P = .001, and r = 0.296/P = .015) but not with conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Lactate was not correlated with total bilirubin, unconjugated bilirubin, albumin, and serum creatinine, but base excess was correlated with total bilirubin, unconjugated bilirubin, alanine aminotransferase, and albumin. PO₂ and Pco₂ were not correlated with liver function, although PO₂ was correlated with albumin. No correlations were shown between intrathoracic blood volume index, extravascular lung water, and liver function, but metabolic parameters, including base excess and lactate, were correlated with liver function. Pulse indicator continuous cardiac output monitoring may be a useful method to assess organ function and tissue perfusion in organ transplant.

Application effect of respiratory stepwise management in patients with septic shock combined with acute lung injury

To observe the application effect of respiratory stepwise management in patients with septic shock combined with acute lung injury (ALI). 100 patients with septic shock combined with ALI were selected as the research objects in Haikou Hospital Affiliated to Xiangya Medical College of Central South University from January 2018 to June 2020. Fifty patients were given endotracheal intubation or invasive ventilation on the basis of conventional treatment (conventional treatment group). According to the respiratory situation and blood gas, 50 patients were given systematic respiratory support step-by-step treatment according to the principle of simple to complex, and appropriate and scientific respiratory support was given according to the sequence from unarmed to mechanical (respiratory stepwise management group). The differences of cardiac index (CI), central venous pressure (CVP), mean arterial pressure (MAP), extravascular lung water index (EVLWI), arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2) before and after treatment were compared between the two groups, the therapeutic effects of the two groups were evaluated, and the resuscitation effect, postoperative complications rate, tracheotomy rate, utilization rate of invasive ventilator of the two groups were recorded. After treatment, CI, CVP, EVLWI, PaO2, PaO2/FiO2 levels of the two groups were significantly higher than before treatment, MAP and PaCO2 levels were significantly lower than before treatment; MAP and PaCO2 levels after treatment of the respiratory stepwise management group were significantly lower than those of the conventional treatment group [MAP (mmHg, 1 mmHg = 0.133 kPa): 68.2±7.0 vs. 74.4±6.8, PaCO2 (mmHg): 37.82±4.05 vs. 41.76±4.59], the levels of EVLWI, PaO2 and PaO2/FiO2 in the respiratory stepwise management group were significantly higher than those in the conventional treatment group [EVLWI (mL/kg): 15.34±3.03 vs. 13.64±3.32, PaO2 (mmHg): 84.44±4.83 vs. 79.03±5.54, PaO2/FiO2 (mmHg): 452.42±51.32 vs. 431.73±50.03, all P < 0.05]. There was no significant difference in CI or CVP after treatment between respiratory stepwise management group and conventional treatment group [CI (mL×s-1×m-2): 70.01±21.67 vs. 66.68±18.34, CVP (mmHg): 11.1±3.2 vs. 12.3±3.2, both P > 0.05]. Compared with the conventional treatment group, the average recovery time of the respiratory stepwise management group was earlier (hours: 2.04±0.54 vs. 4.29±0.20, P < 0.05), the stable breathing time was shorter (hours: 3.07±0.22 vs. 5.36±0.35, P < 0.05), the total effective rate and the success rate of recovery were significantly improved [86.0% (43/50) vs. 60.0% (30/50), 94.0% (47/50) vs. 74.0% (37/50), both P < 0.05], the incidence of ventilator associated pneumonia (VAP) and airway complications were significantly reduced [14.0% (7/50) vs. 32.0% (16/50), 12.0% (6/50) vs. 40.0% (20/50), both P < 0.05], and the tracheotomy rate and the utilization rate of invasive ventilator were significantly reduced [8.0% (4/50) vs. 28.0% (14/50), 30.0% (15/50) vs. 60.0% (30/50), both P < 0.05]. Respiratory stepwise management can effectively improve the resuscitation effect of septic shock patients with ALI, improve cardiopulmonary function, blood gas index and the treatment efficiency, effectively reduce the incidence of iatrogenic trauma and complications.

Application of pulse contour cardiac output monitoring technology in fluid resuscitation of severe burn patients in shock period

Objective: To investigate the application of pulse contour cardiac output (PiCCO) monitoring technology in fluid resuscitation of severe burn patients in shock period. Methods: From January 2015 to December 2019, 33 patients with severe burns who were hospitalized in Guangzhou Red Cross Hospital, meeting the inclusion criteria, were recruited into a retrospective cohort study with their clinical information collected. The patients were divided into PiCCO monitoring group with 15 cases (13 males and 2 females, aged (43±13) years) and routine monitoring group with 18 cases (14 males and 4 females, aged (39±9) years) according to the monitoring method used. After admission, all the patients were rehydrated following the rehydration formula of the Third Military Medical University for shock period. In routine monitoring group, the fluid resuscitation of patients was performed by monitoring indicators such as urine volume and blood pressure, while PiCCO monitoring was performed among patients in PiCCO monitoring group, and their fluid resuscitation was guided by the patient's condition and the hemodynamic parameters (without pursuing normal levels of the parameters) of PiCCO monitoring on the basis of normal monitoring indicators in routine monitoring group. The colloids coefficients, the electrolyte coefficients (compared with the corresponding rehydration formula value of 0.75 mL·kg(-1)·% total body surface area (TBSA)(-1) of the Third Military Medical University for shock period during the first 24 h post injury), the total rehydration coefficients, and the urine volumes during the first and second 24 h post injury, the lactic acid level, the base excess level, and the oxygenation index at admission and 24, 48 h after admission, and the mechanical ventilation time, the wound healing time, and the death ratio of patients in the two groups were recorded. The cardiac index, the global end-diastolic volume index (GEDVI), the intrathoracic blood volume index (ITBVI), the extravascular lung water index (EVLWI), and the systemic vascular resistance index (SVRI) of patients in PiCCO monitoring group at post injury hour 24, 48, and 72 and the abnormal cases were recorded. Data were statistically analyzed with Fisher's exact probability test, independent-sample or one-sample t test, analysis of variance for repeated measurement, and Bonferroni correction. Results: During the first 24 h post injury, the colloids coefficients of patients in PiCCO monitoring group was (0.69±0.15) mL·kg(-1)·%TBSA(-1), which was significantly less than (0.85±0.16) mL·kg(-1)·%TBSA(-1) in routine monitoring group (t=-2.612, P<0.05). Compared with the rehydration formula value of the Third Military Medical University for shock period, only the colloids coefficient of patients in routine monitoring group during the first 24 h post injury was significantly increased (t=2.847, P<0.05). There were no statistically significant differences between the two groups in the colloids coefficients of patients during the second 24 h post injury, or the electrolyte coefficients, the total rehydration coefficients, the urine volumes of patients during the first and the second 24 h post injury (t=0.579, -0.011, 0.417, -1.321, -0.137, 0.031, 1.348, P>0.05). The lactic acid level, the base excess level, the oxygenation index of patients at admission and 48 h after admission, and the oxygenation index of patients at 24 h after admission between the two groups were similar (t=-1.837, 0.620, 0.292, -1.792, 1.912, -0.167, 1.695, P>0.05). The levels of lactic acid and base excess of patients in PiCCO monitoring group were (4.8±1.4) and (1.2±5.5)mmol/L, respectively, which were significantly better than (7.0±1.5) and (-2.8±3.0) mmol/L in routine monitoring group at 24 h after admission (t=-3.904, 2.562, P<0.05 or P<0.01). There were no statistically significant differences between the two groups in the mechanical ventilation time or the wound healing time of patients (t=-0.699, -0.697, P>0.05), or the death ratio of patients (P>0.05). In PiCCO monitoring group, the GEDVI, and the ITBVI of patients were lower than the normal low values at post injury hour 24 and 48, which were in the normal range at post injury hour 72; the cardiac index of patients increased gradually and recovered to normal at post injury hour 48; the SVRI of patients increased significantly at post injury hour 24 and then gradually decreased to normal; the EVLWI average of patients at all time points post injury were less than 10 mL/kg. At post injury hour 24, most of the hemodynamic parameters of more than or equal to 8/15 patients in PiCCO monitoring group were abnormal, and the abnormal proportion decreased later. Conclusions: On the basis of traditional monitoring indicators, the use of PiCCO monitoring technology combined with the patient's condition (without pursuing normal levels of the parameters) in guiding the fluid resuscitation in severe burn patients can reduce the usage of colloid and better improve tissue perfusion, with the resuscitation effect being better than conventional monitoring.

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.

Hemodynamic Characteristics of Mechanically Ventilated COVID-19 Patients: A Cohort Analysis

Background Solid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients. Methods A retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system. Results The mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p < 0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p < 0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Qs/Qt) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p < 0.001), but static lung compliance remained unchanged. Conclusions In general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange.

The prognosis evaluation of sICAM-1, KL-6 combined with EVLWI in severe pneumonia patients with acute respiratory distress syndrome

Objective To evaluate the prognostic value of extravascular lung water index (EVLWI), soluble intercellular adhesion molecule-1(sICAM-1) and Krebs yon den lungen-6 (KL-6) in severe pneumonia patients with Severe Acute Respiratory Syndrome (ARDS). Methods A prospective study was conducted in Respiratory Intensive Care Unit of the Affiliated Zhengzhou Central Hospital of Zhengzhou University from October 2017 to February 2020. The study included 65 severe pneumonia patients with ARDS, who was performed by measurement of pulse index continuous cardiac output and survived more than 3days after admission. The Extravascular Lung Water Index（EVLWI）, sICAM-1, KL-6 and Oxygenation Index(OI) on 1st, 3rd and 5th day were detected. APACHE Ⅱ score, patient survival events (days) and survival outcome were recorded. Correlation analysis between EVLWI, sICAM-1, KL-6 and OI was performed on the 1st，3rd and 5th day after admission. Independent risk factors of mortality in severe pneumonia patients with ARDS were analyzed by multiple logistic regression. Receiver operating characteristic curve was drawn，and the prognostic value of each parameter was assessed finally. Results The PCT, EVLWI, sICAM-1, KL-6 and APACHE Ⅱ score in the death group were significantly higher than those in the survival group (P 0.05）. These parameters including levels of EVLWI, sICAM-1, KL-6, Procalcitonin and APACHE Ⅱ score in the death group were significantly higher than those in the survival group on the 1st，3rd and 5th day (P<0.05), whereas the OI was significantly lower than that of the survival group on the 3rd and 5th day (P<0.05). Logistic regression analysis showed that EVLWI, sICAM-1, KL-6 level were significantly related with the mortality of these patients. The levels of sICAM-1, kl-6 and EVLWI on 1st，3rd and 5th day after RICU admission showed a significant negative correlation with OI (P<0.001). Whereas, The levels of sICAM-1, kL-6 on 1st，3rd and 5th day showed a significant positive correlation with EVLWI (P<0.001). The sensitivity and specificity of sICAM-1, KL-6 combined with EVLWI in prognosis evaluation on 1st，3rd and 5th day were 75.0%，84.4%, 85.0%，66.7%，80.0%，86.7%, respectively. The AUC was 0.864，0.881，0.892 on 1st，3rd and 5th day, respectively (P<0.001), which had a better prognostic value than each of them. Conclusions EVLWI, sICAM-1 and KL-6 were independent risk factors for the prognosis of severe pneumonia patients with ARDS. The combination of EVLWI, sICAM-1 and KL-6 might be important in early predicting the prognosis of the 28d mortality. © 2021 Chinese Medical Association. All rights reserved.

Physiologic and hemodynamic changes in patients undergoing open abdominal cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

ObjectiveWe aimed to determine the physiological and hemodynamic changes in patients who were undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgeries.MethodsThis prospective, observational study enrolled 21 patients who were undergoing elective cytoreductive surgery with HIPEC at our hospital over 2 years. We collected vital signs, hemodynamic parameters including global end-diastolic volume index (GEVI) and extravascular lung water index (ELWI) using the VolumeView™ system, and arterial blood gas analysis from all patients. Data were recorded before skin incision (T1); 30 minutes before HIPEC initiation (T2); 30 (T3), 60 (T4), and 90 (T5) minutes after HIPEC initiation; 30 minutes after HIPEC completion (T6); and 10 minutes before surgery completion (T7).ResultsPatients showed an increase in body temperature and cardiac index and a decrease in the systemic vascular resistance index. GEDI was 715.4 (T1) to 809.7 (T6), and ELWI was 6.9 (T1) to 7.3 (T5).ConclusionsHIPEC increased patients’ body temperature and cardiac output and decreased systemic vascular resistance. Although parameters that were extracted from the VolumeView™ system were within their normal ranges, transpulmonary thermodilution approach is helpful in intraoperative hemodynamic management during open abdominal cytoreductive surgery with HIPEC.Trial registry name: ClinicalTrials.govTrial registration number: NCT02325648URL: https://clinicaltrials.gov/ct2/results?cond=NCT02325648&term

Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury.

Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.

B-Lines Scores Derived From Lung Ultrasound Provide Accurate Prediction of Extravascular Lung Water Index: An Observational Study in Critically Ill Patients.

Introduction:Visualization of B-lines via lung ultrasound provides a non-invasive estimation of pulmonary hydration. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) assessed by transpulmonary thermodilution (TPTD) represent the most validated parameters of lung water and alveolocapillary permeability, but measurement is invasive and expensive. This study aimed to compare the correlations of B-lines scores from extensive 28-sector and simplified 4-sector chest scan with EVLWI and PVPI derived from TPTD in the setting of intensive care unit (primary endpoint).Methods:We performed scoring of 28-sector and 4-sector B-Lines in 50 critically ill patients. TPTD was carried out with the PiCCO-2-device (Pulsion Medical Systems SE, Maquet Getinge Group). Median time exposure for ultrasound procedure was 12 minutes for 28-sector and 4 minutes for 4-sector scan.Results:Primarily, we found close correlations of 28-sector as well as 4-sector B-Lines scores with EVLWI (R2 = 0.895 vs. R2 = 0.880) and PVPI (R2 = 0.760 vs. R2 = 0.742). Both B-lines scores showed high accuracy to identify patients with specific levels of EVLWI and PVPI. The extensive 28-sector B-lines score revealed a moderate advantage compared to simplified 4-sector scan in detecting a normal EVLWI ≤ 7 (28-sector scan: sensitivity = 81.8%, specificity = 94.9%, AUC = 0.939 versus 4-sector scan: sensitivity = 81.8%, specificity = 82.1%, AUC = 0.902). Both protocols were approximately equivalent in prediction of lung edema with EVLWI ≥ 10 (28-sector scan: sensitivity = 88.9%, specificity = 95.7%, AUC = 0.977 versus 4-sector scan: sensitivity = 81.5%, specificity = 91.3%, AUC = 0.958) or severe pulmonary edema with EVLWI ≥ 15 (28-sector scan: sensitivity = 91.7%, specificity = 97.4%, AUC = 0.995 versus 4-sector scan: sensitivity = 91.7%, specificity = 92.1%, AUC = 0.978). As secondary endpoints, our evaluations resulted in significant associations of 28-sector as well as simplified 4-sector B-Lines score with parameters of respiratory function.Conclusion:Both B-line protocols provide accurate non-invasive evaluation of lung water in critically ill patients. The 28-sector scan offers a marginal advantage in prediction of pulmonary edema, but needs substantially more time than 4-sector scan.

Prognostic value of the extravascular lung water and pulmonary vascular permeability indices in severe adult respiratory distress syndrome managed with extracorporeal membrane oxygenation

Prognostic value of the extravascular lung water and pulmonary vascular permeability indices in severe adult respiratory distress syndrome managed with extracorporeal membrane oxygenation

The value of growth differentiation factor-15 and extravascular lung water index in severity grading of acute respiratory distress syndrome patients and their prognosis prediction

To investigate the value of growth differentiation factor-15 (GDF-15) and extravascular lung water index (EVLWI) in severity grading and prognosis prediction of patients with acute respiratory distress syndrome (ARDS). Patients with ARDS aged 18-75 years admitted to the department of respiratory intensive care unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2019 to February 2020 were enrolled. All patients were treated with conventional therapies such as mechanical ventilation, anti-infection, stabilization of water, electrolytes and acid-base environment, blood purification and nutritional support according to their conditions. Besides, the pulse-indicated continuous cardiac output (PiCCO) was performed after admission to the department, and EVLWI before treatment and at 24, 48 and 72 hours of treatment were recorded. Serum GDF-15 level was measured by enzyme linked immunosorbent assay (ELISA) during the same period. Patients were classified as mild, moderate, and severe degree according to the 2012 Berlin Definition of ARDS, and EVLWI and GDF-15 levels in patients with different disease levels before and after treatment were compared. In addition, the length of intensive care unit (ICU) stay, ICU mortality, and 28-day mortality of patients with different GDF-15 or EVLWI levels were analyzed comparatively, with the GDF-15 3 458 ng/L and EVLWI 15 mL/kg as the cut point. A total of 82 patients with ARDS were enrolled, including 22 patients with mild ARDS, 28 patients with moderate ARDS, and 32 patients with severe ARDS. The GDF-15 and EVLWI levels in patients with moderate and severe ARDS at each time point before and after treatment were higher than those in patients with mild ARDS. Both GDF-15 and EVLWI levels in patients with severe ARDS were higher than those in the patients with moderate ARDS. The differences were statistically significant at all the time points except for the difference of GDF-15 levels at 24 hours after treatment (ng/L: 3 900.41±546.43 vs. 3 695.66±604.73, P > 0.05). [GDF-15 (ng/L): 3 786.11±441.45 vs. 3 106.83±605.09 before treatment, 3 895.48±558.96 vs. 3 333.29±559.66 at 48 hours, 3 397.33±539.56 vs. 3 047.53±499.57 at 72 hours; EVLWI (mL/kg): 19.06±1.91 vs. 14.31±1.50 before treatment, 18.56±2.23 vs. 13.26±1.69 at 24 hours, 17.23±1.76 vs. 12.45±1.36 at 48 hours, 15.47±1.81 vs. 11.13±2.19 at 72 hours, all P < 0.05]. According to the cut-off value, there were 23 patients with GDF-15 ≥ 3 458 ng/L and GDF-15 < 3 458 ng/L respectively and there were 23 patients with EVLWI ≥ 15 mL/kg and EVLWI < 15 mL/kg respectively. The length of ICU stay and 28-day mortality in patients with high GDF-15 were significantly higher than those in patients with low GDF-15 [length of ICU stay (days): 21.22±2.69 vs. 15.37±3.14, 28-day mortality: 56.5% vs. 21.7%, both P < 0.05]. The length of ICU stay and 28-day mortality in patients with high EVLWI were also significantly higher than those in patients with low EVLWI [length of ICU stay (days): 18.45±2.61 vs. 14.98±2.75, 28-day mortality: 47.8% vs. 17.4%, both P < 0.05]. To some extent, GDF-15 and EVLWI levels reflect the severity of patients with ARDS, and high GDF-15 and EVLWI levels are significantly associated with poor prognosis in patients with ARDS.

Use of perfusion index to detect hemodynamic changes in endotoxemic pigs.

The perfusion index (PI) derived from plethysmographic signals provides a noninvasive indication of peripheral perfusion. This study aimed to investigate changes in PI and other hemodynamic variables in pigs subjected to endotoxemia. Prospective experimental study. University teaching hospital. Twelve healthy pigs weighing a mean (± standard deviation [SD]) of 31.7 ± 2.0kg. Pigs were divided into control and endotoxin groups (n=6 each). Endotoxemia was induced by IV infusion of lipopolysaccharide. Heart rate, mean arterial pressure, cardiac index (CI), central venous pressure, systemic vascular resistance index (SVRI), extravascular lung water index (ELWI), Global end-diastolic volume (GEDV) index, and pulmonary permeability index were measured using a transpulmonary thermodilution monitor in all pigs. PI was measured using a pulse oximeter probe attached to the tail. Pao2 , Paco2 , and plasma lactate concentration were measured by blood gas analysis. Measurements were taken at baseline (T0 ). Saline or lipopolysaccharide was then administered for 30min to all pigs (control or endotoxemia group, respectively), and each parameter was measured every 30min up to 270min. Data were analyzed by analysis of variance and Student's t-tests. There were no significant changes in any variables in the control group, but CI, SVRI, PI, ELWI, blood lactate concentration, and Pao2 changed significantly from baseline in the endotoxin group (P< 0.001, P= 0.0048, P< 0.001, P= 0.0064, P< 0.001, and P= 0.0220, respectively). In the endotoxin group, mean (± SD) %PI increased from T0 to 154 ± 34% at T60 (P=.001) and 135 ± 50% at T90 (P=0.004), which mirrored significant changes in %CI and %SVRI. The PI may be useful to detect changes in CI and SVRI.

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

BACKGROUNDTumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α.OBJECTIVEThe current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy.DESIGNRandomised double-blind (sponsor unblind), placebo-controlled, parallel group study.SETTINGEight secondary care centres, the United Kingdom between April 2015 and June 2017.PATIENTSThirty-three patients undergoing elective transthoracic oesophagectomy.INTERVENTIONSPatients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study.MAIN OUTCOME MEASUREMENTSPhysiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models.RESULTSThe mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (−0.23, 0.39) in the placebo and 0.00 (−0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms.CONCLUSIONPre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation.TRIAL REGISTRATIONclinicaltrials.gov: NCT02221037.

Prediction of outcome in patients with ARDS: A prospective cohort study comparing ARDS-definitions and other ARDS-associated parameters, ratios and scores at intubation and over time.

BackgroundEarly recognition of high-risk-patients with acute respiratory distress syndrome (ARDS) might improve their outcome by less protracted allocation to intensified therapy including extracorporeal membrane oxygenation (ECMO). Among numerous predictors and classifications, the American European Consensus Conferenece (AECC)- and Berlin-definitions as well as the oxygenation index (OI) and the Murray-/Lung Injury Score are the most common. Most studies compared the prediction of mortality by these parameters on the day of intubation and/or diagnosis of ARDS. However, only few studies investigated prediction over time, in particular for more than three days.ObjectiveTherefore, our study aimed at characterization of the best predictor and the best day(s) to predict 28-days-mortality within four days after intubation of patients with ARDS.MethodsIn 100 consecutive patients with ARDS severity according to OI (mean airway pressure*FiO2/paO2), modified Murray-score without radiological points (Murray_mod), AECC- and Berlin-definition, were daily documented for four days after intubation. In the subgroup of 49 patients with transpulmonary thermodilution (TPTD) monitoring (PiCCO), extravascular lung water index (EVLWI) was measured daily.Primary endpointPrediction of 28-days-mortality (Area under the receiver-operating-characteristic curve (ROC-AUC)); IBM SPSS 26.ResultsIn the totality of patients the best prediction of 28-days-mortality was found on day-1 and day-2 (mean ROC-AUCs for all predictors/scores: 0.632 and 0.620). OI was the best predictor among the ARDS-scores (AUC=0.689 on day-1; 4-day-mean AUC = 0.625). AECC and Murray_mod had 4-day-means AUCs below 0.6. Among the 49 patients with TPTD, EVLWI (4-day-mean AUC=0.696) and OI (4-day-mean AUC=0.695) were the best predictors. AUCs were 0.789 for OI on day-1, and 0.786 for EVLWI on day-2. In binary regression analysis of patients with TPTD, EVLWI (B=-0.105; Wald=7.294; p=0.007) and OI (B=0.124; Wald=7.435; p=0.006) were independently associated with 28-days-mortality. Combining of EVLWI and OI provided ROC-AUCs of 0.801 (day-1) and 0.824 (day-2). Among the totality of patients, the use of TPTD-monitoring „per se“ and a lower SOFA-score were independently associated with a lower 28-days-mortality.ConclusionsPrognosis of ARDS-patients can be estblished within two days after intubation. The best predictors were EVLWI and OI and their combination. TPTD-monitoring „per se“ was independently associated with reduced mortality.

Prognostic value of plasma microRNA-30b-5p combined with extravascular lung water index in patients with acute respiratory distress syndrome

To evaluate the prognostic value of plasma microRNA-30b-5p (miR-30b-5p) combined with extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS). 120 ARDS patients admitted to Danzhou People's Hospital from January 2016 to June 2019 were enrolled. The gender, age, body mass index (BMI), underlying diseases, etiology and baseline values of heart rate (HR), respiratory rate (RR), oxygenation index (OI), arterial partial pressure of carbon dioxide (PaCO2) and acute physiology and chronic health evaluation II (APACHE II) score were collected. According to the survival outcome during hospitalization, the patients were divided into survival group and death group. According to OI, the patients were divided into mild-moderate group (OI > 100 mmHg, 1 mmHg = 0.133 kPa) and severe group (OI ≤ 100 mmHg). The expression of plasma miR-30b-5p was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR), and EVLWI was measured. The receiver operating characteristic (ROC) curve was drawn to analyze the value of plasma miR-30b-5p and EVLWI in predicting the death of patients with ARDS. Pearson correlation method was used to analyze the correlation between miR-30b-5p and EVLWI in ARDS patients with different prognosis during hospitalization. 120 patients with ARDS were enrolled in the analysis, with 42 patients in the death group, and 78 in the survival group; with 67 patients in the mild-moderate group, and 53 in the severe group. APACHE II score in the death group was higher than that in the survival group, but there was no significant difference in gender, age, BMI, underlying diseases, etiology or baseline values of HR, RR, OI, or PaCO2 between the two groups. The expression of plasma miR-30b-5p and EVLWI level in the death group were significantly higher than those in the survival group [miR-30b-5p (2-ΔΔCt): 2.28±0.74 vs. 0.52±0.06, EVLWI (mL/kg): 15.38±4.60 vs. 10.24±2.15,both P < 0.01]. The expression of plasma miR-30b-5p, EVLWI and mortality during hospitalization in the severe group were significantly higher than those in the mild-moderate group [miR-30b-5p (2-ΔΔCt): 2.05±0.65 vs. 0.93±0.17, EVLWI (mL/kg): 14.65±4.20 vs. 11.36±2.28, mortality during hospitalization: 58.5% (31/53) vs. 16.4% (11/67), all P < 0.01]. ROC curve analysis showed that the best cut-off value of plasma miR-30b-5p and EVLWI in predicting the death during hospitalization of ARDS patients were 1.62 and 13.28 mL/kg, respectively. Moreover, the area under ROC curve (AUC) of the combination of two parameters was significantly higher than that of the two alone (0.897 vs. 0.827, 0.785), with high sensitivity and specificity, 90.5% and 84.2%, respectively. Pearson correlation analysis showed that plasma miR-30b-5p in dead ARDS patients was significantly positively correlated with EVLWI (r = 0.768, P < 0.01), but the correlation was not found in surviving patients (r = 0.118, P > 0.05). The expression of plasma miR-30b-5p and EVLWI are related to the severity and prognosis of patients with ARDS, and the combination of the two has certain evaluation value for the prognosis of ARDS patients.

Application of lung ultrasonography on evaluating extravascular lung water and prognosis in patients with acute respiratory distress syndrome

To evaluate the value of lung ultrasonography score (LUS) on assessing extravascular lung water (EVLW) and prognosis in patients with acute respiratory distress syndrome (ARDS). The clinical data of 46 patients meeting ARDS Berlin definition admitted to intensive care unit (ICU) of Ningbo Yinzhou People's Hospital from July 2016 to December 2019 were retrospectively collected. The general data, vital signs, blood lactic acid (Lac), oxygenation index (OI), LUS, extravascular lung water index (EVLWI), sequential organ failure assessment (SOFA) score, clinical pulmonary infection score (CPIS) and the length of ICU stay were collected. According to the prognosis of patients during ICU treatment, the patients were divided into survival group and non-survival group, and the clinical characteristics between the two groups were compared. The correlation between LUS and OI, EVLWI, SOFA, and CPIS were analyzed by Pearson correlation analysis. Receiver operator characteristic (ROC) curve was plotted to determine the prognostic value of LUS for ARDS patients during ICU treatment. Forty-six patients were enrolled in the analysis, of whom 32 patients survived (69.6%), and 14 patients died (30.4%) during ICU treatment. There was no significant difference in gender, age, left ventricular ejection fraction (LVEF) or heart rate (HR) between the two groups. Compared with the survival group, the mean arterial pressure (MAP) and OI in the non-survival group were significantly lowered [MAP (mmHg, 1 mmHg = 0.133 kPa): 57.48±33.34 vs. 85.45±19.56, OI (mmHg): 74.50±18.40 vs. 233.06±28.28, both P < 0.05], while Lac, LUS, EVLWI, SOFA and CPIS were significantly increased [Lac (mmol/L): 6.78±2.56 vs. 2.21±1.42, LUS score: 23.57±2.03 vs. 15.58±2.24, EVLWI (mL/kg): 22.93±2.56 vs. 12.96±2.18, SOFA score: 20.21±3.35 vs. 12.43±2.97, CPIS score: 8.07±1.38 vs. 4.59±1.04, all P < 0.01], and the length of ICU stay was significantly shortened (days: 9.33±3.28 vs. 16.89±4.12, P < 0.05]. Pearson correlation analysis showed that a significant negative linear correlation was found between LUS and OI (r = -0.823, P < 0.01), and positive linear correlations were found between LUS and EVLWI, SOFA, CPIS (r values were 0.745, 0.614, 0.757, respectively, all P < 0.01). ROC curve analysis showed that both LUS and EVLWI could predict the prognosis of ARDS patients during ICU treatment, and the areas under ROC curve (AUC) of LUS and EVLWI were 0.936 and 0.991, respectively. When the cut-off of LUS score was 20.5, the sensitivity and specificity were 85.7% and 81.2% respectively. LUS score has a good correlation with EVLWI monitored by pulse index continuous cardiac output (PiCCO), which can reflect lung water content. LUS score can be used as an early prognostic indicator for ARDS patients.

Effects of ulinastatin combined with glutamine on early hemodynamics in patients with severe burns

Objective: To observe the effect of ulinastatin combined with glutamine on early hemodynamics in patients with severe burns. Methods: Thirty-two patients with severe burns who met the inclusion criteria and hospitalized in the Affiliated Huaihai Hospital of Xuzhou Medical University from January 2016 to December 2018 were selected for conducting a prospective randomized controlled trial. According to the random number table, the patients were divided into conventional treatment group (4 males and 4 females), ulinastatin group (5 males and 3 females), glutamine group (5 males and 3 females), and ulinastatin+ glutamine group (4 males and 4 females), with ages of (36±8), (34±8), (35±9), and (38±13) years in turn. From post injury day 2, patients in the 4 groups were given nutritional support of equal nitrogen and equal calories, of which protein was 2.0 g/kg daily. In addition, patients in the ulinastatin group received intravenous injection of 100 kU ulinastatin every 8 hours for 7 consecutive days; 0.3 g/kg of protein given to patients in the glutamine group was provided by alanine glutamine for 7 consecutive days; patients in the ulinastatin+ glutamine group received corresponding treatments of both ulinastatin group and glutamine group. With the help of pulse contour cardiac output (PiCCO) monitoring technology, the cardiac index, stroke volume index (SVI), global end-diastolic volume index (GEDI), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) of patients in each group were measured on treatment day (TD) 1, 3, and 7. Data were processed with Fisher's exact probability method, one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni method. Results: The cardiac index was low and the SVI value was lower than the normal value on TD 1 in patients of the 4 groups, without statistically significant differences between any two groups (P>0.05), and then they were all gradually increased. On TD 3 and 7, compared with those of the conventional treatment group, the cardiac index and SVI of patients in the other three groups were all increased, and the cardiac index and SVI of patients in the ulinastatin+ glutamine group were significantly increased (P<0.05 or P<0.01). On TD 1, the GEDI of patients in the conventional treatment group, ulinastatin group, glutamine group, and ulinastatin+ glutamine group were at normal low levels, which were (659±58), (661±79), (659±88), and (653±71) mL/m(2) respectively, without statistically significant differences between any two groups (P>0.05), and then they all gradually increased. On TD 3 and 7, compared with (684±82) and (742±46) mL/m(2) of the conventional treatment group, the GEDI of patients in the ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all elevated, which were (732±53) and (777±33), (725±58) and (783±49), (813±65) and (849±27) mL/m(2) respectively, and the GEDI of patients in the ulinastatin+ glutamine group was significantly increased (P<0.05). The SVRI of patients in the four groups were all at high levels on TD 1, without statistically significant differences between any two groups (P>0.05), and then they all gradually decreased. On TD 3 and 7, compared with those of the conventional treatment group, the SVRI of patients in the other three groups were all increased, and the SVRI in the ulinastatin+ glutamine group was significantly increased (P<0.05). On TD 1, the EVLWI of patients in the conventional treatment group, ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all in the normal range, which were (6.6±0.6), (6.3±0.4), (6.5±0.4), and (6.6±0.6) mL/kg respectively, without statistically significant differences between any two groups (P>0.05), and then they all showed the increasing trend. On TD 3 and 7, compared with (7.1±0.9) and (7.9±0.5) mL/kg of the conventional treatment group, the EVLWI of patients in the ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all decreased, which were (6.2±0.6) and (7.1±0.4), (6.3±1.0) and (7.2±0.9), (5.8±0.7) and (6.7±0.6) mL/kg respectively, and the EVLWI of patients in the ulinastatin+ glutamine group was significantly decreased (P<0.05). On TD 1, the PVPI of patients in the four groups were all in the normal range, without statistically significant differences between any two groups (P>0.05), and then they all gradually decreased. On TD 3 and 7, compared with those of the conventional treatment group, the PVPI of patients in the other three groups were all decreased, and the PVPI in the ulinastatin+ glutamine group was significantly decreased (P<0.05). Conclusions: Ulinastatin combined with glutamine can increase the cardiac index, SVI, GEDI, and SVRI and reduce the EVLWI and PVPI in treating patients with severe burns, thereby increasing early cardiac output after injury, promoting tissue and organ perfusion, and reducing pulmonary edema, resulting in significant improvement in early hemodynamics of patients with severe burns.

Goal-directed dehydration therapy in sepsis and acute respiratory distress syndrome guided by volumetric hemodynamic monitoring

The aim of our study was to improve results of treatment of critically ill patients with sepsis and acute respiratory distress syndrome (ARDS) using the goal-directed dehydration therapy (DT).Sixty adult patients with sepsis and ARDS receiving mechanical ventilation for at least 24 hours were enrolled into a prospective randomized study. The patients were randomized into groups of dehydration guided either by extravascular (group of extravascular lung water index ‒ EVLWI,n= 30) or intravascular (group of global end-diastolic volume index ‒ GEDVI,n= 30) compartment. Dehydration was performed over 48 hours by administering diuretics or controlled extracorporeal ultrafiltration. We measured ventilation parameters, blood gases, and parameters of volumetric monitoring. The baseline characteristics of the patients did not differ between the groups. By 48 hours, the target fluid balance was achieved in both groups. In the EVLWI group at 48 hours, we found reduction of EVLWI by 15.4% (p&lt; 0.001) and increase in PaO2/FiO2by 23.3% as compared with baseline (p&lt; 0.001). In parallel, we observed decrease in creatinine and urea (p&lt; 0.05). In the GEDVI group, PaO2/FiO2 rose by 12.5% (p = 0.021), whereas EVLWI remained unchanged (p= 0.4). Maximal decrease in EVLWI and improvement of PaO2/FiO2 were achieved in direct ARDS.Thus, in patients with sepsis and ARDS the de-escalation goal-directed therapy resulted in the improvement of arterial oxygenation and organ function. The efficacy of dehydration was increased in direct ARDS. The extravascular compartment dehydration algorithm attenuated pulmonary edema and acute kidney injury more efficiently. Therefore, sepsis-induced ARDS may require personalized therapeutic approach.