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Impedance cardiographic assessment of symptomatic patent ductus arteriousus
April 1980 The Journal of P E D I A T R I C S
711
Impedance cardiographic assessment of symptomatic patent ductus arteriosus A modified impedance cardiographic technique was developed using a tetrapolar apnea monitor and minicomputer system. Evaluation of this. technique in premature infants with and without symptomatic patent ductus arteriosus indicates that the magnitude of the cardiac-related deflection in the impedance signal is useful in the assessment of duetus shunting. Since the infant under study is involved only by the attachment of two double electrodes to the thorax, continuous assessment of ductus shunting is possible without disturbing routine care.
Robert B. Cotton, M.D., Daniel P. Lindstrom, Ph.D., Torsten Olsson, Ph.D., Martin Riha, Ph.D., Thomas P. Graham, M.D., Urban Selstam, M.D., and William Z. Catterton, M.D.,* Nashville, Tenn., and Gothenburg, S w e d e n
IMPEDANCE CARDIOGRAPHY has been validated as a
noninvasive method to measure cardiac output in adults and experimental animals, comparing favorably with indicator dilution techniques and direct measurements using implanted flow cuffs. 1-s Determinations of cardiac output by this method have also correlated with pulmonary blood flow measured by nitrous oxide rebreathing in premature infants without cardiopulmonary disease, and with pulmonary blood flow measured by the Fick principle at cardiac catheterization in children with left-to-right shunts through the ductus arteriosus and ventricular septal defects?' 7 A markedly increased pulmonary blood flow is a primary feature of premature infants with symptomatic patent ductus arteriosus? The magnitude and fluctuations of this total pulmonary blood flow are dominated by left-to-right blood flow through the ductus. Under these
From the Department of Pediatrics, Vanderbilt University School of Medieine, and the Department of Applied Medical Electronics, Chalmers University of Technology. Supported by a National Heart and Lung Institute SCOR Grant-HL 14214 and the Tennessee Heart Association. *Recipient of American Lung Association Training Fellowship in Pulmonary Disease.
0022-3476/80/040711 +05500.50/0 9 1980 The C. V. Mosby Co.
circumstances, impedance cardiography might be expected to detect changes in left-to-right ductus flow, providing a useful noninvasive method to assess management, and a monitor for the pharmacologic effect of agents such as indomethacin on ductus constriction. Abbreviations used PDA: patent ductus arteriosus ECG: electrocardiogram AZ: cardiac-related negative deflection Zo: baselinetransthoracic impedance A modified impedance cardiographic technique was developed using a commercially available apnea monitor and minicomputer signal processing. This technique provides minute-by-minute display of the impedance cardiograph so that waveform dimensions can be monitored continually without disturbing the patient. The usefulness of this technique to assess symptomatic ductus shunting is evaluated in this report.
METHODS In these studies, impedanc e cardiography was carried out either off-line from a tape recording of thoracic impedance and electrocardiogram signals, or on-line with the signals directly transmitted from the patient to the minicomputer. The signals were taken from a Saab
VoL 96, No. 4, pp. 711-7t5
712
The Journal of Pediatrics April 1980
Cotton et al.
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Fig. 1, Sequential impedance cardiograms from a 1.7 kg infant with hyaline membrane disease. The duration of each tracing is approximately one second and is centered about the R wave of the ECG, indicated by the central vertical line. Delta Z is measured as the vertical distance from the peak of the waveform at the central vertical line to the following valley. In this example, clinical evidence of ductus shunting was first detected at 75 hours after birth. The ductus closed spontaneously between the ninth and tenth day.
Respimeter (Saab-Scania, Medical Section, S-581 88, Link6ping, Sweden), which detected the thoracic impedance changes and the ECG by means of a tetrapolar electrode system. A pair of double electrodes (SaabScania) was attached to the skin on each lateral surface of the thorax using adhesive paper rings and electrode jelly. Each electrode pair was aligned with the midaxillary line, with the emitting electrodes closest to the axillae. The thoracic impedance signal was derived from the voltage drop across the detecting electrodes during injection Jof a 50 KHz, 0.03 mA current across the emitting electrodes. A PDP 11/34 (Digital Equipment Corporation, Maynard, Mass.) laboratory minicomputer was used to extract the impedance cardiogram waveform from the thoracic impedance signal, using a digital signal averaging process synchronized with the ECG R or S wave. One-hundred fifty one-second segments of digitized impedance signal were averaged to produce the impedance cardiogram. The center of each segment coincided in time with the R or S wave of the ECG. The system was calibrated by switching the electrode input of the Respimeter to a 10-turn
Fig. 2. Distribution of corresponding AZ and left ventricular end diastolic dimension values before and after ductus constriction accompanying indomethacin administration. Left ventricular end diastolic dimension is expressed as percent of the upper limits of normal? Solid lines indicate _-!-SEM, and broken lines indicate _+ 1 SD. The "normal" range of both variables is indicated by the area enclosed by broken lines. potentiometer set to approximate the patient's transthoracic impedance and intermittently adding a 1.0 ohm offset. Each resulting impedance cardiogram displays the cardiac-related thoracic impedance deflections remaining after larger deflections due to respiratory activity and movement have been filtered out by the averaging process (Fig. 1). The magnitude in ohms of the negative deflection beginning at the onset of electrical systole was chosen to correlate with clinical evidence of left-to-right ductus shunting. Patients studied by impedance cardiography were selected from the Vanderbilt Newborn Intensive Care Unit and included premature infants with and without symptomatic PDA. The evaluation of this technique was approved by the Vanderbilt Committee for the Protection of Human Subjects; during the evaluation phase, a written informed consent was obtained from the parents of each infant studied. All infants with symptomatic PDA had the characteristic ductus murmur, an active precordium, bounding pulses, and rales. These clinical findings were confirmed by radiographic evidence of cardiomegaly and pulmonary vascular engorgement or pulmonary edema. In most cases, the diagnosis was substantiated by echocardiographic evidence of left atrial or left ventricular enlargement according to the criteria of Baylen et al. 9 Control studies were obtained from premature infants who never had evidence of symptomatic PDA.
Volume 96 Number 4
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Fig. 3. Twenty-four hour course of impedance cardiographic AZs from four symptomatic PDA infants receiving indomethacin. Each point represents the AZ from a single impedance cardiogram9Echocardiographic studies were taken at the time shown except in A, where the final study was taken at 72 hours9 The arrow in each panel indicates the time of indomethacin administration, 0.2 mg/kg, orally in A and intravenously in B; C, and D: The patietLtsweighed 900, 1,300, 1,200, and 1,490 gin, respectively. They received indomethacin on the eighth, seventh, third, and second day, respectively, after birth. Each patient had clinical evidence of ductus constriction within 24 hours following ind.omethacin. RESULTS One-hundred forty-two impedance cardiograms were obtained from 20 infants with Symptomatic PDA on different days during the course of clinically apparent ductus shunting. The average birth Weight of this group of infants was 1,244 gm (SD = 313 gin) and studies were obt~tined between three and 28 days after birth. Fortyseven impedance cardiograms were obtained between one and 12 days after birth from 12 infants without symptomatic PDA whose average birth weight was 1,240 gm (SD = 416 gin). The mean AZ of the symptomatic PDA stfidies was 0.235 f~ (SD - 0.218 f~), and the mean AZ of the studies from infants without symtomatic PDA was 0.093 f~ (SD -- 0.041 ~2); 70% of the symptomatic PDA studies had a AZ greater than 0.175 ~, or 2 SD above the mean of the nonsymptomatic PDA studies. All symptomatic PDA infants had at least one impedance card 9 graphic h,Z greater than 0.175 f~. Fig. 1 shows representative impedance cardiograms from a 1,700 gm infant Whose recovery from hyaline membrane disease was complicated by symptomatic PDA
and whose ductus subsequently closed spontaneously between nine and ten days after birth. At 29 hours after birth there was no evidence of ductus shunting and AZ was within the "normal" control range. By 75 hours, the infant had a soft systolic murmur and tachycardia, and AZ had increased substantially above the upper limits of normal. Subsequently the intensity of the murmur increased, accompanied by bounding pulses and a hyperactive precordium. During this period, AZ remained markedly increased, followed by a return to normal after clinical evidence of Shunting disappeared between the ninth and tenth days. Impedanc e and echocardiography were carried out i n 14 infants with symptomatic PDA before and after clinical evidence of ductus constriction following ind0methacin administration. Both hZ and the left ventricular end diastolic dimension decreased following ductus constriction in all cases. Delta Z decreased to less than 0.175 ~2 in 12 of 14 patients. The decrease in AZ ranged from 0.052 to 0.362 ~. These results are illustrated in Fig. 2. The Ypplicabflity of this technique to the continuous
714
Cotton et al.
on-line monitoring of infants with symptomatic PDA is illustrated in Fig. 3 which shows the 24-hour course of four infants receiving indomethacin. These records were obtained by automatically processing a n d storing onto computer disks successive impedance cardiograms every five minutes. The graphs were plotted off-line after the extraction of AZ from each waveform by'the computer. Distorted waveforms were rejected by visual inspection. DISCUSSION The modified impedance cardiography described here differs from the conventional technique in several ways. Instead of using four circumferential band electrodes, a pair of double electrodes routinely used for ~apnea detection are attached to the thorax With adhesive paper rings. This electrode system allows continuous impedance cardiographic monitoring without disturbing the infant or interfering with patient care. The calculation of stroke volume with conventional impedance cardiography is based on the product of the ventricular ejection time and the steepest Slope of the negative impedance defleciion. 1 Based on our studies, AZ alone appears to be acceptable when the technique is used to detect changes in ductus Shunting. The stroke volume algorithm also includes three other factors: the baseline transthoracic impedance upon which thecardiac deflections are imposed, the distance between the detecting electrodes, and the resistivity of blood. The baseline transthoracic impedance is determined by two factors: the electrical field established by the electrode configuration and the electrical properties of the thorax and its contents. With the electrode configuration used by us, the field factor is predominantly dependent on the distance between the injection and detection electrodes within each pail This dimension is constant from baby to baby. The field factor is only minimally influenced by the distance between the electrode pairs. The electrical properties of the thoraX are not determined by its dimensions, but result from the relative amounts of conductive and nonconductive components present. A detailed theoretical analysis of these factors is published elsewhere, 1~ The resistivity of blood is a function of hematocrit. This factor was disregarded since the hematocrit of these infants was maintained within the midforties. That Z0, the distance between electrode pairs, and hematocrit indeed had only a minimal effect on AZ is supported by the observations in this study that AZ alone was a reliable indicator of the estimated magnitude of ductus shunting in infants with birth weights ranging from 812 to 2,395 gm. In addition, based on 122 pairs of AZ and Zo measurements, we found only a weak correlation (r = 0.25) between AZ and Zo.
The Journal of Pediatrics April 1980
Several~ important considerations prevent the comparison of results obtained with this technique with cardiac output calculated in the standard way using circumferential band electrodes. The use of four band electrodes around the head, neck, and abdomen would be hazardous in critically ill premature infants with fragile skin. Meticulous attention must be given when using ordinary small monitoring electrodes in order to avoid damage or destruction to the underlying skin In addition, methods to measure ventricular ejection time do not lend themselves to continuous application in these circumstances. Furthermore, in the presence of left-to-right ductus shunting, ventricular ejection time may not be equivalent to the time interval over which the pulmonary vascular bed accepts the volume increment of a cardiac cycle. For these reasons, meaningful comparison of the two techniques will require an experimental animal model. Previous applications of impedance cardiography base the calculation of cardiac output on the dimensions of individual cardiac-related impedance deflections. Separation of the individual deflections from the larger impedance variations due to breathing and movement is difficult in the infant with a rapid respiratory rate. Computer averaging of 150 segments of impedance signal centered about the QRS complex in time eliminates those variations uncorrelated with the cardiac cycle in most studies. The physiologic origin of the cardiac-related impedance deflection is speculative. Transthoracic impedance may be expressed as a function of the relative amounts of intrathoracic air (high impedance) and fluid (low impedance), considering the thorax as a volume conductor. 1~ The negative impedance deflection beginning at the onset of systole may result from the pulmonary vascular bed accepting an incremental volume of blood during systole. The results reported here are consistent with this hypothesis, since infants with large left-to-right ductus shunting have enormously increased pulmonary blood flow, up to four or five times systemic flow. '1 In these infants, whose total pulmonary blood flow is predominantly derived from the ductus rather than the right ventricle, it is reasonable to expect that changes in the left-to-right ductus flow could be detected by changes in the impedance cardiogram. In the absence of published experimental animal studies addressing this question, the important observations of Lababidi et aF that impedance cardiographic cardiac output correlates closely (r = 0.96) with pulmonary blood flow in children with left-to-right interventricular and ductus shunting provides support for this hypothesis. In those studies, pulmonary and systemic blood flows were measured at cardiac catheterization. using the Fick principle and an assumed oxygen consumption.
Volume 96 Number 4
The clinical evaluation of this technique indicates a highly useful correlation between AZ and estimated magnitude of ductus shunting. However, the hypothesis that AZ directly reflects volume fluctuation in the pulmonary vascular bed cannot be estab!ished from these studies. This relationship must remain tentative until validation studies are carried out in an experimental animal model. Other conditions in the premature infant associated with increased cardiac output and increased pulmonary blood flow might be expected to PrOduce an increased impedance cardiographic AZ. Thermal stress, crying, recovery from endotracheal suctioning, and anemia should be considered in the interpretation of AZ changes. In addition, the interpretation of AZ should take into consideration the effects of myocardial performance on left ventricular output. The technique is especially valuable as a way to assess continuously the magnitude of ductus shunting without disturbing the infant and without reqmrxng an indwelling arterial catheter. It lends itself to the study of factors such as changes in oxygenation and airway pressure, which may transiently affect ductus constriction or pulmonary blood flow. The early detection of ductus constriction following indomethacin (Fig. 3) is possible with this technique. Although the development of this technique has been facilitated by our PDP 11/34 minicomputer system, much less elaborate implementation has been shown possible using available signal averaging equipment. 1~ In summary, this modified impedance cardiographic technique appears to be a useful, noninvasive method for the assessment of left-to-right ductus shunting in small premature infants. The technique can be applied on-line continuously without disturbing the infant, making it possible to monitor changes in ductus flow under experimenta !, clinical, and therapeutic conditions.
Impedance cardiographic assessment o f PDA
7 15
REFERENCES
1. Kubicek WG, Karnegis JN, Patterson RP, et al: Development and evaluation of an impedance cardiac output system, Aerospace Med 37:1208, 1966. 2. Kubicek WG, Witsoe DA, Patterson RP, et al: Development and evaluation of an impedance cardiographic system to measure cardiac output and other cardiac parameters. A collection of 24 papers by various authors published by the U.S. DeP~}rtmentof Commerce Clearinghouse of Federal Scientific and Technical Information, Document No. N7010001-025, June, 1969. 3. Baker LE, Judy WV, Geddes LE, et al: Measurement of cardiac output by means of electrical impedance, Cardiovas Res Center Bull 9:135, 1971. 4. pate TD, Baker LE, and Rosborough JP: The simultaneous comparison of the electrical impedance method for measuring stroke volume and cardiac output with four other methods, Cardiovas Res Center Bull 14:39, 1975. 5. Denniston JC, Maher JT, Reeves JT, et al: Measurement of cardiac output by electrical impedance at rest and during exercise, J~Appl Physiol 40:1, 1976. 6. CosteloeK, Stocks J, and Godfrey S: Cardiac output in the neonatal period using impedance cardiography, Pediatr Res 11:1171, 1977. 7. Lababidi Z, Ehmke DA, Durnin RE, et al: Evaluation of impedance cardiac output in children, Pediatrics 47:870, 1971. 8. Cotton RB, Stahlman MT, Kovar I, and Catterton WZ: Medical management of small preterm infants with symptomatic patent ductus arteriosus, J PEmATR92:467, 1978. 9. Baylen BG, Meyer RA, Kaplan S, et al: The critically ill premature infant with patent ductus arter!osus and pulmonary disease--an echocardiographic assessment, J PED1ATR 86:423, 1975. 10. Olsson T, Daily W, and Victorin L: Transthoracic impedance: I. Theoretical consideration and technical approach, Acta Paediatr Scand Suppl 207:15, 1970. 11. Rudolph AM, Mayer FE, Nadas AS, et al: Patent ductus arteriosusl A clinical and hemodynamic study of 23 patients in the first year of life, Pediatrics 22:892, 1958. !2. Halpern B, arid Mannino F: Right-to-left (sic) cardiac shunting in neonates determined by tetrapolar cardiac thoracic impedance measurements, Clin Res 27:125A, 1979..
711
Impedance cardiographic assessment of symptomatic patent ductus arteriosus A modified impedance cardiographic technique was developed using a tetrapolar apnea monitor and minicomputer system. Evaluation of this. technique in premature infants with and without symptomatic patent ductus arteriosus indicates that the magnitude of the cardiac-related deflection in the impedance signal is useful in the assessment of duetus shunting. Since the infant under study is involved only by the attachment of two double electrodes to the thorax, continuous assessment of ductus shunting is possible without disturbing routine care.
Robert B. Cotton, M.D., Daniel P. Lindstrom, Ph.D., Torsten Olsson, Ph.D., Martin Riha, Ph.D., Thomas P. Graham, M.D., Urban Selstam, M.D., and William Z. Catterton, M.D.,* Nashville, Tenn., and Gothenburg, S w e d e n
IMPEDANCE CARDIOGRAPHY has been validated as a
noninvasive method to measure cardiac output in adults and experimental animals, comparing favorably with indicator dilution techniques and direct measurements using implanted flow cuffs. 1-s Determinations of cardiac output by this method have also correlated with pulmonary blood flow measured by nitrous oxide rebreathing in premature infants without cardiopulmonary disease, and with pulmonary blood flow measured by the Fick principle at cardiac catheterization in children with left-to-right shunts through the ductus arteriosus and ventricular septal defects?' 7 A markedly increased pulmonary blood flow is a primary feature of premature infants with symptomatic patent ductus arteriosus? The magnitude and fluctuations of this total pulmonary blood flow are dominated by left-to-right blood flow through the ductus. Under these
From the Department of Pediatrics, Vanderbilt University School of Medieine, and the Department of Applied Medical Electronics, Chalmers University of Technology. Supported by a National Heart and Lung Institute SCOR Grant-HL 14214 and the Tennessee Heart Association. *Recipient of American Lung Association Training Fellowship in Pulmonary Disease.
0022-3476/80/040711 +05500.50/0 9 1980 The C. V. Mosby Co.
circumstances, impedance cardiography might be expected to detect changes in left-to-right ductus flow, providing a useful noninvasive method to assess management, and a monitor for the pharmacologic effect of agents such as indomethacin on ductus constriction. Abbreviations used PDA: patent ductus arteriosus ECG: electrocardiogram AZ: cardiac-related negative deflection Zo: baselinetransthoracic impedance A modified impedance cardiographic technique was developed using a commercially available apnea monitor and minicomputer signal processing. This technique provides minute-by-minute display of the impedance cardiograph so that waveform dimensions can be monitored continually without disturbing the patient. The usefulness of this technique to assess symptomatic ductus shunting is evaluated in this report.
METHODS In these studies, impedanc e cardiography was carried out either off-line from a tape recording of thoracic impedance and electrocardiogram signals, or on-line with the signals directly transmitted from the patient to the minicomputer. The signals were taken from a Saab
VoL 96, No. 4, pp. 711-7t5
712
The Journal of Pediatrics April 1980
Cotton et al.
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Fig. 1, Sequential impedance cardiograms from a 1.7 kg infant with hyaline membrane disease. The duration of each tracing is approximately one second and is centered about the R wave of the ECG, indicated by the central vertical line. Delta Z is measured as the vertical distance from the peak of the waveform at the central vertical line to the following valley. In this example, clinical evidence of ductus shunting was first detected at 75 hours after birth. The ductus closed spontaneously between the ninth and tenth day.
Respimeter (Saab-Scania, Medical Section, S-581 88, Link6ping, Sweden), which detected the thoracic impedance changes and the ECG by means of a tetrapolar electrode system. A pair of double electrodes (SaabScania) was attached to the skin on each lateral surface of the thorax using adhesive paper rings and electrode jelly. Each electrode pair was aligned with the midaxillary line, with the emitting electrodes closest to the axillae. The thoracic impedance signal was derived from the voltage drop across the detecting electrodes during injection Jof a 50 KHz, 0.03 mA current across the emitting electrodes. A PDP 11/34 (Digital Equipment Corporation, Maynard, Mass.) laboratory minicomputer was used to extract the impedance cardiogram waveform from the thoracic impedance signal, using a digital signal averaging process synchronized with the ECG R or S wave. One-hundred fifty one-second segments of digitized impedance signal were averaged to produce the impedance cardiogram. The center of each segment coincided in time with the R or S wave of the ECG. The system was calibrated by switching the electrode input of the Respimeter to a 10-turn
Fig. 2. Distribution of corresponding AZ and left ventricular end diastolic dimension values before and after ductus constriction accompanying indomethacin administration. Left ventricular end diastolic dimension is expressed as percent of the upper limits of normal? Solid lines indicate _-!-SEM, and broken lines indicate _+ 1 SD. The "normal" range of both variables is indicated by the area enclosed by broken lines. potentiometer set to approximate the patient's transthoracic impedance and intermittently adding a 1.0 ohm offset. Each resulting impedance cardiogram displays the cardiac-related thoracic impedance deflections remaining after larger deflections due to respiratory activity and movement have been filtered out by the averaging process (Fig. 1). The magnitude in ohms of the negative deflection beginning at the onset of electrical systole was chosen to correlate with clinical evidence of left-to-right ductus shunting. Patients studied by impedance cardiography were selected from the Vanderbilt Newborn Intensive Care Unit and included premature infants with and without symptomatic PDA. The evaluation of this technique was approved by the Vanderbilt Committee for the Protection of Human Subjects; during the evaluation phase, a written informed consent was obtained from the parents of each infant studied. All infants with symptomatic PDA had the characteristic ductus murmur, an active precordium, bounding pulses, and rales. These clinical findings were confirmed by radiographic evidence of cardiomegaly and pulmonary vascular engorgement or pulmonary edema. In most cases, the diagnosis was substantiated by echocardiographic evidence of left atrial or left ventricular enlargement according to the criteria of Baylen et al. 9 Control studies were obtained from premature infants who never had evidence of symptomatic PDA.
Volume 96 Number 4
Impedance card9149
assessment of PDA
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Fig. 3. Twenty-four hour course of impedance cardiographic AZs from four symptomatic PDA infants receiving indomethacin. Each point represents the AZ from a single impedance cardiogram9Echocardiographic studies were taken at the time shown except in A, where the final study was taken at 72 hours9 The arrow in each panel indicates the time of indomethacin administration, 0.2 mg/kg, orally in A and intravenously in B; C, and D: The patietLtsweighed 900, 1,300, 1,200, and 1,490 gin, respectively. They received indomethacin on the eighth, seventh, third, and second day, respectively, after birth. Each patient had clinical evidence of ductus constriction within 24 hours following ind.omethacin. RESULTS One-hundred forty-two impedance cardiograms were obtained from 20 infants with Symptomatic PDA on different days during the course of clinically apparent ductus shunting. The average birth Weight of this group of infants was 1,244 gm (SD = 313 gin) and studies were obt~tined between three and 28 days after birth. Fortyseven impedance cardiograms were obtained between one and 12 days after birth from 12 infants without symptomatic PDA whose average birth weight was 1,240 gm (SD = 416 gin). The mean AZ of the symptomatic PDA stfidies was 0.235 f~ (SD - 0.218 f~), and the mean AZ of the studies from infants without symtomatic PDA was 0.093 f~ (SD -- 0.041 ~2); 70% of the symptomatic PDA studies had a AZ greater than 0.175 ~, or 2 SD above the mean of the nonsymptomatic PDA studies. All symptomatic PDA infants had at least one impedance card 9 graphic h,Z greater than 0.175 f~. Fig. 1 shows representative impedance cardiograms from a 1,700 gm infant Whose recovery from hyaline membrane disease was complicated by symptomatic PDA
and whose ductus subsequently closed spontaneously between nine and ten days after birth. At 29 hours after birth there was no evidence of ductus shunting and AZ was within the "normal" control range. By 75 hours, the infant had a soft systolic murmur and tachycardia, and AZ had increased substantially above the upper limits of normal. Subsequently the intensity of the murmur increased, accompanied by bounding pulses and a hyperactive precordium. During this period, AZ remained markedly increased, followed by a return to normal after clinical evidence of Shunting disappeared between the ninth and tenth days. Impedanc e and echocardiography were carried out i n 14 infants with symptomatic PDA before and after clinical evidence of ductus constriction following ind0methacin administration. Both hZ and the left ventricular end diastolic dimension decreased following ductus constriction in all cases. Delta Z decreased to less than 0.175 ~2 in 12 of 14 patients. The decrease in AZ ranged from 0.052 to 0.362 ~. These results are illustrated in Fig. 2. The Ypplicabflity of this technique to the continuous
714
Cotton et al.
on-line monitoring of infants with symptomatic PDA is illustrated in Fig. 3 which shows the 24-hour course of four infants receiving indomethacin. These records were obtained by automatically processing a n d storing onto computer disks successive impedance cardiograms every five minutes. The graphs were plotted off-line after the extraction of AZ from each waveform by'the computer. Distorted waveforms were rejected by visual inspection. DISCUSSION The modified impedance cardiography described here differs from the conventional technique in several ways. Instead of using four circumferential band electrodes, a pair of double electrodes routinely used for ~apnea detection are attached to the thorax With adhesive paper rings. This electrode system allows continuous impedance cardiographic monitoring without disturbing the infant or interfering with patient care. The calculation of stroke volume with conventional impedance cardiography is based on the product of the ventricular ejection time and the steepest Slope of the negative impedance defleciion. 1 Based on our studies, AZ alone appears to be acceptable when the technique is used to detect changes in ductus Shunting. The stroke volume algorithm also includes three other factors: the baseline transthoracic impedance upon which thecardiac deflections are imposed, the distance between the detecting electrodes, and the resistivity of blood. The baseline transthoracic impedance is determined by two factors: the electrical field established by the electrode configuration and the electrical properties of the thorax and its contents. With the electrode configuration used by us, the field factor is predominantly dependent on the distance between the injection and detection electrodes within each pail This dimension is constant from baby to baby. The field factor is only minimally influenced by the distance between the electrode pairs. The electrical properties of the thoraX are not determined by its dimensions, but result from the relative amounts of conductive and nonconductive components present. A detailed theoretical analysis of these factors is published elsewhere, 1~ The resistivity of blood is a function of hematocrit. This factor was disregarded since the hematocrit of these infants was maintained within the midforties. That Z0, the distance between electrode pairs, and hematocrit indeed had only a minimal effect on AZ is supported by the observations in this study that AZ alone was a reliable indicator of the estimated magnitude of ductus shunting in infants with birth weights ranging from 812 to 2,395 gm. In addition, based on 122 pairs of AZ and Zo measurements, we found only a weak correlation (r = 0.25) between AZ and Zo.
The Journal of Pediatrics April 1980
Several~ important considerations prevent the comparison of results obtained with this technique with cardiac output calculated in the standard way using circumferential band electrodes. The use of four band electrodes around the head, neck, and abdomen would be hazardous in critically ill premature infants with fragile skin. Meticulous attention must be given when using ordinary small monitoring electrodes in order to avoid damage or destruction to the underlying skin In addition, methods to measure ventricular ejection time do not lend themselves to continuous application in these circumstances. Furthermore, in the presence of left-to-right ductus shunting, ventricular ejection time may not be equivalent to the time interval over which the pulmonary vascular bed accepts the volume increment of a cardiac cycle. For these reasons, meaningful comparison of the two techniques will require an experimental animal model. Previous applications of impedance cardiography base the calculation of cardiac output on the dimensions of individual cardiac-related impedance deflections. Separation of the individual deflections from the larger impedance variations due to breathing and movement is difficult in the infant with a rapid respiratory rate. Computer averaging of 150 segments of impedance signal centered about the QRS complex in time eliminates those variations uncorrelated with the cardiac cycle in most studies. The physiologic origin of the cardiac-related impedance deflection is speculative. Transthoracic impedance may be expressed as a function of the relative amounts of intrathoracic air (high impedance) and fluid (low impedance), considering the thorax as a volume conductor. 1~ The negative impedance deflection beginning at the onset of systole may result from the pulmonary vascular bed accepting an incremental volume of blood during systole. The results reported here are consistent with this hypothesis, since infants with large left-to-right ductus shunting have enormously increased pulmonary blood flow, up to four or five times systemic flow. '1 In these infants, whose total pulmonary blood flow is predominantly derived from the ductus rather than the right ventricle, it is reasonable to expect that changes in the left-to-right ductus flow could be detected by changes in the impedance cardiogram. In the absence of published experimental animal studies addressing this question, the important observations of Lababidi et aF that impedance cardiographic cardiac output correlates closely (r = 0.96) with pulmonary blood flow in children with left-to-right interventricular and ductus shunting provides support for this hypothesis. In those studies, pulmonary and systemic blood flows were measured at cardiac catheterization. using the Fick principle and an assumed oxygen consumption.
Volume 96 Number 4
The clinical evaluation of this technique indicates a highly useful correlation between AZ and estimated magnitude of ductus shunting. However, the hypothesis that AZ directly reflects volume fluctuation in the pulmonary vascular bed cannot be estab!ished from these studies. This relationship must remain tentative until validation studies are carried out in an experimental animal model. Other conditions in the premature infant associated with increased cardiac output and increased pulmonary blood flow might be expected to PrOduce an increased impedance cardiographic AZ. Thermal stress, crying, recovery from endotracheal suctioning, and anemia should be considered in the interpretation of AZ changes. In addition, the interpretation of AZ should take into consideration the effects of myocardial performance on left ventricular output. The technique is especially valuable as a way to assess continuously the magnitude of ductus shunting without disturbing the infant and without reqmrxng an indwelling arterial catheter. It lends itself to the study of factors such as changes in oxygenation and airway pressure, which may transiently affect ductus constriction or pulmonary blood flow. The early detection of ductus constriction following indomethacin (Fig. 3) is possible with this technique. Although the development of this technique has been facilitated by our PDP 11/34 minicomputer system, much less elaborate implementation has been shown possible using available signal averaging equipment. 1~ In summary, this modified impedance cardiographic technique appears to be a useful, noninvasive method for the assessment of left-to-right ductus shunting in small premature infants. The technique can be applied on-line continuously without disturbing the infant, making it possible to monitor changes in ductus flow under experimenta !, clinical, and therapeutic conditions.
Impedance cardiographic assessment o f PDA
7 15
REFERENCES
1. Kubicek WG, Karnegis JN, Patterson RP, et al: Development and evaluation of an impedance cardiac output system, Aerospace Med 37:1208, 1966. 2. Kubicek WG, Witsoe DA, Patterson RP, et al: Development and evaluation of an impedance cardiographic system to measure cardiac output and other cardiac parameters. A collection of 24 papers by various authors published by the U.S. DeP~}rtmentof Commerce Clearinghouse of Federal Scientific and Technical Information, Document No. N7010001-025, June, 1969. 3. Baker LE, Judy WV, Geddes LE, et al: Measurement of cardiac output by means of electrical impedance, Cardiovas Res Center Bull 9:135, 1971. 4. pate TD, Baker LE, and Rosborough JP: The simultaneous comparison of the electrical impedance method for measuring stroke volume and cardiac output with four other methods, Cardiovas Res Center Bull 14:39, 1975. 5. Denniston JC, Maher JT, Reeves JT, et al: Measurement of cardiac output by electrical impedance at rest and during exercise, J~Appl Physiol 40:1, 1976. 6. CosteloeK, Stocks J, and Godfrey S: Cardiac output in the neonatal period using impedance cardiography, Pediatr Res 11:1171, 1977. 7. Lababidi Z, Ehmke DA, Durnin RE, et al: Evaluation of impedance cardiac output in children, Pediatrics 47:870, 1971. 8. Cotton RB, Stahlman MT, Kovar I, and Catterton WZ: Medical management of small preterm infants with symptomatic patent ductus arteriosus, J PEmATR92:467, 1978. 9. Baylen BG, Meyer RA, Kaplan S, et al: The critically ill premature infant with patent ductus arter!osus and pulmonary disease--an echocardiographic assessment, J PED1ATR 86:423, 1975. 10. Olsson T, Daily W, and Victorin L: Transthoracic impedance: I. Theoretical consideration and technical approach, Acta Paediatr Scand Suppl 207:15, 1970. 11. Rudolph AM, Mayer FE, Nadas AS, et al: Patent ductus arteriosusl A clinical and hemodynamic study of 23 patients in the first year of life, Pediatrics 22:892, 1958. !2. Halpern B, arid Mannino F: Right-to-left (sic) cardiac shunting in neonates determined by tetrapolar cardiac thoracic impedance measurements, Clin Res 27:125A, 1979..