Nathalie Janssen

Comparison of functional residual capacity and static compliance of the respiratory system during a positive end-expiratory pressure (PEEP) ramp procedure in an experimental model of acute respiratory distress syndrome

IntroductionFunctional residual capacity (FRC) measurement is now available on new ventilators as an automated procedure. We compared FRC, static thoracopulmonary compliance (Crs) and PaO2 evolution in an experimental model of acute respiratory distress syndrome (ARDS) during a reversed, sequential ramp procedure of positive end-expiratory pressure (PEEP) changes to investigate the potential interest of combined FRC and Crs measurement in such a pathologic state.MethodsARDS was induced by oleic acid injection in six anesthetised pigs. FRC and Crs were measured, and arterial blood samples were taken after induction of ARDS during a sequential ramp change of PEEP from 20 cm H2O to 0 cm H2O by steps of 5 cm H2O.ResultsARDS was responsible for significant decreases in FRC, Crs and PaO2 values. During ARDS, 20 cm H2O of PEEP was associated with FRC values that increased from 6.2 ± 1.3 to 19.7 ± 2.9 ml/kg and a significant improvement in PaO2. The maximal value of Crs was reached at a PEEP of 15 cm H2O, and the maximal value of FRC at a PEEP of 20 cm H2O. From a PEEP value of 15 to 0 cm H2O, FRC and Crs decreased progressively.ConclusionOur results indicate that combined FRC and Crs measurements may help to identify the optimal level of PEEP. Indeed, by taking into account the value of both parameters during a sequential ramp change of PEEP from 20 cm H2O to 0 cm H2O by steps of 5 cm H2O, the end of overdistension may be identified by an increase in Crs and the start of derecruitment by an abrupt decrease in FRC.

Alteration of Right Ventricular-Pulmonary Vascular Coupling in a Porcine Model of Progressive Pressure Overloading

In acute pulmonary embolism, right ventricular (RV) failure may result from exceeding myocardial contractile resources with respect to the state of vascular afterload. We investigated the adaptation of RV performance in a porcine model of progressive pulmonary embolism. Twelve anesthetized pigs were randomly divided into two groups: gradual pulmonary arterial pressure increases by three injections of autologous blood clot (n = 6) or sham-operated controls (n = 6). Right ventricular pressure-volume (PV) loops were recorded using a conductance catheter. Right ventricular contractility was estimated by the slope of the end-systolic PV relationship (Ees). After load was referred to as pulmonary arterial elastance (Ea) and assessed using a four-element Windkessel model. Right ventricular-arterial coupling (Ees/Ea) and efficiency of energy transfer (from PV area to external mechanical work [stroke work]) were assessed at baseline and every 30 min for 4 h. Eaincreased progressively after embolization, from 0.26 ± 0.04 to 2.2 ± 0.7 mmHg mL−1 (P < 0.05). Ees increased from 1.01 ±0.07 to 2.35 ± 0.27 mmHg mL−1 (P < 0.05) after the first two injections but failed to increase any further. As a result, Ees/Ea initially decreased to values associated with optimal SW, but the last injection was responsible for Ees/Ea values less than 1, decreased stroke volume, and RV dilation. Stroke work/PV area consistently decreased with each injection from 79% ± 3% to 39% ± 11% (P < 0.05). In response to gradual increases in afterload, RV contractility reserve was recruited to a point of optimal coupling but submaximal efficiency. Further afterload increases led to RV-vascular uncoupling and failure.

Expiratory model-based method to monitor ARDS disease state

IntroductionModel-based methods can be used to characterise patient-specific condition and response to mechanical ventilation (MV) during treatment for acute respiratory distress syndrome (ARDS). Conventional metrics of respiratory mechanics are based on inspiration only, neglecting data from the expiration cycle. However, it is hypothesised that expiratory data can be used to determine an alternative metric, offering another means to track patient condition and guide positive end expiratory pressure (PEEP) selection.MethodsThree fully sedated, oleic acid induced ARDS piglets underwent three experimental phases. Phase 1 was a healthy state recruitment manoeuvre. Phase 2 was a progression from a healthy state to an oleic acid induced ARDS state. Phase 3 was an ARDS state recruitment manoeuvre. The expiratory time-constant model parameter was determined for every breathing cycle for each subject. Trends were compared to estimates of lung elastance determined by means of an end-inspiratory pause method and an integral-based method. All experimental procedures, protocols and the use of data in this study were reviewed and approved by the Ethics Committee of the University of Liege Medical Faculty.ResultsThe overall median absolute percentage fitting error for the expiratory time-constant model across all three phases was less than 10 %; for each subject, indicating the capability of the model to capture the mechanics of breathing during expiration. Provided the respiratory resistance was constant, the model was able to adequately identify trends and fundamental changes in respiratory mechanics.ConclusionOverall, this is a proof of concept study that shows the potential of continuous monitoring of respiratory mechanics in clinical practice. Respiratory system mechanics vary with disease state development and in response to MV settings. Therefore, titrating PEEP to minimal elastance theoretically results in optimal PEEP selection. Trends matched clinical expectation demonstrating robustness and potential for guiding MV therapy. However, further research is required to confirm the use of such real-time methods in actual ARDS patients, both sedated and spontaneously breathing.

Visualisation of time-varying respiratory system elastance in experimental ARDS animal models

BackgroundPatients with acute respiratory distress syndrome (ARDS) risk lung collapse, severely altering the breath-to-breath respiratory mechanics. Model-based estimation of respiratory mechanics characterising patient-specific condition and response to treatment may be used to guide mechanical ventilation (MV). This study presents a model-based approach to monitor time-varying patient-ventilator interaction to guide positive end expiratory pressure (PEEP) selection.MethodsThe single compartment lung model was extended to monitor dynamic time-varying respiratory system elastance, Edrs, within each breathing cycle. Two separate animal models were considered, each consisting of three fully sedated pure pietrain piglets (oleic acid ARDS and lavage ARDS). A staircase recruitment manoeuvre was performed on all six subjects after ARDS was induced. The Edrs was mapped across each breathing cycle for each subject.ResultsSix time-varying, breath-specific Edrs maps were generated, one for each subject. Each Edrs map shows the subject-specific response to mechanical ventilation (MV), indicating the need for a model-based approach to guide MV. This method of visualisation provides high resolution insight into the time-varying respiratory mechanics to aid clinical decision making. Using the Edrs maps, minimal time-varying elastance was identified, which can be used to select optimal PEEP.ConclusionsReal-time continuous monitoring of in-breath mechanics provides further insight into lung physiology. Therefore, there is potential for this new monitoring method to aid clinicians in guiding MV treatment. These are the first such maps generated and they thus show unique results in high resolution. The model is limited to a constant respiratory resistance throughout inspiration which may not be valid in some cases. However, trends match clinical expectation and the results highlight both the subject-specificity of the model, as well as significant inter-subject variability.

Veno‐venous extracorporeal CO2 removal improves pulmonary hemodynamics in a porcine ARDS model

Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno‐venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function.

Arterial dP/dtmax accurately reflects left ventricular contractility during shock when adequate vascular filling is achieved

BackgroundPeak first derivative of femoral artery pressure (arterial dP/dtmax) derived from fluid-filled catheter remains questionable to assess left ventricular (LV) contractility during shock. The aim of this study was to test if arterial dP/dtmax is reliable for assessing LV contractility during various hemodynamic conditions such as endotoxin-induced shock and catecholamine infusion.MethodsVentricular pressure-volume data obtained with a conductance catheter and invasive arterial pressure obtained with a fluid-filled catheter were continuously recorded in 6 anaesthetized and mechanically ventilated pigs. After a stabilization period, endotoxin was infused to induce shock. Catecholamines were transiently administrated during shock. Arterial dP/dtmax was compared to end-systolic elastance (Ees), the gold standard method for assessing LV contractility.ResultsEndotoxin-induced shock and catecholamine infusion lead to significant variations in LV contractility. Overall, significant correlation (r = 0.51; p < 0.001) but low agreement between the two methods were observed. However, a far better correlation with a good agreement were observed when positive-pressure ventilation induced an arterial pulse pressure variation (PPV) ≤ 11% (r = 0.77; p < 0.001).ConclusionWhile arterial dP/dtmax and Ees were significantly correlated during various hemodynamic conditions, arterial dP/dtmax was more accurate for assessing LV contractility when adequate vascular filling, defined as PPV ≤ 11%, was achieved.

Physiological relevance and performance of a minimal lung model – an experimental study in healthy and acute respiratory distress syndrome model piglets

BackgroundMechanical ventilation (MV) is the primary form of support for acute respiratory distress syndrome (ARDS) patients. However, intra- and inter- patient-variability reduce the efficacy of general protocols. Model-based approaches to guide MV can be patient-specific. A physiological relevant minimal model and its patient-specific performance are tested to see if it meets this objective above.MethodsHealthy anesthetized piglets weighing 24.0 kg [IQR: 21.0-29.6] underwent a step-wise PEEP increase manoeuvre from 5cmH2O to 20cmH2O. They were ventilated under volume control using Engström Care Station (Datex, General Electric, Finland), with pressure, flow and volume profiles recorded. ARDS was then induced using oleic acid. The data were analyzed with a Minimal Model that identifies patient-specific mean threshold opening and closing pressure (TOP and TCP), and standard deviation (SD) of these TOP and TCP distributions. The trial and use of data were approved by the Ethics Committee of the Medical Faculty of the University of Liege, Belgium.Results and discussions3 of the 9 healthy piglets developed ARDS, and these data sets were included in this study. Model fitting error during inflation and deflation, in healthy or ARDS state is less than 5.0% across all subjects, indicating that the model captures the fundamental lung mechanics during PEEP increase. Mean TOP was 42.4cmH2O [IQR: 38.2-44.6] at PEEP = 5cmH2O and decreased with PEEP to 25.0cmH2O [IQR: 21.5-27.1] at PEEP = 20cmH2O. In contrast, TCP sees a reverse trend, increasing from 10.2cmH2O [IQR: 9.0-10.4] to 19.5cmH2O [IQR: 19.0-19.7]. Mean TOP increased from average 21.2-37.4cmH2O to 30.4-55.2cmH2O between healthy and ARDS subjects, reflecting the higher pressure required to recruit collapsed alveoli. Mean TCP was effectively unchanged.ConclusionThe minimal model is capable of capturing physiologically relevant TOP, TCP and SD of both healthy and ARDS lungs. The model is able to track disease progression and the response to treatment.

Visualisation of Time-Variant Respiratory System Elastance in ARDS Models

Model-based mechanical ventilation (MV) can be used to characterise patient-specific condition and response to MV. This paper presents a novel method to visualise respiratory mechanics during MV of patients suffering from acute respiratory distress syndrome. The single compartment lung model is extended to monitor time-varying respiratory system elastance within each breathing cycle. Monitoring continuous in-breath me- chanics allows changes to be observed continuously, providing more insight into lung physiology. Thus, this new monitoring method may potentially aid clinicians to guide MV in a heterogeneous population.

Assessment of ventricular contractility and ventricular-arterial coupling with a model-based sensor

Estimation of ventricular contractility and ventricular arterial coupling is clinically important in diagnosing and treating cardiac dysfunction in the critically ill. However, experimental assessment of indexes of ventricular contractility, such as the end-systolic pressure-volume relationship, requires a highly invasive maneuver and measurements that are not typical in an intensive care unit (ICU). This research describes the use of a previously validated cardiovascular system model and parameter identification process to evaluate the right ventricular arterial coupling in septic shock. Model-based ventricular arterial coupling is defined by the ratio of the end systolic right ventricular elastance (E(esrvf)) over the pulmonary artery elastance (E(pa)) or the mean pulmonary inflow resistance (R(pulin)). Results are compared to the clinical gold-standard assessment (conductance catheter method). Six anesthetized healthy pigs weighing 20-30kg received a 0.5mg kg(-1) endotoxin infusion over a period of 30min from T0 to T30, to induce septic shock and veno-venous hemofiltration was used from T60 onward. The results show good agreement with the gold-standard experimental assessment. In particular, the model-based right ventricular elastance (E(esrvf)) correlates well with the clinical gold standard (R(2)=0.69) and the model-based non-invasive coupling (E(esrvf)/R(pulin)) follow the same trends and dynamics (R(2)=0.37). The overall results show the potential to develop a model-based sensor to monitor ventricular-arterial coupling in clinical real-time.

Effects of Large-Pore Hemofiltration in a Swine Model of Fulminant Hepatic Failure

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation might be in part responsible for an increase in cerebral blood flow (CBF) and brain water content. In this study, the authors used a validated ischemic FHF swine model to evaluate the effects of 80 kDa large-pore membrane hemofiltration (LPHF) on intracranial pressure (ICP) and CBF, in relation with the clearance of proinflammatory cytokines and blood liver tests, as primary end points. Fifteen pigs were randomized into one of three groups: SHAM, FHF, and FHF + LPHF. All experiments lasted 6 h. In the FHF groups, liver failure was induced by liver ischemia. After 2 h, the FHF + LPHF group underwent 4 h of a zero-balance continuous veno-venous hemofiltration using a 0.7-m(2), large-pore (78 Å) membrane with a cutoff of 80 kDa. ICP, CBF, mean arterial pressure, central venous pressure, and heart rate were continuously monitored and recorded. Arterial aspartate aminotransferase, total bilirubin, creatinine, international normalized ratio, glucose, lactate and serum cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α were measured at T0, T120, and T360. Over the 6 h following liver ischemia, the FHF group developed a significant increase in ICP. This ICP rise was not observed in the SHAM group and was attenuated in the FHF + LDHF group. However, the ICP levels were not different at T360 in the FHF + LDHF group compared to the FHF group. No significant effect of LPHF on liver tests or levels of proinflammatory cytokines could be demonstrated. In this model, 80 kDa LPHF was not efficient to control FHF intracranial hypertension and to decrease serum cytokine levels.