Biomedical subjects
R A Epstein
Publications and source records attributed to R A Epstein.
A new ventilator for physiologic studies during high-frequency ventilation.
Research in the field of high frequency ventilation (HFV) has been hampered by the difficulty of collecting and analyzing expired gas, uncontaminated by gas of inspiratory composition, at ventilatory frequencies in the relevant range. A new mechanical ventilator is described, which has been designed to facilitate studies on the respiratory physiology of small animals during HFV. Ventilation is controlled by a single rotary valve, which alternately switches the airway to an approximately constant-flow gas source during inspiration, and to gas measurement and analysis apparatus during expiration, which takes place passively. Theoretical and experimental studies, using the techniques of mechanical and mathematical modelling, are used to measure the performance of the ventilator and to demonstrate that it allows the quantitative collection of expired gas during ventilation at rates up to at least 20 Hz. The advantages and limitations of this approach are discussed.
Constancy of physiological dead space during high-frequency ventilation.
A ventilator, specially designed to allow the direct measurement of expired gas volume and composition, was used to maintain gas exchange in anesthetized, paralyzed, New Zealand White rabbits at ventilatory frequencies up to 22 Hz. A total of eleven studies were carried out on seven animals. Determinations of the minute ventilation required to maintain a normal steady-state PCO2, together with the FECO2 and arterial PO2, PCO2, and pH, were made at a number of frequencies. The results so obtained were used to calculate the physiological dead space. It was found that this value remained remarkably constant for each individual rabbit over a range of ventilatory frequencies from 1 to 22 Hz. Our findings in rabbits are in contrast to those of other workers (in dogs) that adequate gas exchange can be maintained at high ventilatory frequencies with the use of tidal volumes much smaller than the volume of anatomical dead space.
Halothane adsorption complicating the use of soda-lime to humidify anaesthetic gases.
If the anaesthetic circle system is arranged to increase the humidity of fresh anaesthetic gases by placing the carbon dioxide absorbent canister between the fresh gas inlet and the patient, drying of the soda-lime can occur. Very dry soda-lime adsorbs significant quantities of halothane. Using fresh soda-lime, effluent halothane concentration reached 50% of the input concentration in 35s, but this time increased to 500 s when dry soda-lime was used. The use of dry soda-lime can result in a slow inhalation induction or in the release of absorbed halothane during a subsequent anaesthetic.
Mechanisms of halothane adsorption by dry soda-lime.
Using fresh soda-lime (15% water by weight) the soda lime/air partition coefficient of halothane was found to decrease as a function of vapour phase halothane concentration from 2.40 at 0.3% halothane by volume to 1.15 at 2.6%, but adsorption generally followed Henry's law. However, soda-lime dried to a constant weight and subsequently exposed to various concentrations of halothane adsorbed approximately 320 microlitre of vaporized liquid halothane per 100 g before a measurable concentration of halothane was detected in the vapour phase. Adding additional halothane then caused a linear increase in vapour concentration. We conclude that dry soda-lime can absorb large quantities of halothane by a mechanism which is similar to that of a molecular sieve. After these "high affinity" sites are satisfied, additional halothane is absorbed by a mechanism following Henry's law.
Breath-to-breath variations in rate and depth of ventilation in sleeping infants.
Ventilatory measurements were made noninvasively over 2- to 3-h periods during sleep in each of nine normal infants at 1 mo of age. To assess the changes that occur in ventilation on a breath-to-breath basis, we 1) examined the variations of each of tidal volume (VT), respiratory cycle time (Ttot), expiratory time (TE), and inspiratory time (TI) and 2) studied their interrelationships. We found that the variations of VT, Ttot, and TE but not of TI were significantly greater in rapid-eye-movement (REM) than in quiet sleep. In addition, on a breath-to-breath basis, VT had a positive linear relationship and strong correlation with TI; however, the correlation between VT and TE was weak in both sleep states. VT/Ttot was found to be moderately and negatively correlated with Ttot in both REM and quiet sleep. VT was weakly correlated with Ttot in REM sleep and was, on the average, more correlated with Ttot in quiet sleep. We suggest that in infants 1) on a breath-to-breath basis, VT/Ttot is likely to drop if respiratory frequency is decreased and 2) VT is nonlinearly related to Ttot during sleep; this lack of linearity depends on the lack of constancy of VT/Ttot, which is in turn closely related to the variability of the "on-switching" of inspiratory activity.
Flow to lung compartments with different time constants: effect of choice of model.
The thesis that an accelerating flow generator provides more even ventilation than a constant flow generator originated from studies using mechanical lung models. We simulated such studies by use of mathematical models. We found that the conclusions of these previous studies were dependent on the particular characteristics of their mechanical models. Studies employing more commonly used models indicate that constant flow generators, in fact, tend to provide more uniform ventilation, especially with long inspiratory times.
Automatic rezeroing of drifting physiologic signals.
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Determinants of distortions in CO2 catheter sampling systems: a mathematical model.
A mathematical model was developed to predict the distortions in the measured expiratory CO2 concentration time profile caused by catheter sampling systems. Parameters considered included the expiratory flow and concentration profiles, the sample flow rate, the sample tube dimensions and the sample cell volume. Unless care is taken in choosing the parameters of a catheter sampling system, particularly in the presence of low expiratory flow rates and short expiratory times, the CO2 concentration profile may be severely distorted. In worst case situations end tidal CO2 plateaux may not be recognized or alternately artifactual plateaux may be produced. Sample flow rate and sample cell volume are the most important parameters while distortion within the sample tube itself is relatively less important.
Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome.
Heart rate and heart rate variability were studied during sleep at monthly intervals in 18 normal infants and 12 infants with aborted sudden infant death syndrome during the first four months of life. At each age studied and in both REM and quiet sleep, the aborted SIDS infants had a 5 to 10% faster heart rate. Moreover, the aborted SIDS infants had a 10 to 45% smaller beat-to-beat and overall heart rate variability. Although the differences in overall variability persisted after normalization by the absolute heart rate, the differences in the beat-to-beat variability narrowed. These findings, when taken in conjunction with our previous observation that aborted SIDS infants have a smaller QT index than normal infants, suggest that infants with aborted SIDS have an increase in sympathetic activity or in circulating levels of catecholamines.
Ventilatory requirements of critically ill neonates.
Ventrilatory requirement was assessed in 15 critically ill neonates on a total of 31 occasions. All were either currently receiving mechanical ventilation or had had mechanical ventilation in the recent past. Minute ventilation, respiratory frequency, carbon dioxide production (VCO2) and arterial blood PaCO2 were measured. Dead space-to-tidal volume ratios (VD/VT) were calculated. The ventilatory requirements of the infants ranged from 1.16 to 4.30 times normal. Derived parameters related the increased ventilatory requirement to pulmonary (VD/VT) and metabolic (VCO2) factors. The increased requirement was not significantly related more often to either of these two factors, although one or the other was frequently predominant in individual cases. Data presented allow specification of the minute volume range needed for ventilators designed for neonates, and the maximal compressible volume that can be tolerated when expired volume monitoring is desired.
CO2-induced changes in ventilation and ventilatory pattern in normal sleeping infants.
The effect of CO2 on the ventilatory pattern of 18 normal infants was studied during sleep at monthly intervals through the age of 4 mo. Using the barometric method, we measured tidal volume (VT), respiratory cycle time (Ttot), inspiratory time (TI), and expiratory time (TE). Two percent CO2 produced no change in TI and a significant increase in VT and mean inspiratory flow (VT/TI). There was no consistent change in TE or Ttot in either sleep state at any age. The percent increase from base line in instantaneous minute ventilation (VT/Ttot) during REM sleep was similar to that during quiet sleep. We conclude that with inhalation of 2% CO2 in the first 4 mo of life 1) the increase in VT/Ttot results solely from an increase in VT and the percent increase in VT/Ttot is the same in both sleep states and 2) the reflex termination of inspiration by inflation does not play an important role in eupnea during sleep because the increase in VT is not associated with a decrease in TI.
Practical implementation of the barometric method for measurement of tidal volume.
The barometric method is unique in permitting measurement of tidal volume in a totally noninvasive manner. Its application and accuracy have been limited by several complex problems. These include control of inspired gas composition, base-line stability, and asymmetry of processes occurring during inspiration and expiration. A new method is described that addresses these problems and facilitates long-term measurements. New calculations, which avoid previous errors that caused the method to systematically underestimate tidal volume, are illustrated.
Relation of beat-to-beat variability to heart rate in normal sleeping infants.
The relationship of beat-to-beat heart rate variability (delta RR) and instantaneous heart rate was studied in eight normal infants while asleep during the first four months of life. The sleep state (REM or quiet) was determined using neurophysiologic and behavioral criteria. The results of regression analyses indicated that the delta RR values were positively correlated with the instantaneous heart rate (RR intervals). The correlation coefficient range was 0.49 to 0.92 in quiet sleep and 0.50 to 0.93 in REM sleep. Regression analyses supported a linear approximation of the delta RR to RR relation over the RR range investigated (400 to 520 msec). The median slope was 0.124 in REM and 0.117 in quiet sleep. The slopes of these linear functions were similar in both sleep states and at all ages. If beat-to-beat variability is to be used as an index of the integrity of the autonomic nervous system, these results suggest that delta RR be corrected for RR. A model is presented which relates the demonstrated positive correlation of delta RR to RR with the physiology of cardiac output control.
The R-R interval and R-R variability in normal infants during sleep.
Eighteen normal infants were studied in the first 2 wk of life during sleep and subsequently at their monthly birthdays for the first 4 months of life. The R-R interval was measured with an accuracy of 0.2 msec. Sleep staging was performed visually using electroencephalogram, electrooculogram, and electromyogram, and behaviroal criteria. Our results show that the R-R interval and the beat-to-beat variability are, in general, smaller in rapid eye movement than in quiet sleep. The two sleep states, however, are best differentiated by the overall variability which is characteristically higher in rapid eye movement sleep. The R-R interval as well as the overall and the beat-to-beat variability show minimal values at 1 month and maximal rates of increase between 2 and 3 months of age, indicating that the R-R interval and R-R variability are not simple linear functions of age.
Airway flow patterns during mechanical ventilation of infants: a mathematical model.
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High-resolution determination of the R-R interval.
A preprocessor is described that determines the time interval between successive R waves of the electrocardiogram with an error of less than 0.2 ms. It accomplishes this by sepearting in hardware the function of determining the approximate location of the R wave from the function of localizing with great accuracy the peak of the wave form. With this device it is possible to detect abnormal heart rate patterns characterized by exceedingly small beat-to-beat variability. The approach may be useful for other bioelectric signals.
Maturation of ventilation and ventilatory pattern in normal sleeping infants.
Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured tidal volume (VT), total respiratory cycle time (Ttot), inspiratory time (Ti), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/Ttot). Vt, Ttot, TI, TE, VT/TI, and VT/Ttot but not TI/Ttot increased with age. In all age groups, Ttot, TI, and TE but not VT/TI were greater in quiet than in REM sleep. In the first 2 mo of life, VT was greater in quiet than in REM sleep; in the older infants, VT/Ttot was smaller in quiet than in REM sleep. TI/Ttot was not dependent on sleep state. Thus, because VT/Ttot = VT/TI X TI/Ttot, the increase in VT/Ttot with age results from an increase in mean inspiratory flow rather than from changes in respiratory "duty cycle". Further, the "on-switching" as well as the "off-switching" of inspiratory activity depends on sleep state.