Patterns of pleural pressure amplitude and respiratory rate changes during therapeutic thoracentesis.

BACKGROUND: Although the impact of therapeutic thoracentesis on lung function and blood gases has been evaluated in several studies, some physiological aspects of pleural fluid withdrawal remain unknown. The aim of the study was to assess the changes in pleural pressure amplitude (Pplampl) during the respiratory cycle and respiratory rate (RR) in patients undergoing pleural fluid withdrawal. METHODS: The study included 23 patients with symptomatic pleural effusion. Baseline pleural pressure curves were registered with a digital electronic manometer. Then, the registrations were repeated after the withdrawal of consecutive portions of pleural fluid (200 ml up to 1000 ml and 100 ml above 1000 ml). In all patients the pleural pressure curves were analyzed in five points, at 0, 25%, 50%, 75% and 100% of the relative volume of pleural effusion withdrawn in particular patients. RESULTS: There were 11 and 12 patients with right sided and left sided pleural effusion, respectively (14 M, 9F, median age 68, range 46-85 years). The most common cause of pleural effusion were malignancies (20 pts., 87%). The median total volume of withdrawn pleural fluid was 1800 (IQR 1500-2400) ml. After termination of pleural fluid withdrawal Pplampl increased in 22/23 patients compared to baseline. The median Pplampl increased from 3.4 (2.4-5.9) cmH2O to 10.7 (8.1-15.6) cmH2O (p < 0.0001). Three patterns of Pplampl changes were identified. Although the patterns of RR changes were more diversified, a significant increase between RR at baseline and the last measurement point was found (p = 0.0097). CONCLUSIONS: In conclusion, therapeutic thoracentesis is associated with significant changes in Pplampl during the respiratory cycle. In the vast majority of patients Pplampl increased steadily during pleural fluid withdrawal. There was also an increase in RR. The significance of these changes should be elucidated in further studies. TRIAL REGISTRATION: ClinicalTrial.gov, registration number: NCT02192138 , registration date: July 1st, 2014.

Cough during therapeutic thoracentesis: friend or foe?

We report intriguing preliminary observations on the effect of cough on pleural pressure changes during therapeutic thoracentesis. We found that cough-related elevation of pleural pressure persisted even when the cough had stopped. Thus, we hypothesize that cough during therapeutic thoracentesis may have a beneficial effect preventing the excessive drop in pleural pressure. The true role of cough-related elevation of pleural pressure is unknown, but it seems to be an interesting subject for further research.

A new endotracheal tube for infants--laboratory and clinical assessment: a preliminary study.

BACKGROUND: Conventional endotracheal pediatric tubes offer high resistance due to their small diameters and relatively high flow during ventilation. Any increase of the diameter of the tube lumen decreases the airway resistance and subsequently, the work of breathing (WOB). We compared ventilation mechanics using a new, cone-shaped endotracheal tube of our design to the Cole and standard tubes. METHODS: The study has been divided into three parts: (i) preliminary laboratory tests, (ii) in vitro study with infant lung model, and (iii) clinical study in infants. Flow resistance and WOB were compared, using standard, Cole (in experimental phase only) and cone tubes. RESULTS: We proved that inspiratory (Ri ) and expiratory (Re ) resistance, and WOB, were significantly lower in patients ventilated via a cone tube. Mean Ri decreased by 37%, compared with the baseline values, Re - by 35%, and total WOB - by 12%. CONCLUSION: The cone tube offers lower resistance to gas flow than the standard, used nowadays in clinical practice. It can be especially beneficial to spontaneously breathing patients reducing WOB and improving gas exchange.

The impact of spontaneous cough on pleural pressure changes during therapeutic thoracentesis.

Cough during therapeutic thoracentesis (TT) is considered an adverse effect. The study was aimed to evaluate the relationship between cough during TT and pleural pressure (Ppl) changes (∆P). Instantaneous Ppl was measured after withdrawal of predetermined volumes of pleural fluid. Fluid withdrawal (FW) and Ppl measurement (PplM) periods were analyzed separately using the two sample Kolmogorov-Smirnov test and the nonparametric skew to assess differences between ∆P distributions in periods with and without cough. The study involved 59 patients, median age 66 years, median withdrawn fluid volume 1800 mL (1330 ÷ 2400 mL). In total, 1265 cough episodes were recorded in 52 patients, in 24% of FW and 19% of PplM periods, respectively. Cough was associated with significant changes in ∆P distribution (p < 0.001), decreasing the left tail of ∆P distribution for FW periods (the skew = - 0.033 vs. - 0.182) and increasing the right tail for PplM periods (the skew = 0.182 vs. 0.088). Although cough was more frequent in 46 patients with normal pleural elastance (p < 0.0001), it was associated with significantly higher ∆P in patients with elevated elastance (median Ppl increase 2.9 vs. 0.2 cmH2O, respectively). Cough during TT is associated with small but beneficial trend in Ppl changes, particularly in patients with elevated pleural elastance, and should not be considered solely as an adverse event.

Modeling of Inhalation Profiles Through Dry Powder Inhaler in Healthy Adults and Asthma Patients As a Prerequisite for Further In Vitro and In Silico Studies.

Background: The severity of airway obstruction may affect patient's ability to perform an effective drug inhalation from a dry powder inhaler (DPI). Also, an incorrect inhalation technique may negatively affect the efficacy of asthma treatment. The aims of the study were (1) to analyze and compare inhalation profiles recorded with the use of different inhalation techniques, and thus, (2) to establish model inhalation profiles representative for healthy subjects and subjects with mild and moderate-to-severe asthma. Methods: This study was performed in healthy volunteers, patients with mild and moderate-to-severe asthma. A modified flow-volume test to define two different expiratory levels (to residual volume and half-way to residual volume) was performed. Inspiratory flow parameters were extracted: peak inspiratory flow rate (PIFinh), time at which peak inspiratory flow rate occurs (tPIFinh), total inhalation time (T), and inhaled volume (V). Test of frequency for tPIFinh100% and tPIFinh50% by asthma severity was performed, to provide information about initial flow accelerations. The impact of two different expiratory levels preceding inhalation (with severity of asthma as a categorical factor) on inspiratory flow parameters was examined. Results: PIFinh was dependent upon asthma severity (p = 0.046). Type of exhalation before inhalation had no effect on PIFinh values. V value was significantly affected both by asthma severity (p = 0.024) and type of exhalation before inhalation (p < 0.0001). Mean T value was influenced by type of exhalation before inhalation (p = 0.0003), but not by asthma severity. Mean tPIFinh value was affected by the type of exhalation before inhalation only in healthy subjects (p = 0.01). Conclusions: Both asthma severity and type of exhalation before inhalation have little impact on the dynamics of inhalation through a DPI. An alternative form of equation describing inhalation profiles demonstrating a relationship between lung mechanics and dynamics of inspiratory profile has been proposed.

Impact of therapeutic thoracentesis and pleural pressure changes on breathing pattern, dyspnea, lung function, and arterial blood gases.

INTRODUCTION: Therapeutic thoracentesis is highly effective in providing symptomatic improvement in patients with large volume pleural effusion (PE). However, some physiological effects of pleural fluid (PF) withdrawal are still not fully elucidated. OBJECTIVES: The study aimed to evaluate alterations in the breathing pattern, pulmonary function, and arterial blood gases (ABG) in relation to both withdrawn PF volume and pleural pressure (Ppl) changes in patients undergoing therapeutic thoracentesis. PATIENTS AND METHODS: This prospective, observational, cross­sectional study included 37 patients with large volume PE. Respiratory rate (RR), dyspnea, pulmonary function, and ABG were assessed before the thoracentesis, at the termination of the PF withdrawal and 1, 3, and 24 hours after the procedure. The volume of PF drained, Ppl, and tidal volume (TV) were monitored during the thoracentesis. RESULTS: Thoracentesis resulted in a transient but significant increase in RR directly after the procedure, and a transient decrease, followed by subsequent increase in TV. There was a significant and constant increase in forced vital capacity up to 24 hours after thoracentesis (P = 0.001). Oxygen partial pressure (PaO2) significantly improved directly after PF withdrawal (P = 0.01) and returned to baseline values after 24 hours. Thoracentesis was invariably associated with a significant increase in the amplitude of Ppl (Ppl_ampl) changes during the respiratory cycle (P <0.001). CONCLUSIONS: Therapeutic thoracentesis results in a modest improvement in pulmonary function, tran-sient increase in PaO2 and increase in Ppl_ampl. The improvement in pulmonary function and ABG is closely related to the volume of PF drained and pleural elastance. The increase in Ppl_ampl probably represents a more efficient work of the respiratory muscles.

Automatic air volume control system for ventilation of two patients using a single ventilator: a large animal model study.

The COVID-19 pandemic outbreak led to a global ventilator shortage. Hence, various strategies for using a single ventilator to support multiple patients have been considered. A device called Ventil previously validated for independent lung ventilation was used in this study to evaluate its usability for shared ventilation. We performed experiments with a total number of 16 animals. Eight pairs of pigs were ventilated by a ventilator or anesthetic machine and by Ventil for up to 27 h. In one experiment, 200 ml of saline was introduced to one subject's lungs to reduce their compliance. The experiments were analyzed in terms of arterial blood gases and respiratory parameters. In addition to the animal study, we performed a series of laboratory experiments with artificial lungs (ALs). The resistance and compliance of one AL (affected) were altered, while the tidal volume (TV) and peak pressure (Ppeak) in the second (unaffected) AL were analyzed. In addition, to assess the risk of transmission of pathogens between AL respiratory tracts, laboratory tests were performed using phantoms of virus particles. The physiological level of analyzed parameters in ventilated animals was maintained, except for CO2 tension, for which a permissive hypercapnia was indicated. Experiments did not lead to injuries in the animal's lungs except for one subject, as indicated by CT scan analysis. In laboratory experiments, changes in TV and Ppeak in the unaffected AL were less than 11%, except for 2 cases where the TV change was 20%. No cross-contamination was found in simulations of pathogen transmission. We conclude that ventilation using Ventil can be considered safe in patients undergoing deep sedation without spontaneous breathing efforts.

Development of an electronic manometer for intrapleural pressure monitoring.

BACKGROUND: Measurement of intrapleural pressure is useful during various pleural procedures. However, a pleural manometer is rarely available. OBJECTIVES: The aim of this study was to (1) construct an electronic pleural manometer, (2) assess the accuracy of the measurements done with the new device, (3) calculate the costs of the manometer construction and (4) perform an initial evaluation of the device in a clinical setting. METHODS: Only widely accessible elements were used to construct the device. A vascular pressure transducer was used to transform pressure into an electronic signal. Reliability of the measurements was evaluated in a laboratory setting in a prospective, single-blind manner by comparing the results with those measured by a water manometer. Functionality of the device was assessed during therapeutic thoracentesis. The cost of the new pleural manometer was calculated. RESULTS: We built a small, portable device which can precisely measure intrapleural pressure. The measurement results showed very high agreement with those registered with a water manometer (r = 0.999; p < 0.001). The initial evaluation of the electronic manometer during therapeutic thoracentesis showed it was easy to use. The total time needed for 6 measurements after withdrawal of different volumes of pleural fluid in 1 patient did not exceed 6 min. The total cost of the device was calculated to be <2,000 EUR. CONCLUSIONS: In the face of very limited offer of commercially available pleural manometers, it is possible to successfully construct a self-made, reliable, electronic pleural manometer at modest costs. The device is easy to use and enables data display and storage in the personal computer.

Inhalation Profiles Through a Dry Powder Inhaler: Relation Between Inhalation Technique and Spirometric Measures.

Background: The understanding of the real flow profiles through a dry powder inhaler (DPI), generated by asthma patients, is a prerequisite for satisfactory drug delivery to the lungs. The aims of the study were to assess the relationship between spirometric measures and inhalation profiles through a low-resistance DPI, and to compare parameters of those profiles between optimal and suboptimal inhalation technique type. Methods: Both healthy adult volunteers and patients with asthma were included in the study. Spirometry was conducted along with modified flow-volume test to detect expiratory levels (maximum "100%" exhalation to residual volume [RV] and halfway "50%" to RV). These were the reference levels of the depth of exhalation for each patient to simulate the effect of incomplete exhalation. Individual inhalation profiles were recorded using spirometry in-house software as the volumetric airflow through the inhaler versus time. Inspiratory flow parameters were extracted: time to peak inspiratory flow through inhaler (PIFinh), time at which peak inspiratory flow occurs (tPIFinh), total inhalation time (T), and inhaled volume during maneuver (V). Results and Conclusions: There are significant relationships between spirometric indices and parameters of inhalation through a low-resistance, cyclohaler-type DPI (assessed by single-factor analysis of Spearman's rank correlation coefficient). Multiple regression models were constructed, predicting inspiratory flow parameters (including spirometric indices, demographic parameters, and inhaler's usage history as determinants). The exhalation halfway to RV before inhalation did not affect significantly PIFinh and tPIFinh (and, thus, initial flow dynamics) in asthma patients. T and V parameters were then significantly decreased, but seemed sufficient for successful DPI performance. Both exhalation to RV and incomplete exhalation halfway to RV preceding inhalation allow for effective usage of low-resistance DPI.

Independent Lung Ventilation-Experimental Studies on a 3D Printed Respiratory Tract Model.

Independent lung ventilation (ILV) is a life-saving procedure in unilateral pulmonary pathologies. ILV is underused in clinical practice, mostly due to the technically demanding placement of a double lumen endotracheal tube (ETT). Moreover, the determination of ventilation parameters for each lung in vivo is limited. In recent years, the development of 3D printing techniques enabled the production of highly accurate physical models of anatomical structures used for in vitro research, considering the high risk of in vivo studies. The purpose of this study was to assess the influence of double-lumen ETT on the gas transport and mixing in the anatomically accurate 3D-printed model of the bronchial tree, with lung lobes of different compliances, using various ventilation modes. The bronchial tree was obtained from Respiratory Drug Delivery (RDD Online, Richmond, VA, USA), processed and printed by a dual extruder FFF 3D printer. The test system was also composed of left side double-lumen endotracheal tube, Siemens Test Lung 190 and anesthetic breathing bag (as lobes). Pressure and flow measurements were taken at the outlets of the secondary bronchus. The measured resistance increased six times in the presence of double-lumen ETT. Differences between the flow distribution to the less and more compliant lobe were more significant for the airways with double-lumen ETT. The ability to predict the actual flow distribution in model airways is necessary to conduct effective ILV in clinical conditions.

Pleural Pressure Pulse in Patients with Pleural Effusion: A New Phenomenon Registered during Thoracentesis with Pleural Manometry.

Pleural manometry enables the assessment of physiological abnormalities of lung mechanics associated with pleural effusion. Applying pleural manometry, we found small pleural pressure curve oscillations resembling the pulse tracing line. The aim of our study was to characterize the oscillations of pleural pressure curve (termed here as the pleural pressure pulse, PPP) and to establish their origin and potential significance. This was an observational cross-sectional study in adult patients with pleural effusion who underwent thoracentesis with pleural manometry. The pleural pressure curves recorded prior to and during fluid withdrawal were analyzed. The presence of PPP was assessed in relation to the withdrawn pleural fluid volume, lung expandability, vital and echocardiographic parameters, and pulmonary function testing. A dedicated device was developed to compare the PPP to the pulse rate. Fifty-four patients (32 women) median age 66.5 (IQR 58.5-78.7) years were included. Well visible and poorly visible pressure waves were detected in 48% and 35% of the patients, respectively. The frequency of PPP was fully concordant with the pulse rate and the peaks of the oscillations reflected the period of heart diastole. PPP was more visible in patients with a slower respiratory rate (p = 0.008), a larger amount of pleural effusion, and was associated with a better heart systolic function assessed by echocardiography (p < 0.05). This study describes a PPP, a new pleural phenomenon related to the cyclic changes in the heart chambers volume. Although the importance of PPP remains largely unknown, we hypothesize that it could be related to lung atelectasis or lower lung and visceral pleura compliance.

The impact of early therapeutic intervention on the central pattern generator in premature newborns - a preliminary study and literature review.

OBJECTIVE: The aim: To study the effect of therapeutic intervention on the improvement of the rhythmicity of non-nutritive and nutritive sucking in premature newborns and on the suck central pattern generator. PATIENTS AND METHODS: Material and methods: Stimulation of the breast zone was performed in two premature newborns by means of the Vojta method. Intraoral pressure was measured during non-nutritive and nutritive sucking before and after this therapeutic intervention. The maximum negative pressures generated during individual sucks and the intervals between sucks were analysed. RESULTS: Results: The stimulation of the breast zone using the Vojta method seems to have no impact on the duration of individual sucking episodes. However, a significant improvement in the rhythmicity and regularity of sucking was observed in both newborns: the coefficient of quartile deviation for the intervals decreased from 15% and 11% to 13% and 6%, respectively, and for the maximum negative pressures it decreased from 24% and 27% to 9% and 19%, respectively. Additionally, the median value of the maximum negative pressure decreased in both newborns: from -39 and -37 mmHg to -45 and -60 mmHg, respectively. CONCLUSION: Conclusions: The stimulation of the breast zone using the Vojta method seems to have a direct impact on the central pattern generator, which improves the rhythmicity as well as the regularity of both non-nutritive and nutritive sucking.

The use of a virtual patient to follow changes in arterial blood gases associated with therapeutic thoracentesis.

PURPOSES:: Some controversies exist on the effect of therapeutic thoracentesis (TT) on arterial blood oxygen tension. The aim of this study was to evaluate this issue using a previously developed virtual patient. METHODS:: The analysis was based and supported by clinical data collected during 36 TT. Pleural pressure and transcutaneous oxygen and carbon dioxide pressures (PtcO2 and PtcCO2) were measured during pleural fluid withdrawal. Arterial blood oxygen tension and arterial CO2 tension (PaO2 and PaCO2) were analysed in simulations that mimicked TT. Minute ventilation was adjusted to maintain arterial CO2 tension at a constant level unless arterial blood oxygen tension fell below 8 kPa. Specifically, the influence of hypoxic pulmonary vasoconstriction efficiency was tested. RESULTS:: In patients, PtcCO2 remained at an approximately constant level (average amplitude: 0.63 ± 0.29 kPa), while some fluctuations of PtcO2 were observed (amplitude: (1.65 ± 1.18 kPa) were observed. In 42% of patients, TT was associated with decrease in PtcCO2. Simulations showed the following: (a) there were similar PaO2 fluctuations in the virtual patient; (b) the lower the hypoxic pulmonary vasoconstriction efficiency, the more pronounced the PaO2 fall during fluid withdrawal; and (c) the lower the atelectatic lung areas recruitment rate, the slower the PaO2 normalization. The decrease in PaO2 was caused by an increase of pulmonary shunt. CONCLUSION:: Therapeutic thoracentesis may cause both an increase and a decrease in PaO2 during the procedure. Pleural pressure decrease, caused by pleural fluid withdrawal, improves the perfusion of atelectatic lung areas. If the rate of recruitment of these areas is low, a lack of ventilation causes the arterial blood oxygen tension to fall. Effective hypoxic pulmonary vasoconstriction may protect against the pulmonary shunt.

The use of a virtual patient to follow pleural pressure changes associated with therapeutic thoracentesis.

PURPOSE: Influence of therapeutic thoracentesis on the pleural pressure (Pp) has been discussed in many clinical studies, however reasons of Pp changes are not precisely established. The aim of the study was to use a previously elaborated virtual cardiopulmonary patient (VP) in analysis of impact of physiological factors on Pp during the procedure. METHODS: Simulations were performed on VP with default values of parameters for which VP simulated the respiratory system of the average 50-year-old healthy Polish woman according to spirometric examination. Alterations of Pp and the amplitude of Pp changes related to breathing (AP) were analyzed. Model parameters related to chosen factors were deviated from their default values to analyze the degree of their impact on Pp and AP. The analysis was based on and supported by our own clinical data. RESULTS: The Pp and AP alteration intensity appeared to be most sensitive to the compliances of the rib cage and mediastinum, and the nonlinearity of the dependence between the recoil pressure and the lung volume: the lower the compliances and the higher the nonlinearity were, the deeper the Pp fall during the procedure and the bigger the AP increase were observed. CONCLUSIONS: Experiments in silico are very useful in analyzing sophisticated physiological and medical problems. They made it possible to show which factors are particularly responsible for changes in Pp during thoracentesis. In the future, they may be useful in establishing objective conditions under which thoracentesis needs to be stopped.