• cirrhosis
• extravascular lung water index
• pulmonary vascular permeability index
• sepsis

• CMRPG3A1091 Chang Gung Memorial Hospital

• Agreement analysis
• Hemodynamic monitoring
• Liver transplantation
• PiCCO
• Pulmonary artery catheterization
• Trending ability.

• Liver Transplantation/methods
• Humans
• Catheterization, Swan-Ganz/methods
• Cardiac Output/physiology
• Male
• Middle Aged
• Female
• Hemodynamics/physiology
• Monitoring, Intraoperative/methods
• Aged
• Adult
• Pulmonary Artery/physiology

• B-lines
• Bedside lung ultrasound
• Extravascular lung water
• Intensive care unit
• Learning ultrasound in critical care
• Ultrasound

• Congestion
• Critical care
• Diastolic function
• Doppler echocardiography
• Hemodynamics
• Intensive care
• Left ventricle
• Mechanical ventilation
• Right ventricle

• Humans
• Critical Illness/therapy
• Ventricular Dysfunction, Left/diagnostic imaging
• Ventricular Dysfunction, Left/therapy
• Echocardiography
• Ventricular Function, Left
• Echocardiography, Doppler

• VILI (ventilator induced lung injury)
• cardiopulmonary interactions
• endothelial injury
• lung deflation injury
• vascular shearing

• EVLWI
• LUS
• UCA1
• acute lung injury
• prediction

• SARS-CoV-2
• acute respiratory distress syndrome
• driving pressure
• lung compliance
• mechanical ventilation
• transpulmonary thermodilution

• Critically ill patients
• Hemodynamic monitoring
• Lung edema
• Transpulmonary thermodilution

• Critical Illness/mortality
• Extravascular Lung Water
• Humans
• Prognosis
• Reproducibility of Results
• Thermodilution/methods

• Lung deflation
• Pulmonary oedema
• Pulmonary vascular resistance

• Animals
• Lung Injury
• Positive-Pressure Respiration/methods
• Pulmonary Edema/etiology
• Respiration, Artificial
• Respiratory Distress Syndrome
• Swine

• 156336 CIHR
• 152898 CIHR
• Canadian Institutes of Health Research

• acute respiratory distress syndrome
• children
• extracorporeal membrane oxygenation
• lung ultrasound (LUS) score
• prognosis

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11–38) vs. 11 (6–26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0–5.2) versus 1.9 (1.0–5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = − 0.60; p = 0.001) and within-subjects correlation (r = − 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

• Ischemia reperfusion injury
• Pulmonary edema

Early 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.

Therefore, 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.

In 100 consecutive patients with ARDS severity according to OI (mean airway pressure*F_iO₂/p_aO₂), 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.

Prediction of 28-days-mortality (Area under the receiver-operating-characteristic curve (ROC-AUC)); IBM SPSS 26.

In 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.

Prognosis 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.

• APACHE
• Aged
• Area Under Curve
• Extracorporeal Membrane Oxygenation
• Extravascular Lung Water
• Female
• Germany
• Hospitals, University
• Humans
• Intensive Care Units
• Intubation, Intratracheal/methods
• Male
• Middle Aged
• Oxygen Consumption
• Prognosis
• Prospective Studies
• ROC Curve
• Respiratory Distress Syndrome/mortality
• Respiratory Distress Syndrome/therapy
• Thermodilution
• Treatment Outcome

• acute respiratory distress syndrome
• cholecalciferol
• esophagectomy
• vitamin d

• Acute Lung Injury/prevention & control
• Aged
• Biomarkers
• Cholecalciferol/administration & dosage
• Dietary Supplements
• Dose-Response Relationship, Drug
• Double-Blind Method
• Esophagectomy/methods
• Extravascular Lung Water/metabolism
• Female
• Hospitals, University
• Humans
• Male
• Middle Aged
• Respiratory Function Tests
• United Kingdom
• Vitamin D/blood

• G0701603 Medical Research Council
• MR/J011266/1 Medical Research Council
• MR/L002736/1 Medical Research Council
• MR/N021185/1 Medical Research Council
• G1100196 Medical Research Council

• Doppler ultrasound
• acute kidney injury
• cardiac surgery
• point-of-care ultrasound

• ex-vivo lung perfusion
• extravascular lung water index
• lung edema
• primary graft dysfunction
• single transpulmonary thermodilution

• intubation
• point-of-care ultrasound
• pulmonary ultrasonography
• respiratory insufficiency

• Adult
• Aged
• Aged, 80 and over
• Asthma/diagnostic imaging
• Asthma/mortality
• Asthma/physiopathology
• Cohort Studies
• Critical Illness/mortality
• Female
• Humans
• Male
• Middle Aged
• Point-of-Care Systems
• Prospective Studies
• Pulmonary Disease, Chronic Obstructive/diagnostic imaging
• Pulmonary Disease, Chronic Obstructive/mortality
• Pulmonary Disease, Chronic Obstructive/physiopathology
• Respiratory Distress Syndrome/diagnostic imaging
• Respiratory Distress Syndrome/mortality
• Respiratory Distress Syndrome/physiopathology
• Respiratory Insufficiency/diagnostic imaging
• Respiratory Insufficiency/mortality
• Respiratory Insufficiency/physiopathology
• Ultrasonography/methods
• Young Adult

Sepsis is a major risk factor for acute respiratory distress syndrome (ARDS). However, there remains a paucity of literature examining risk factors for ARDS in septic patients early in their course. This study examined the role of early fluid administration and identified other risk factors within the first 6 h of hospital presentation associated with developing ARDS in septic patients.

This was a secondary analysis of septic adult patients presenting to the Emergency Department or being admitted for high-risk elective surgery from the multicenter observational cohort study, US Critical Injury and Illness trial Group-Lung Injury Prevention Study 1 (USCIITG-LIPS 1, NCT00889772). Multivariable logistic regression was performed to identify potential early risk factors for ARDS. Stratified analysis by shock status was performed to examine the association between early fluid administration and ARDS.

Of the 5584 patients in the original study cohort, 2534 (45.4%) met our criteria for sepsis. One hundred and fifty-six (6.2%) of these patients developed ARDS during the hospital stay. In multivariable analyses, Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR 1.10, 95% CI 1.07–1.13), age (OR 0.97, 95% CI 0.96–0.98), total fluid infused in the first 6 h (in liters) (OR 1.15, 95% CI 1.03–1.29), shock (OR 2.57, 95% CI 1.62–4.08), pneumonia as a site of infection (OR 2.31, 95% CI 1.59–3.36), pancreatitis (OR 3.86, 95% CI 1.33–11.24), and acute abdomen (OR 3.77, 95% CI 1.37–10.41) were associated with developing ARDS. In the stratified analysis, total fluid infused in the first 6 h (in liters) (OR 1.05, 95% CI 0.87–1.28) was not associated with the development of ARDS in the shock group, while there was an association in the non-shock group (OR 1.21, 95% CI 1.05–1.38).

In septic patients, the following risk factors identified within the first 6 h of hospital presentation were associated with ARDS: APACHE II score, presence of shock, pulmonary source of infection, pancreatitis, and presence of an acute abdomen. In septic patients without shock, the amount of fluid infused during the first 6 h of hospital presentation was associated with developing ARDS.

The online version of this article (doi:10.1186/s13613-017-0233-1) contains supplementary material, which is available to authorized users.

• Acute lung injury
• Acute respiratory distress syndrome
• Fluid resuscitation
• Pneumonia
• Sepsis

The primary goal of septic shock management is optimization of organ perfusion, often at the risk of overloading the interstitium and causing pulmonary edema. The conventionally used end points of resuscitation do not generally include volumetric parameters such as extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI).

This study aimed to assess the prognostic value of EVLWI and PVPI by calculating their correlation with the severity of lung injury.

This prospective observational study included twenty mechanically ventilated critically ill patients with Acute Physiology and Chronic Health Evaluation score (APACHE II) >20.

EVLWI and PVPI were measured using transpulmonary thermodilution, and simultaneously, PaO₂:FiO₂ ratio, alveolar-arterial gradient of oxygen (AaDO₂), and chest radiograph scores from two radiologists were obtained.

The correlation of EVLWI and PVPI with chest radiograph scores, PaO₂:FiO₂ ratio, and AaDO₂ were calculated. The inter-observer agreement between the two radiologists was tested using kappa test.

EVLWI and PVPI correlated modestly with PaO₂:FiO₂ (r = −0.32, P = 0.0004; r = −0.39, P = 0.0001). There was a better correlation of EVLWI and PVPI with PaO₂:FiO₂ ratio (r = −0.71, P < 0.0001; r = −0.58, P = 0.0001) in the acute respiratory distress syndrome (ARDS) subgroup. The EVLWI values correlated significantly with corresponding chest radiograph scores (r = 0.71, P < 0.0001 for observer 1 and r = 0.68, P < 0.0001 for observer 2).

EVLWI and PVPI may have a prognostic significance in the assessment of lung injury in septic shock patients with ARDS. Further research is required to reveal the usefulness of EVLWI as an end point of fluid resuscitation in the management of septic shock with ARDS.

• Acute respiratory distress syndrome
• extravascular lung water
• septic shock
• thermodilution

• Adrenal Cortex Hormones/adverse effects
• Humans
• Hypoxia/etiology
• Prone Position
• Respiration, Artificial/methods
• Respiratory Distress Syndrome/diagnosis
• Respiratory Distress Syndrome/diagnostic imaging
• Water-Electrolyte Balance

• G0701690 Medical Research Council
• MC_G1002460 Medical Research Council

• levosimendan
• neurogenic pulmonary edema
• pulse indicate contour cardiac output
• traumatic brain injury

• Critical ill-therapeutic plasma exchange
• Transfusion-related acute lung injury-Intensive care unit
• Transpulmonary thermodilution

• Acute lung injury
• Acute respiratory distress syndrome
• Clinical trials
• Positive-pressure respiration
• Respiratory mechanics
• Ventilator-induced lung injury

• Global end-diastolic volume index
• Hemodynamics
• Indexation
• Monitoring
• Transpulmonary thermodilution

Increased extravascular lung water (EVLW) may contribute to respiratory failure in neonates. Accurate measurement of EVLW in these patients is limited due to the lack of bedside methods. The aim of this pilot study was to investigate the reliability of the transpulmonary ultrasound dilution (TPUD) technique as a possible method for estimating EVLW in a neonatal animal model. Pulmonary edema was induced in 11 lambs by repeated surfactant lavages. In between the lavages, EVLW indexed by bodyweight was estimated by TPUD (EVLWI_tpud) and transpulmonary dye dilution (EVLWI_tpdd) (n = 22). Final EVLWI_tpud measurements were also compared with EVLWI estimations by gold standard post mortem gravimetry (EVLWI_grav) (n = 6). EVLWI was also measured in two additional lambs without pulmonary edema. Bland–Altman plots showed a mean bias between EVLWI_tpud and EVLWI_tpdd of −3.4 mL/kg (LOA ± 25.8 mL/kg) and between EVLWI_tpud and EVLWI_grav of 1.7 mL/kg (LOA ± 8.3 mL/kg). The percentage errors were 109 and 43 % respectively. The correlation between changes in EVLW measured by TPUD and TPDD was r² = 0.22. Agreement between EVLWI measurements by TPUD and TPDD was low. Trending ability to detect changes between these two methods in EVLWI was questionable. The accuracy of EVLWI_tpud was good compared to the gold standard gravimetric method but the TPUD lacked precision in its current prototype. Based on these limited data, we believe that TPUD has potential for future use to estimate EVLW after adaptation of the algorithm. Larger studies are needed to support our findings.

• Cardiac output
• Children
• Dilution technique
• Extravascular lung water
• Hemodynamics
• Indicator
• Monitoring
• Neonate

• Algorithms
• Animals
• Cardiac Output
• Catheterization
• Extravascular Lung Water
• Femoral Artery/pathology
• Hemodynamics
• Lung Injury/pathology
• Pulmonary Edema/therapy
• Reproducibility of Results
• Sheep
• Thermodilution/methods
• Thermogravimetry
• Ultrasonography

Extravascular lung water (EVLW) is the amount of fluid that is accumulated in the interstitial and alveolar spaces. In lung oedema, EVLW increases either because of increased lung permeability or because of increased hydrostatic pressure in the pulmonary capillaries, or both. Increased EVLW is always potentially life-threatening, mainly because it impairs gas exchange and reduces lung compliance. The only technique that provides an easy measurement of EVLW at the bedside is transpulmonary thermodilution. The validation of EVLW measurements by thermodilution was based on studies showing reasonable correlations with gravimetry or thermo-dye dilution in experimental and clinical studies. EVLW should be indexed to predicted body weight. This indexation reduces the proportion of ARDS patients for whom EVLW is in the normal range. Compared to non-indexed EVLW, indexed EVLW (EVLWI) is better correlated with the lung injury score and the oxygenation and it is a better predictor of mortality of patients with acute lung injury or acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution also provides the pulmonary vascular permeability index (PVPI), which is an indirect reflection of the integrity of the alveolocapillary barrier. As clinical applications, EVLWI and PVPI may be useful to guide fluid management of patients at risk of fluid overload, as during septic shock and ARDS. High EVLWI and PVPI values predict mortality in several categories of critically ill patients, especially during ARDS. Thus, fluid administration should be limited when EVLWI is already high. Whatever the value of EVLWI, PVPI may indicate that fluid administration is particularly at risk of aggravating lung oedema. In the acute phase of haemodynamic resuscitation during septic shock and ARDS, high EVLWI and PVPI values may warn of the risk of fluid overload and prevent excessive volume expansion. At the post-resuscitation phase, they may prompt initiation of fluid removal thereby achieving a negative fluid balance.

• Acute lung injury
• Acute respiratory distress syndrome
• Extravascular lung water
• Fluid management
• Fluid responsiveness
• Hemodynamic monitoring
• Lung oedema
• Pulmonary vascular permeability index
• Transpulmonary thermodilution

• APACHE II score
• Fluid resuscitation
• ICU
• Pulse indicator continuous cardiac output
• SIRS
• Severe acute pancreatitis

• Cardiac index
• Cardiovascular dynamics
• Hemodynamic monitoring
• Hemodynamics
• Intensive care
• Monitoring

• Adult
• Age Factors
• Biometry
• Body Mass Index
• Body Surface Area
• Body Weight/physiology
• Cardiac Output/physiology
• Critical Illness/therapy
• Female
• Hemodynamics/physiology
• Humans
• Intensive Care Units
• Male
• Thermodilution/methods

Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated.

To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity.

Human, murine and in vitro primary alveolar epithelial cell work were included in this study.

Vitamin D deficiency (plasma 25(OH)D levels <50 nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients.

Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed.

UKCRN ID 11994.

• ARDS
• Innate Immunity

• Edwards EV-1000
• Modelflow technique
• PiCCO
• arterial waveform analysis
• cardiac output
• hemodynamic monitoring
• transcardiopulmonary thermodilution

• Acute lung injury
• Extravascular lung water
• Pulmonary edema
• Pulmonary vascular permeability index
• Transpulmonary thermodilution technique

• Acute lung injury
• Acute respiratory distress syndrome
• Agua pulmonar extravascular
• Balance hídrico negativo
• Extravascular lung water
• Hypoxemic patients
• Intensive Care Unit
• Lesión pulmonar aguda
• Negative fluid balance
• Pacientes hipoxémicos
• Síndrome de distress respiratorio agudo
• Unidad Cuidados Intensivos

Transpulmonary thermodilution (TPTD) derived parameters are used to direct fluid management in ICU-patients. Extravascular lung water EVLW and its ratio to pulmonary blood volume (pulmonary vascular permeability index PVPI) have been associated with mortality. In single indicator TPTD pulmonary blood volume (PBV) is estimated to be 25% of global end-diastolic volume (GEDV). A recent study demonstrated marked overestimation of GEDV indexed to body-surface area (BSA; GEDVI) when using a femoral central venous catheter (CVC) for indicator injection due to the additional volume measured in the vena cava inferior. Therefore, a correction formula derived from femoral TPTD and biometric data has been suggested. Consequence, one of the commercially available TPTD-devices (PiCCO; Pulsion Medical Systems, Germany) requires information about CVC site. Correction of GEDVI for femoral CVC can be assumed. However, there is no data if correction also pertains to unindexed GEDV, which is used for calculation of PBV and PVPI. Therefore, we investigated, if also GEDV, PBV and PVPI are corrected by the new PiCCO-algorithm.

In this prospective study 110 triplicate TPTDs were performed within 30 hours in 11 adult ICU-patients with PiCCO-monitoring and femoral CVC. We analyzed if the femoral TPTD correction formula for GEDVI was also applied to correct GEDV. Furthermore, we compared PVPI_displayed to PVPI_calculated which was calculated as EVLW_displayed/(0.25*GEDV_displayed).

Multiplication of GEDVI_displayed by BSA resulted in GEDV_calculated which was not significantly different to GEDV_displayed (1459 ± 365 mL vs. 1459 ± 366 mL) suggesting that correction for femoral indicator injection also pertains to GEDV_displayed. However, PVPI_displayed was significantly lower than PVPI_calculated (1.64 ± 0.57 vs. 2.27 ± 0.72; p < 0.001). In addition to a bias of -0.64 ± 0.22 there was a percentage error of 22%. Application of the correction formula suggested for GEDVI to PVPI_displayed reduced the bias of PVPI_displayed compared to EVLW/PBV from -0.64 ± 0.22 to -0.10 ± 0.05 and the percentage error from 22% to 4%.

Correction for femoral CVC in the PiCCO-device pertains to both GEDVI_displayed and GEDV_displayed, but not to PVPI_displayed. To provide consistent information, PVPI should be calculated based on GEDV_corrected in case of femoral CVC.

• LiDCO
• PiCCO
• dogs
• hemodynamic monitoring
• thermodilution

The features of early-phase acute respiratory distress syndrome (ARDS) are leakage of fluid into the extravascular space and impairment of its reabsorption, resulting in extravascular lung water (EVLW) accumulation. The current study aimed to identify how the initial EVLW values and their change were associated with mortality.

This was a post hoc analysis of the PiCCO Pulmonary Edema Study, a multicenter prospective cohort study that included 23 institutions. Single-indicator transpulmonary thermodilution-derived EVLW index (EVLWi) and conventional prognostic factors were prospectively collected over 48 h after enrollment. Associations between 28-day mortality and each variable including initial (on day 0), mean, maximum, and Δ (subtracting day 2 from day 0) EVLWi were evaluated.

We evaluated 192 ARDS patients (median age, 69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant differences were found in initial, mean, or maximum EVLWi, Δ-EVLWi was significantly higher (i.e., more reduction in EVLWi) in survivors than in non-survivors (3.0 vs. −0.3 mL/kg, p = 0.006). Age, maximum, and Δ-SOFA scores and Δ-EVLW were the independent predictors for survival according to the Cox proportional hazard model. Patients with Δ-EVLWi > 2.8 had a significantly higher incidence of survival than those with Δ-EVLWi ≤ 2.8 (log-rank test, χ² = 7.08, p = 0.008).

Decrease in EVLWi during the first 48 h of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be useful for understanding the pathophysiologic conditions in ARDS patients. A large multination confirmative trial is required.

• Acute lung injury
• Hemodynamics
• Pulmonary edema
• Transpulmonary thermodilution
• Vascular permeability