Infant Pulmonary Mechanics During Tidal Breathing

After completing this article, readers should be able to: Tests of infant pulmonary function continue to evolve, broadening our understanding of normal growth and development of infant lungs and airways and providing diagnostic and therapeutic approaches for management of respiratory disease. Traditionally, measurements made during tidal breathing in infants have provided valuable information about lung mechanics, namely, compliance and resistance. In this article, we discuss the physiology on which these measurements are made and briefly describe how several tests are performed in infants to calculate tidal mechanics. Both clinical applications and limitations of the various techniques also are reviewed.Compliance describes the change in volume for a given change in pressure (ΔV/ΔP). When used to describe the respiratory system, compliance represents the elastic properties of the airways, pulmonary parenchyma, and chest wall. Resistance is defined as the amount of pressure required for a given flow rate (ΔP/V̇) and describes the nonelastic or frictional properties of the respiratory system, including resistance to airflow and tissue resistance. Because pressure change (ΔP=P1-P2), is a common factor in both compliance and resistance measurements, the choice of where P1 and P2 are measured defines the system or structures described by these mechanics. Thus, if pressures are measured at the proximal and distal ends of an airway, compliance and resistance of the airway can be calculated. If pressures are measured at the airway opening and in the pleural space (transpulmonary pressure), the airways, alveoli, and lung parenchyma are included, and lung compliance and resistance can be calculated. If pressures are measured at the airway opening and at the body surface (usually referred to as atmospheric pressure and, therefore, 0 cm H2O), then all of the structures of the respiratory system, including the chest wall, are included, and the resultant calculations yield respiratory system compliance and resistance.Infant lung mechanics often can be measured under conditions of natural sleep, especially in preterm infants and infants who are mechanically ventilated. However, it is difficult to perform these tests in older and spontaneously breathing infants without some form of sedation. Thus, the use of sedation depends primarily on the age and condition of the infant. Currently, the most commonly used sedative agents are chloral derivatives, such as chloral hydrate. Doses from 25 to 100 mg/kg have been used; the usual dose is 80 to 100 mg/kg. Sedation with chloral hydrate does not alter lung mechanics appreciably, as general anesthesia or other agents can.Dynamic tidal mechanics are measurements of compliance and resistance made during spontaneous breathing or assisted mechanical ventilation. The calculations of dynamic compliance and resistance are based on the assumption that the lung can be represented by a single-compartment series elastic-resistive model, similar to a balloon attached to a straw. In this case, the balloon represents the elastic components and the straw represents the resistive components of the respiratory system. The total pressure required to move air into the lungs (the driving pressure) is the sum of the elastic and resistive pressures as well as inertial forces of gas acceleration (Fig. 1).Thus, assessment of lung elastance (the reciprocal of compliance, E=1/C), and resistance can be derived from the general Equation of Motion of the Respiratory System: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{P}_{\mathrm{tot}}{=}\mathrm{P}_{\mathrm{e}1}{+}\mathrm{P}_{\mathrm{res}}{+}\mathrm{P}_{\mathrm{in}}\] \end{document} where Ptot is the driving pressure, Pel is the pressure required to overcome lung elasticity, Pres is the pressure to overcome airway resistance, and Pin is the pressure needed to accelerate the gas. Because the pressure needed to accelerate the gas under conditions of normal respiratory rates is extremely small relative to the other pressures, Pin can be dropped from the equation, simplifying it to: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{P}_{\mathrm{tot}}{=}\mathrm{P}_{\mathrm{e}1}{+}\mathrm{P}_{\mathrm{res}}\] \end{document} This assumption would not be valid under conditions of extremely high respiratory rates, such as during high-frequency ventilation. In such circumstances, Pin becomes a predominant force.Using the equation of motion to calculate compliance and resistance, since \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{E}{=}1/\mathrm{C},{=}1/({\Delta}\mathrm{V}/{\Delta}\mathrm{P}_{\mathrm{e}1}),\ \mathrm{E}{=}{\Delta}\mathrm{P}_{\mathrm{e}1}/{\Delta}\mathrm{V}\] \end{document} Rearranging this equation, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathbf{{\Delta}\mathrm{P}_{\mathrm{e}1}{=}\mathrm{E}{\ast}{\Delta}\mathrm{V}}\] \end{document}In addition: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{R}{=}{\Delta}\mathrm{P}_{\mathrm{res}}/{\dot{\mathrm{V}}};\] \end{document} Rearranging once again, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathbf{{\Delta}\mathrm{P}_{\mathrm{res}}{=}\mathrm{R}{\ast}{\dot{\mathrm{V}}}}\] \end{document} then Pel and Pres can be substituted as follows: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{P}_{\mathrm{tot}}{=}\mathrm{E}{\ast}\mathrm{V}{+}\mathrm{R}{\ast}{\dot{\mathrm{V}}}\] \end{document} where E=elastance, C=compliance, V=volume, R=resistance, and V̇=flow.Calculations of compliance and resistance are determined by simultaneous measurements of tidal flow, volume, and pressures. Pressure at the airway opening is measured easily, but pleural pressure must be estimated from the esophageal pressure (Pes). Esophageal pressure is measured from either an air-filled esophageal balloon or a water-filled catheter. The reliability of these measurements depends on accurate placement of the esophageal balloon or catheter; comparing the esophageal pressure to the airway opening pressure during an inspiratory effort against an occluded airway confirms the proper placement. During this occlusion, there is no airflow, thereby allowing pressures throughout the respiratory system to equilibrate. A satisfactory occlusion test requires less than a 5% difference between the Pao and Pes. Of note, esophageal pressure measurement may be unreliable in infants who have had prior surgery of the esophagus or infants who have esophagospasm. Esophageal pressure also will not reflect pleural pressure accurately when chest wall distortion is present during inspiration.Flow is measured at the airway opening by a pneumotachograph (PNT) attached to a face mask placed over the mouth and nose or directly to the end of an endotracheal or tracheostomy tube. Tidal volume is calculated by integration of the flow signal. Care must be taken to prevent leaks or flow and volume measurements will be artificially low.When transpulmonary pressure is measured, the resultant calculations yield pulmonary compliance and resistance. When transpulmonary pressure is measured during conditions of no flow (at end inspiration and end exhalation), the resistance factor of the equation of motion drops out (V̇=0), and the Ptot=E*V, allowing calculation of elastance and its reciprocal, compliance (Fig. 2). This method of calculating dynamic lung compliance has been used for more than 75 years. (1) Over the last 2 decades, however, computerized numerical methods, such as a least mean squares analysis, have been used in which multiple points along the pressure-volume tracing are analyzed for goodness of fit to yield compliance. (2)To calculate resistance in a similar manner, the elastance term of the equation of motion must be eliminated. This is accomplished by taking measurements at the same volume, eg, mid-inspiration and mid-exhalation. Because V now equals 0, pressure is directly related to R*V̇ (Fig. 2).One situation in which dynamic mechanics can be measured without the use of esophageal manometry involves preterm infants who are being mechanically ventilated. Because the chest walls of these infants are so much more compliant than the lungs, the difference between transpulmonary and respiratory system pressures is small. Using the positive-pressure breaths of the mechanical ventilator, the lungs are inflated passively and the pressure required to move air into the respiratory system is the pressure measured at the airway opening. This yields a reasonable estimate of dynamic mechanics.Measurements of dynamic lung mechanics in infants has allowed for determination of normal growth and development in term and preterm infants. Gerhardt and colleagues (3) measured dynamic pulmonary compliance and resistance in 40 healthy infants and children (newborn to 5 y) to establish normative data. They found that for the age period they studied, lung compliance increased 25-fold; pulmonary conductance (the reciprocal of resistance) only rose fivefold. Their findings suggested that in the third trimester of pregnancy, the airways already are well developed, and postnatal lung growth occurs primarily by the formation of new alveoli, leading to a proportional increase in lung compliance and functional residual capacity (FRC). However, conductance increases slower than FRC postnatally, resulting in a rapid drop in conductance normalized for FRC (specific conductance). To analyze the effects of preterm birth on the postconceptional pattern of pulmonary maturation, Abassi and Bhutani (4) measured dynamic pulmonary compliance and resistance in 33 nonventilated preterm infants (28 to 34 weeks’ gestation). They found that when corrected for weight, dynamic pulmonary compliance decreased with age, and pulmonary resistance peaked at 2 weeks postnatal age regardless of gestational age, subsequently decreasing. Their findings suggested a postnatal lag in pulmonary and airway growth relative to gestational maturation.Dynamic mechanics have been used in conjunction with blood gas monitoring, radiologic, and clinical assessments in the neonatal intensive care unit to help determine optimal ventilator parameters and decrease morbidity in ventilated infants. (5) They also have been used to predict survival outcome for neonates receiving extracorporal membrane oxygenation and have been used as a guide for weaning patients from it. (6)(7) Measurements of dynamic compliance within the first postnatal week have been proposed to predict which ventilated neonates eventually may develop bronchopulmonary dysplasia (BPD) and have been used to monitor disease progression in these infants. (8)(9) Gerhardt and colleagues (9) measured pulmonary compliance, conductance, and FRC at regular intervals in 39 infants who had mild BPD to monitor whether their initial abnormal lung function returned to normal or persisted as chronic obstructive pulmonary disease later in life. They found that pulmonary compliance initially was only 50% of normal at 1 month, but increased with growth and weight gain to 80% of normal at the end of follow-up at 36 months. They concluded that in infants who have chronic lung disease after mechanical ventilation, lung volume gradually increases, presumably by formation of new alveoli, leading to an improvement in lung compliance.Finally, dynamic mechanics have been used to evaluate therapeutic interventions such as the use of bronchodilators, diuretics, steroids, and surfactant treatment in infants who have chronic lung disease. (9)(10)(11)(12) In one study, researchers measured dynamic pulmonary compliance and resistance in six children (ages 5 to 43 mo) who had moderate-to-severe BPD before and after treatment with intravenous furosemide, inhaled isoproterenol, and inhaled atropine. (12) Dynamic pulmonary compliance increased significantly after treatment with furosemide and atropine. Although a decrease in resistance and work of breathing was observed during treatment with isoproterenol, the response was not statistically significant. The authors concluded that the improvement in lung compliance after diuretic administration was due to a decrease in pulmonary edema and pulmonary vascular pressures. They postulated that the improvement observed with atropine was the result of a decrease in bronchial obstruction that had been caused by reflex vagally mediated pulmonary edema.Although dynamic tidal mechanics have provided invaluable information for diagnosis and management of infants who have respiratory disease, the assumptions underlying the calculations may not always be satisfied. For example, if the lung does not behave as a single-compartment model, the calculations of dynamic compliance and resistance become less reliable. In disease states, asynchronous filling and emptying of lung units can occur when no flow is apparent at the mouth. The rate at which lung units empty is described by the time constant (t) for that unit, defined as t=resistance × compliance. Those units that have high resistance or high compliance have a long time constant and empty more slowly. When time constants throughout the lung are heterogenous because of disease, those that have longer time constants become overdistended as the respiratory rate increases because there is inadequate time for them to empty. As the rate increases, so does overdistension of the long time constant units, and those units that have shorter time constants can become compressed. Together, these effects combine to cause an overall decrease in dynamic compliance, especially when compared with compliance measurements made under quasi-static conditions. This phenomenon is referred to as frequency dependence of compliance. It is not present in the young, healthy lung at rates up to 60 breaths/min, but it becomes more apparent in infants who have obstructive lung disease and tachypnea.Increased upper airway resistance is yet another possible cause for measurement inaccuracies. In the nonintubated infant, flows are measured through the mouth and nose. Nasal congestion or positioning of the head so as to promote upper airway obstruction also results in falsely elevated values of resistance and lower values of compliance.Another problem that occurs, especially in preterm infants, term infants during rapid eye movement sleep, or older infants who have severe obstructive lung disease, is paradoxic movement of the rib cage and chest wall distortion. In these situations, measurements of esophageal pressure are reflective of local pressure swings rather than an average of pleural pressure changes. (13) Thus, measurements of both compliance and resistance become inaccurate. Finally, the use of esophageal catheters is considered to be invasive and may not be well tolerated by older infants. For these reasons, quasi-static measurements of passive respiratory mechanics were devised as a less invasive method, unaffected by chest wall distortion.Passive mechanics are measured in the absence of respiratory muscle activity during a passive exhalation. These measurements rely on invoking the Hering-Breuer inflation reflex to produce complete relaxation of both inspiratory and expiratory muscles. By maintaining lung volume above FRC, either by inflation or by airway occlusion after inspiration, stretch receptors in the muscles are stimulated, resulting in an inhibition of the next inspiratory effort and relaxation of the respiratory muscles. During this period, there is no airflow, and the pressure within the entire respiratory system equilibrates. Thus, the pressure at the airway opening reflects the elastic recoil pressure of the entire respiratory system. Again using the equation of motion, the total pressure, or driving pressure of the respiratory system, is equal to the sum of the elastic and resistive pressures. However, if there is an absence of respiratory muscle activity, the driving pressure will be zero, making the equation of motion: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{P}_{\mathrm{e}1}{+}\mathrm{P}_{\mathrm{res}}{=}0\] \end{document} or \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{P}_{\mathrm{e}1}{=}-\mathrm{P}_{\mathrm{res}}\] \end{document} Thus, the elastic recoil force is equal and opposite to the resistive forces during a passive expiration.Several techniques are used to assess passive respiratory mechanics in infants, including the multiple occlusion test (MOT) and the single-breath technique (SBT).The occlusion techniques measure the pressure difference between the airway opening and the body surface. As such, they include all of the structures of the respiratory system (ie, both lung and chest wall). The values calculated, therefore, represent compliance (Crs), resistance (Rrs), and time constant of the respiratory system (trs). Because these measurements are obtained during a brief apnea, they are considered to represent characteristics of the respiratory system under static conditions, and the compliance calculated is called the static compliance.To perform these measurements, a PNT is applied to the airway opening via a face mask or directly to an artificial airway. Pressure is measured at the airway opening, and volume is calculated by integration of the flow signal. Expiratory flow is interrupted by occluding the airway opening for up to 250 msec or long enough to produce a pressure plateau.In performing the MOT, a series of brief airway occlusions are made at different lung volumes during the first two thirds of expiration. A volume-pressure plot is constructed from these measurements, with the slope of this plot representing the compliance of the respiratory system (Fig. 3).The SBT involves occluding the airway at end inspiration and initiating the Hering-Breuer inflation reflex to relax the respiratory muscles and prolong the respiratory phase. The occlusion then is released, the expiratory flow during a passive exhalation is measured, and a flow-volume plot is constructed. Assuming a single-compartment model, this plot results in a linear relationship, with the slope of the plot representing the reciprocal of the expiratory time constant of the respiratory system. Extrapolation of the slope to the intercept of the volume axis estimates the total volume that would be exhaled if the infant emptied to the elastic equilibrium volume (EEV) of the respiratory system. Compliance then can be calculated from the ratio of volume above the EEV where the occlusion is made to the end-inspiratory recoil pressure at this volume. Resistance is calculated using this measured compliance and the expiratory time constant, where t=compliance × resistance (Fig. 4).Measurements of passive respiratory mechanics are noninvasive and well tolerated by infants. Techniques may be applied to both spontaneously breathing and mechanically ventilated infants. Gerhardt and colleagues (14) compared dynamic and static measurements of respiratory mechanics on 39 spontaneously breathing, preterm infants who had received mechanical ventilation. Using the SBT, they measured static Crs and Rrs and compared these values with dynamic lung compliance (Cdyn) and expiratory resistance (Re) of the previous unoccluded breath. In the younger infants, dynamic and static measurements correlated well. In older infants, Crs was 80% of Cdyn, and Rrs was 24% higher than Re. This lower Crs and higher Rrs were expected because the static measurements include the chest wall. In the more immature infants, the very compliant chest wall and higher breathing frequency (which underestimates Cdyn) may obscure this difference. The authors concluded that the occlusion technique is easily applied and well tolerated and provides accurate and reproducible results.Both the MOT and SBT have provided valuable information on normal growth and development of the lung in preterm, term, and older infants (15)(16) and have broadened our understanding of the physiology behind disease states such as respiratory distress syndrome, BPD, and cystic fibrosis. (17)(18)The MOT and SBT also have been used to monitor response to therapeutic interventions with bronchodilators, surfactant therapy, and steroid therapy. (19)(20)(21) For example, Baraldi and coworkers (22) measured static respiratory mechanics in 20 preterm infants before and 24 hours following treatment with surfactant. Static Crs and Rrs as well as the expiratory time constant were measured during spontaneous and mechanical ventilation using the SBT. They found a 45% increase in Crs hours after surfactant The expiratory time constants also were significantly higher after Rrs and colleagues used the SBT to measure Rrs and Crs in preterm infants before and after treatment with a They found a decrease in Rrs and an increase in Crs are a of how passive respiratory mechanics can as to guide treatment and monitor in spontaneously breathing or mechanically ventilated the MOT and SBT rely on complete relaxation of the respiratory muscles by the Hering-Breuer inflation reflex and that the pressures throughout the airways will such that the pressure at the airway opening will reflect the elastic recoil pressure of the respiratory system. of expiratory muscle activity falsely the measured compliance to be and resistance to be Thus, it is to monitor for respiratory muscle Because the use of during infant pulmonary function is not the of a pressure is used to muscle to measurements of dynamic respiratory mechanics, measurements of passive mechanics a single-compartment such that there is one expiratory time constant for the entire respiratory system. This is represented on a flow-volume as a linear expiratory These of the occlusion techniques them less in infants who have obstructive disease because those use muscles of exhalation to overcome their obstruction to a pressure), and their expiratory flow-volume often are the or can alter measurements of resistance and cause a falsely elevated volume on the passive flow-volume falsely the measured of infant lung mechanics have increased our of normal growth and development of the respiratory system as well as our understanding of the underlying infant lung disease. Both the dynamic and passive measurement techniques described have and and no technique has measurements of dynamic and passive pulmonary mechanics are being used more in the neonatal intensive care unit, along with radiologic, and blood gas monitoring, to about on of these may increase their clinical applications and