ELECTROPHRENIC RESPIRATION. II. ITS USEIN MAN

James L. Whittenberger, … , Stanley J. Sarnoff, EstherHardenbergh

J Clin Invest. 1949;28(1):124-128. https://doi.org/10.1172/JCI102040.

Research Article

Find the latest version:

http://jci.me/102040-pdf

ELECTROPHRENICRESPIRATION. II. ITS USE IN MAN'

By JAMES L. WHITTENBERGER,STANLEY J. SARNOFF, ANDESTHERHARDENBERGH

(From the Department of Physiology, Harvard School of Public Health, Boston)

(Received for publication August 6, 1948)

In a previous investigation it was shown that ar-tificial respiration could be effectively administeredto the cat, dog, monkey and rabbit in the absenceof spontaneous respiration by electrical stimulationof one or both phrenic nerves (1, 2). During thedevelopment of the applications of the technique,an opportunity occurred for testing the method inman. A patient with severe chronic, diaphrag-matic flutter was operated on for the purpose of1) crushing the left phrenic nerve and 2) tem-porarily blocking the right phrenic with procaine.At the time of operation a single, slender, multiple-strand, plastic-covered wire was spirally woundaround the right phrenic nerve in its exposed por-tion and the other end of the lead wire was broughtout through a simple needle puncture wound about2 cm. lateral to the site of incision. The operationwas performed under local anesthesia. Five hourslater, electrophrenic respiration was begun.

The method is described in detail in a previous com-munication (2). Briefly, it is the following. An ECGplate secured at the wrist functions as an indifferent elec-trode for the single stimulating electrode on the phrenicnerve. The stimulating current is derived from a Grassstimulator set for a frequency of 40/sec. and an impulseduration of 2 milliseconds. The current is run througha rotating potentiometer which rhythmically varies thevoltage in such a way as to cause the diaphragm to per-form a gradual contraction and relaxation similar to thatwhich it performs during spontaneous breathing.

Air flow patterns were obtained with the pneumo-tachograph developed by Silverman (3) and Silvermanand Whittenberger (4). From the pneumotachogram oneis able to derive information related not only to the rateand contour of the respiratory pattern but also precisevalues for the patient's ventilation volume. The level ofarterial oxygen saturation was observed throughout theperiod of phrenic nerve stimulation by means of theMillikan oximeter (5).

The experiments on this patient were designedto achieve five objectives:

1. To ascertain whether electrophrenic respira-tion could maintain minute volumes equal to or

1 Aided by a grant from The National Foundation forInfantile Paralysis.

greater than the spontaneous resting minute vol-ume with submaximal stimulation of one phrenicnerve.

2. To ascertain the ease with which a smoothdiaphragmatic motion can be obtained in man.

3. To find out if the unanesthetized patientwould cease spontaneous respiratory activity whenadequate aeration was supplied by means of phrenicstimulation (as was previously found to be thecase in the experimental animal under anesthesia).

4. To estimate the amount of pain or discomfortproduced by effective electrical stimulation of thephrenic nerve.

5. To ascertain whether adequate arterial oxy-gen saturation could be maintained with the sub-maximal stimulation of one phrenic nerve.

RESULTS

1. Figure 1 shows the pneumotachograms ofA) spontaneous respiration and B) electrophrenicrespiration. Table I compares values obtained

TABLE I

Respiratory measurements during spontaneous breathingand electrophrenic respiration

Spon- Electro-taneous phrenicrespira- respira-

tion tion

Rate per minute 26.6 23.3Minute volume in liters 5.18 7.52Tidal volume in liters 0.195 0.323Average flow rate during inspiration, in 12.0 15.9

liters per minuteRatio of time of inspiration to time of total 43.1 47.3

respiratory cycle, in per cent

during spontaneous respiration and electrophrenicrespiration for respiratory rate, minute and tidalvolumes, average flow rate during inspiration, andthe fraction of the respiratory cycle taken by theinspiratory phase. These results were obtained ata rate of artificial respiration slightly slower thanthe patient's spontaneous rate and with submaxi-mal stimulation of one phrenic nerve. It can be

124

ELECTROPHRENICRESPIRATION. II. ITS USE IN MAN

seen that an exchange of air significantly largerthan the patient's spontaneous exchange is readilyachieved at a slower than the spontaneous rate.A still larger exchange of air resulted from maxi-mal stimulation. It was established in this patient,as in the experimental animal, that the depth ofrespiration is proportional to the peak voltage ap-plied. The regularity of the tracing in Figure IBindicates that the patient was not contributing tothe respiratory effort. This phenomenon will bediscussed later.

2. It is apparent from Figure 1B that the dia-phragmatic contraction produced by electrical stim-ulation of the phrenic nerve in this patient was asmooth motion. (The minor irregularities duringdiaphragmatic relaxation in the record are due tothe diaphragmatic flutter.) A smooth inspiratorycurve was, in fact, predicted from the theoreticalbasis on which electrophrenic respiration is based;namely, that increasingly forceful contraction ofthe diaphragm results from the spread of currentto include more and more fibers of the phrenicnerve as the voltage is increased. Since the phrenicnerve in man is a single trunk and is considerablylarger than that of the experimental animal, agraded voltage spread is more easily and smoothlyobtained. As observed visually, the movement of

the right diaphragm resulting from phrenic nervestimulation closely resembled that seen duringspontaneous respiration.

3. It was apparent from simple observation ofthe patient that during artificial respiration therewas no respiratory effort other than that of theright diaphragm, .which resulted from electricalstimulation. In order to obtain graphic evidenceof this fact, two additional maneuvers were carriedout. Figure 2 is a pneumotachogram of spontane-ous respiration interrupted by the onset of elec-trical artificial respiration. There is no evidencethat spontaneous respiratory activity occurred afterphrenic nerve stimulation had been started. Spon-taneous activity would be evident as irregularitiesin the pattern. The reverse sequence was em-ployed to find out whether, upon abruptly termi-nating artificial respiration, the lack of spontane-ous respiratory activity would be apparent fromthe lack of air flow as registered on the pneumo-tachogram. Figure 3 is the result. Artificialrespiration was stopped at the signal and it can beseen that no respiratory activity was present untilthe apnea had persisted for over 16 seconds.Breathing then returned with a gradual increase inamplitude until it regained its pre-stimulus con-tours. This interesting observation, namely, that

FIG. 1. A, PNEUMOTACHOGRAMOF SPONTANEOUSRESPIRATION; B, PNEUMOTACHOGRAMDURING ELECTRO-PHRENIC RESPIRATION

Area under the base line represents volume of air flow during inspiration; that above the base line rep-resents expiration. The size of the area is directly proportional to the volume of air exchanged.

125

JAMES L. WHITTENBERGER,STANLEY J. SARNOFF, AND ESTHER HARDENBERGH

FIG. 2. PNEUMOTACHOGRAMOF SPONTANEOUSRESPIRATION INTERRUPTED BY THE ONSETOF ELECTRO-

PHRENIC RESPIRATION

Phrenic nerve stimulation was started at the signal. The two strips are continuous.

J

I

.ntttt +.tn Mr~~~~~~~~~~~~~~~~~~~~~....r...

*., . . n . ;. , , . i s. .. . -

; ft

Z~~~~ ~ ~ ~ ~ ~ ~ ~ ~ 4M~~~~~~M

., .. .... .. .......... ... ,.......... i. lR''.......... .....

The patient was on artificial respiration at the start of this pneumotachogram. At the signal, phrenic

stimulation was discontinued and the tracing shows the absence of spontaneous respiratory effort during

the period immediately following cessation of artificial respiration. The minor irregularities are due to

the diaphragmatic flutter. The three strips are continuous.

126

. ...L.

k.

at: :~,Q

....

.... .......

ELECTROPHRENICRESPIRATION. II. ITS USE IN MAN

the individual completely relinquishes spontane-ous control of respiration while on electrophrenicrespiration, is not yet fully explained. Animal ex-periments in which blood gas tensions were ob-served indicate that the prompt cessation of spon-taneous respiration is not due to a fall in carbondioxide brought about by overventilation. Theneural pathways involved in this phenomenon arebeing investigated.

4. The evaluation of pain in this patient was noteasy. During phrenic nerve stimulation the pa-tient experienced discomfort referred to the rightshoulder along the ridge of the trapezius muscle.This information was obtained only on direct ques-tioning, was never volunteered. The patient didnot appear to be in pain and fell asleep severaltimes during the longer periods of artificial respira-tion. Conclusions as to the degree and importanceof the intensity of the discomfort produced willhave to be deferred until a variety of patients havebeen studied.

5. It was thought, prior to our experience withthis patient, that the relatively stable mediastinumof the human subject might prevent the adequateaeration of the contralateral lung when only onephrenic nerve was stimulated, even though reason-able respiratory minute volumes were achieved.In order to obtain evidence in this matter, arterialoxygen saturation (by the oximeter method) wasobserved during spontaneous respiration and dur-ing artificial respiration in the absence of spon-

a 9g

391

0 30 60 90TIME - SECONDS

FIG. 4. EFFECT OF ELECTROPHRENICRESPIRATION ON

ARTERIAL OXYGEN SATURATION IN THE ABSENCE OF

SPONTANEOUSRESPIRATORY ACTIVITYThe patient breathed room air throughout.

taneous respiratory activity. Figure 4 shows theresults. It is clear that a small but definite risein arterial saturation occurred within 60 seconds ofthe onset of electrophrenic respiration. A rise of 1per cent in saturation at the upper range of theoxyhemoglobin dissociation curve indicates a riseof 10 mm. Hg or more in the mean effective al-veolar partial pressure of oxygen. This signifiesan improvement in lung ventilation out of propor-tion to a 1 per cent rise in oxygen saturation.The oximeter was calibrated by having the pa-tient inhale 99.6 per cent oxygen.

Artificial respiration by phrenic nerve stimula-tion was induced in this patient for several periodsvarying in length from five to 76 minutes on twooccasions during the five days following electrodeapplication. The procedure apparently resultedin no functional damage to the nerve, since fluoro-scopic examination of spontaneous diaphragmaticactivity on the day of electrode removal revealedexcursions equal in amplitude to those observedbefore the experiment.

CONCLUSIONS

1. Artificial respiration by phrenic nerve stimu-lation can be performed in man.

2. A smooth, gradual, diaphragmatic contrac-tion occurs when an increasing voltage is appliedto the phrenic nerve. The diaphragm thus per-forms a motion closely resembling that which itperforms during natural inspiration.

3. Respiratory minute volumes in excess of thepatient's spontaneous minute volumes can readilybe obtained with the submaximal stimulation ofone phrenic nerve.

4. The depth of respiration is proportional tothe peak voltage applied to the phrenic nerve inman as in the experimental animal.

5. Adequate oxygenation of the blood can bemaintained by electrophrenic respiration in theabsence of spontaneous respiration.

6. The human subject, like the experimentalanimal, completely relinquishes spontaneous con-trol of respiration when electrophrenic respirationis induced.

ACKNOWLEDGMENTS

The authors wish to express their thanks to DoctorsK. Emerson, J. L. Blodgett, and Lewis Dexter for theopportunity of studying this patient.

I I I I I I I I I I I I

I I I I I I I

127

128 JAMES L. WHITTENBERGER,STANLEY

BIBLIOGRAPHY

1. Sarnoff, S. J., Hardenbergh, E., and Whittenberger,J. L., Electrophrenic respiration. Science, 1948,108, 482.

2. Sarnoff, S. J., Hardenbergh, E., and Whittenberger,J. L., Electrophrenic respiration. Am. J. Physiol.,in press.

3. Silverman, L., Respiratory air flow characteristics and

J. SARNOFF, AND ESTHER HARDENBERGH

their relation to certain lung conditions occurringin industry. J. Indust. Hyg. & Toxicol., 1946, 28,183.

4. Silverman, L., and Whittenberger, J. L. In prepara-tion.

5. Millikan, G. A., The oximeter, an instrument formeasuring continuously the oxygen saturation ofarterial blood in man. Rev. Scient. Instruments,1942, 13, 434.