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J Appl Physiol 89: 364-372, 2000;
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Vol. 89, Issue 1, 364-372, July 2000

SPECIAL COMMUNICATION
Detecting lung overdistention in newborns treated with high-frequency oscillatory ventilation

Kaye Weber1, Sherry E. Courtney1, Kee H. Pyon1, Gordon Y. Chang1, Paresh B. Pandit1, and Robert H. Habib2

1 Department of Pediatrics, Robert Wood Johnson Medical School at Camden, The Children's Regional Hospital at Cooper Hospital/University Medical Center, Camden, New Jersey 08103; and 2 Mercy Children's Hospital and Department of Pediatrics, Medical College of Ohio, Toledo, Ohio 43608


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES

Positive airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV) increases lung volume and can lead to lung overdistention with potentially serious adverse effects. To date, no method is available to monitor changes in lung volume (Delta VL) in HFOV-treated infants to avoid overdistention. In five newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct current-coupled respiratory inductive plethysmography (RIP) for this purpose by evaluating it against whole body plethysmography. Animals were instrumented, fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP and plethysmography were simultaneously calibrated, and HFOV was instituted at varying Paw settings before (6-14 cmH2O) and after (10-24 cmH2O) repeated warm saline lung lavage to induce experimental surfactant deficiency. Estimates of Delta VL from both methods were in good agreement, both transiently and in the steady state. Maximal changes in lung volume (Delta VLmax) from all piglets were highly correlated with Delta VL measured by RIP (in ml) = 1.01 × changes measured by whole body plethysmography - 0.35; r2 = 0.95. Accuracy of RIP was unchanged after lavage. Effective respiratory system compliance (Ceff) decreased after lavage, yet it exhibited similar sigmoidal dependence on Delta VLmax pre- and postlavage. A decrease in Ceff (relative to the previous Paw setting) as Delta VLmax was methodically increased from low to high Paw provided a quantitative method for detecting lung overdistention. We conclude that RIP offers a noninvasive and clinically applicable method for accurately estimating lung recruitment during HFOV. Consequently, RIP allows the detection of lung overdistention and selection of optimal HFOV from derived Ceff data.

respiratory inductance plethysmography; infants; mechanical ventilation; lung mechanics; respiratory distress syndrome


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES

LUNG OVERDISTENTION HAS BEEN implicated in the development of chronic lung disease (CLD), such as bronchopulmonary dysplasia, air leaks, and cardiovascular depression, in infants with respiratory failure who require mechanical ventilation (9, 13, 31, 32). Several studies show that prolonged conventional ventilation with tidal breathing in newborn infants can lead to lung injury that can subsequently progress to CLD (6, 11, 21, 30, 41).

High-frequency oscillatory ventilation (HFOV) is an alternative mode of ventilation believed to reduce the incidence of CLD in some infants (10). HFOV uses nontidal ventilation to effect gas exchange, whereas alveolar volume is recruited and maintained by positive mean airway pressure (Paw). However, if Paw settings exceed optimal values, lung overdistention can occur with undesirable effects, such as pneumothorax, pulmonary interstitial emphysema, and CLD, as well as reduced oxygen delivery to the tissues as a result of cardiovascular depression (12, 18, 19). Moreover, the optimal Paw is itself dependent on the underlying lung mechanics, which vary with the disease process and treatments.

Therefore, a method that 1) can accurately measure changes in lung volume (Delta VL) during HFOV and 2) is sufficiently practical to allow repeated assessments in infants would be useful for clinicians managing infants with HFOV. A number of candidate methods have been investigated in the past; however, no clinically applicable method has been described to date (8, 36, 40).

Respiratory inductance plethysmography (RIP) is commonly used to assess breathing synchrony, tidal ventilation, and respiratory rate in infants (25-27, 38, 39). If direct current (DC) coupled, RIP is also able to continuously measure changes in static lung volume (Delta VL); i.e., changes above functional residual capacity (FRC; Refs. 7, 27, 42). The noninvasive nature of RIP and its ease of application make it especially attractive for use in critically ill neonates on HFOV. However, the accuracy of measuring Paw-induced Delta VL by using RIP has not been verified nor has a method to interpret such data been described.

The goals of this study were 1) to test whether RIP provides accurate, continuous estimates of Paw-induced Delta VL during HFOV and 2) to describe, if RIP is accurate, a method of how it may be used in clinical settings to detect and avoid lung overdistention. Here, we speculated that the Paw-Delta VL and compliance-Delta VL relationships derived from RIP data allow identification of the optimal Paw. Toward this end, we compared simultaneous whole body plethysmography and RIP measurements of Delta VL over a wide range of Paw settings in piglets with healthy and surfactant-deficient lungs.


    MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES

Measurements were done in five newborn piglets (age 6-15 days, weight 2.2-4.2 kg) under healthy and diseased (experimental surfactant deficiency) conditions. The animal protocol was approved and monitored by the Institutional Animal Care and Use Committee according to National Institute of Health Guide for the Care and Use of Laboratory Animals.

Model Preparation

Piglets were initially anesthetized with an intramuscular injection of ketamine hydrochloride (14 mg/kg). Anesthesia was maintained with pentobarbital sodium, and pancuronium bromide (0.1 mg/kg) was used to induce and maintain paralysis.

Animals were placed supine on a warming blanket to maintain rectal temperature between 38 and 40°C. We inserted catheters into the animal's carotid artery to enable blood-gas sampling, medication delivery, and blood pressure monitoring. We cannulated the jugular vein for continuous infusion of fluids. A 3.0-mm (ID) endotracheal tube was inserted via tracheostomy to a depth of 4 cm. Controlled mechanical ventilation (CMV; Bear Cub Infant Ventilator, BP 2001, Bear Medical Systems, Riverside, CA) with peak inspiratory pressure of 12-15 cmH2O, positive end-expiratory pressure (PEEP) of 2-3 cmH2O, breathing rate of 40-50 breaths/min, inspiratory time of 0.5 s, and inspired O2 fraction (FIO2) of 1.0 initial settings, and skeletal muscle paralysis were started simultaneously. Maintenance doses of pancuronium bromide were administered at 20-min intervals. To ensure hydration, we infused 5% dextrose and lactated Ringer solution at 10 ml/h.

Abdominal and thoracic RIP bands (RespiBands, SensorMedics, Yorba Linda, CA) were placed to encircle the abdomen and the ribcage just above the umbilicus and at the level of the axillae. The effective band lengths were secured in position by tight clips to avoid loosening with time or due to repeated oscillations. We also marked each piglet's abdomen skin to ensure similar band placement before and after lung lavage. Once normal blood-gas values and blood pressure had been verified, we placed the animal in the plethysmograph. Pass-through ports in the wall of the plethysmograph enabled connection of the catheters, temperature probe, RIP bands, and endotracheal tube. The seal of the plethysmograph was confirmed by injecting 40 ml of air and observing a nondecaying pressure, or equivalently volume, tracing.

Measurement Protocol

Measurements were always performed after the internal temperature of the plethysmograph had stabilized (20-45 min). In healthy piglets, HFOV (3100 Oscillator, SensorMedics) initial settings varied slightly among the piglets (Paw 5-8 cmH2O, frequency 8-10 Hz, amplitude 55-70 cmH2O, FIO2 1.0, and inspiratory time at 33% of the total breathing cycle) based on verification of normal arterial blood gases. In each piglet, six to eight simultaneous measurements of RIP and plethysmographic volume changes were made at increasing Paw to elicit larger changes in Delta VL. We calibrated both RIP and plethysmograph after every change in Paw. After data collection with each Paw, changes in HFOV frequency and amplitude were made in response to variations in arterial blood-gas values. Derecruitment back to FRC, or Paw = 0, after each measurement was confirmed by RIP and plethysmograph readings returning to baseline.

After data collection in the healthy animal was complete, the animal was removed from the plethysmograph and placed back on CMV. Serial lung lavages were next performed by using aliquots of 30 ml/kg warmed normal saline administered via the endotracheal tube (24). The chest was massaged to circulate the liquid, and the lung affluent was allowed to exit passively while the animal was placed in a gravity-dependent drainage position. CMV pressure settings were increased after the first lavage to peak inspiratory pressure of 20 cmH2O, and PEEP was increased to 5 cmH2O to offset the alveolar derecruitment postlavage. The animal was allowed to recover (stable heart rate and oxygen saturation >90%), and then lavage was repeated. Lavages were continued until the animal's arterial partial pressure of O2 (PaO2) was <100 Torr on FIO2 1.0. Once the target PaO2 was reached, the animal was returned to the plethysmograph, and a leak-free seal was confirmed as before. HFOV was restarted at an initial Paw of 12-18 cmH2O, frequency of 8-10 Hz, pressure amplitude of 55-70 cmH2O, FIO2 of 1.0, and inspiratory time of 33%. As before lavage, initial settings were determined in each piglet on the basis of blood-gas values, and measurements were repeated for increasing Paw settings.

At the conclusion of the experiment, animals were killed with an overdose of pentobarbital sodium administered via the jugular vein, according to the Guidelines of the Panel on Euthanasia of the American Veterinary Medical Association.

Data Acquisition and Analysis

RIP volume data was computed from the sum of the rib cage and abdominal data. Each was sampled at 50 Hz and collected by using the Somnostar PT (model 105-042-01, SensorMedics). Changes in plethysmograph pressure (Ppleth) were similarly sampled and collected by using an auxiliary analog channel on the Somnostar. These were then used to indicate absolute Delta VL on the basis of a linear calibration. Plethysmograph and RIP measurements were simultaneously calibrated by using a five-point (0, 10, 20, 30, and 40 ml) volume calibration before each change in Paw (Fig. 1). A sufficient interval of time was allowed to elapse between consecutive volume injections to allow for a semblance of a plateau in both RIP and Ppleth. Ppleth and RIP data were adjusted by their respective calibration factors to provide volume data in milliliters.


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  		Fig. 1.   Tracings from an example piglet showing the simultaneous calibration of respiratory inductive plethysmography (RIP) and whole body plethysmography (pleth); unfiltered change in lung volume (Delta VL) by both techniques (Delta VLRIP and Delta VLpleth) in response to a positive mean airway pressure (Paw) of 14 cmH2O; and Delta VLRIP and Delta VLpleth after low-pass filtering. Maximal Delta VL (Delta VLmax), representing an estimate of the maximal alveolar recruitment (or plateau value), was computed as the averaged Delta VL over a 3- to 5-s interval. Zero value on either y-axis represents the end-expiratory lung volume when Paw = 0 [or functional residual capacity (FRC)]. Calibrations (0-40 ml) were done while high-frequency oscillatory ventilation was disconnected, and tracings show greater effects of cardiogenic oscillations on plethysmograph measurements.

An example of Delta VL data in a healthy piglet measured with both methods in response to a Paw of 14 cmH2O is shown in Fig. 1. Before analysis, these data were digitally low-pass filtered (characteristic frequency = 2 Hz, -92 dB Blackman) to remove the superimposed oscillatory ventilation effects on both signals (MP 100, BioPac Systems, Santa Barbara, CA) as illustrated in Fig. 1. Accuracy of transient and steady-state Delta VL estimated by RIP (Delta VLRIP) was then verified as follows.

Transient volume changes. We compared the time-dependent rise in lung volume [Delta VL(t)] as estimated by RIP [Delta VLRIP(t)] vs. plethysmograph [Delta VLpleth(t)] using standard linear regression analysis (Fig. 2). In addition, the between-method bias and limits of agreement analysis were determined from the difference function [Delta VLRIP(t)-Delta VLpleth(t)] according to the method of Bland and Altman (5). These comparisons were repeated for each change in Paw in each piglet before and after lung lavage.


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  		Fig. 2.   A: comparison of RIP vs. plethysmograph time tracings [Delta VL(t)] between FRC (Delta VL = 0) and FRC + Delta VLmax for a single Paw setting in an example piglet. B: corresponding linear regression analysis results of Delta VLRIP in terms of Delta VLpleth; solid line represents the line of identity; regression results are shown as dashed (regression line) and dotted (prediction interval) lines. C: between-methods bias and limits of agreement analysis results derived from the difference data (Delta VLRIP-Delta VLpleth). Bias was defined as the mean Delta VLRIP-Delta VLpleth throughout the comparison. Upper (UL) and lower limits (LL) of agreement were computed as bias + 2 SD and Bias-2 SD, respectively; SD = standard deviation of the overall Delta VLRIP-Delta VLpleth. Regression and bias analysis results from all piglets are summarized in Table 1.

Maximal or steady-state volume changes. After every change in Paw, lung volume increased in a time-dependent fashion until it reached a maximal plateau or steady-state value (Delta VLmax; see example in Fig. 1). The Delta VLmax estimated from each method and those for all Paw settings were combined and contrasted by using linear regression analysis. Here also, between-method Delta VLmax bias and limits of agreement were estimated as per Bland and Altman (5).

Lung Recruitment and Mechanics

As Paw settings were modified, changes in lung mechanical properties were quantified by deriving the following relationships before and after lung lavage: 1) Delta VLmax vs. Paw, 2) effective compliance (Ceff, in ml/cmH2O) vs. Paw, and 3) Ceff vs. Delta VLmax.

Ceff is computed as the ratio of Delta VLmax (ml) to Paw (cmH2O). It primarily reflects the mechanical properties of the respiratory tissues (Cti) and to a lesser extent that of the alveolar gas volume (Cg); or Ceff = Cti + Cg with Cti > Cg. Note that the change in Cg relative to Paw = 0 may be approximated as follows
&Dgr;Cg<IT>=&Dgr;</IT>V<SC>l</SC><SUB>max</SUB><IT>/</IT>(Patm<IT>−</IT>P<SC>h</SC><SUB>2</SUB><SC>o</SC>) (1)
where Patm and PH2O are the atmospheric (1,033 cmH2O) and vapor pressures (64 cmH2O), respectively.

Lung Overdistention

When the lung is derecruited after lavage, Ceff should decrease relative to its healthy or prelavage value. In contrast, as more alveolar volume is recruited at higher Paw, one expects that Ceff should increase as a result of 1) the necessary increase in Cg and 2) a greater Cti. The latter is true except when overdistention occurs. Thus interpreting changes in Ceff in terms of Paw (or equivalently Delta VLmax) is the main element of how Delta VL measurements may be used to avoid overdistention during HFOV (Fig. 3).


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  		Fig. 3.   A cartoon depicting the separate contributions of mechanical properties of respiratory tissue (Cti) and of gas volume (Cg) to effective respiratory system compliance (Ceff) as lung volume is increased by alveolar recruitment (i.e., Delta VLmax). Cg is always an increasing function (linear as per Eq. 1), reflecting the increased alveolar gas volume. Alternatively, Cti will increase with Delta VLmax until the respiratory tissues become overstretched, or true overdistention (ODactual). Ceff is the algebraic sum of Cti and Cg and hence may continue to increase with further lung recruitment despite tissue OD (see Cti). Indeed, detection of OD based on Ceff (ODobserved) is necessarily delayed until the decrease in Cti is of greater magnitude than the increase in Cg. au, Arbitrary units.

We propose that a simple method to arrive at optimal Paw settings during HFOV may be based on Ceff vs. Delta VLmax relationships. These curves can be determined by methodically increasing Paw over a physiologically relevant range and allowing for a stable Delta VL plateau after each change. If alveoli are recruited without overdistention, the change in Ceff (Delta Ceff) should exceed the increase in Cg (Delta Cg) due to the alveolar volume change (Fig. 3); i.e., Delta Ceff > Delta Cg. This would also reflect an increase in Cti. Alternatively, a relative drop in Cti would result if overdistention of respiratory tissues is present, and hence a Delta Ceff < Delta Cg. Consequently, the Ceff vs. Delta VLmax relation would exhibit a Ceff, relative to the previous or lower Paw setting, that is either 1) decreased, 2) unchanged, or 3) increased by less than Delta Cg (Fig. 3).


    RESULTS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES

Validation of RIP

Transient volume changes. Results of the between-methods comparison for estimating transient volume changes, or time response, induced by increasing Paw are summarized in Table 1. First, the range of Paw settings varied slightly between piglets mainly 1) because of different initial (or lowest) Paw needed in each piglet before and after lavage to maintain normal blood-gas limits, and 2) to provide for a range of Paw settings for evaluation.

                              
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  		Table 1.   Summary of RIP vs. plethysmograph linear regression and bias analysis results

Our analysis indicated that, in all piglets, the transient lung volume changes estimated by both techniques [Delta VLRIP(t) and Delta VLpleth(t)] were similar for all Paw. Averaged linear regression results (Table 1) demonstrated a slope of nearly 1 (0.99 ± 0.04 prelavage and 0.98 ± 0.04 postlavage); small intercept values of 1.3 ± 0.9 ml before and 1.6 ± 0.6 ml after lavage; and r2 > 0.95. Furthermore, the average between-method bias (-0.9 ± 0.8 ml prelavage and 1.0 ± 0.9 ml postlavage) and the SD (1.1 ± 0.3 ml prelavage and 1.1 ± 0.4 ml postlavage) that describe the limits of agreement or accuracy between RIP and plethysmography were also small for both healthy and diseased lungs.

Maximal or steady-state volume changes (Delta VLmax). As expected, Delta VLmax increased as Paw was increased to higher settings (Fig. 4). Delta VLmax, or the effective change in lung volume with Paw, did not differ for plethysmography and RIP throughout the range of Paw settings both pre- and postlavage [Fig. 5A; Delta VLRIP (ml) = 1.01 × Delta VLpleth (ml)-0.35; r2 = 0.95]. Here also, the between-method difference in Delta VLmax indicated a near-zero (0.07 ml) bias and with relatively small upper (5.0 ml) and lower (-4.9 ml) limits of agreement (Fig. 5B). Consequently, the similarity of Delta VLmax obtained from both plethysmography and RIP lead to essentially identical lung mechanics results or Delta VLmax vs. Paw, Ceff vs. Paw, and Ceff vs. Delta VLmax relationships.


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  		Fig. 4.   Delta VLRIP(t) from an example piglet illustrating the effective increase in alveolar gas volume (i.e., Delta VLmax) at increasing Paw settings.



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  		Fig. 5.   A: comparison of RIP vs. plethysmograph at Delta VLmax at all Paw settings from all piglets before (open circle ) and after () lung lavage; solid line is the line of identity. B: between-methods bias and limits of agreement analysis results derived from the Delta VLmax difference data (RIP-Pleth).

Lung Mechanics and Detection of Overdistention

The RIP-derived Delta VLmax vs. Paw relationships before and after lung lavage are shown in Fig. 6. Note that the range of Paw values used and the maximal lung recruitment were both expectedly higher postlavage. In either case, however, Delta VLmax was generally an increasing nonlinear function of Paw.


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  		Fig. 6.   Comparison of the change in Delta VLmax (mean ± SE) as a function of Paw from all piglets before (open circle ) and after () lung lavage. Only postlavage data show multiple inflection points in the Delta VLmax-Paw relation, which might indicate inhomogeneous expansion of the lung at increasing Paw settings.

Figure 7 illustrates the dramatic decrease in respiratory system compliance after lung lavage in two example piglets. In one of these piglets (postlavage), increasing Paw beyond 21 cmH2O resulted in a slightly lower Ceff despite the greater volume recruitment. Such a drop in Ceff as Paw is increased probably reflects overdistention of lung tissues, and it certainly indicates that HFOV at these Paw or lung volumes is disadvantageous and may compromise gas exchange.


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  		Fig. 7.   Comparison of the change in Ceff as a function of Paw in two example piglets before and after lung lavage. The smallest and largest subjects, spanning the size range (2.2-4.2 kg) of the study piglets, were purposely chosen to show the reproducibility of the results among piglets. Note that Ceff values were normalized to the respective body weight to account for size dependence of lung compliance.

Ceff and Delta VLmax from all piglets were averaged for the same Paw setting (independent variable). The resulting Ceff vs. Delta VLmax relationships exhibited strong nonlinear characteristics both pre- (r2 = 0.98) and postlavage (r2 = 0.99) that were best approximated by the following sigmoid equations (Fig. 8)
Ceff(prelavage)

=2.1+1.0/[1−exp<SUP><IT>−</IT>(<IT>&Dgr;</IT>V<SC>l</SC><IT>−8.9</IT>)<IT>/1.3</IT></SUP>] (2)

Ceff(postlavage)

=1.6+1.5/[1−exp<SUP><IT>−</IT>(<IT>&Dgr;</IT>V<SC>l</SC><IT>−13</IT>)<IT>/2.5</IT></SUP>] (3)
where Ceff is in units of ml/cmH2O and Delta VL in units of ml/kg.


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  		Fig. 8.   Comparison of Ceff as Delta VL is increased by imposed positive Paw relative to no Paw support (0 cmH2O). Each data point represents the mean ± SE Ceff and corresponding average Delta VLmax at equal Paw before (open circle ) and after () lavage. Variance of Delta VLmax with Paw was provided in Fig. 5 and was excluded here for graph clarity. Solid lines through data represent "best fit" sigmoidal relationships of the form Ceff (ml/cmH2O) = Y0 + a/[1-e-(Delta VL-X0)/b] where Y0 = minimum Ceff, Y0 + a = maximum Ceff, and X0 is Delta VL value representing the point of inflection in the sigmoid curve.

Ceff for the same lung recruitment, or Delta VLmax, was significantly lower postlavage. This is explained by the derecruitment, or lower starting lung volumes at Paw = 0, in the surfactant-deficient lungs. Otherwise, pre- and postlavage Ceff-Delta VLmax curves had similar characteristics: 1) Ceff is lowest at the lower Delta VLmax values (or effective lung volumes); 2) Ceff increased as lung volume increased until it reached a maximum value; 3) the average Ceff appears to peak at ~3.1 ml/cmH2O in both healthy (for Delta VLmax > 12 ml/kg) and surfactant deficient (for Delta VLmax > 18 ml/kg) piglets. The latter probably reflected the reduced compliance (i.e., overdistention) at higher Paw settings in some piglets (see example in Fig. 6). The same maximal Ceff before and after lavage also suggests that the net effect of the lavage was alveolar derecruitment with no changes in the intrinsic tissue properties.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES

Many infants who are born before term require mechanical ventilation for respiratory failure because of respiratory distress syndrome (RDS) (17). Advances in the management of sick neonates during the past two decades have decreased the mortality associated with RDS (1, 17, 20). However, despite decreased mortality in very-low-birth-weight infants (500-1,500 g), the incidence of CLD remains unchanged (20, 28, 31). CLD is caused, in part, by the lung injury inflicted by mechanical ventilation and the use of supplemental oxygen (31).

HFOV in neonates is widely used today. Evidence is mounting that HFOV is less likely to induce lung injury in infants than CMV (10, 16, 19, 34, 35, 37). The most commonly used high-frequency oscillator operates using a bidirectional piston that functions near the resonance frequency of the infant lung (10-15 Hz). Tidal volume may be less than the volume of the anatomic dead space, and lung volume is higher than FRC. Applying HFOV to infants carries a substantial risk of lung overdistention because, as the infant's lung compliance improves, lung volume may increase to harmful levels, resulting in alveolar and/or bronchiolar rupture (36). A method to estimate lung volume during HFOV is needed to alert clinicians as lung volume increases.

Gas dilution techniques (helium dilution and nitrogen washout) have been widely used in the pulmonary function laboratory setting to measure lung volume (22). In mechanically ventilated patients, these techniques are cumbersome, are not readily available, and at best provide discrete lung volume measurements. More importantly, they require prolonged interruption of HFOV and hence cannot provide information about Paw-induced lung recruitment and lung mechanics to detect and avoid overdistention during HFOV.

Whole body plethysmography has been widely used in cooperative adults and in animal research to measure thoracic gas volume, from which FRC can be calculated (14, 15, 29). Although this method can be used to measure Delta VL during HFOV (as we did in this study), it is rarely employed in infants, particularly those who are intubated and require intravenous infusions. This method limits access to the infant for some period and is difficult to perform (22). For change in lung volume to be continuously assessed, infants would need to remain in a leak-free plethysmograph, which is not clinically feasible or safe.

Fumey et al. (15) have reported using a planimetric method for estimating lung volume from chest radiographs in infants with CLD. Measurements using their planimetry method closely correlated with plethysmographic measurements of thoracic gas volume in infants with CLD. Although promising, this technique depends on the availability and timeliness of chest radiographs. Other methods of estimating lung volume from chest radiographs have been reported (3, 4, 33), but their clinical value is controversial.

Clinicians assess lung volume using periodic chest radiographs. The optimum position of the dome of each hemidiaphragm is between the top of the eighth rib and the bottom of the ninth rib (40). As the position of the diaphragms varies, Paw is increased or decreased to maintain lung inflation at the desired level. This technique may provide a crude estimate of lung volume; however, it is not continuous, is not immediately available, and exposes infants to radiation. More important, recent evidence suggests a poor correlation between this radiographic assessment and actual measurements of lung volume using helium dilution (40). Dramatic Delta VL leading to air leaks may ensue before lung volume can be assessed by radiography.

Measuring Delta VL with RIP

RIP is a commonly used method for assessing and quantifying thoracoabdominal asynchrony in infants and children (25-27, 38, 39). When DC coupled, the RIP signal carries information on how the static lung volume is changing above FRC (25). Several investigators have used RIP to measure Delta VL in adult patients and normal volunteers. Valta and co-workers (42) studied alveolar recruitment with changes in PEEP using RIP. Chandra et al. (7) used RIP estimates of Delta VL and breathing synchrony to study the effects of hyperpnea on PEEP-induced alveolar recruitment. Although these investigators have used RIP to estimate Delta VL, to our knowledge no studies have validated RIP for measuring Delta VL during HFOV.

In piglets with both healthy and surfactant-deficient lungs, we found that Paw-induced Delta VL during HFOV estimated by RIP over a wide range of settings were in excellent agreement with those independently provided by whole body plethysmography. Indeed, both methods provided similar estimates of the overall recruitment as a function of Paw (Delta VLmax; Fig. 5) as well as of the transient change in lung volume between FRC and FRC + Delta VLmax (Fig. 2; Table 1). In both cases, the bias and limits of agreement between RIP and plethysmography were relatively small. This agreement was obtained despite 1) the fact that RIP (unlike plethysmography) measurements depend on incomplete sampling of the thorax (one rib cage and one abdominal RIP band), 2) varying effects of extraneous noise such as cardiogenic oscillations on RIP compared with plethysmography (Fig. 1), and 3) the possibility of very slow undetectable leaks within the plethysmograph.

Besides its noninvasiveness and apparent accuracy for measuring lung volume changes, other aspects of RIP make it highly attractive for the proposed use with HFOV. First, RIP bands are easy to use and should not interfere with the medical care of patients. Ensuring that these bands are correctly placed and do not move during the assessment on HFOV is, however, critical.

Second, RIP bands exhibit a linear quality over the physiological range of Delta VL values (see Fig. 1), and hence the nontrivial task of absolute calibration of RIP measurements to units of volume (ml) may not be necessary for the purpose of detecting overdistention. This is because the latter is determined from the change in Ceff as Paw is increased rather than from absolute Ceff values. Calibration of RIP requires additional equipment and measurements (e.g., flow/volume) to be done on infants while HFOV is discontinued. Calibration is also possible by briefly switching to conventional ventilation, in which tidal ventilation and RIP data may be combined to determine calibration coefficients. Absolute calibration, though, is advantageous because it provides 1) physiologically meaningful recruitment (ml/kg) and Ceff (ml/cmH2O) values for comparison to healthy values and 2) a mathematical separation of changes in Cti and Cg from measured Ceff changes.

Finally, unlike volume measurements derived from flows at the proximal airway (e.g., pneumotachography), RIP measurements reflect volume changes at the chest wall and hence are unaffected by airway leaks at the endotracheal tube-airway interface. When airway leaks are present, flow measurements at the proximal endotracheal tube can be substantially inaccurate in infants. Worse, the relative magnitude of the airway leak will depend on the load impedance, which will change as the lung is recruited.

Clinical and Physiological Implications of RIP-derived Delta VL

Given the validity of RIP derived estimates of Delta VLmax, we were able to construct Delta VLmax vs. Paw (Fig. 6), Ceff vs. Paw (Fig. 7), and Ceff vs. Delta VLmax (Fig. 8) relationships before and after lung lavage. The obtained curves conveyed important physiological information about the underlying lung mechanics (healthy vs. diseased) and also provided a quantitative basis for detection of lung overdistention. Specifically, we show how the characteristics of the Ceff vs. Paw, or equivalently Ceff vs. Delta VLmax, curves can be used to indicate overdistention. This aspect of using RIP has important clinical implications as to how such measurements can be used to determine optimal HFOV settings and how these settings ought to be changed during weaning of HFOV support.

On the basis of our findings, we propose that a method to arrive at optimal HFOV settings is possible from consideration of the changes in Ceff as Paw is methodically increased over its physiologically relevant range of values. Briefly, Ceff vs. Paw and Ceff vs. Delta VLmax relationships are then derived by allowing for a stable plateau for lung recruitment after each Paw change.

An increase in Delta Ceff is advantageous provided that it exceeds the expected rise in alveolar gas compression compliance (i.e., Delta Cg) alone at the higher lung volume. A Delta Ceff < Delta Cg indicates a relative decrease in Cti or lung tissue overdistention. A decreased or unchanged Ceff at higher Paw (or Delta VLmax) also suggests overdistention for the same reason. Arguably, removing the chest wall component of Cti would increase the sensitivity of this method to parenchymal overdistention. This, however, is only possible at the price of inserting an invasive esophageal balloon and additional equipment requirement so that separation of lung and chest wall mechanical properties is facilitated.

In conclusion, we have shown that DC-coupled RIP can accurately estimate lung recruitment (i.e., Delta VLmax) during HFOV and that combining RIP-derived Delta VLmax and Paw data can provide important insight on changes in lung mechanics via Ceff vs. Paw and Ceff vs. Delta VLmax relationships. These relationships were then used to develop a possible clinically useful method for detecting and avoiding lung overdistention, with or without absolute calibration of RIP. According to this method, the optimal HFOV settings are those that maximize lung volume and compliance via Paw-induced alveolar recruitment without overdistention of the parenchymal tissues. Oxygenation is also promoted as lung volume is increased provided that the deleterious effects of overdistention on the pulmonary vascular bed, and hence gas exchange, are avoided.

Although this method offers a promising approach for optimizing HFOV management in infants, some technical and clinical factors must be addressed to facilitate its clinical use. First, currently available RIP devices provide volume change data only. Integration of RIP measurements with HFOV and automation of the proposed assessment procedure (e.g., sweeping through Paw values) including computation and plotting of the change in all compliance values (Ceff, Cti, and Cg) are essential steps if this method is to be widely implemented in nurseries (see Fig. 3).

Other factors not addressed in this study may affect the optimal HFOV settings. Overdistention stemming from the superimposed oscillatory ventilation is plausible, but this risk is small given the amplitude of these oscillations and may be accounted for during recruitment. Finally, the implicit assumption that the lungs are expanded as a homogenous mechanical unit is not always accurate, particularly in the surfactant-deficient lung during treatment. Although RDS affects the infant fairly homogeneously, delivery of exogenous surfactant in the premature infant lung is almost invariably nonuniform (2) and will lead to nonhomogeneous lung mechanical properties. Arguably, overdistention of healthier lung units (or those with the highest regional compliance) may go undetected if a cumulative or single-compartment measure such as Ceff is used. Related to this is the fact that, even if inhomogeneity is not present, overdistention may occur at lower Paw as the lungs become healthier during treatment. Conversely, if the disease worsens, applied HFOV settings may become suboptimal. We believe that these scenarios are best avoided, or minimized, by periodic (and perhaps frequent) application of the proposed method for determining appropriate support levels. Consequently, future efforts should attempt 1) to refine the proposed technique to account for lung inhomogeneity and 2) to automate this technique so that its clinical implementation is facilitated.


    ACKNOWLEDGEMENTS

This research was supported by a grant from the Foundation of the University of Medicine and Dentistry of New Jersey.


    FOOTNOTES

K. Weber was a visiting scientist at Robert Wood Johnson Medical School at Camden, NJ, during this study.

Present address of G. Y. Chang: Thomas Jefferson Hospital, 111 South 11th St., Philadelphia, PA 19107.

Address for reprint requests and other correspondence: R. H. Habib, Director, Cardiopulmonary Research, Mercy Children's Hospital, 2213 Cherry St., ACC Bldg., Suite 309, Toledo, OH, 43608 (E-mail: Robert_Habib{at}mhsnr.org).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Received 26 January 2000; accepted in final form 14 March 2000.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
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J APPL PHYSIOL 89(1):364-372
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