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 The study involved 59 patients, median age 66 years, median withdrawn fluid volume 1800 mL (1330 ÷ 2400 mL).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.

Virtual and Artificial Cardiorespiratory Patients in Medicine and Biomedical Engineering.

Recently, 'medicine in silico' has been strongly encouraged due to ethical and legal limitations related to animal experiments and investigations conducted on patients. Computer models, particularly the very complex ones (virtual patients-VP), can be used in medical education and biomedical research as well as in clinical applications. Simpler patient-specific models may aid medical procedures. However, computer models are unfit for medical devices testing. Hybrid (i.e., numerical-physical) models do not have this disadvantage. In this review, the chosen approach to the cardiovascular system and/or respiratory system modeling was discussed with particular emphasis given to the hybrid cardiopulmonary simulator (the artificial patient), that was elaborated by the authors. The VP is useful in the education of forced spirometry, investigations of cardiopulmonary interactions (including gas exchange) and its influence on pulmonary resistance during artificial ventilation, and explanation of phenomena observed during thoracentesis. The artificial patient is useful, inter alia, in staff training and education, investigations of cardiorespiratory support and the testing of several medical devices, such as ventricular assist devices and a membrane-based artificial heart.

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.

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.

Spirometry: A Need for Periodic Updates of National Reference Values.

The aim of the study was to assess the need for changes in spirometry reference values in the Polish population with time lapse, as the aftereffect of a radical socioeconomic overturn of the 1990. We retrospectively analyzed data files on forced expiratory volume in 1 s (FEV1), vital capacity (VC), and forced VC (FVC) in healthy, never-smoking Caucasians (731 females and 327 males) obtained in in 1993-1998. We assessed a discrepancy between the then measured values of these variables, on the one side, and the corresponding European Community for Steel and Coal (ECSC) predicted values or the current updated predicted values for the Polish population, on the other side. We found that those old measured values approximately corresponded to the ECSC reference, but they were appreciably lower than the current Polish reference values; the younger the subjects the greater the difference. The current Polish reference values of FVC were much closer to the old measured VC than to the old measured FVC values, which introduces a substantial discrepancy between the past and present FVCs. We conclude that the spirometry reference values may change with time lapse. Thus, accuracy of prediction equations should be periodically updated, which seems to particularly concern the equations elaborated for the nations that undergo rapid economic developments connected with changes in living standards.

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.

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.

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.

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 mathematical reason for FEV1/FVC dependence on age.

BACKGROUND: Recent studies have showed that FEV1/FVC describing correspondence between the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) depends significantly on age. However, the nature of this dependence is uncertain. The study aim is to analyze mathematically the relationship between FEV1 and FVC to find a cause of the FEV1/FVC dependence on age in healthy subjects. METHODS: The relationship was examined for 1,120 males and 1,625 females--Polish (Caucasian) population, healthy, never-smoking, aged 18 - 85 years, who performed a technically adequate spirometry maneuver. Lung functions were measured using the LungTest1000 (MES, Poland) with maximal effort according to the ATS/ERS guidelines. RESULTS: A very strong, age-independent linear relationship between FEV1 and FVC was found in healthy individuals (the correlation coefficient r = 0.96). It can be described with the equation FEV1 = A x FVC + C, where A = 0.84 and C = -0.23 (-0.36) for females (males). As C is different from zero, FEV1/FVC depends on FVC because FEV1/FVC = A + C/FVC, in average. And thus, since FVC is significantly age-dependent, FEV1/FVC has to be also age-dependent because of the term C/FVC. In particular, the smaller the FVC value because of advanced age, the more significant the fall of FEV1/FVC. CONCLUSIONS: FEV1/FVC dependence on age in healthy individuals is of mathematical rather than biological nature. Due to the strong correlation between FEV1 and FVC in healthy subjects, the difference between patient's FEV1 and the FEV1 value expected for patient's FVC seems to be a more natural, age-independent description of the correspondence between patient's FEV1 and FVC.

[Spirometry: a comparison of prediction equations proposed by Lubinnski for the Polish population with those proposed by the ECSC/ERS and by Falaschetti et al]. / Spirometria--porównanie polskich wartosci naleznych Lubinskiego z naleznymi ECSC/ERS i Falaschetti.

INTRODUCTION: Ethnic-specific equations are commonly acknowledged, however, either generally-European ECSC/ERS prediction equations or equations worked out by Falaschetti et al. for the English population are recommended to be used in Poland. The aim of the study is to compare those equations with equations elaborated by Lubinski and Golczewski for the Polish population. MATERIAL AND METHODS: ECSC/ERS equations and Falaschetti's ones as well as Polish equations (elaborated on the basis of data for healthy, non-smoking Poles aged 18-85--1120 males, 1625 females--who performed spirometry manoeuvre according to ATS/ERS criteria) were analysed from the point of methodological correctness. RESULTS: Main ECSC/ERS imperfections: a) the onset age of lung function variable (LF) decline with age is assumed a priori as the same for all LF and equal to 25 yrs; b) simple linear equations describing LF dependences on age higher than 25 yrs can reflect nonlinearity of these dependences inaccurately; c) lower limits of normal are determined as equations for means minus 1.645*SD (SD- standard deviation of differences between observed and predicted values of LF); d) the equations are old, i.e. they have been prepared for previous generations and old procedures of examinations. Main Falaschetti imperfections: a) unnecessarily complex nonlinearity of equations, b) wrong age distributions of general population samples (too low numbers of older subjects). Lubinski's equations have not those imperfections. In particular, age distribution is uniform, and separately for each individual LF: a) the onset age is determined mathematically together with the other equation coefficients; b) statistical significance of nonlinearity of dependence on age is examined. Moreover, Lubinski's predictions for advanced age are equal to results obtained by authors examining in detail the elderly group. CONCLUSIONS: All the above suggest that Lubinski's equations should be used in Poland instead of ECSC/ERS or Falaschetti equations.

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.

Physiologically interpretable prediction equations for spirometric indexes.

The need for ethnic-specific reference values of lung function variables (LFs) is acknowledged. Their estimation requires expensive and laborious examinations, and therefore additional use of results in physiology and epidemiology would be profitable. To this end, we proposed a form of prediction equations with physiologically interpretable coefficients: a baseline, the onset age (A0) and rate (S) of LF decline, and a height coefficient. The form was tested with data from healthy, nonsmoking Poles aged 18-85 yr (1,120 men, 1,625 women) who performed spirometry maneuvers according to American Thoracic Society criteria. The values of all the coefficients (also A0) for several LFs were determined with regression of LF on patient's age and deviation of patient's height from the mean height in the year group of this patient. S values for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow, and maximal expiratory flow at 75% of FVC (MEF75) were very similar in both sexes (1.03+/-0.07%/yr). FEV1/FVC declines four to five times slower. S for MEF25 appeared age dependent. A0 was smallest (28-32 yr) for MEF25 and FEV1. About 50% of each age subgroup (18-40, 41-60, 61-85 yr) exhibited LFs below the mean, and 4-6% were below the 5th percentile lower limits of normal, and thus the form of equations proposed in the paper appeared appropriate for spirometry. Additionally, if this form is accepted, epidemiological and physiological comparison of different LFs and populations will be possible by means of direct comparison of the equation coefficients.

Virtual respiratory system in investigation of CPAP influence on optimal breathing frequency in obstructive lungs disease.

BACKGROUND: Continuous Positive Airway Pressure (CPAP) is a commonly accepted method of spontaneous breathing support in obstructive lung disease. Previous work suggested that the cause of the CPAP efficacy in the obstructive lung disease localized in bronchi of middle order (OLDMO) is not as obvious as, for example, in the obstructive sleep apnea. Since CPAP reduces obstruction and the optimal breathing frequency (BF) depends on the obstruction level, it seems to be important to analyze the dependence of the optimal BF on CPAP. AIM: To analyze the support efficacy cause in OLDMO, esp. the relationship between the CPAP value and optimal BF. METHOD: Investigations utilized previously built virtual respiratory system. Its most important factors: nonlinear lungs compliance and changeability of nonlinear airway resistance (Raw). Influence of BF and the CPAP value on the tidal volume and minute ventilation was analyzed for four exemplary virtual patients: healthy ("standard") and suffering from moderate, severe, and the very severe OLDMO (the other parameters, esp. respiratory muscles effort, were unchanged). Minute inspiratory work as a criterion of the BF optimization. RESULTS: CPAP decreased Raw making breathing easier, however, it shifted the working point of the respiratory system towards the smaller lungs compliance making breathing harder. The final result depended on the Raw value: CPAP improved breathing of patients with the serious OLDMO while it worsened healthy person breathing. The optimal CPAP value depended on the Raw value. If a virtual patient suffering from the serious OLDMO was not supported with CPAP, he had to breathe with low frequency because minute ventilation did not rise with BF increase. The optimal BF depended on the CPAP value (the greater the value, the greater the frequency). CONCLUSION: The CPAP efficacy depends on the level of OLDMO. CPAP is efficient in the severe OLDMO because it increases the optimal BF, which makes possible less energy-consuming breathing with frequency close to the normal one (greater BF means smaller tidal volume and thus smaller work against lungs compliance).