Transpulmonary Thermodilution Research Articles

Role of invasive hemodynamics monitoring in sepsis intensive care

The objective was to study the effect of early planned use of transpulmonary thermodilution (TPTD) and therapeutic measures to stabilize blood circulation on the clinical outcome of sepsis.Materials and methods. The cohort study involved 132 patients with abdominal sepsis with SOFA >7 and blood lactate >1.6 mmol/L. Septic shock was diagnosed in 56 % of patients. TPTD in the early periods of intensive care was began in 53.8 % of patients. Logistic regression and ROC-analysis were used to process the data.Results. Early use of invasive monitoring (OR 2,3715, 95 % CI 1,1107–5,0635, p=0,026, AUC 0.655) and infusion volume >43 ml/kg per day (OR 1.0313, 95 % CI 1.0073–1.0558, p=0.01, AUC 0.677) were predictors of survival in patients with abdominal sepsis. The use of TPTD compared to patients of group II was accompanied by an increase in the daily infusion volume (53.7 [38.1–63.5] vs 38.2 [29.9–47.2], ml/kg per day, p = 0.0001), more frequent use of inotropic drugs (39.4 vs 16.4 %, p = 0.004), and higher level of the inotropic scale (0 [0–4.7] vs 0 [0–0], p = 0.01). There were no differences in the frequency of prescription (57.7 vs 65.5 %, p = 0.376) and dosages (0.2 [0.1–0.4] vs 0.3 [0.2–0.4] μg/kg/min, p = 0.554) of norepinephrine. Twenty-eight-day mortality in groups I and II was 31 and 50.8 % (p = 0.022), hospital mortality was 32.9 and 54.0 % (p = 0.014).Conclusion. When assessed by SOFA > 7 points and lactatemia > 1.6 mmol/L, the onset of TPTD and infusion volume > 43 mL/kg/day increase the likelihood of survival of patients with abdominal sepsis, as a result, 28-day and hospital mortality decrease by 1.6 times. The use of invasive monitoring of central hemodynamics in this clinical situation is accompanied by an increase in the prescription of inotropes by 2.4 times with an unchanged intensity of norepinephrine use.

Injection Site Matters: A Comparative Analysis of Transpulmonary Thermodilution via Simultaneous Femoral and Jugular Indicator Injections under Veno-Venous Extracorporeal Membrane Oxygenation Therapy.

Background: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) in acute lung failure has witnessed a notable increase. The PiCCO system is frequently used for advanced hemodynamic monitoring in this cohort. Our study aimed to investigate whether the choice of indicator injection site (jugular vs. femoral) in patients undergoing vv-ECMO therapy affects transpulmonary thermodilution (TPTD) measurements using the PiCCO® device (Pulsion Medical Systems SE, Munich, Germany). Methods: In a retrospective single-center analysis, we compared thermodilution-derived hemodynamic parameters after simultaneous jugular and femoral injections in 28 measurements obtained in two patients with respiratory failure who were undergoing vv-ECMO therapy. Results: Elevated values of the extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI) were observed following femoral indicator injection compared to jugular indicator injection (EVLWI: 29.3 ± 10.9 mL/kg vs. 18.3 ± 6.71 mL/kg, p = 0.0003; ITBVI: 2163 ± 631 mL/m2 vs. 806 ± 125 mL/m2, p < 0.0001; GEDVI: 1731 ± 505 mL/m2 vs. 687 ± 141 mL/m2, p < 0.0001). The discrepancy between femoral and jugular measurements exhibited a linear correlation with extracorporeal blood flow (ECBF). Conclusions: In a PiCCO®-derived hemodynamic assessment of patients on vv-ECMO, the femoral indicator injection, as opposed to the jugular injection, resulted in an overestimation of all index parameters. This discrepancy can be attributed to mean transit time (MTt) and downslope time-dependent (DSt) variations in GEDVI and cardiac function index and is correlated with ECBF.

Cardiac output measured with cold saline transpulmonary thermodilution in dogs: comparison with room temperature injectate and with pulse wave-derived continuous cardiac output

Cardiac output measured with cold saline transpulmonary thermodilution in dogs: comparison with room temperature injectate and with pulse wave-derived continuous cardiac output

The diagnostic accuracy of lung ultrasound to determine PiCCO-derived extravascular lung water in invasively ventilated patients with COVID-19 ARDS

BackgroundLung ultrasound (LUS) can detect pulmonary edema and it is under consideration to be added to updated acute respiratory distress syndrome (ARDS) criteria. However, it remains uncertain whether different LUS scores can be used to quantify pulmonary edema in patient with ARDS.ObjectivesThis study examined the diagnostic accuracy of four LUS scores with the extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution in patients with moderate-to-severe COVID-19 ARDS.MethodsIn this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were enrolled within 48 hours after intubation and underwent LUS and EVLWi measurement on the first and fourth day after enrolment. EVLWi and ∆EVLWi were used as reference standards. Two 12-region scores (global LUS and LUS–ARDS), an 8-region anterior–lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi > 15 mL/kg) was calculated.Results26 out of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 out of 29 patients (83%) at time point 2. The global LUS (r = 0.54), LUS–ARDS (r = 0.58) and anterior–lateral score (r = 0.54) correlated significantly with EVLWi, while the B-line score did not (r = 0.32). ∆global LUS (r = 0.49) and ∆anterior–lateral LUS (r = 0.52) correlated significantly with ∆EVLWi. AUROCC for EVLWi > 15 ml/kg was 0.73 for the global LUS, 0.79 for the anterior–lateral and 0.85 for the LUS–ARDS score.ConclusionsOverall, LUS demonstrated an acceptable diagnostic accuracy for detection of pulmonary edema in moderate–to–severe COVID-19 ARDS when compared with PICCO. For identifying patients at risk of severe pulmonary edema, an extended score considering pleural morphology may be of added value.Trial registration: ClinicalTrials.gov identifier NCT04794088, registered on 11 March 2021. European Clinical Trials Database number 2020–005447-23.

Pressure- vs. volume-controlled ventilation and their respective impact on dynamic parameters of fluid responsiveness: a cross-over animal study

Background and goal of studyPulse pressure variation (PPV) and stroke volume variation (SVV), which are based on the forces caused by controlled mechanical ventilation, are commonly used to predict fluid responsiveness. When PPV and SVV were introduced into clinical practice, volume-controlled ventilation (VCV) with tidal volumes (VT) ≥ 10 ml kg− 1 was most commonly used. Nowadays, lower VT and the use of pressure-controlled ventilation (PCV) has widely become the preferred type of ventilation. Due to their specific flow characteristics, VCV and PCV result in different airway pressures at comparable tidal volumes. We hypothesised that higher inspiratory pressures would result in higher PPVs and aimed to determine the impact of VCV and PCV on PPV and SVV.MethodsIn this self-controlled animal study, sixteen anaesthetised, paralysed, and mechanically ventilated (goal: VT 8 ml kg− 1) pigs were instrumented with catheters for continuous arterial blood pressure measurement and transpulmonary thermodilution. At four different intravascular fluid states (IVFS; baseline, hypovolaemia, resuscitation I and II), ventilatory and hemodynamic data including PPV and SVV were assessed during VCV and PCV. Statistical analysis was performed using U-test and RM ANOVA on ranks as well as descriptive LDA and GEE analysis.ResultsComplete data sets were available of eight pigs. VT and respiratory rates were similar in both forms. Heart rate, central venous, systolic, diastolic, and mean arterial pressures were not different between VCV and PCV at any IVFS. Peak inspiratory pressure was significantly higher in VCV, while plateau, airway and transpulmonary driving pressures were significantly higher in PCV. However, these higher pressures did not result in different PPVs nor SVVs at any IVFS.ConclusionVCV and PCV at similar tidal volumes and respiratory rates produced PPVs and SVVs without clinically meaningful differences in this experimental setting. Further research is needed to transfer these results to humans.

Cardiac arrest related lung edema: examining the role of downtimes in transpulmonary thermodilution analysis.

Pulmonary edema and its association with low flow times has been observed in postcardiac arrest patients. However, diagnosis of distinct types of lung pathology is difficult.The aim of this study was to investigate pulmonary edema by transpulmonary thermodilution (TPTD) after out-of-hospital cardiac arrest (OHCA), and the correlation to downtimes. In this retrospective single-center study consecutive patients with return of spontaneous circulation (ROSC) following OHCA, age ≥ 18, and applied TPTD were enrolled. According to downtimes, patients were divided into a short and a long no-flow-time group, and data of TPTD were analysed. We identified 45 patients (n = 25 short no-flow time; n = 20 long no-flow time) who met the inclusion criteria. 24h after ROSC, the extra vascular lung water index (EVLWI) was found to be lower in the group with short no-flow time compared to the group with long no-flow time (10.7 ± 3.5ml/kg vs. 12.8 ± 3.9ml/kg; p = 0.08) and remained at a similar level 48h (10.9 ± 4.3ml/kg vs. 12.9 ± 4.9ml/kg; p = 0.25) and 72h (11.1 ± 5.0ml/kg vs. 13.9 ± 7.7ml/kg; p = 0.27) post-ROSC. We found a statistically significant and moderate correlation between no-flow duration and EVLWI 48h (r = 0.51; p = 0.002) and 72h (r = 0.54; p = 0.004) post-ROSC. Pulmonary vascular permeability index (PVPI) was not correlated with downtimes. Our observation underlines the presence of cardiac arrest-related lung edema by determination of EVLWI. The duration of no-flow times is a relevant factor for increased extravascular lung water index.

Phenylephrine and norepinephrine increase blood pressure through opposing physiologic mechanisms in isoflurane-anesthetized dogs receiving acepromazine.

To elucidate the cardiovascular effects of escalating doses of phenylephrine and norepinephrine in dogs receiving acepromazine and isoflurane. 8 beagles aged 1 to 2 years (7.4 to 11.2 kg). All dogs received acepromazine 0.01 mg/kg, propofol 4 to 5 mg/kg, and isoflurane and were mechanically ventilated. Mean arterial pressure (MAP) from a femoral artery catheter and continuous electrocardiogram were recorded. Cardiac output (CO) was measured with transpulmonary thermodilution. Systemic vascular resistance (SVR), global end-diastolic volume (GEDV), and global ejection fraction (GEF) were subsequently calculated. Phenylephrine and norepinephrine were infused in random order at 0.07, 0.3, 0.7, and 1.0 μg/kg/min. All variables were measured after 15 minutes of each infusion rate. The effects of dose, agent, and their interaction on the change of each variable were evaluated with mixed-effect models. A P < .05 was used for significance. Atrial premature complexes occurred in 3 dogs during norepinephrine infusion at doses of 0.3, 0.7, and 1 μg/kg/min; no dysrhythmias were seen with phenylephrine administration. MAP increased during dose escalation (P < .0001) within each agent and did not differ between agents (P = .6). The decrease in HR was greater for phenylephrine (P < .0001). Phenylephrine decreased CO and GEF and increased GEDV and SVR (all P < .03). Norepinephrine decreased the SVR and increased CO, GEDV, and GEF (all P < .03). Our results confirm that phenylephrine increases arterial pressures mainly through vasoconstriction in acepromazine-premedicated dogs while norepinephrine, historically considered a vasopressor, does so primarily through an increase in inotropism.

A deep learning model enables accurate prediction and quantification of pulmonary edema from chest X-rays

BackgroundA quantitative assessment of pulmonary edema is important because the clinical severity can range from mild impairment to life threatening. A quantitative surrogate measure, although invasive, for pulmonary edema is the extravascular lung water index (EVLWI) extracted from the transpulmonary thermodilution (TPTD). Severity of edema from chest X-rays, to date is based on the subjective classification of radiologists. In this work, we use machine learning to quantitatively predict the severity of pulmonary edema from chest radiography.MethodsWe retrospectively included 471 X-rays from 431 patients who underwent chest radiography and TPTD measurement within 24 h at our intensive care unit. The EVLWI extracted from the TPTD was used as a quantitative measure for pulmonary edema. We used a deep learning approach and binned the data into two, three, four and five classes increasing the resolution of the EVLWI prediction from the X-rays.ResultsThe accuracy, area under the receiver operating characteristic curve (AUROC) and Mathews correlation coefficient (MCC) in the binary classification models (EVLWI < 15, ≥ 15) were 0.93 (accuracy), 0.98 (AUROC) and 0.86(MCC). In the three multiclass models, the accuracy ranged between 0.90 and 0.95, the AUROC between 0.97 and 0.99 and the MCC between 0.86 and 0.92.ConclusionDeep learning can quantify pulmonary edema as measured by EVLWI with high accuracy.

Hemodynamic monitoring in liver Transplantation patients in the third millennium

In patients undergoing orthotopic liver transplantation (OLTx) surgery, the intraoperative hemodynamic monitoring technique that is most utilized is still the pulmonary artery catheter (PAC). The popularity of transesophageal echocardiography (TEE) is increasing, so today's updated issue is the following: should the use of PAC and/or volumetric monitoring with transpulmonary thermodilution and/or advanced volumetric PAC be limited in clinical practice, only for some high risk patients? Could we use the TEE, if necessary, in less critical ill patients undergoing OLTx surgery? We can integrate all of the aforementioned monitoring techniques in an increasing modular step wise monitoring concept. But in an uncertain hemodynamic situation, transthoracic and/or transoesophageal echocardiographic evaluation represents a cornerstone. The use of echocardiography during OLTx is more and more common with several benefits demonstrated particularly by the TEE in this patient population. To achieve and maintain adequate tissue perfusion becomes difficult in case of major bleeding, an event quite possible to occur during OLTx, affecting the immediate and the late outcome. All the clinicians agree that bleeding interfere with the choice of hemodynamic monitoring and or vice versa. A reasonable compromise is to find a balance between the need to extend monitoring in high-risk surgical patients and the average consumption of blood products that characterizes each individual transplant center. This is also in line with what is shown in literature in terms of Maximum Surgical Blood Ordering Schedule (MSBOS).

Accuracy of hemodynamic parameters derived by GE E-PiCCO in comparison with PiCCO® in patients admitted to the intensive care unit

To evaluate the agreement and accuracy of a novel advanced hemodynamic monitoring (AHM) device, the GE E-PiCCO module, with the well-established PiCCO® device in intensive care patients using pulse contour analysis (PCA) and transpulmonary thermodilution (TPTD). A total of 108 measurements were performed in 15 patients with AHM. Each of the 27 measurement sequences (one to four per patient) consisted of a femoral and a jugular indicator injection via central venous catheters (CVC) and measurement using both PiCCO (PiCCO® Jug and Fem) and GE E-PiCCO (GE E-PiCCO Jug and Fem) devices. For statistical analysis, Bland–Altman plots were used to compare the estimated values derived from both devices. The cardiac index measured via PCA (CIpc) and TPTD (CItd) was the only parameter that fulfilled all a priori-defined criteria based on bias and the limits of agreement (LoA) by the Bland–Altman method as well as the percentage error by Critchley and Critchley for all three comparison pairs (GE E-PiCCO Jug vs. PiCCO® Jug, GE E-PiCCO Fem vs. PiCCO® Fem, and GE E-PiCCO Fem vs. GE E-PiCCO Jug), while the GE E-PiCCO did not accurately estimate EVLWI, SVRI, SVV, and PPV values measured via the jugular and femoral CVC compared with values assessed by PiCCO®. Consequently, measurement discrepancy should be considered on evaluation and interpretation of the hemodynamic status of patients admitted to the ICU when using the GE E-PiCCO module instead of the PiCCO® device.

Evaluation of organ perfusion and intravascular volume status by ultrasound

This review article is devoted to ultrasound monitoring of intravascular volume status and organ perfusion in critically ill patients. In particular, approaches to determination of fluid responsiveness using Doppler-estimated blood flow in peripheral arteries are discussed. The reliability and accuracy of these parameters are substantiated by their comparison with the parameters obtained by prepulmonary and transpulmonary thermodilution methods. The technicalities of ultrasound examination of the abovementioned parameters are considered.

New Developments in Continuous Hemodynamic Monitoring of the Critically Ill Patient.

Hemodynamic monitoring is a cornerstone in the assessment of patients with circulatory shock. Timely recognition of hemodynamic compromise and proper optimisation is essential to ensure adequate tissue perfusion and maintain renal, hepatic, abdominal, and cerebral functions. Hemodynamic monitoring has significantly evolved since the first inception of the pulmonary artery catheter more than 50 years ago. Bedside echocardiography, when combined with noninvasive and minimally invasive technologies, provides tools to monitor and quantify the cardiac output to promptly react and improve hemodynamic management in an acute care setting. Commonly used technologies include noninvasive pulse-wave analysis, pulse-wave transit time, thoracic bioimpedance and bioreactance, esophageal Doppler, minimally invasive pulse-wave analysis, transpulmonary thermodilution, and pulmonary artery catheter. These monitoring strategies are reviewed here, along with detailed analysis of their operating mode, particularities, and limitations. The use of artificial intelligence to enhance performance and effectiveness of hemodynamic monitoring is reviewed to apprehend future possibilities.

Adjunctive Hydrocortisone Improves Hemodynamics in Critically Ill Patients with Septic Shock: An Observational Study Using Transpulmonary Thermodilution.

Introduction: Septic shock is associated with high mortality and hemodynamic impairment. The use of corticoids is a common therapeutic tool in critically ill patients. However, data on the mechanisms and prognostic ability of hemodynamic improvement by adjunctive steroids are rare. This study primarily aimed to evaluate short-term effects of hydrocortisone therapy on catecholamine requirement and hemodynamics derived from transpulmonary thermodilution (TPTD) in 30 critically ill patients with septic shock and a 28 days mortality rate of 50%. Methods: Hydrocortisone was administered with an intravenous bolus of 200 mg, followed by a continuous infusion of 200 mg per 24 h. Hemodynamic assessment was performed immediately before as well as 2, 8, 16, and 24 h after the initiation of corticoids. For primary endpoint analysis, we evaluated the impact of hydrocortisone on vasopressor dependency index (VDI) and cardiac power index (CPI). Results: Adjunctive hydrocortisone induced significant decreases of VDI from 0.41 (0.29-0.49) mmHg-1 at baseline to 0.35 (0.25-0.46) after 2 h (P < .001), 0.24 (0.12-0.35) after 8 h (P < .001), 0.18 (0.09-0.24) after 16 h (P < .001) and 0.11 (0.06-0.20) mmHg-1 after 24 h (P < .001). In parallel, we found an improvement in CPI from 0.63 (0.50-0.83) W/m2 at baseline to 0.68 (0.54-0.85) after 2 h (P = .208), 0.71 (0.60-0.90) after 8 h (P = .033), 0.82 (0.6-0.98) after 16 h (P = .004) and 0.90 (0.67-1.07) W/m2 after 24 h (P < .001). Our analyses revealed a significant reduction in noradrenaline requirement in parallel with a moderate increase in mean arterial pressure, systemic vascular resistance index, and cardiac index. As a secondary endpoint, our results showed a significant decrease in lung water parameters. Moreover, changes in CPI (ΔCPI) and VDI (ΔVDI) after 24 h of hydrocortisone therapy revealed accurate prognostic ability to predict 28 days mortality (AUC = 0.802 vs 0.769). Conclusion: Adjunctive hydrocortisone leads to a rapid decrease in catecholamine requirement and a substantial circulatory improvement in critically ill patients with septic shock.

Does tidal volume challenge improve the feasibility of pulse pressure variation in patients mechanically ventilated at low tidal volumes? A systematic review and meta-analysis

BackgroundPulse pressure variation (PPV) has been widely used in hemodynamic assessment. Nevertheless, PPV is limited in low tidal volume ventilation. We conducted this systematic review and meta-analysis to evaluate whether the tidal volume challenge (TVC) could improve the feasibility of PPV in patients ventilated at low tidal volumes.MethodsPubMed, Embase and Cochrane Library inception to October 2022 were screened for diagnostic researches relevant to the predictability of PPV change after TVC in low tidal volume ventilatory patients. Summary receiving operating characteristic curve (SROC), pooled sensitivity and specificity were calculated. Subgroup analyses were conducted for possible influential factors of TVC.ResultsTen studies with a total of 429 patients and 457 measurements were included for analysis. The predictive performance of PPV was significantly lower than PPV change after TVC in low tidal volume, with mean area under the receiving operating characteristic curve (AUROC) of 0.69 ± 0.13 versus 0.89 ± 0.10. The SROC of PPV change yielded an area under the curve of 0.96 (95% CI 0.94, 0.97), with overall pooled sensitivity and specificity of 0.92 (95% CI 0.83, 0.96) and 0.88 (95% CI 0.76, 0.94). Mean and median cutoff value of the absolute change of PPV (△PPV) were 2.4% and 2%, and that of the percentage change of PPV (△PPV%) were 25% and 22.5%. SROC of PPV change in ICU group, supine or semi-recumbent position group, lung compliance less than 30 cm H2O group, moderate positive end-expiratory pressure (PEEP) group and measurements devices without transpulmonary thermodilution group yielded 0.95 (95%0.93, 0.97), 0.95 (95% CI 0.92, 0.96), 0.96 (95% CI 0.94, 0.97), 0.95 (95% CI 0.93, 0.97) and 0.94 (95% CI 0.92, 0.96) separately. The lowest AUROCs of PPV change were 0.59 (95% CI 0.31, 0.88) in prone position and 0.73 (95% CI 0.60, 0.84) in patients with spontaneous breathing activity.ConclusionsTVC is capable to help PPV overcome limitations in low tidal volume ventilation, wherever in ICU or surgery. The accuracy of TVC is not influenced by reduced lung compliance, moderate PEEP and measurement tools, but TVC should be cautious applied in prone position and patients with spontaneous breathing activity.Trial registration PROSPERO (CRD42022368496). Registered on 30 October 2022.

ARTERIAL DIAMETER VARIATIONS AS A NEW INDEX FOR STROKE VOLUME ASSESSMENT: AN EXPERIMENTAL STUDY ON A CONTROLLED HEMORRHAGIC SHOCK MODEL IN PIGLETS.

Background: The assessment of cardiac output (CO) is a major challenge during shock. The criterion standard for CO evaluation is transpulmonary thermodilution, which is an invasive technique. Speckle tracking is an automatized method of analyzing tissue motion using echography. This tool can be used to monitor pulsed arterial diameter variations with low interobserver variability. An experimental model of controlled hemorrhagic shock allows for multiple CO variations. The main aim of this study is to show the correlation between the femoral arterial diameter variations (fADVs) and the stroke volume (SV) measured by thermodilution during hemorrhagic shock management and the resuscitation of anesthetized piglets. The secondary objective is to explore the respective correlations between SV and subaortic time-velocity index, abdominal aorta ADV, carotid ADV, and subclavian ADV. Methods : Piglets were bled until mean arterial pressure reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes before randomizing the piglets to three resuscitation groups-the fluid-filling group (reanimated with saline solution only), NEph group (norepinephrine + saline solution), and Eph group (epinephrin + saline solution). Speckle tracking, echocardiographic, and hemodynamic measures were performed at different stages of the protocol. Results : Thirteen piglets were recruited and included for statistical analysis. Of all the piglets, 164 fADV measures were attempted and 160 were successful (98%). The correlation coefficient between fADV and SV was 0.71 (95% confidence interval [CI], 0.62 to 0.78; P < 0.01). The correlation coefficient between SV and abdominal aorta ADV, subclavian ADV, and carotid ADV was 0.30 (95% CI, 0.13 to 0.46; P < 0.01), 0.56 (95% CI, 0.45 to 0.66, P < 0.01), and 0.15 (95% CI, -0.01 to 0.30, P = 0.06), respectively. Conclusions : In this hemorrhagic shock model using piglets, fADV was strongly correlated with SV.

Transpulmonary thermodilution: A revised correction formula for global end-diastolic volume index derived after femoral indicator injection.

Transpulmonary thermodilution (TPTD) is usually performed by jugular indicator injection. In clinical practice, femoral venous access is often used instead, resulting in substantial overestimation of global end-diastolic volume index (GEDVI). A correction formula compensates for that. The objective of this study is to first evaluate the efficacy of the currently implemented correction function and then further improve this formula. The performance of the established correction formula was investigated in our prospectively collected dataset of 98 TPTD measurements from 38 patients with both, jugular and femoral venous access. Subsequently, a new correction formula was developed: cross validation revealed the favourite covariate combination and a general estimating equation provided the final version, which was tested in a retrospective validation on an external dataset. Investigating the current correction function revealed a considerable reduction of bias compared to no correction. Concerning the objective of formula development, the covariate combination of GEDVI obtained after femoral indicator injection, age and body surface area is even favoured, when compared to the parameters of the previously published correction formula, as a further reduction of mean absolute error (68 vs. 61 ml/m2), a better correlation (0.90 vs. 0.91) and an increased adjusted R2 (0.72 vs 0.78) is noticed in the cross validation results. Of particular clinical importance is, that more measurements were correctly assigned to the same GEDVI category (decreased / normal / increased) using the revised formula, compared with the gold standard of jugular indicator injection (72.4 vs. 74.5%). In a retrospective validation, the newly developed formula showed a greater reduction of bias (to 2 vs. 6 %) than the currently implemented formula. The currently implemented correction function partly compensates for GEDVI overestimation. Applying the new correction formula on GEDVI measured after femoral indicator administration enhances the informative value and reliability of this preload parameter.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock

BackgroundNo direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model.MethodsThirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300–400), mild-to-moderate ARDS (100–300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers.ResultsUsing CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98–1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS.ConclusionThe pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Extravascular lung water index, pulmonary vascular permeability index, and global end-diastolic volume index in mechanically ventilated COVID-19 patients requiring prone position ventilation: a preliminary retrospective study.

There is a lack of data on extravascular lung water index (EVLWi), pulmonary vascular permeability index (PVPi), and global end-diastolic volume index (GEDVi) during prone position ventilation (PPV) in coronavirus disease 2019 (COVID-19) patients. The objectives of this study were to analyze trends in EVLWi, PVPi, and GEDVi during PPV and the relationships between these parameters and PaO2/FiO2. In this preliminary retrospective observational study, we performed transpulmonary thermodilution (TPTD) in seven mechanically ventilated COVID-19 patients without cardiac and pulmonary comorbidities requiring PPV for 18 hours, at specific times (30 minutes pre-PPV, 18 hours after PPV, and 3 hours after supination). EVLWi, PVPi and GEDVi were measured. The relationships between PaO2/FiO2 and EVLWi, and PVPi and GEDVi values, in the supine position were analyzed by linear regression. Correlation and determination coefficients were calculated. EVLWi was significantly different between three time points (analysis of variance, P=0.004). After 18 hours in PPV, EVLWi was lower compared with values before PPV (12.7±0.9 ml/kg vs. 15.3±1.5 ml/kg, P=0.002). Linear regression showed that only EVLWi was correlated with PaO2/FiO2 (β =-5.757; 95% confidence interval, -10.835 to -0.679; r=-0.58; R2 =0.34; F-test P=0.029). EVLWi was significantly reduced after 18 hours in PPV and values measured in supine positions were correlated with PaO2/FiO2. This relationship can help clinicians discriminate whether deterioration in gas exchange is related to fluid overload or disease progression. Further clinical research should evaluate the role of TPTD parameters as markers to stratify disease severity and guide clinical management.

N-terminal Pro-B-Type Natriuretic Peptide is a Myocardial Biomarker in Pulmonary Sepsis and Septic Shock

The objective: to study changes and prognostic significance of the blood NT-proBNP in the patients with pulmonary sepsis.Subjects and Methods. The study included 34 patients aged 54.5 ± 2.9 years with pulmonary sepsis or septic shock. Lethality in the intensive care unit (ICU) was 47.1%. NT-proBNP, procalcitonin (PCT) levels, blood lactate and hemodynamic parameters were registered on the 1st day (stage 1) and on the 4th-5th day of the ICU stay (stage 2). Hemodynamics was assessed through transpulmonary thermodilution. The differences were considered statistically significant at p &lt; 0.05.Results: At stage 1, NT-proBNP level was 5,220 [1,380‒17,850] pg/ml, did not decrease (p = 0.726) at stage 2 and amounted to 1,760 [631‒847] pg/ml. At stage 1, NT-proBNP correlated with extravascular lung water index (rho = 0.445; p = 0.038) and systolic pulmonary artery pressure (rho = 0.414; p = 0.023). At stage 2, NT-proBNP correlated with PCT (rho = 0.569; p = 0.003), blood lactate (rho = 0.525; p = 0.001), and mean arterial pressure to norepinephrine dosage ratio (rho = -0.422; p = 0.035). At stage 1, NT-proBNP was no predictor of lethality in the ICU: OR 1.0000; 95% CI 1.0000-1.0001. At stage 2, NT-proBNP &gt; 4,260 pg/ml (sensitivity 87.5%, specificity 94.4%) was a predictor of lethality: OR 1.0004, 95% CI 1.0000-1.0008, p = 0.046 (AUC 0.893, 95% CI 0.732-0.974). Any increase of NT-proBNP level (&gt; 0 pg/ml) between stages 2 and 1 was a predictor of lethality (sensitivity 87.5%, specificity 94.4%): OR 119.0, 95% CI 9.7432‒1,453.4241, p = 0.0002 (AUC 0.903, 95% CI 0.751-0.977).Conclusion: Patients with pulmonary sepsis are characterized by a significant increase of blood NT-proBNP. At stage 1, the biomarker correlated with pulmonary hypertension and moderate pulmonary edema and was no predictor of lethality. At stage 2, NT-proBNP correlated with the indices of infection and sepsis severity (procalcitonin, blood lactate, and mean arterial blood pressure/norepinephrine dosage ratio). At this stage, NT-proBNP levels greater than 4,000 pg/mL and/or any degree of increase in blood levels of the biomarker were both sensitive and specific predictors of a lethal outcome. Specific features of etiopathogenesis of BNP hyperproduction in pulmonary sepsis make it difficult to interpret the elevation of NT-proBNP as an indicator of septic cardiomyopathy but does not reduce its value as a sensitive and specific predictor of lethality.

Effects of changes in veno-venous extracorporeal membrane oxygenation blood flow on the measurement of intrathoracic blood volume and extravascular lung water index: a prospective interventional study

In severe acute respiratory distress syndrome (ARDS), veno-venous extracorporeal membrane oxygenation (V-V ECMO) has been proposed as a therapeutic strategy to possibly reduce mortality. Transpulmonary thermodilution (TPTD) enables monitoring of the extravascular lung water index (EVLWI) and cardiac preload parameters such as intrathoracic blood volume index (ITBVI) in patients with ARDS, but it is not generally recommended during V-V ECMO. We hypothesized that the amount of extracorporeal blood flow (ECBF) influences the calculation of EVLWI and ITBVI due to recirculation of indicator, which affects the measurement of the mean transit time (MTt), the time between injection and passing of half the indicator, as well as downslope time (DSt), the exponential washout of the indicator. EVLWI and ITBVI were measured in 20 patients with severe ARDS managed with V-V ECMO at ECBF rates from 6 to 4 and 2 l/min with TPTD. MTt and DSt significantly decreased when ECBF was reduced, resulting in a decreased EVLWI (26.1 [22.8–33.8] ml/kg at 6 l/min ECBF vs 22.4 [15.3–31.6] ml/kg at 4 l/min ECBF, p < 0.001; and 13.2 [11.8–18.8] ml/kg at 2 l/min ECBF, p < 0.001) and increased ITBVI (840 [753–1062] ml/m2 at 6 l/min ECBF vs 886 [658–979] ml/m2 at 4 l/min ECBF, p < 0.001; and 955 [817–1140] ml/m2 at 2 l/min ECBF, p < 0.001). In patients with severe ARDS managed with V-V ECMO, increasing ECBF alters the thermodilution curve, resulting in unreliable measurements of EVLWI and ITBVI. German Clinical Trials Register (DRKS00021050). Registered 14/08/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021050