An evaluation of the tissue pH electrode for fetal monitoring using the fetal sheep as an experimental model

FETUS, PLACENTA, AND NEWIiORN

An evaluation of the tissue pH electrode for fetal monitoring using the fetal sheep as an experimental model LUCA

FUSI,

M.D.*

MARGARET

WALMSLEY,

HUBERT

G. BRITTON,

DAVID

REDSTONE,

PAULINE

D.

RICHARD London,

B.Sc.,

W.

M.A., M.B.,

B.CH.,

CH.B.,

ALEXANDER, BEARD,

PH.D. M.B.,

PH.D

D.C.H.

M.Sc. M.D.,

F.R.C.O.G.

England

The performance of the Roche tissue pH electrode has been assessed by comparison of values recorded by the electrode with the pH of arterial blood, in fetal sheep. Observations were made under controlled conditions when the fetal pH was steady, during hypoxia, and after hypoxia. The results showed a highly significant correlation of the values recorded by the electrodes with the pH of arterial blood (r = 0.89, p < 0.001 during control; and r = 0.86, p < 0.001 during hypoxia and recovery). However, in about 10% of cases the insertion proved to be unsatisfactory, and in one half of the successful insertions there was a rapid initial drift which lasted up to 45 min. After stabilization, tissue pH values were symmetrically distributed about the arterial pH, with a SD of 0.07 unit. Multiple electrodes in the same fetus gave the same scatter. Movements of the electrode caused significant artefacts. During hypoxia (produced by compression of the cord or administration of gas mixtures low in 0,) the electrodes lagged behind the changes in arterial pH by up to 10 min. The conclusion is that the inherent variability of the tissue pH electrode makes it unsuitable as an absolute indicator of fetal well-being, and that it cannot be used alone as an indication for operative intervention. Nevertheless, because of the limitations of conventional techniques, it should be valuable as an adjunct and, in particular, it should help in the interpretation of equivocal fetal heart rate tracings, thereby reducing the risk of fetal death. (AM. J. OBSTET. GYNECOL. 140:953, 1981.)

From the Departments of Obstetrics and Gynaecology, Physiology, and Paediutrics, St. Mary’s Hospital Medical School. This work was supported by the National Research into Crippling Diseases.

Fund fo7

Presented in part at the Fetal and Neonatal Physiological Measurements Conference, Oxford, September, 1979. Received fw

publication

)002-9378/81/160953i08$00.80/0

September

Revised

February

Accepted March

24, 1981 2, 1981.

Reprints requests: Dr. L. Fusi, Department of Obqdetics and Gynaecology, St. Maly’s Hospital Medical School, Praed Street, London, W2 IPG, England. *Supported

by a grant from

the Wellcome

Trust.

30, 1980.

0 1981 The C. V. Mosby

Co.

Ss%

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Fusi et al.

CONTINUOUS fetal heart rate (FHR) monitoring and measurement of scalp blood pH have given the obstetrician the opportunity to evaluate the condition of the fetus more accurately than hitherto. The pH value assists in the interpretation of the FHR record, thereby improving the reliability of the diagnosis of fetal asphyxia. Since Saling’ first described a technique to obtain samples of fetal blood from the presenting part for measurement of pH, several author? have demonstrated the usefulness and reliability of the method in the diagnosis of fetal acidosis, but its application has been neither widespread nor sustained. Clinicians have found the technique difficult to master, and acceptability of the procedure by the patient has been poor, especially when it is necessary to repeat samples. The recent development” of a micro-glass electrode which is able to give a continuous record of tissue pH, rather than blood pH, overcomes some of these drawbacks. The effectiveness of this new pH electrode was demonstrated by Stamm and associates6 in newborn infants, when he showed that the tissue pH (tpH) correlated well with arterial pH. Sturbois and associates’ studied 42 fetuses and was able to show that tpH readings in labor correlated reasonably well with umbilical blood pH at delivery. However, technical difficulties with insertion and fixation of the electrode significantly reduced the usefulness of the technique. Lauersen and associates’ using a modified electrode holder, studied 40 fetuses during labor and demonstrated in 76.9% of the cases a significant correlation between tpH and coincident scalp capillary blood pH. Wood and associate? have also reported a study with the modified electrode. However, tpH is a new and as yet poorly understood index of acid-base status. The electrode is immersed in a wound fluid of undetermined composition and unknown relationship with other body fluids. Some data on the relationship between blood and tissue pH in experimental animals have been published,‘“-‘* but before tpH can become part of the routine care of the at-risk fetus, its value must be fully established under a variety of controlled conditions in experimental animal preparations. Therefore, this study was designed to investigate systematically the performance and reliability of the tpH electrode under controlled conditions of hypoxia in the fetal sheep.

Matedal and methods Nine pregnant Shropshire Clun sheep, age 130 to 135 days (term, 150), were used. withheld for 24 hr before the experiments reduce ruminal distention. After epidural (Nupercaine, Ciba Laboratories, Horsham, the ewes were transferred to a cradle which

gestational Solids were in order to anesthesia England); kept them

in a semisupine position throughout the experiment. Anesthesia was supplemented when necessary with intravenous sodium thiopentone (Pentothal, May 8c Baker, Dagenham, England). Hysterotomy was performed and the fetus was delivered and placed upon a platform maintained at the uterine level between the ewe’s legs. The uterus and abdomen were then partially sutured around the umbilical cord so as to leave the umbilical circulation undisturbed. A rubber bag filled with saline solution at 37” C was placed over the fetal head to prevent the onset of breathing. Fetal temperature was maintained by means of insulating covers and radiant heat, and temperature values at various sites were recorded continuously with an Ellab electric thermometer (Ellab, Staniforth, Penarth, Wales). Arterial blood pressure of the ewe and fetus was monitored continuously by vascular pressure transducers (Devices, Ltd., Welwyn Garden City, England). and FHR was recorded with the use of scalp clips and a Hewlett-Packard monitor, Model 8028 (Hewlett-Packard, Winniesh, England). Fetal transcutaneous PO,, was also measured with a micro-electrode (Drager Medical, Ltd., Hemel Hempstead, England) applied to the side of the neck after shaving or depilation. Polythene catheters were inserted into the maternal dorsalis pedis artery and vein and into the fetal femoral artery. They were slowly infused with heparinized saline solution in order to prevent the formation of clots. Generally, about 1 hour elapsed between the operation and the insertion of the tissue pH electrode. The Roche tissue pH electrode (Roche-Kontron Instruments, Ltd., St. Albans, England) was calibrated at 37” C with the use of Radiometer buffers 6.84 and 7.38. Up to four electrodes were inserted in the side of the neck according to the manufacturer’s instructions with use of a special holder which incorporates an electrocardiographic electrode. This secures the tpH electrode in position in a central stab wound made with a 2 by 2 mm limited-depth blade. We used the side of the neck instead of the scalp because, in the absence of edema, the subcutaneous tissue of the scalp proved to be too thin to maintain the electrode in position. A drop of saline solution was placed on the site of the wound just before introduction of the electrode in order to exclude air. The tpH electrode values were recorded either with the Roche 540 monitor or special digital pH meters (Analox Instruments, Alpha Laboratories, Eastleigh, England). After each experiment the tpH electrode was removed, washed with saline solution, and reimmersed in the calibration buffers to check drift. Samples of arterial blood were withdrawn simultaneously from mother and fetus for the determination of

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pH, Paz, Pco,, and lactate. The analysesof pH, PoZ,and Pco, were made on an I.L. 613 blood gasanalyzer (Instrumentation Laboratory (U.K.), Warrington, England). For measurementof blood lactate, 50 ~1samples of arterial blood were precipitated with four volumesof ice-cold 6% perchloric acid. After centrifugation, lactate was estimated in the supernatant by the Boehringer adaptation of the Gutman method.13 Hypoxia was induced in our experiments either by administration to the mother of a gasmixture containing 8% 0,. 3% Cot, and 89% N*, with a polythene bag placed over the head, or by manual occlusion of the cord. The umbilical cord was occluded either continuously for periods of 3 to 10 minutes, or intermittently for 1 min followed by 3 min of releaseover a period of about 40 min.

955

insertlon

=

0.2

i I

I

P

I

0

10

I

20

30

I

I

/

minutes

Fig. 1. Typicalpatternsof changesin ApH (tissue-arterial pH) immediatelyafter electrodeinsertionbased, on data from 41 insertions.Percentages of the different patternsareindicated.

Results during the control period. Forty-three insertions were made in nine animals during a mean study time of 6 hr for each animal. Becauseof skin laxity, there wassomedifficulty with inserting the electrode into the side of the neck, so that a satisfactory record was not obtained in 10% of the cases.In these insertions, the recorded tpH showeda very rapid drift, with values usually becoming rapidly more acid until those outside the limits compatible with life were reached. This behavior often seemedto be associated with inadequate depth of insertion and a partial exposure of the electrode to air. In the caseof insertions from which steady values were eventually obtained, it was found important to maintain the electrode perpendicular to the skin and to avoid pronounced movements. Movements causedartefacts in two ways: flexion of the cable alone causedlarge but brief excursionsin the record, whereas major movements of the electrode in the tissueproduced a smaller disturbance but with a slower recovery. In 48% of the successful insertions, the electrode was steady from the outset, whereasin the other 52% there wasa relatively rapid initial drift. When the drift wasarbitrarily defined as having ended when successivereadings over 10 min periods varied by not more than 0.03 pH unit, 75% of the electrodesstabilized within 30 min, and 25% of the electrodesrequired up to 45 min. The four most common patterns of electrode responseand their frequenciesare shown in Fig. 1. The behavior of the electrode during the initial period gave no indication of the sign or magnitude of ApH at stabilization. This varied widely in different experiments, and a histogram of ApH at stabilization is given in Fig. 2. The mean ApH was0.01 unit, but there wasa wide symmetrical distribution of ApH, with a range of +0.14 to -0.18 unit Observation

Fig. 2. Distributionof ApH at stabilization.

(SD, .07). This scatter of valueswasnot due to changes in calibration of the electrodes. The mean arterial pH at stabilization was 7.29, and the correlation with tpH was 0.87 (p < 0.005). Four different electrodes were used in the study, but the performances of the individual electrodesdid not differ significantly. However, in any one animal, the tissue pH values recorded by electrodes at different sites differed widely. Indeed, the mean and standard deviations of tpH values obtained from electrodesinserted at various positionsin a single fetus were of the sameorder as those calculated for the collected data in Fig. 2. Thus, the scatter in ApH can be largely accounted for by differences in tpH at different insertion sites,and the electrode in the control period is not measuringtissuepH characteristic of a particular fetus. In 11 of the insertions, the long-term stability was assessed by following the electrodes for an additional hour after stabilization. Of the 11 recordings, eight remained relatively stable,with a drift of lessthan 0.03 pH unit, and three showed a mean drift of 0.06 pH unit (range, 0.05 to 0.07) (Fig. 3). Despite these fluctuations in pH, which appeared to be random, the limits remained within the histogram shown in Fig. 2. The overall correlation between tissue and arterial

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Fig. 3. Long-term stability of the electrodes. The observations were made during control periods when there was little change in arterial pH.

Fig. 4. Relationship between tissue and arterial pH in the control periods, with the regression line and 95% confidence limits. pH in the control period after stabilization was highly significant (r = 0.89, p < 0.005) (Fig. 4), thus confirming that arterial pH is a determinant of tpH. Observations during hypoxia and in the posthypoxic period. Total occlusion of cord. Total occlusion of the cord not only produced rapid changes in pH in the fetus but also initiated circulatory changes associated with arrest of umbilical flow. Fig. 5 illustrates an experiment in which the cord was totally occluded intermittently for periods of 3 to 10 min, with recovery periods of up to 80 min between the episodes of asphyxia. With each occlusion there was a sharp fall in pH and a rise in Pco~. The response of the tissue electrode was delayed, particularly with the first occlusion, where the lowest tpH value occurred approximately 10 min after the beginning of hypoxia, at a time when arterial pH had shown considerable recovery. As will be discussed later,

15, 19x1 Gynecol.

at least part of t’he delay would appear to have been due to subcutaneous vasoconstriction. and, in this context, the rise in blood pressure due to occlusion of the cord was most marked during the first occlusion. The blood lactate rose rapidly, with the highest value corresponding with the lowest tpH, and returning to the preocclusion values only slowly, following tpH rather than arterial pH. Intermittent occlusion gcord. Intermittent occlusion of the cord was used to produce a reduction in fetal placental blood flow, and was preferred to partial occlusion of the cord since the latter preferentially restricted venous flow, with pooling of blood in the placenta and fetal hypovolemia. A representative experiment is shown in Fig. 6. The arterial pH fell more gradually than with total occlusion of the cord, and under these conditions the tissue electrode followed the arterial pH relatively closely. The large but temporary increases in tpH after the first occlusion and the small increases seen between 25 and 40 min after the start of hypoxia were associated with displacement of the electrode caused by movement of the animal. Throughout the recovery periods, tpH tended to be lower than arterial pH. A marked bradycardia was associated with each occlusion of the cord, followed by short episodes of tachycardia with increased variability. A return toward the prehypoxic rate and variability was detected in the final recovery period. The development of hypoxic acidosis was associated with a marked rise in blood lactate, which remained high during the recovery period. Administration of 8% oxygen to the mother. The administration of 8% oxygen to the mother was used to simulate a reduction in placental perfusion. The gas mixture produced a very marked hypoxia and hypercapnia (Fig. 7). Three electrodes were inserted into this animal, and they all showed a virtually immediate response to hypoxia. However, quantitatively, there were appreciable differences between them, with one electrode recording markedly lower values than the others. During hypoxia, there was a severe bradycardia, followed in the recovery period by a persistent tachycardia associated with the persistence of a severe acidosis and lactacidemia. Pooled data from the various experiments showing the relationship between tissue and arterial pH during hypoxia and the recovery period are illustrated in Fig. 8. Despite the scatter, wider than in the control period, the correlation was still highly significant (r = 0.86, p < 0.001). Lactate levels during hypoxia and recovery from the various experiments correlated well with both arterial pH (Fig. 9) and tissue pH (r = -0.72 and -0.84, respectively, with p < 0.001). When the influence of Pco,

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Fetal response to the hypoxia produced by total occlusion of the cord for periods of 5.3, and 10 min. Arterial pH v---v. Tissue pH S---W Arterial PO* A---A. Transcutaneous PO, V-V.

Fig. 5.

on the arterial pH was taken into account, the correlation coefficient between the latter and the blood lactate was improved to r = -0.87. In this respect, it appears that the arterial pH was more influenced than tissue pH by the rapid rises in PCO,associated in our experiments with the induction of hypoxia.

Comment All investigators have found that tpH correlates significantly with arterial pH, and this has been confirmed in the present work not only in the control periods but also during and after hypoxia. Therefore, tpH can be regarded as an indirect measure of arterial pH. However, it is apparent that other factors influence the tpH substantially, and one of the main objectives of the present study was to determine the error introduced by these other factors. Previous work had given somewhat discordant results. Thus, in the adult catlo and rabbit,*’ the tpHs were generally lower than arterial blood pHs, whereas the reverse was found for the dog.g In fetal goats, I5 the tpH was more acid during the control periods and more alkaline during hypoxia. In human be-

ings, two studies have reported that the tpH was more acid than scalp capillary blood,‘* s whereas in a third study9 the mean tpH and scalp capillary pHs were in relatively close agreement. In the present work, under controlled conditions (i.e., when the arterial pH of the fetus was virtually constant) and after an initial equilibration period, the tpH was distributed uniformly about the arterial pH, with a SD of 0.07 pH unit (Fig. 2). Also established was the fact that tpH varied between insertion sites as much as it did between different animals. Thus, it is unlikely that tpH can be used as an independent indication of fetal condition apart from its relationship to arterial pH. During the period subsequent to insertion of the electrodes, the differences between the tpH and arterial pH are likely to be somewhat greater than at stabilization. Furthermore, the tpH may change fairly rapidly and this change may be falsely attributed to changes in the condition of the fetus. Our data on long-term stability of the electrode indicate that additional random drifts may occur after initial stabilization,

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August 15, 1981 Am. J. Obstet. Gynecol.

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Fig. 6. Fetal response was occluded Arterial PO,,

for l

to the hypoxia induced by intermittent 1 min periods between the vertical lines. l . Transcutaneous PO *-----’

but the value of tpH will usually stay within 0.14 pH (2 2 SD) of arterial pH. Some of the fluctuations in tpH found in the present experiments have been caused by movements of the electrode. This sensitivity to mechanical disturbance is difficult to quantitate, but it could be important clinically. Electrodes which were deeply inserted were less sensitive to movement. The substantial differences of up to 0.17 pH unit between the tpH and the arterial blood pH question the nature of the fluid in which the electrode is immersed. It will not be interstitial fluid alone, since local tissue damage exists, and local disturbance in the circulation will favor the accumulation of CO, and the production of lactic acid. These factors may be expected to lead to a lower pH in the fluid surrounding the electrode. On the other hand, the loss of CO, to the atmosphere through the incision will make the pH more alkaline. Thus, the measured values of tpH will represent a balance between various factors. Under the transient condition of hypoxia, the tissue pH electrode lags behind the arterial pH. This is to be expected since the lactic acid and carbon dioxide are largely generated in the fetal heart and brain rather than in the peripheral tissues into which the electrode is inserted. This lag varied remarkably, and in one

total occlusion of the cord. The cord Arterial pH V---D. Tissue pH o-----e.

experiment in which the cord was briefly occluded, the minimum in the tpH did not occur until 15 min later. However, the lag did not seriously distort the record when the pH was falling slowly, and this may be expected to approximate more closely the usual clinical situation. In the recovery period, the tpH tended to fall considerably below the blood pH, and in some cases the lowest values for tpH were recorded when there had been a substantial recovery of the arterial pH. This pattern of behavior may reflect the lack of carbonic anhydrase in the peripheral tissue, so that CO,, which has diffused into the tissue, only slowly dissociates into H+ and HCO, ions. The applicability of these findings to clinical practice depends upon the validity of our experimental model. Since the metabolic effects of hypoxia in the adult and fetus are different, we used a fetal preparation. The use of the neck of the lamb rather than the scalp as a site for the measurement of tpH raises an uncertainty, but its vascularization is probably similar to that of the human fetal scalp. l6 Cooling of the electrode and the subcutaneous tissue should also be considered, since cooling will not occur in the clinical situation. However, care was taken to keep the skin warm with

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Fig. 7. Fetal response to hypoxia produced by administration to the mother of low 0, gas mixture. CO2 was present in the gas mixture and there was a rise in the fetal arterial Pco, to 85 mm Hg, as well as a fall in PO,. Arterial pH V---V. Tissue pH (three different electrodes) D--O; H; A-A. Arterial PO, V-V. Tr&cutaneous PO, i----r. radiant heat, and thermocouples inserted into the incision indicated temperatures in excess of 35” C. The variability reported in human clinical data7-g also appears to be consistent with the present findings. Heart rate was routinely monitored in our preparation. In all cases, there was a marked bradycardia in the severe episodes of hypoxia, however induced. Nevertheless, after the termination of hypoxia, there was a rapid return of the heart rate and variability to the normal pattern, despite the persistence of acidosis, which in some cases was severe. To summarize the above, the tissue pH electrode responds to variations in the fetal arterial pH but may present a rather large intrinsic difference (SD + 0.07 pH unit). During hypoxic acidosis, the electrode re-

sponse is variable and may be delayed. Thus, except in very severe cases of fetal acidosis, it seems unlikely that the absolute readings of the electrode can be used alone to diagnose fetal acidosis with sufficient certainty for clinical purposes. Nevertheless, a falling value of the tpH is presumptive evidence of progressive tissue hypoxia. The fetal sheep heart shows a response to severe hypoxia, but it tends to return toward prehypoxic rate and variability after the hypoxic episode, even if a severe acidosis persists. If this applies in the human being, then it is apparent that the continuous measurement of tpH together with FHR will give a better indication of fetal condition than FHR alone. It should also be of value when the onset of fetal hypoxia is marked by

960

August 15, 1981 .4m. J. Obstet. Gynecol.

Fusi et al.

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episodes of bradycardia, since it should give some quantitative indication of the severity of the hypoxia, which may not be apparent from the FHR records.i7 The present work emphasizes the need for a reliable and continuous indication of fetal pH. It seems to be worthwhile to attempt to improve the performance of the tpH electrode, since relatively small improvements in the technique of insertion and maintenance should greatly increase its value. We wish to express

our thanks to Mike

Carter

and

REFERENCES

I. Saling, 2.

3. 4.

5.

6.

E.: A new method for examination of the child during labour, Arch. Gynecol. 197:108, 1962. (German.) Beard, R. W.. Morris, E. D., and Clayton, S. G.: pH of fetal capillary blood as an indicator of the condition of the fetus, J. Obstet. Gynaecol. Br. Commonw. 74:812, 1967. Kubli, F. W.: Influence of labor on fetal acid-base balance, Clin. Obstet. Gynecol. 11:168, 1968. Boenisch, H., and Saling, E.: The reliability of pH values in fetal blood samples. A study in the second stage, J. Perinat. Med. 4:45, 1976. Stamm, O., Janecek, P., and Campana, A.: Kontinuierlithe pH. Messung am Kindlichen Kopf post partum und sub partu, Z. Geburtshilfe Perinatol. 178:368, 1974.

Stamm, O., Latscha, U., Janecek, P., and Campana, A.: Development of a special electrode for continuous sub-

cutaneous measurement in the infant scalp, AM. J. OBSTET. GYNECOL. 124:193, 1976. 7. Sturbois, G., Uzan, S., Rotten, D., Breart, G., and Sureau, C.: Continuous subcutaneous pH measurement in human fetuses. Correlation with scalp and umbilical blood pH, AM. J. OBSTET. GYNECOL. 148:901, 1977. 8. Lauersen, N. H., Miller, F. C., and Paul, R. H.: Continuous intrapartum monitoring of fetal scalp pH, AM. J, OBSTET. GYNECOL. 133:44, 1979. 9. Wood, C., Anderson, I., Reddy, S., and Shekleton, P.: Continuous measurement of tissue pH in the human fetal scalp, Br. J. Obstet. Gynaecol. 85:668, 1978.

I

! 6.9

7.0

7.1

7.2

7.3

7.4

7.5

Tissue pH Fig. 9. Relationship centrations during

between hypoxia

tissue pH and blood and recovery periods.

lactate

con-

Chee Beng Tan for skillful technical assistance, and to Philip Steer for criticism of the manuscript. We also thank Dr. W. Mindt and Kontron Instruments Ltd. for advice and for providing instrumentation.

10. Boos, R., Heinrich, D., Muliawan, D., Ruttgers, H., Mittman, U., and Kubli, F.: In vivo performance of the pH tissue electrode during acute acid-base changes in the dog, Arch. Gynecol. 426r45, 1978. 11. Hochberg, H. M., Lauersen, N. H., George, M. E. D.,

Van-Poznak,

A.: A study of tissue pH monitor in cats,

AM. J. OBSTET. GYNECOL. 131:770, 1978. 12. Dunn, L., Redstone, D., Roe, H. L., Steer, P. J., and Beard, R. W.: The relationship between tissue and arterial pH in

hvpercarbic rabbits, Arch. Gvnecol. 2!$&51. 1978. 13. H&h, A., Huch, R., Schneider, H., and R&h, G.: Continuous transcutaneous monitoring of fetal oxygen tension during labour, Br. J, Obstet. %ynaecol. 84t Suppl. 1, 1977. 14. Gutmann, I., and Wahlenfeld, A. W.: L+ lactate determination with lactate dehydrogenase and NAD, in Burgmeyer, H. U., editor: Methods of Enzymatic Analysis, ed. 2, New York, 1974, Academic Press, Inc. 15. Kellner, K. R., Nelson, R. M., Cruz, A. C., and Spellacy, W. N.: An evaluation of a continuous tissue pH monitor in the fetal and neonatal goat, AM. J. O~sm. GYNECOL. 135:502, 1979. 16. Fusi, L., and Beard, R. W.: Capillaries in the fetal scalp, Lancet 1:483, 1980. 17. Britton, H. G., Nixon, D. A., and Wright, G. H.: The effect of acute hypoxia on the sheep fetus and some ob-

servations on recovery from hy@xia, 11:277,

1967.

Biol. Neonate