Quantifying heterogeneity in an animal model of acute respiratory distress syndrome, a comparison of inspired sinewave technique to computed tomography.

The inspired sinewave technique (IST) is a non-invasive method to measure lung heterogeneity indices (including both uneven ventilation and perfusion or heterogeneity), which reveal multiple conditions of the lung and lung injury. To evaluate the reproducibility and predicted clinical outcomes of IST heterogeneity values, a comparison with a quantitative lung computed tomography (CT) scan is performed. Six anaesthetised pigs were studied after surfactant depletion by saline-lavage. Paired measurements of lung heterogeneity were then taken with both the IST and CT. Lung heterogeneity measured by the IST was calculated by (a) the ratio of tracer gas outputs measured at oscillation periods of 180 s and 60 s, and (b) by the standard deviation of the modelled log-normal distribution of ventilations and perfusions in the simulation lung. In the CT images, lungs were manually segmented and divided into different regions according to voxel density. A quantitative CT method to calculate the heterogeneity (the Cressoni method) was applied. The IST and CT show good Pearson correlation coefficients in lung heterogeneity measurements (ventilation: 0.71, and perfusion, 0.60, p < 0.001). Within individual animals, the coefficients of determination average ventilation (R2 = 0.53) and perfusion (R2 = 0.68) heterogeneity. Strong concordance rates of 98% in ventilation and 89% when the heterogeneity changes were reported in pairs measured by CT scanning and IST methods. This quantitative method to identify heterogeneity has the potential to replicate CT lung heterogeneity, and to aid individualised care in ARDS.

Lung simulation to support non-invasive pulmonary blood flow measurement in Acute Respiratory Distress Syndrome in animals.

Patients undergoing mechanical lung ventilation are at risk of lung injury. A noninvasive bedside lung monitor may benefit these patients. The Inspired Sinewave Test (IST) can measure cardio-pulmonary parameters noninvasively. We propose a lung simulation to improve the measurement of pulmonary blood flow using IST. The new method was applied to 12 pigs' data before lung injury (control) and after lung injury (ARDS model). Results using the lung simulation shown improvements in correlation in both simulated data (R2 increased from 0.98 to 1) and pigs' data (R2 increased from <0.001 to 0.26). Paired blood flow measurements were performed by both the IST (noninvasive) and thermodilution (invasive). In the control group, the bias of the two methods was negligible (0.02L/min), and the limit of agreement was from -1.20 to 1.18 L/min. The bias was -0.68 L/min in the ARDS group and with a broader limit of agreement (-2.49 to 1.13 L/min).Clinical Relevance- the inspired sinewave test can be used to measure cardiac output noninvasively in mechanically ventilated subjects with and without acute respiratory distress syndrome.

A tidal lung simulation to quantify lung heterogeneity with the Inspired Sinewave Test.

We have created a lung simulation to quantify lung heterogeneity from the results of the inspired sinewave test (IST). The IST is a lung function test that is non-invasive, non-ionising and does not require patients' cooperation. A tidal lung simulation is developed to assess this test and also a method is proposed to calculate lung heterogeneity from IST results. A sensitivity analysis based on the Morris method and linear regression were applied to verify and to validate the simulation. Additionally, simulated emphysema and pulmonary embolism conditions were created using the simulation to assess the ability of the IST to identify these conditions. Experimental data from five pigs (pre-injured vs injured) were used for validation. This paper contributes to the development of the IST. Firstly, our sensitivity analysis reveals that the IST is highly accurate with an underestimation of about 5% of the simulated values. Sensitivity analysis suggested that both instability in tidal volume and extreme expiratory flow coefficients during the test cause random errors in the IST results. Secondly, the ratios of IST results obtained at two tracer gas oscillation frequencies can identify lung heterogeneity (ELV60/ELV180 and Qp60/Qp180). There was dissimilarity between simulated emphysema and pulmonary embolism (p < 0.0001). In the animal model, the control group had ELV60/ELV180 = 0.58 compared with 0.39 in injured animals (p < 0.0001).

Lung heterogeneity and deadspace volume in animals with acute respiratory distress syndrome using the inspired sinewave test.

Acute respiratory distress syndrome (ARDS) is associated with a high rate of morbidity and mortality, as patients undergoing mechanical ventilation are at risk of ventilator-induced lung injuries.Objective: To measure the lung heterogeneity and deadspace volume to find safer ventilator strategies. The ventilator settings could then offer homogeneous ventilation and theoretically equalize and reduce tidal strain/stress in the lung parenchyma.Approach: The inspired sinewave test (IST) is a non-invasive lung measurement tool which does not require cooperation from the patient. The IST can measure the effective lung volume, pulmonary blood flow and deadspace volume. We developed a computational simulation of the cardiopulmonary system to allow lung heterogeneity to be quantified using data solely derived from the IST. Then, the method to quantify lung heterogeneity using two IST tracer gas frequencies (180 and 60 s) was introduced and used in lung simulations and animal models. Thirteen anaesthetized pigs were studied with the IST both before and after experimental lung injury (saline-lavage ARDS model). The deadspace volume was compared between the IST and the SF6washout method.Main results: The IST could measure lung heterogeneity using two tracer gas frequencies. Furthermore, the value of IST ventilation heterogeneity in ARDS lungs was higher than in control lungs at a positive end-expiratory pressure of 10 cmH2O (area under the curve = 0.85,p<0.001). Values for the deadspace volume measured by the IST have a strong relationship with the measured values of SF6(9 ml bias and limits of agreement from -79 to 57 ml in control animals).Significance: The IST technique has the potential for use in the identification of ventilation and perfusion heterogeneity during ventilator support.

Validating the inspired sinewave technique to measure the volume of the 'baby lung' in a porcine lung-injury model.

BACKGROUND: Bedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model. METHODS: Anaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELVIST) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELVSF6] and computed tomography (CT) [ELVCT]). Measured volumes were used to calculate changes in ELV (ΔELV) between PEEP levels for each method (ΔELVIST, ΔELVSF6, and ΔELVCT). RESULTS: The coefficient of variation was <5% for repeated ELVIST measurements (n=13 pigs). There was a strong linear relationship between ELVIST and ELVSF6 in uninjured lungs (r2=0.97), and with both ELVSF6 and ELVCT in the ARDS model (r2=0.87 and 0.92, respectively). ELVIST had a mean bias of -12 to 13% (95% limits=±17 - 25%) compared with ELVSF6 and ELVCT. ΔELVIST was concordant with ΔELVSF6 and ΔELVCT in 98-100% of measurements, and had a mean bias of -73 to -77 ml (95% limits=±128 - 186 ml) compared with ΔELVSF6 and -1 ml (95% limits ±333 ml) compared with ΔELVCT. CONCLUSIONS: IST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.