Continuous pO, monitoring in the neonate by skin electrodes* P. Eberhard
W. Mindt
Bioelectronics Department, F. Hoffmann-La Roche & Co., AG, Basel, Switzerland
F. Jann
K. H a m m a c h e r
Universit~its-Frauenklinik, Basel, Switzerland
A b s t r a c t - - A noninvasive method for the continuous monitoring of the oxygenation of neonates is described. The oxygen partial pressure is measured cutaneously by a specially developed Clark- type oxygen sensor attached to the surface of the skin. By directly heating the sensor to 42~ hyperemisation of the tissue underneath the sensor is achieved. The method allows an approximate determination of arterial p02, the accuracy being sufficient for controlling the oxygen therapy of neonates.
Keywo rds-- Oxygen sensor, Neonatal p Ox monitoring Introduction MONITORING of the arterial pO2 during oxygen therapy in neonates is of considerable importance in. preventing the deleterious effects of both hypo- and hyperoxygenation, such as damages to brain, eyes and lungs. At present, the only reliable method for controlling the oxygenation of the neonate is to periodically withdraw arterial blood, either from an umbilical artery catheter or by puncturing the radial, temporal or brachial arteries. Analysing arterialised capillary blood from the heel is not unanimously considered to be conclusive for the estimation of arterial pO2 (Koch and WENDE, 1967). Besides the fact that blood sampling from arteries in neonates is cumbersome, often subject to errors and not without hazard, it g~ves information that is relevant only to the time of sampling. A continuous measurement would be preferable since pathological changes and toxic levels of pO2 can be recognised immediately. Furthermore, information of prognostic value may be obtained from observing the trend of the neeHate's state of oxygenation. Several recent studies have been devoted to this problem, Although oxymetric methods would have the advantages of being noninvasive and of requiring a relatively simple procedure, they are not suitable here because the fiat slope of the oxygen dissociation curve at an elevatedpO2 makes oxygen saturation an unreliable parameter to monitor hyperoxia (KRAMER, 1960). Thus, most work has been concerned with the determination of oxygen partial pressure. In particular, the measurement of pO2 in tissues has been evaluated by several authors as a means of estimating pa02, or of qualitatively determining the state of oxygenation of the neonate (RODGER et al., 1968; WALKER et al., 1968; HuCH et aL, 1969; NEUMAN et al., 1971; SCH()NJAHNet aL, 1972; STRAUSSet al., 1972). "First received 12 March and in final form 30th June 1973
436
The present paper describes a noninvasive method for the measurement ofpO2 by electrodes attached at the surface of the skin, which allows a continuous determination of the oxygenation of the tissue adjacent to the electrode and, under certain conditions, an estimation of the arterial pO2. The phenomenon that oxygen diffuses readily through body tissues and skin has been utilised already by BAUMBERGERand GOODFRIEND(1951) to determine arterial /702. They immersed a finger into an electrolyte solution heated to 45~ and demonstrated that, within 15-60 min, the pO2 of the solution was equilibrated with that of arterial blood. Oxygen skin electrodes that are in direct contact with the skin surface were first described by EVANSand NAYLOR(1967). HucrI and Li:raBERS(1969) reported pO2 measurements by surface electrodes on the scalp of neonates. Their experiments showed that pO2 values close to the arterial level may be obtained if hyperemisation of the tissue adjacent to the electrode is induced by vasodilating agents. As an improvement of this method, we report here the application of heat stimulation by directly heating the electrodes to 42~ to achieve a constant hyperemisation over longer time periods. Method (a) Sensor and instrumentation The principle of the p O 2 measurement due to CLARK (1956), utilised here, is based on,the electrochemical reduction of oxygen at a noble metal cathode that is coated with an oxygen-permeable, hydrophobic membrane. The noble-metal cathode, in our case gold, is polarised with - 9 0 0 mV to an Ag/AgCI anode. The current measured between both electrodes is proportional to the pO2 in the adjacent medium, provided that diffusion of oxygen through the membrane limits the rate of oxygen transport to the cathode. Medical and Biological Engineering
May 1975
Contrary to conventional Clark-type electrodes, in which the cathode diameter is kept small, we use a large-size cathode (diameter 4 mm) to obtain an average pO2 value over a sufficiently large skin area. The permeability of the membrane for oxygen has to be kept low to avoid disturbance of the oxygen profile in the tissue as a result of the consumption of the sensor. In the ideal case (Fig. la), with a membrane of sufficiently low permeability, the current is
(a ~ d+5) considered here. According to eqn. 1, the current becomes independent of the oxygen transport parameters in the tissue, when diP, >>&/Pt. In our case, Mylar membranes (polyterephthalate) 6 pm thick were used. The permeability coefficient of this material for 02 at 42~ has been determined by us as Pm = 3'2 X 10 -1~ ml O2/cm s atm. It follows that d/P== 18.6 x 105 cm 2 s atm/ml 02. To calculate ~/P,, the following approximations are made: = l m m (estimated as an upper limit) and Pt~_Pn2o=7.9xlO-TmlO2/cmsatm (at 42~ (Handbook, Respiration, 1958). Thus, with ~/P, = 1.3 x 105 cm 2 s atm/ml 02, the requirement of d/Pm >~t~/P, is fulfilled sufficiently. It is, of course, a rough approximation to assume that the oxygen permeability in tissues is equal to that in water. However, since almost all experimental values of P, are higher than Pn2o (TREGAR,1966; SCHEUPLEIN and BLANK, 1971), the result of this estimation remains valid.
Fig. 1 Oxygen profile in membrane and in tissue adjacent to sensor (a) Ideal case with membrane of low permeability: p 02 gradient is limited to membrane (b) Membrane of high permeability: p02 profile in the tissue is disturbed by oxygen consumption of the sensor limited by diffusion of oxygen through the membrane and is a measure of thepO2 at the surface of the skin. On the other hand, if a more permeable membrane is used (Fig. 1b), a pO2 gradient does not only exist in the membrane, but also within the tissue. Thus the current measured at the cathode is an additional function of diffusion and convection processes within the tissue. With the approximation that a linear pO2 profile exists in the tissue as well as in the membrane, the solution of the diffusion equation for the onedimensional case gives the following relation (SCHULER and KREUZER, 1967): i = 41ra2 F
pO2
d/Pm+&/Pt
.
.
.
.
.
(1)
With i = current, A a = electrode radius, cm F = Faraday constant, A s d = thickness of the membrane, cm P,, = permeability coefficient of the membrane for 02, ml O2/crn s atm & = thickness of the oxygen depletion layer in the tissue in cm (see Fig. 1) Pt = permeability coefficient of the tissue for 02, ml O2/cm s atm In the derivation of eqn. 1, diffusion in a radial direction at the edges of the electrode was neglected; this is allowed in the case of the large electrodes Medical and Biological Engineering
May 1975
Fig. 2 Sensor ( I ) Skin; (2) Membrane; (3) Cathode; (4) Anode; (5) Heating element; (6) Thermistor; (7) Cap for holding the membrane To verify experimentally that the current is independent of diffusion and convection processes in the test medium, the calibration curves of the sensor were determined in water and in the gas phase. It was found that both calibration curves are congruent. The influence of convection on the electrode current in water is negligible (2Yo increase during heavy stirring). It can be concluded therefore that the oxygen consumption of the electrode is sufficiently small to not affect the oxygen profile in the test medium (water as well as tissue) and that the electrode current is a measure of the oxygen partial pressure at the skin surface. One disadvantage of using a membrane of low permeability is that the response time of the sensor is long. In our case, 795~ (i.e. the time in which 95% of the steady-state value is reached after application of a step change of pO2) is 60 s. For monitoring slow changes ofpO2, this response time is sufficient. Also, rapid pO2 changes may still be detected since Tsovo is 10 s only. A schematic diagram of the oxygen sensor is shown in Fig. 2. The gold cathode (3) is surrounded by a Ag/AgCI counter electrode (4). A buffered hygroscopic solution is used as the electrolyte which 437
guarantees the stability of the electrode at 42~ for several days. The membrane (2) is held by a cap (7), the shape of which was chosen so that diffusion of oxygen from the surrounding air to the cathode is prevented. The tightness of the seal on hairless skin was tested by blowing pure oxygen against the sensor. This did not cause any alteration of the measured signal. A heating element (5) consisting of a coil of resistance wire and a thermistor (6) for the control of the heating temperature are located inside the sensor. The total diameter of the sensor, including the cap, is 14 mm and its thickness 3 ram.
small and it does not cause compression of blood vessels underneath the electrode. In general, movements of the infant do not disturb the measurement. Only extremely strong movements may cause artefacts, particularly if the sensor is attached to one of the extremities. Such artefacts, however, can be identified immediately in the recording. The following measuring positions were investigated: subclavicular part on both sides of the thorax, temporal part of the forehead and both thighs and upper arms. Most measurements were performed
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Fig. 3 Block diagram of electronic circuit
ELECTRODE "~-/ The electronic circuit consists essentially of three parts (Fig. 3 a, b and c): (a) electrode bias and current amplifier with variable gain and zero compensation. Analogue output for a recorder (b) circuit for heating the electrode and temperature control (c) safety circuit to prevent the electrode temperature from exceeding the permitted value. In Fig. 4, a laboratory prototype of the device is shown which consists of two channels for simultaneous measurement with two sensors. A built-in recorder allows the direct recording of both signals. (b) Procedure The sensor is attached to the skin of the neonate by a double adhesive tape ring, as is commonly used for e.c.g, electrodes (Fig. 5). With this method, the pressure of the sensor against the skin is extremely
438
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H
AUDO I -
with two sensors, one of them being placed on the thorax. Before each measurement, the electrolyte and the membrane of the sensor were renewed. The sensor was then calibrated in nitrogen and in air, and corrections for barometric pressure and humidity were made. The value of the current in nitrogen is needed only if a high precision of calibration is required, since the zero current of the sensor is small compared with the current at normal pO2 values
(< 4%). After application of the sensor to the skin, the current reaches a steady-state value within 5-7 min. This time is needed for the induction of hyperemisation by heat stimulation. By treating the skin with vasodilating agents (e.g. histamine) prior to the attachment of the sensor, this time may be shortened. The stability of the oxygen sensor in situ was tested after each measurement by repeating the calibration Medical and Biological Engineering
May 1975
performed immediately after taking the blood sample. The cutaneously measured pO2 was read at the time of sampling. Results
Fig. 4 Laboratory prototype of 2-channel device for simultaneous measurement with two sensors
(a) Correlation between arterial and skin p 02 Comparative measurements between the umbilical artery pO2 and cutaneously determined pO2 were performed in 15 neonates. The results of 51 measurements are compiled in Fig. 6, whereby all cutaneous values were determined on the subclavicular part of the thorax. For the statistical analysis of the data, the skin pOz has been chosen as the independent variable. Actually, the clinical application of the method is, in general, the estimation of the arterial pO2 from the cutaneous measurement. It has been assumed that, within the population of the data, a linear relation exists between the two variables (linear regression). The correlation coefficient is 0.93 with a confidence interval of 0.87 to 0.96. The regression coefficients of the r e l a t i o n (PO2)ar,. = A (pO2)cut. -[- B are A = 1' 30, with a standard error of 0.08, and B = - 14 mm Hg with a standard error of 6 mm Hg. The standard error of the estimate is 9 mm Hg. Fig. 6 shows the 95% confidence interval limits for the ordinate to the true regression line and the 95% prediction interval limits for individual values of (pO2)art. For these investigations, thorax values have been evaluated as, for long-term studies, the thorax was found to be the best measuring position. The fiat region is well suited for the fixation of the electrode, movement artefacts occur very rarely and the site is the most practical one for the care of the child. In addition, the skin of the thorax of neonates is relatively thin and well perfused.
Fig. 5 Two oxygen sensors attached to the thorax (lower left," e.c,g, electrode)
in air. In most cases, the calibration value after eight hours of operation agreed within 5% with the initial value. The temperature of the electrode was kept at 42~ in all measurements. This temperature was found to be tolerated well by the skin over longer periods of time. Oversensitivity or burns have never been observed. The longest continuous measurement lasted for 84 h; after this time, there remained only a red spot on the skin, which disappeared after 8 h. Comparative measurements with the arterial pO2 were performed by sampling blood from a centrally located catheter introduced through the umbilical artery. The blood was withdrawn into a heparinised glass syringe and analysed with an AVL or an IL 213 blood gas analyser. Sampling was done very carefully (avoiding air bubbles and mixing the blood with infusion solution), and the analysis was Medical and Biological Engineering
M a y 1975
/ /
150
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100
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cuteneoustymeasured pl~(mm Hg} electrode position:chest Fig. 6 Relationship between umbilical artery P 0 2 and cutaneously measured p O~ ~true regression line . . . . 95% confidence interval limits for the ordinate to the true regression line - - 9 - - 9 5 % predition interval limits for individual values of arterial/302
439
Fig. 7 Response of cutaneous p 0 2 to change of oxygen concentration in inspired air. During breathing of room air, the cutaneous p 0 2 varies between 54 and 60ram Fig. A t the time A, the neonate receives air enriched with oxygen by means of a mask (3 litres/min). After an induction time of 20 s, the cutaneous p O 2 increases, and within 6min reaches a new "steady stare'with fluctuations between 106 and 128 mm Fig. The indices I and 2 refer to sensor positions on the right thigh and on the right temple, respectively. The shift of the time axis of the two channels is one-fifth of one scale unit (corresponding to 12s)
(b) Applications to monitoring To illustrate the performance and applicability of the method, a few typical curves are shown below (Figs. 7-12).
Discussion and conclusion The results of the comparative measurements compiled in Fig. 6 show that the correlation between arterial pO2 and skin pO2 allows a fairly good estimation of the arterial-oxygen partial pressure from the cutaneous measurement. Of course, the method cannot be as accurate as a direct p02 determination in arterial blood. However, its value
Fig. 8 Blood pressure, heart rate and cutaneous p 0 2 are recorded simultaneously. The p 02 scale has been expanded to obtain a better resolution of the fluctuations of the signal. One recognises two spontaneous drops of heart rate and increases of blood pressure (caused by brief apnoea), each folio wed by a significant decrease of p02. The time delay between the fall in heart rate and the decrease of p02 is approximately 20 s. The position of the oxygen sensor is the thorax
lies in the continuity of the measurement, which allows the immediate detection of changes of the noonato's state of oxygenation and facilitates the control of oxygen therapy. It must be considered in this context that high accuracy in the determination of arterial p02 is not really needed. It is generally agreed that the aim of oxygen therapy in high-risk neonates is to adjust the inspired oxygen level, so
Fig. 9 Apnoea : After spontaneous inhalation of 26% oxygen, transient cessation of breathing occurred, and was not immediately noticed by the nurse. The cutaneous p02 decreases from 60 mm I-/g to about 20 mm Hg within 3 rain. After the resumption of breathing, the p02 slowly returns to normal values. Positions of the sensors: Thorax, subclavicular, left ( I ) and right (2) side
440
Medical and Biological Engineering
May 1975
Fig. 10 Interruption of artificial respiration during intratracheal drainage (neonate with respiratory distress syndrome). A t time A, the Bird respirator is disconnected. The cutaneous p 0 2 decreases from 75/80 mm Hg to values below 30 mm Hg within 2"S min. After resumption of artificial respiration (time B), the p 02 returns to normal levels. Sensor positions are as in Fig. 9
that the arterial pO2 values lie between 60 and 90 mm Hg (RoBERTONet al., 1968). The accuracy of the estimation of arterial pO2 by the method reported here is sufficient to meet this demand. The correlation established in Fig. 6 is no longer valid in certain pathological conditions, especially in the case of centralisation of the blood circulation, since the skin of the thorax is scarcely perfused by arterial blood during shock. There exists, however, the possibility of recognising at an early stage the beginning of centralisation or of other complications, as has been shown in one case reported above (Fig. 12). In conclusion, the cutaneous measurement ofpO2 by heated skin electrodes represents a simple method
Fig. 11 Cardiac arrest: 19 h after defivery cardiac arrest occurred during spontaneous respiration; it was folio wed by a rapid drop of cutaneous p 02. The disturbances at the end of the curve are movement artefacts due to heart massage. The child was reanimated. In this case, the cardiac arrest was detected first by the decline of p 0 2 . The e.c.g, was not monitored because of the absence of pathology. Sensor 1 : Inner side of left thigh. Sensor 2 : Subclavicular part of thorax
Medical and Biological Engineering
May 1975
Fig. 12 Prelethal decline of cutaneous p 0 2 (male neonate, 28th week, spontaneous birth, 650 g). Sensor positions: outer side of right thigh (1) and right thorax (2). About two hours before death, the cutaneous p 0 2 declined at both measuring sites (part a). Because of centralisation of the circulation, the decrease of cutaneous pO 2 occurs much earlier than that of central arterial blood. One recognises, in parts b and c, the wave-shaped fluctuations of the p 0 2 measured on the thorax. They correspond almost symmetrically to fluctuations of the heart rate, which were recorded simultaneously. As is expected, the p O 2 waves are less pronounced at the peripheral measuring site (curve I )
for continuous monitoring and control of the oxygenation of neonates. Furthermore, information of prognostic value may be obtained from observing the trend of the cutaneously determined pO2. 441
References BAUMBERGER, J. P. and GOODFR1END, R. B. (1951) Determination of arterial oxygen tension in man by equilibration through intact skin. Federation Proc., 10, I0-11. CLA~:, L. C., jun. (1956) Monitor and control of blood and tissue oxygen tensions, Trans. Am. Soc. Artif Intcrn. Organs 2, 4148. EVANS, N. T. S. and NAYLOR, P. F. D. (1967). The systemic oxygen supply to the surface of human skin. Resp. Phys. 3, 21-37. Handbook of re.~piration (1958) DITTMER, D. S. and GREBE, R. M. (eds.) HccI-I, A., HUCH, R. and LUBBERS, D. W. (1969) Quantitative polarographische Sauerstoffdruckmessung auf der Kopfhaut des Neugeborenen, Arch. GyniT"k, 207, 443-451. KocH, G. and WENDEL, H. (1967) Comparison of pH, carbon dioxide tension, standard bicarbonate and oxygen tension in capillary blood and in arterial blood during the neonatal period, Acta Paediatrica Scandinavia, 56, 10-16. KRAMER, K. (1960) Oxymetrie, Theorie und klinische Anwendung. Georg Thieme Verlag, Stuttgart. NEUMANN, M. R., BROWN, E. G., McDONNEL, F. E. and LIv, C. C. (1971) Application of oxygen cathodes in perinatology, Proc. 24th ACEMB. Las Vegas, Nevada, 1971.
PIEROG, S. H. and FERRARA, A. (1971) Approach to the medical care of the sick newborn. C. V. Mosby Co., Saint Louis. ROBERTON, N. R. C., GUPTA, J. M., DAHLMBURG,G. W. and T1ZARD, J. P. M. (1968) Oxygen therapy in the newborn, Lancet, 1968, 1, 1323-29,13. RODGER, J. C., KERR, M. M., RICHAROS, I. D. G. and HUTCmNSON, J. H. (1968) Measurements of oxygen tension in subcutaneous tissues of newborn infants under normobaric and hyperbaric conditions, Lancet, 1968, 2, 232-236. SCHEUPLEIN, R. J. and BLANK, I. H. (1971) Permeability of the skin, Physiol. Rev., 51,702-747. SCHt3NJAIIN, V., BELLE, H., B/3CHNER, M., FRANKE, R. (1972) Einstichelektrode zur kontinuierlichen pO2 Messung im lebenden Hautgewebe, Patentschrift 88 835, GDR. SCHULER, R. and KREUZER, F. (1967) Rapid polarographic in vivo oxygen catheter electrodes, Reap. Physiol., 3, 90-110. STRAUSS,J., BERAN, A. V., BAKER, R. (1972) Continuous 02 monitoring of newborn and older infants and of children. J. Appl. Physiol., 33, 238-243. TREGAR, R. T. (1966) Physicalfunctions of skin. Academic Press. WALKER, A., PmLL1FS, L., POWE, L., WOOD, C. (1968) A new instrument for the measurement of tissue pO2 of human fetal scalp. Am. J. Obst. Gynecol., 100, 63-71.
Surveillance continue de I'oxyg6nation des nouveaux-n6s par 61ectrodes attach6es & la peau Sommaire--Une m&hode non envahissante pour la surveillance continue de l'oxyg6nation des nouveaux-n~s est d6crite. La pression partielle d'oxyg~ne est mesur~e avec une 61ectrode fl oxyg~ne du type Clark, attach6e fl la surface de la peru. En chauffant directement l'61ectrode fi 42~ une hyperh6misation du tissue situ6 sous l'61ectrode est obtenue. La m6thode permet une d6termination approximative de la pO 2 art6rielle; la pression de la mesure est suffisante pour surveiller l'oxyg6nation des nouveaux-n~s sous th6rapie d'oxyg6ne.
Kontinuierliche Ueberwachung der Partialoxygenierung yon Neugeboren mit Hilfe eines Hautsensors Zusammenfassung--Es wird eine nichtinvasive Methode zur kontinuierlichen Ueberwachung der Oxygenierung von Neugeborenen beschrieben. Der Sauerstoffpartialdruck wird mit Hilfe eines speziell entwickelten Clark'schen Sauerstoffsensors gemessen, der an dcr Oberflfiche der Haut befestigt ist. Durch direkte Erw/irmung des Sensors auf 42~ wird eine Hyperfimisierung des an die Elektrode angrenzenden Gewebes erreicht. Die Methode erm6glicht eine ann~ihernde Bestimmung des arterielIen pO2. Die Genauigkeit ist ffir eine Kontrolle der Sauerstofftherapie bei Neugeborenen ausreichend.
442
Medical and Biological Engineering
May 1975
W. Mindt
Bioelectronics Department, F. Hoffmann-La Roche & Co., AG, Basel, Switzerland
F. Jann
K. H a m m a c h e r
Universit~its-Frauenklinik, Basel, Switzerland
A b s t r a c t - - A noninvasive method for the continuous monitoring of the oxygenation of neonates is described. The oxygen partial pressure is measured cutaneously by a specially developed Clark- type oxygen sensor attached to the surface of the skin. By directly heating the sensor to 42~ hyperemisation of the tissue underneath the sensor is achieved. The method allows an approximate determination of arterial p02, the accuracy being sufficient for controlling the oxygen therapy of neonates.
Keywo rds-- Oxygen sensor, Neonatal p Ox monitoring Introduction MONITORING of the arterial pO2 during oxygen therapy in neonates is of considerable importance in. preventing the deleterious effects of both hypo- and hyperoxygenation, such as damages to brain, eyes and lungs. At present, the only reliable method for controlling the oxygenation of the neonate is to periodically withdraw arterial blood, either from an umbilical artery catheter or by puncturing the radial, temporal or brachial arteries. Analysing arterialised capillary blood from the heel is not unanimously considered to be conclusive for the estimation of arterial pO2 (Koch and WENDE, 1967). Besides the fact that blood sampling from arteries in neonates is cumbersome, often subject to errors and not without hazard, it g~ves information that is relevant only to the time of sampling. A continuous measurement would be preferable since pathological changes and toxic levels of pO2 can be recognised immediately. Furthermore, information of prognostic value may be obtained from observing the trend of the neeHate's state of oxygenation. Several recent studies have been devoted to this problem, Although oxymetric methods would have the advantages of being noninvasive and of requiring a relatively simple procedure, they are not suitable here because the fiat slope of the oxygen dissociation curve at an elevatedpO2 makes oxygen saturation an unreliable parameter to monitor hyperoxia (KRAMER, 1960). Thus, most work has been concerned with the determination of oxygen partial pressure. In particular, the measurement of pO2 in tissues has been evaluated by several authors as a means of estimating pa02, or of qualitatively determining the state of oxygenation of the neonate (RODGER et al., 1968; WALKER et al., 1968; HuCH et aL, 1969; NEUMAN et al., 1971; SCH()NJAHNet aL, 1972; STRAUSSet al., 1972). "First received 12 March and in final form 30th June 1973
436
The present paper describes a noninvasive method for the measurement ofpO2 by electrodes attached at the surface of the skin, which allows a continuous determination of the oxygenation of the tissue adjacent to the electrode and, under certain conditions, an estimation of the arterial pO2. The phenomenon that oxygen diffuses readily through body tissues and skin has been utilised already by BAUMBERGERand GOODFRIEND(1951) to determine arterial /702. They immersed a finger into an electrolyte solution heated to 45~ and demonstrated that, within 15-60 min, the pO2 of the solution was equilibrated with that of arterial blood. Oxygen skin electrodes that are in direct contact with the skin surface were first described by EVANSand NAYLOR(1967). HucrI and Li:raBERS(1969) reported pO2 measurements by surface electrodes on the scalp of neonates. Their experiments showed that pO2 values close to the arterial level may be obtained if hyperemisation of the tissue adjacent to the electrode is induced by vasodilating agents. As an improvement of this method, we report here the application of heat stimulation by directly heating the electrodes to 42~ to achieve a constant hyperemisation over longer time periods. Method (a) Sensor and instrumentation The principle of the p O 2 measurement due to CLARK (1956), utilised here, is based on,the electrochemical reduction of oxygen at a noble metal cathode that is coated with an oxygen-permeable, hydrophobic membrane. The noble-metal cathode, in our case gold, is polarised with - 9 0 0 mV to an Ag/AgCI anode. The current measured between both electrodes is proportional to the pO2 in the adjacent medium, provided that diffusion of oxygen through the membrane limits the rate of oxygen transport to the cathode. Medical and Biological Engineering
May 1975
Contrary to conventional Clark-type electrodes, in which the cathode diameter is kept small, we use a large-size cathode (diameter 4 mm) to obtain an average pO2 value over a sufficiently large skin area. The permeability of the membrane for oxygen has to be kept low to avoid disturbance of the oxygen profile in the tissue as a result of the consumption of the sensor. In the ideal case (Fig. la), with a membrane of sufficiently low permeability, the current is
(a ~ d+5) considered here. According to eqn. 1, the current becomes independent of the oxygen transport parameters in the tissue, when diP, >>&/Pt. In our case, Mylar membranes (polyterephthalate) 6 pm thick were used. The permeability coefficient of this material for 02 at 42~ has been determined by us as Pm = 3'2 X 10 -1~ ml O2/cm s atm. It follows that d/P== 18.6 x 105 cm 2 s atm/ml 02. To calculate ~/P,, the following approximations are made: = l m m (estimated as an upper limit) and Pt~_Pn2o=7.9xlO-TmlO2/cmsatm (at 42~ (Handbook, Respiration, 1958). Thus, with ~/P, = 1.3 x 105 cm 2 s atm/ml 02, the requirement of d/Pm >~t~/P, is fulfilled sufficiently. It is, of course, a rough approximation to assume that the oxygen permeability in tissues is equal to that in water. However, since almost all experimental values of P, are higher than Pn2o (TREGAR,1966; SCHEUPLEIN and BLANK, 1971), the result of this estimation remains valid.
Fig. 1 Oxygen profile in membrane and in tissue adjacent to sensor (a) Ideal case with membrane of low permeability: p 02 gradient is limited to membrane (b) Membrane of high permeability: p02 profile in the tissue is disturbed by oxygen consumption of the sensor limited by diffusion of oxygen through the membrane and is a measure of thepO2 at the surface of the skin. On the other hand, if a more permeable membrane is used (Fig. 1b), a pO2 gradient does not only exist in the membrane, but also within the tissue. Thus the current measured at the cathode is an additional function of diffusion and convection processes within the tissue. With the approximation that a linear pO2 profile exists in the tissue as well as in the membrane, the solution of the diffusion equation for the onedimensional case gives the following relation (SCHULER and KREUZER, 1967): i = 41ra2 F
pO2
d/Pm+&/Pt
.
.
.
.
.
(1)
With i = current, A a = electrode radius, cm F = Faraday constant, A s d = thickness of the membrane, cm P,, = permeability coefficient of the membrane for 02, ml O2/crn s atm & = thickness of the oxygen depletion layer in the tissue in cm (see Fig. 1) Pt = permeability coefficient of the tissue for 02, ml O2/cm s atm In the derivation of eqn. 1, diffusion in a radial direction at the edges of the electrode was neglected; this is allowed in the case of the large electrodes Medical and Biological Engineering
May 1975
Fig. 2 Sensor ( I ) Skin; (2) Membrane; (3) Cathode; (4) Anode; (5) Heating element; (6) Thermistor; (7) Cap for holding the membrane To verify experimentally that the current is independent of diffusion and convection processes in the test medium, the calibration curves of the sensor were determined in water and in the gas phase. It was found that both calibration curves are congruent. The influence of convection on the electrode current in water is negligible (2Yo increase during heavy stirring). It can be concluded therefore that the oxygen consumption of the electrode is sufficiently small to not affect the oxygen profile in the test medium (water as well as tissue) and that the electrode current is a measure of the oxygen partial pressure at the skin surface. One disadvantage of using a membrane of low permeability is that the response time of the sensor is long. In our case, 795~ (i.e. the time in which 95% of the steady-state value is reached after application of a step change of pO2) is 60 s. For monitoring slow changes ofpO2, this response time is sufficient. Also, rapid pO2 changes may still be detected since Tsovo is 10 s only. A schematic diagram of the oxygen sensor is shown in Fig. 2. The gold cathode (3) is surrounded by a Ag/AgCI counter electrode (4). A buffered hygroscopic solution is used as the electrolyte which 437
guarantees the stability of the electrode at 42~ for several days. The membrane (2) is held by a cap (7), the shape of which was chosen so that diffusion of oxygen from the surrounding air to the cathode is prevented. The tightness of the seal on hairless skin was tested by blowing pure oxygen against the sensor. This did not cause any alteration of the measured signal. A heating element (5) consisting of a coil of resistance wire and a thermistor (6) for the control of the heating temperature are located inside the sensor. The total diameter of the sensor, including the cap, is 14 mm and its thickness 3 ram.
small and it does not cause compression of blood vessels underneath the electrode. In general, movements of the infant do not disturb the measurement. Only extremely strong movements may cause artefacts, particularly if the sensor is attached to one of the extremities. Such artefacts, however, can be identified immediately in the recording. The following measuring positions were investigated: subclavicular part on both sides of the thorax, temporal part of the forehead and both thighs and upper arms. Most measurements were performed
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Fig. 3 Block diagram of electronic circuit
ELECTRODE "~-/ The electronic circuit consists essentially of three parts (Fig. 3 a, b and c): (a) electrode bias and current amplifier with variable gain and zero compensation. Analogue output for a recorder (b) circuit for heating the electrode and temperature control (c) safety circuit to prevent the electrode temperature from exceeding the permitted value. In Fig. 4, a laboratory prototype of the device is shown which consists of two channels for simultaneous measurement with two sensors. A built-in recorder allows the direct recording of both signals. (b) Procedure The sensor is attached to the skin of the neonate by a double adhesive tape ring, as is commonly used for e.c.g, electrodes (Fig. 5). With this method, the pressure of the sensor against the skin is extremely
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with two sensors, one of them being placed on the thorax. Before each measurement, the electrolyte and the membrane of the sensor were renewed. The sensor was then calibrated in nitrogen and in air, and corrections for barometric pressure and humidity were made. The value of the current in nitrogen is needed only if a high precision of calibration is required, since the zero current of the sensor is small compared with the current at normal pO2 values
(< 4%). After application of the sensor to the skin, the current reaches a steady-state value within 5-7 min. This time is needed for the induction of hyperemisation by heat stimulation. By treating the skin with vasodilating agents (e.g. histamine) prior to the attachment of the sensor, this time may be shortened. The stability of the oxygen sensor in situ was tested after each measurement by repeating the calibration Medical and Biological Engineering
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performed immediately after taking the blood sample. The cutaneously measured pO2 was read at the time of sampling. Results
Fig. 4 Laboratory prototype of 2-channel device for simultaneous measurement with two sensors
(a) Correlation between arterial and skin p 02 Comparative measurements between the umbilical artery pO2 and cutaneously determined pO2 were performed in 15 neonates. The results of 51 measurements are compiled in Fig. 6, whereby all cutaneous values were determined on the subclavicular part of the thorax. For the statistical analysis of the data, the skin pOz has been chosen as the independent variable. Actually, the clinical application of the method is, in general, the estimation of the arterial pO2 from the cutaneous measurement. It has been assumed that, within the population of the data, a linear relation exists between the two variables (linear regression). The correlation coefficient is 0.93 with a confidence interval of 0.87 to 0.96. The regression coefficients of the r e l a t i o n (PO2)ar,. = A (pO2)cut. -[- B are A = 1' 30, with a standard error of 0.08, and B = - 14 mm Hg with a standard error of 6 mm Hg. The standard error of the estimate is 9 mm Hg. Fig. 6 shows the 95% confidence interval limits for the ordinate to the true regression line and the 95% prediction interval limits for individual values of (pO2)art. For these investigations, thorax values have been evaluated as, for long-term studies, the thorax was found to be the best measuring position. The fiat region is well suited for the fixation of the electrode, movement artefacts occur very rarely and the site is the most practical one for the care of the child. In addition, the skin of the thorax of neonates is relatively thin and well perfused.
Fig. 5 Two oxygen sensors attached to the thorax (lower left," e.c,g, electrode)
in air. In most cases, the calibration value after eight hours of operation agreed within 5% with the initial value. The temperature of the electrode was kept at 42~ in all measurements. This temperature was found to be tolerated well by the skin over longer periods of time. Oversensitivity or burns have never been observed. The longest continuous measurement lasted for 84 h; after this time, there remained only a red spot on the skin, which disappeared after 8 h. Comparative measurements with the arterial pO2 were performed by sampling blood from a centrally located catheter introduced through the umbilical artery. The blood was withdrawn into a heparinised glass syringe and analysed with an AVL or an IL 213 blood gas analyser. Sampling was done very carefully (avoiding air bubbles and mixing the blood with infusion solution), and the analysis was Medical and Biological Engineering
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150
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o
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'
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cuteneoustymeasured pl~(mm Hg} electrode position:chest Fig. 6 Relationship between umbilical artery P 0 2 and cutaneously measured p O~ ~true regression line . . . . 95% confidence interval limits for the ordinate to the true regression line - - 9 - - 9 5 % predition interval limits for individual values of arterial/302
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Fig. 7 Response of cutaneous p 0 2 to change of oxygen concentration in inspired air. During breathing of room air, the cutaneous p 0 2 varies between 54 and 60ram Fig. A t the time A, the neonate receives air enriched with oxygen by means of a mask (3 litres/min). After an induction time of 20 s, the cutaneous p O 2 increases, and within 6min reaches a new "steady stare'with fluctuations between 106 and 128 mm Fig. The indices I and 2 refer to sensor positions on the right thigh and on the right temple, respectively. The shift of the time axis of the two channels is one-fifth of one scale unit (corresponding to 12s)
(b) Applications to monitoring To illustrate the performance and applicability of the method, a few typical curves are shown below (Figs. 7-12).
Discussion and conclusion The results of the comparative measurements compiled in Fig. 6 show that the correlation between arterial pO2 and skin pO2 allows a fairly good estimation of the arterial-oxygen partial pressure from the cutaneous measurement. Of course, the method cannot be as accurate as a direct p02 determination in arterial blood. However, its value
Fig. 8 Blood pressure, heart rate and cutaneous p 0 2 are recorded simultaneously. The p 02 scale has been expanded to obtain a better resolution of the fluctuations of the signal. One recognises two spontaneous drops of heart rate and increases of blood pressure (caused by brief apnoea), each folio wed by a significant decrease of p02. The time delay between the fall in heart rate and the decrease of p02 is approximately 20 s. The position of the oxygen sensor is the thorax
lies in the continuity of the measurement, which allows the immediate detection of changes of the noonato's state of oxygenation and facilitates the control of oxygen therapy. It must be considered in this context that high accuracy in the determination of arterial p02 is not really needed. It is generally agreed that the aim of oxygen therapy in high-risk neonates is to adjust the inspired oxygen level, so
Fig. 9 Apnoea : After spontaneous inhalation of 26% oxygen, transient cessation of breathing occurred, and was not immediately noticed by the nurse. The cutaneous p02 decreases from 60 mm I-/g to about 20 mm Hg within 3 rain. After the resumption of breathing, the p02 slowly returns to normal values. Positions of the sensors: Thorax, subclavicular, left ( I ) and right (2) side
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Fig. 10 Interruption of artificial respiration during intratracheal drainage (neonate with respiratory distress syndrome). A t time A, the Bird respirator is disconnected. The cutaneous p 0 2 decreases from 75/80 mm Hg to values below 30 mm Hg within 2"S min. After resumption of artificial respiration (time B), the p 02 returns to normal levels. Sensor positions are as in Fig. 9
that the arterial pO2 values lie between 60 and 90 mm Hg (RoBERTONet al., 1968). The accuracy of the estimation of arterial pO2 by the method reported here is sufficient to meet this demand. The correlation established in Fig. 6 is no longer valid in certain pathological conditions, especially in the case of centralisation of the blood circulation, since the skin of the thorax is scarcely perfused by arterial blood during shock. There exists, however, the possibility of recognising at an early stage the beginning of centralisation or of other complications, as has been shown in one case reported above (Fig. 12). In conclusion, the cutaneous measurement ofpO2 by heated skin electrodes represents a simple method
Fig. 11 Cardiac arrest: 19 h after defivery cardiac arrest occurred during spontaneous respiration; it was folio wed by a rapid drop of cutaneous p 02. The disturbances at the end of the curve are movement artefacts due to heart massage. The child was reanimated. In this case, the cardiac arrest was detected first by the decline of p 0 2 . The e.c.g, was not monitored because of the absence of pathology. Sensor 1 : Inner side of left thigh. Sensor 2 : Subclavicular part of thorax
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Fig. 12 Prelethal decline of cutaneous p 0 2 (male neonate, 28th week, spontaneous birth, 650 g). Sensor positions: outer side of right thigh (1) and right thorax (2). About two hours before death, the cutaneous p 0 2 declined at both measuring sites (part a). Because of centralisation of the circulation, the decrease of cutaneous pO 2 occurs much earlier than that of central arterial blood. One recognises, in parts b and c, the wave-shaped fluctuations of the p 0 2 measured on the thorax. They correspond almost symmetrically to fluctuations of the heart rate, which were recorded simultaneously. As is expected, the p O 2 waves are less pronounced at the peripheral measuring site (curve I )
for continuous monitoring and control of the oxygenation of neonates. Furthermore, information of prognostic value may be obtained from observing the trend of the cutaneously determined pO2. 441
References BAUMBERGER, J. P. and GOODFR1END, R. B. (1951) Determination of arterial oxygen tension in man by equilibration through intact skin. Federation Proc., 10, I0-11. CLA~:, L. C., jun. (1956) Monitor and control of blood and tissue oxygen tensions, Trans. Am. Soc. Artif Intcrn. Organs 2, 4148. EVANS, N. T. S. and NAYLOR, P. F. D. (1967). The systemic oxygen supply to the surface of human skin. Resp. Phys. 3, 21-37. Handbook of re.~piration (1958) DITTMER, D. S. and GREBE, R. M. (eds.) HccI-I, A., HUCH, R. and LUBBERS, D. W. (1969) Quantitative polarographische Sauerstoffdruckmessung auf der Kopfhaut des Neugeborenen, Arch. GyniT"k, 207, 443-451. KocH, G. and WENDEL, H. (1967) Comparison of pH, carbon dioxide tension, standard bicarbonate and oxygen tension in capillary blood and in arterial blood during the neonatal period, Acta Paediatrica Scandinavia, 56, 10-16. KRAMER, K. (1960) Oxymetrie, Theorie und klinische Anwendung. Georg Thieme Verlag, Stuttgart. NEUMANN, M. R., BROWN, E. G., McDONNEL, F. E. and LIv, C. C. (1971) Application of oxygen cathodes in perinatology, Proc. 24th ACEMB. Las Vegas, Nevada, 1971.
PIEROG, S. H. and FERRARA, A. (1971) Approach to the medical care of the sick newborn. C. V. Mosby Co., Saint Louis. ROBERTON, N. R. C., GUPTA, J. M., DAHLMBURG,G. W. and T1ZARD, J. P. M. (1968) Oxygen therapy in the newborn, Lancet, 1968, 1, 1323-29,13. RODGER, J. C., KERR, M. M., RICHAROS, I. D. G. and HUTCmNSON, J. H. (1968) Measurements of oxygen tension in subcutaneous tissues of newborn infants under normobaric and hyperbaric conditions, Lancet, 1968, 2, 232-236. SCHEUPLEIN, R. J. and BLANK, I. H. (1971) Permeability of the skin, Physiol. Rev., 51,702-747. SCHt3NJAIIN, V., BELLE, H., B/3CHNER, M., FRANKE, R. (1972) Einstichelektrode zur kontinuierlichen pO2 Messung im lebenden Hautgewebe, Patentschrift 88 835, GDR. SCHULER, R. and KREUZER, F. (1967) Rapid polarographic in vivo oxygen catheter electrodes, Reap. Physiol., 3, 90-110. STRAUSS,J., BERAN, A. V., BAKER, R. (1972) Continuous 02 monitoring of newborn and older infants and of children. J. Appl. Physiol., 33, 238-243. TREGAR, R. T. (1966) Physicalfunctions of skin. Academic Press. WALKER, A., PmLL1FS, L., POWE, L., WOOD, C. (1968) A new instrument for the measurement of tissue pO2 of human fetal scalp. Am. J. Obst. Gynecol., 100, 63-71.
Surveillance continue de I'oxyg6nation des nouveaux-n6s par 61ectrodes attach6es & la peau Sommaire--Une m&hode non envahissante pour la surveillance continue de l'oxyg6nation des nouveaux-n~s est d6crite. La pression partielle d'oxyg~ne est mesur~e avec une 61ectrode fl oxyg~ne du type Clark, attach6e fl la surface de la peru. En chauffant directement l'61ectrode fi 42~ une hyperh6misation du tissue situ6 sous l'61ectrode est obtenue. La m6thode permet une d6termination approximative de la pO 2 art6rielle; la pression de la mesure est suffisante pour surveiller l'oxyg6nation des nouveaux-n~s sous th6rapie d'oxyg6ne.
Kontinuierliche Ueberwachung der Partialoxygenierung yon Neugeboren mit Hilfe eines Hautsensors Zusammenfassung--Es wird eine nichtinvasive Methode zur kontinuierlichen Ueberwachung der Oxygenierung von Neugeborenen beschrieben. Der Sauerstoffpartialdruck wird mit Hilfe eines speziell entwickelten Clark'schen Sauerstoffsensors gemessen, der an dcr Oberflfiche der Haut befestigt ist. Durch direkte Erw/irmung des Sensors auf 42~ wird eine Hyperfimisierung des an die Elektrode angrenzenden Gewebes erreicht. Die Methode erm6glicht eine ann~ihernde Bestimmung des arterielIen pO2. Die Genauigkeit ist ffir eine Kontrolle der Sauerstofftherapie bei Neugeborenen ausreichend.
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