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The Safety Factor for Electroventilation Measured by Production of Cardiac Ectopy in the Anesthetized Dog
------t
~Ili • ...--1_lb_Or_I_IO_rV_I_Dd_I_DI_m_II_SI_Ud_18_S The safety Factor for Electroventilation Measured by Production of Cardiac Ectopy in the Anesthetized Dog* Christine E. Riseili, M.S.;t Marvin Hinds, Ph.D.;:f: William D. Voorhees Ill, Ph.D.;§ Joe D. Bourland, M.S.E.E., Ph.D.;1I and Leslie A. Geddes, M. E., Ph. D. ~
The safety factor of electroventilation (ie, the ratio of the current required to produce an ectopic beat to the current required to produce an inspired volume of !25 ml, which is approximately twice tidal volume) was determined in 12 pentobarbital-anesthetized dogs using transthoracic electrodes positioned at the optimal electroventilation site. The optimal stimulation site for electroventilation was first determined using hand-held, stimulating electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the optimal stimulation site. The relationship between
The possibility of creating a simple method of electrically mediated artificial respiration dates from the mid-19th century when inspiration was induced using skin-surface electrodes. The method was used in treating respiratory arrest due to chloroform anesthesia l and coal-gas fumes. 2 Geddes et al3 reported successful ventilation in anesthetized dogs by applying bursts of short-duration stimuli to transthoracic electrodes. The name given to this procedure is electroventilation. Because current is passed through the thorax during electroventilation, it is possible to produce cardiac arrhythmias. In the present stud~ with transchest electroventilation electrodes, the current required to produce 225 ml of inspired volume and the threshold current required to produce an ectopic beat were determined over a pulse-duration range of 0.1 to 10 ms. From these data the safety factor for producing cardiac arrhythmias during electroventilation was determined. ·From the Hillenbrand Biomedical Engineering Center, Purdue University, West Lafayette, IN. t Doctoral candidate, graduate student in Veterinary Physiology. *Professor of Biology, Biology Department Coordinator, Marion College, Marion, IN. §Senior Scientist, Associate Research Scholar. II Coordinator for Bioengineering Research. 'Showalter Distinguished Professor, and Director, Hillenbrand Center. Biomedical E~gineering Dr. Riscili, Hillenbrand Biomedical Engineering Center, Purdue University, West Lafayette, IN 47907
214
inspired volume and stimulus intensity was determined using a 0.8-s burst of stimuli (60/s) with a pulse duration of 0.1 ms. Using the same electrodes, the threshold current for producing ectopic beats was determined for single pulses ranging from 0.1 to 10 ms duration. In all dogs, the current required to produce an ectopic beat increased greatly as the pulse duration decreased. At 0.1 ms, the safety factor for electroventilation was calculated to be 25.8. (Chest 1989; 95:214-17)
MATERIAL AND METHODS
Twelve mongrel dogs weighing 16 to 27 kg were anesthetized with 30 mWkg of pentobarbital sodium and placed in dorsal recumbency on a V-shaped board. The forelimbs of each animal were restrained beside the head, and a lead 2 ECG was monitored. Blood pressure was recorded using a 8uid-611ed catheter placed in a femoral artery and connected to a Cobe pressure transducer (Cobe Laboratories). An oxygen-filled recording spirometer with a carbon dioxide absorber was attached to the endotracheal tube to monitor the electrically induced inspired volume. An electronic signal corresponding to the volume of air in the spirometer was recorded on a Physiograph (Narco Bio-Systems). The upper thorax of each animal was shaved and the optimal location for electrode placement was determined using 2.54-cm diameter, gauze-covered, saline-soaked, hand-held stimulating electrodes placed bilaterally on the chest. The optimal location is defined as the site at which the largest volume of inspired air per rnA of electroventilation current is obtained. After locating the optimal site, which was in the anterior axillary region, 4.1-cm diameter stainless steel stimulating electrodes were sutured bilaterally to the skin over the site. Using a prototype electroventilator built at the Hillenbrand Biomedical Engineering Center, inspiration was produced by applying 0.8-s bursts of short-duration (0.1 ms) pulses (6OIs) to the electrodes at a rate of 24 bursts/min. The amplitude of the pulses in each burst was increased linearly to provide a smooth inspiration and reached the maximum amplitude in 0.5 s. With the dogs' forelimbs restrained beside the head and the electrodes at the optimal stimulation site on the upper chest, the volume of air inspired was recorded for bursts of stimuli delivered at different current intensities. To measure the volume inspired due to the electroventilation current only, respiratory arrest was produced during each trial by stimulating the afferent right vagus nerve Safety Factor for Electroventilation (Riseili at al)
_
FIGURE 1. Optimal electroventilation site (inset) for electrode placement in anterior axillary region (A) of dog, and inspired volume vs peak current (I) for a typical animal with electrodes at the optimal stimulation site.
in the neck. Ligation of the vagus and stimulation cranial to the ligature produced respiratory arrest without cardiac effects. After determining the relationship between inspired volume and electroventilation current intensity in each animal, the threshold current required to produce ectopic beats was determined by delivering single pulses (0.1 to 10.0 ms) from a special, high-current generator to the electroventilation electrodes. The current delivered by the current generator was monitored on an oscilloscope. To determine the threshold current necessary for ectopic beats, transient cardiac arrest was produced by efferent vagal stimulation, accomplished by stimulating the nerve caudal to the already present ligature. This maneuver ensured that stimuli were applied during the diastolic interval, when threshold for ectopy is lovv.· When the current pulse was delivered to the transchest electrodes, the presence or absence of an ectopic beat was noted on the Physiograph record. If no ectopic beat was observed, the intensity of the current pulse was increased until an ectopic beat was obtained. Threshold was defined as that current that produced an ectopic beat and at which a 10 percent decrease in current did not produce an ectopic beat. This procedure was repeated for pulse durations ranging from 0.1 to 10 ms, enabling construction of a strength-duration curve. RESULTS
Figure 1 (inset) identifies the optimal electroventilation site for electrode placement on the thorax which is located near the level of the fourth rib and slightly anterior to a midaxillary line. This site was essentially the same among the 12 dogs. Figure 1 also illustrates an inspired volume vs electroventilation current relationship in a typical animal with electrodes at the optimal stimulation site and with the forelimbs restrained beside the head. In all cases an increase in current resulted in an increased inspired volume until a maximum value was reached, typically two to three times tidal volume. The spontaneous tidal volume of this animal was 167 ml. Ectopic beats were produced in the arrested hearts of all 12 dogs over pulse durations ranging from 0.1 to 10 ms. A plot ofthe average threshold current required to produce ectopic beats vs pulse duration is shown in Figure 2. In all dogs, as the pulse duration is shortened, the current required to produce an ectopic beat
increases greatly. The duration of the individual pulses of the electroventilation current is 0.1 ms. Shown also on Figure 2, at 0.1 ms, is the mean current required to produce an inspired volume of 225 ml (approximately twice tidal volume); therefore, the average safety factor (current ratio at 0.1 ms) was calculated to be 25.8. DISCUSSION
The use ofstimuli applied to skin-surface electrodes to provide artificial respiration dates from the latter half of the 19th century, when there were no mechanical ventilators. At this time, sudden respiratory arrest resulting from the use of chloroform as an anesthetic and asphyxiation from coal-gas fumes was common. The appearance of mechanical ventilators, and the discontinuance of chloroform as an anesthetic, probably contributed to the abandonment ofthis technique. The interest in skin-surface electrodes to electrically mediate artificial respiration in humans was revived in the 1950s, when Knodts described use ofthe electric
•o.s DlNTIC* c.sec)
FIGURE 2. Solid line represents average current (n = 12) to produce ectopic beats (± SE) vs pulse duration;· represents average current required to produce an inspired volume of 225 ml in 12 dogs using stimulus pulse duration of 0.1 ms. Average safety factor at 0.1 ms was 25.8.
CHEST I 95 I 1 I JANUAR~
1989
215
lung stimulator built by Hofmann in German}'. The electric lung was a two-channel stimulator that first excited the inspiratory, then the expiratory muscles, using chest-band electrodes and a train of shortduration pulses (at 5O/s). The successful use of chestband electrodes in this case required that the operator have knowledge of the correct electrode placement. Sarnoff et al6 demonstrated that stimulation of one phrenic nerve with an external electrode is capable of producing effective artificial respiration in humans. A thimble- or pen-type electrode was applied to the motor point of the phrenic nerve in the neck by the operator. Training was necessary for the successful use of the electrophrenic respirator. Holmes et al7 continued to investigate artificial respiration using the electric lung to improve lung function in patients with pulmonary disease. They concluded that there was a decrease in the amount of exudate, a return of diaphragmatic function, and decreased morbidity in patients with unilateral medical and surgical pleural disease. Although the tidal volume could be increased by 2¥2 times using the electric lung, no dramatic long-term effect on lung function was observed, and interest was lost in use of the device. In 1959 Gray and Field8 evaluated a two-channel electronic stimulator built by Batrow Laboratories. With this stimulator two sets of electrodes were used: a xiphoid-back electrode current pathway stimulated the diaphragm, and stimulation of the abdominal muscles produced active expiration. Applying the Batrow unit to normal subjects, they concluded that there was an increased tidal volume when the optimal stimulation rate was applied. The Batrow unit provided adequate ventilation in patients with emphysema and showed potential in initiating diaphragmatic breathing exercises in patients with impaired diaphragmatic motion. Because of the two sets of electrodes, careful attention to electrode location was necessary Goldenthal9 investigated use of the Ventilaide stimulator, also manufactured by Batrow Laboratories. This single-channel unit was designed to produce inspiration using an active, argon-filled electrode placed over the xiphoid and referenced to a large metal plate under the feet or buttocks. This stimulator delivered 7-f.Ls pulses at 60/s. Cine£luorography showed that contraction of the diaphragm caused inspiration when the active electrode was placed over the xiphoid. Although the Batrow unit was successful in ventilating human subjects and no accidents occurred with it, the unit was withdrawn from the marketplace. The probable reason was that some who used it were not familiar with the need for careful electrode placement and were unable to obtain adequate ventilation. It was not until 1985 that Geddes et al3 renewed interest in electrically induced artificial respiration, 218
and discovered that there were bilateral transthoracic sites for electrodes to produce inspiration. Later, Riscili et al lO successfully electroventilated six baboons using transthoracic electrodes. Current applied to axillary electrodes stimulates the phrenic nerves (unpublished data). It must be recognized that stimulation of other inspirato~ and perhaps some expirato~ nerves and muscles also occurs. For this reason the optimal stimulation site must be located. The potential hazard with electrodes in the axillary region is the possibility ofproducing a cardiac arrhythmia. As shown in the present stud~ the key to safety with electroventilation is the use of a short-duration stimulus. At the time of this stud~ the shortest pulse duration available on the electroventilator was 0.1 ms. Geddes et alB presented strength-duration curves for cardiac pacing using external electrodes in humans that showed that as the pulse duration was shortened beyond 0.1 ms, the current required for cardiac pacing continued to increase rapidl~ Recent modification of our electroventilator provides a pulse duration of 10 f.Ls. The electroventilator for use in humans will use this pulse duration, which will result in an even higher safety factor. It should be noted that altered Po2 , Pco2 , pH, and electrolyte levels affect the threshold for cardiac arrhythmias. The results of the present study therefore may not be generalized to situations in animals or humans when gas exchange impairment exists. The use of a short-duration electroventilation pulse also minimizes skin sensation. Hon and Hulme, 12 Gray and Field, 8 and Goldenthal, 9 evaluating the Batrow unit, reported that in all cases stimulation produced painless diaphragmatic contraction. Geddes et alII presented strength-duration curves for pain in human subjects and reported that the current intensity for pain increased dramatically as the pulse duration was shortened. The results we obtained, showing an inverse relationship between the current required to produce an ectopic beat and the pulse duration (strength-duration curve), are consistent with the relationship exhibited by all irritable tissues. Geddes 13 showed that the experimentally obtained strength-duration curve can be derived from the knowledge of the electrical nature of cell membranes. In 1985 Geddes and Bourland 14 showed how the mathematical constants describing the strength-duration curve can be obtained. CONCLUSION
The application of rhythmic bursts of short-duration pulses to chest-surface electrodes can provide inspired volumes in excess of tidal volume. The optimal electroventilation stimulation site, near the level of the fourth rib and just anterior to a midaxillary line, was identified and found to be relatively constant among Safety Factor for Electroventilation (Riseili at 81)
12 dogs. Using the electroventilation electrodes, ectopic beats were produced over a pulse duration range of 0.1 to 10 ms. In all cases the current intensity necessary to produce an ectopic beat increased as the pulse duration decreased. The safety factor determined for electroventilation (pulse duration of 0.1 ms) was 25.8. ADDENDUM
Since submitting this paper for revie~ we have had the opportunity to conduct the first clinical trial of electroventilation at Methodist Hospital in Indiana at Indianapolis. The primary goal of the initial human trials is to identify the optimum location for the chestsurface electrodes by "mapping" the thorax with handheld electrodes. The first experiment was successful, and during the trial we were able to monitor the ECG and blood pressure continuously. The electroventilator used in the human trials employs a burst of 10-fJ,s duration pulses applied to the chest-surface electrodes. At no time did we observe any cardiac arrhythmias. The patient was a 40-kg male organ donor. A consent form previously approved by the Institutional Review Board of Methodist Hospital was obtained prior to the trial. The maximum volume obtained during this initial trial was 140 mI. Although this volume is small and represents the approximate dead space volume in this patient, it is important that the goal of identifying an optimal electrode location was achieved. During this first clinical trial the current applied to the transchest electrodes was limited to 1200 rnA. An addendum, approved by the Institutional Review Board, to the original proposal increases the maximum current level to 2,400 rnA for future trials. Once the optimal site for
electrode placement is determined, studies to determine the relationship between increasing current and inspired volume will be conducted. REFERENCES 1 Duchenne G. L'electrisation localisee et de son application a la pathologie et a la therapeutique. Paris: Librairie J. B. Bailliere et Fils, 1872 2 Ziemssen H. Die electricitat in der medicin, 1st ed. Berlin: A. Hirschwald, 1857 3 Geddes LA, Voorhees WD, Babbs CF, Deford JA. Electroventilation. Am J Emerg Med 1985; 3:337-39 4 Jones M, Geddes LA. Strength-duration curves for cardiac pacemaking and ventricular fibrillation. Cardiol Res Cen Bull 1977; 15:101-12 5 Knodt H. Kunstliche beatmung mit der elecktro-Iunge. Artzliche Wochenschr 1951; 6:281-83 6 Sarnoff SJ, Sarnoff LC, Whittenberger HL. Electrophrenic respiration: VII. The motor point of the phrenic nerve in relation to external stimulation. Surg Gynecol Obstet 1951; 93:190-96 7 Holmes G~ Buckingham WB, Cugell D~ Kirchner K. Electric stimulation of breathing in chronic lung diseases. JAMA 1958; 166:1546-51 8 Gray FD, Field AS. The use ofmechanicaI assistance in treating cardiopulmonary diseases. Am J Med Sci 1959; 248:146-52 9 Goldenthal S. Bilateral and unilateral activation ofthe diaphragm in the intact human. Conn Med 1961; 25:236-38 10 Riscili CE, Foster KS, Voorhees WD, Bourland JD, Geddes LA. Electroventilation in the baboon. Am J Emerg Med (in press) 11 Geddes LA, Babbs CF, Voorhees WD, Foster KS, Aronson AL. Choice of the optimum pulse duration for precordial cardiac pacing: a theoretical stud~ PACE 1985; 8:862-69 12 Hon EH, Hulme GW An electronic resuscitator for possible use in asphyxia neonatorum. Yale J BioI Med 1958; 32:58-73 13 Geddes LA. Cardiovascular devices and their applications. 1st ed. New York: John Wiley & Sons, 1984:256-57 14 Geddes LA, Bourland JD. The strength-duration curve. IEEE Thms Biomed Eng 1985; 32:458-59
CHEST I 95 I 1 I JANUAR'1, 1989
217
~Ili • ...--1_lb_Or_I_IO_rV_I_Dd_I_DI_m_II_SI_Ud_18_S The safety Factor for Electroventilation Measured by Production of Cardiac Ectopy in the Anesthetized Dog* Christine E. Riseili, M.S.;t Marvin Hinds, Ph.D.;:f: William D. Voorhees Ill, Ph.D.;§ Joe D. Bourland, M.S.E.E., Ph.D.;1I and Leslie A. Geddes, M. E., Ph. D. ~
The safety factor of electroventilation (ie, the ratio of the current required to produce an ectopic beat to the current required to produce an inspired volume of !25 ml, which is approximately twice tidal volume) was determined in 12 pentobarbital-anesthetized dogs using transthoracic electrodes positioned at the optimal electroventilation site. The optimal stimulation site for electroventilation was first determined using hand-held, stimulating electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the optimal stimulation site. The relationship between
The possibility of creating a simple method of electrically mediated artificial respiration dates from the mid-19th century when inspiration was induced using skin-surface electrodes. The method was used in treating respiratory arrest due to chloroform anesthesia l and coal-gas fumes. 2 Geddes et al3 reported successful ventilation in anesthetized dogs by applying bursts of short-duration stimuli to transthoracic electrodes. The name given to this procedure is electroventilation. Because current is passed through the thorax during electroventilation, it is possible to produce cardiac arrhythmias. In the present stud~ with transchest electroventilation electrodes, the current required to produce 225 ml of inspired volume and the threshold current required to produce an ectopic beat were determined over a pulse-duration range of 0.1 to 10 ms. From these data the safety factor for producing cardiac arrhythmias during electroventilation was determined. ·From the Hillenbrand Biomedical Engineering Center, Purdue University, West Lafayette, IN. t Doctoral candidate, graduate student in Veterinary Physiology. *Professor of Biology, Biology Department Coordinator, Marion College, Marion, IN. §Senior Scientist, Associate Research Scholar. II Coordinator for Bioengineering Research. 'Showalter Distinguished Professor, and Director, Hillenbrand Center. Biomedical E~gineering Dr. Riscili, Hillenbrand Biomedical Engineering Center, Purdue University, West Lafayette, IN 47907
214
inspired volume and stimulus intensity was determined using a 0.8-s burst of stimuli (60/s) with a pulse duration of 0.1 ms. Using the same electrodes, the threshold current for producing ectopic beats was determined for single pulses ranging from 0.1 to 10 ms duration. In all dogs, the current required to produce an ectopic beat increased greatly as the pulse duration decreased. At 0.1 ms, the safety factor for electroventilation was calculated to be 25.8. (Chest 1989; 95:214-17)
MATERIAL AND METHODS
Twelve mongrel dogs weighing 16 to 27 kg were anesthetized with 30 mWkg of pentobarbital sodium and placed in dorsal recumbency on a V-shaped board. The forelimbs of each animal were restrained beside the head, and a lead 2 ECG was monitored. Blood pressure was recorded using a 8uid-611ed catheter placed in a femoral artery and connected to a Cobe pressure transducer (Cobe Laboratories). An oxygen-filled recording spirometer with a carbon dioxide absorber was attached to the endotracheal tube to monitor the electrically induced inspired volume. An electronic signal corresponding to the volume of air in the spirometer was recorded on a Physiograph (Narco Bio-Systems). The upper thorax of each animal was shaved and the optimal location for electrode placement was determined using 2.54-cm diameter, gauze-covered, saline-soaked, hand-held stimulating electrodes placed bilaterally on the chest. The optimal location is defined as the site at which the largest volume of inspired air per rnA of electroventilation current is obtained. After locating the optimal site, which was in the anterior axillary region, 4.1-cm diameter stainless steel stimulating electrodes were sutured bilaterally to the skin over the site. Using a prototype electroventilator built at the Hillenbrand Biomedical Engineering Center, inspiration was produced by applying 0.8-s bursts of short-duration (0.1 ms) pulses (6OIs) to the electrodes at a rate of 24 bursts/min. The amplitude of the pulses in each burst was increased linearly to provide a smooth inspiration and reached the maximum amplitude in 0.5 s. With the dogs' forelimbs restrained beside the head and the electrodes at the optimal stimulation site on the upper chest, the volume of air inspired was recorded for bursts of stimuli delivered at different current intensities. To measure the volume inspired due to the electroventilation current only, respiratory arrest was produced during each trial by stimulating the afferent right vagus nerve Safety Factor for Electroventilation (Riseili at al)
_
FIGURE 1. Optimal electroventilation site (inset) for electrode placement in anterior axillary region (A) of dog, and inspired volume vs peak current (I) for a typical animal with electrodes at the optimal stimulation site.
in the neck. Ligation of the vagus and stimulation cranial to the ligature produced respiratory arrest without cardiac effects. After determining the relationship between inspired volume and electroventilation current intensity in each animal, the threshold current required to produce ectopic beats was determined by delivering single pulses (0.1 to 10.0 ms) from a special, high-current generator to the electroventilation electrodes. The current delivered by the current generator was monitored on an oscilloscope. To determine the threshold current necessary for ectopic beats, transient cardiac arrest was produced by efferent vagal stimulation, accomplished by stimulating the nerve caudal to the already present ligature. This maneuver ensured that stimuli were applied during the diastolic interval, when threshold for ectopy is lovv.· When the current pulse was delivered to the transchest electrodes, the presence or absence of an ectopic beat was noted on the Physiograph record. If no ectopic beat was observed, the intensity of the current pulse was increased until an ectopic beat was obtained. Threshold was defined as that current that produced an ectopic beat and at which a 10 percent decrease in current did not produce an ectopic beat. This procedure was repeated for pulse durations ranging from 0.1 to 10 ms, enabling construction of a strength-duration curve. RESULTS
Figure 1 (inset) identifies the optimal electroventilation site for electrode placement on the thorax which is located near the level of the fourth rib and slightly anterior to a midaxillary line. This site was essentially the same among the 12 dogs. Figure 1 also illustrates an inspired volume vs electroventilation current relationship in a typical animal with electrodes at the optimal stimulation site and with the forelimbs restrained beside the head. In all cases an increase in current resulted in an increased inspired volume until a maximum value was reached, typically two to three times tidal volume. The spontaneous tidal volume of this animal was 167 ml. Ectopic beats were produced in the arrested hearts of all 12 dogs over pulse durations ranging from 0.1 to 10 ms. A plot ofthe average threshold current required to produce ectopic beats vs pulse duration is shown in Figure 2. In all dogs, as the pulse duration is shortened, the current required to produce an ectopic beat
increases greatly. The duration of the individual pulses of the electroventilation current is 0.1 ms. Shown also on Figure 2, at 0.1 ms, is the mean current required to produce an inspired volume of 225 ml (approximately twice tidal volume); therefore, the average safety factor (current ratio at 0.1 ms) was calculated to be 25.8. DISCUSSION
The use ofstimuli applied to skin-surface electrodes to provide artificial respiration dates from the latter half of the 19th century, when there were no mechanical ventilators. At this time, sudden respiratory arrest resulting from the use of chloroform as an anesthetic and asphyxiation from coal-gas fumes was common. The appearance of mechanical ventilators, and the discontinuance of chloroform as an anesthetic, probably contributed to the abandonment ofthis technique. The interest in skin-surface electrodes to electrically mediate artificial respiration in humans was revived in the 1950s, when Knodts described use ofthe electric
•o.s DlNTIC* c.sec)
FIGURE 2. Solid line represents average current (n = 12) to produce ectopic beats (± SE) vs pulse duration;· represents average current required to produce an inspired volume of 225 ml in 12 dogs using stimulus pulse duration of 0.1 ms. Average safety factor at 0.1 ms was 25.8.
CHEST I 95 I 1 I JANUAR~
1989
215
lung stimulator built by Hofmann in German}'. The electric lung was a two-channel stimulator that first excited the inspiratory, then the expiratory muscles, using chest-band electrodes and a train of shortduration pulses (at 5O/s). The successful use of chestband electrodes in this case required that the operator have knowledge of the correct electrode placement. Sarnoff et al6 demonstrated that stimulation of one phrenic nerve with an external electrode is capable of producing effective artificial respiration in humans. A thimble- or pen-type electrode was applied to the motor point of the phrenic nerve in the neck by the operator. Training was necessary for the successful use of the electrophrenic respirator. Holmes et al7 continued to investigate artificial respiration using the electric lung to improve lung function in patients with pulmonary disease. They concluded that there was a decrease in the amount of exudate, a return of diaphragmatic function, and decreased morbidity in patients with unilateral medical and surgical pleural disease. Although the tidal volume could be increased by 2¥2 times using the electric lung, no dramatic long-term effect on lung function was observed, and interest was lost in use of the device. In 1959 Gray and Field8 evaluated a two-channel electronic stimulator built by Batrow Laboratories. With this stimulator two sets of electrodes were used: a xiphoid-back electrode current pathway stimulated the diaphragm, and stimulation of the abdominal muscles produced active expiration. Applying the Batrow unit to normal subjects, they concluded that there was an increased tidal volume when the optimal stimulation rate was applied. The Batrow unit provided adequate ventilation in patients with emphysema and showed potential in initiating diaphragmatic breathing exercises in patients with impaired diaphragmatic motion. Because of the two sets of electrodes, careful attention to electrode location was necessary Goldenthal9 investigated use of the Ventilaide stimulator, also manufactured by Batrow Laboratories. This single-channel unit was designed to produce inspiration using an active, argon-filled electrode placed over the xiphoid and referenced to a large metal plate under the feet or buttocks. This stimulator delivered 7-f.Ls pulses at 60/s. Cine£luorography showed that contraction of the diaphragm caused inspiration when the active electrode was placed over the xiphoid. Although the Batrow unit was successful in ventilating human subjects and no accidents occurred with it, the unit was withdrawn from the marketplace. The probable reason was that some who used it were not familiar with the need for careful electrode placement and were unable to obtain adequate ventilation. It was not until 1985 that Geddes et al3 renewed interest in electrically induced artificial respiration, 218
and discovered that there were bilateral transthoracic sites for electrodes to produce inspiration. Later, Riscili et al lO successfully electroventilated six baboons using transthoracic electrodes. Current applied to axillary electrodes stimulates the phrenic nerves (unpublished data). It must be recognized that stimulation of other inspirato~ and perhaps some expirato~ nerves and muscles also occurs. For this reason the optimal stimulation site must be located. The potential hazard with electrodes in the axillary region is the possibility ofproducing a cardiac arrhythmia. As shown in the present stud~ the key to safety with electroventilation is the use of a short-duration stimulus. At the time of this stud~ the shortest pulse duration available on the electroventilator was 0.1 ms. Geddes et alB presented strength-duration curves for cardiac pacing using external electrodes in humans that showed that as the pulse duration was shortened beyond 0.1 ms, the current required for cardiac pacing continued to increase rapidl~ Recent modification of our electroventilator provides a pulse duration of 10 f.Ls. The electroventilator for use in humans will use this pulse duration, which will result in an even higher safety factor. It should be noted that altered Po2 , Pco2 , pH, and electrolyte levels affect the threshold for cardiac arrhythmias. The results of the present study therefore may not be generalized to situations in animals or humans when gas exchange impairment exists. The use of a short-duration electroventilation pulse also minimizes skin sensation. Hon and Hulme, 12 Gray and Field, 8 and Goldenthal, 9 evaluating the Batrow unit, reported that in all cases stimulation produced painless diaphragmatic contraction. Geddes et alII presented strength-duration curves for pain in human subjects and reported that the current intensity for pain increased dramatically as the pulse duration was shortened. The results we obtained, showing an inverse relationship between the current required to produce an ectopic beat and the pulse duration (strength-duration curve), are consistent with the relationship exhibited by all irritable tissues. Geddes 13 showed that the experimentally obtained strength-duration curve can be derived from the knowledge of the electrical nature of cell membranes. In 1985 Geddes and Bourland 14 showed how the mathematical constants describing the strength-duration curve can be obtained. CONCLUSION
The application of rhythmic bursts of short-duration pulses to chest-surface electrodes can provide inspired volumes in excess of tidal volume. The optimal electroventilation stimulation site, near the level of the fourth rib and just anterior to a midaxillary line, was identified and found to be relatively constant among Safety Factor for Electroventilation (Riseili at 81)
12 dogs. Using the electroventilation electrodes, ectopic beats were produced over a pulse duration range of 0.1 to 10 ms. In all cases the current intensity necessary to produce an ectopic beat increased as the pulse duration decreased. The safety factor determined for electroventilation (pulse duration of 0.1 ms) was 25.8. ADDENDUM
Since submitting this paper for revie~ we have had the opportunity to conduct the first clinical trial of electroventilation at Methodist Hospital in Indiana at Indianapolis. The primary goal of the initial human trials is to identify the optimum location for the chestsurface electrodes by "mapping" the thorax with handheld electrodes. The first experiment was successful, and during the trial we were able to monitor the ECG and blood pressure continuously. The electroventilator used in the human trials employs a burst of 10-fJ,s duration pulses applied to the chest-surface electrodes. At no time did we observe any cardiac arrhythmias. The patient was a 40-kg male organ donor. A consent form previously approved by the Institutional Review Board of Methodist Hospital was obtained prior to the trial. The maximum volume obtained during this initial trial was 140 mI. Although this volume is small and represents the approximate dead space volume in this patient, it is important that the goal of identifying an optimal electrode location was achieved. During this first clinical trial the current applied to the transchest electrodes was limited to 1200 rnA. An addendum, approved by the Institutional Review Board, to the original proposal increases the maximum current level to 2,400 rnA for future trials. Once the optimal site for
electrode placement is determined, studies to determine the relationship between increasing current and inspired volume will be conducted. REFERENCES 1 Duchenne G. L'electrisation localisee et de son application a la pathologie et a la therapeutique. Paris: Librairie J. B. Bailliere et Fils, 1872 2 Ziemssen H. Die electricitat in der medicin, 1st ed. Berlin: A. Hirschwald, 1857 3 Geddes LA, Voorhees WD, Babbs CF, Deford JA. Electroventilation. Am J Emerg Med 1985; 3:337-39 4 Jones M, Geddes LA. Strength-duration curves for cardiac pacemaking and ventricular fibrillation. Cardiol Res Cen Bull 1977; 15:101-12 5 Knodt H. Kunstliche beatmung mit der elecktro-Iunge. Artzliche Wochenschr 1951; 6:281-83 6 Sarnoff SJ, Sarnoff LC, Whittenberger HL. Electrophrenic respiration: VII. The motor point of the phrenic nerve in relation to external stimulation. Surg Gynecol Obstet 1951; 93:190-96 7 Holmes G~ Buckingham WB, Cugell D~ Kirchner K. Electric stimulation of breathing in chronic lung diseases. JAMA 1958; 166:1546-51 8 Gray FD, Field AS. The use ofmechanicaI assistance in treating cardiopulmonary diseases. Am J Med Sci 1959; 248:146-52 9 Goldenthal S. Bilateral and unilateral activation ofthe diaphragm in the intact human. Conn Med 1961; 25:236-38 10 Riscili CE, Foster KS, Voorhees WD, Bourland JD, Geddes LA. Electroventilation in the baboon. Am J Emerg Med (in press) 11 Geddes LA, Babbs CF, Voorhees WD, Foster KS, Aronson AL. Choice of the optimum pulse duration for precordial cardiac pacing: a theoretical stud~ PACE 1985; 8:862-69 12 Hon EH, Hulme GW An electronic resuscitator for possible use in asphyxia neonatorum. Yale J BioI Med 1958; 32:58-73 13 Geddes LA. Cardiovascular devices and their applications. 1st ed. New York: John Wiley & Sons, 1984:256-57 14 Geddes LA, Bourland JD. The strength-duration curve. IEEE Thms Biomed Eng 1985; 32:458-59
CHEST I 95 I 1 I JANUAR'1, 1989
217