Mass spectrometer system for continuous skin-surface and intravascular blood gas measurement of maternal-fetal respiration in labour

MASS SPECTROMETER SYSTEM FOR CONTINUOUS SKIN-SURFACE AND INTRAVASCULAR BLOOD GAS MEASUREMENT OF MATERNAL-FETAL RESPIRATION IN LABOUR J.A.D. Spencer, R.S. Walton*,

Received June 1986; revised

P. Rolfe*

and P. Johnson

and accepted

August

1986

ABSTRACT This paper describes the pe$ormance characteristics of a dual-mlet mass spectrometer7 suitable for continuous monitoring of maternal and fetal blood gases using i&a-arterial mass spectrometer catheters in the pregnant ewe and skin-surface mass spectrometer probes during human labour. Skin-sur$ace measurements in newborn and adult sheep bore a

Keywords:

Patient monitors,

close and easily interpretable relationshtjr to intra-arterial measurements. The pe$ormance of the skin-surface mass spectrometer probe on the human forearm compared favourably with a commercially available transcutaneous electrochemical system for the measurement ofoqvgen and carbon dioxide but the mass spectrometer was capable of measuting additional gases such as nitrogen and argon.

blood gases, fetal monitoring

INTRODUCTION Transcutaneous measurement of arterial blood gas tensions by mass spectrometry has been reported since 19751e3. We have developed a mass spectrometer probe for use on the fetal scalp’ and a preliminary evaluation of continuous measurements of fetal scalp skin-surface oxygen and carbon dioxide tensions during labour has been reporteds. The use of electrochemical systems in labour is well described for continuous fetal scalp Pot-*and more recently for Pco~~‘“. Such systems are limited to measurements of respiratory gases whereas mass spectrometry has the potential for measuring any gaseous substance2. Preliminary results of the assessment of maternal-fetal transfer of the inert gas argon, using maternal and fetal intra-arterial mass spectrometer catheters in pregnant sheep, and maternal forearm and fetal scalp skin-surface mass spectrometer probes in women during labour, have been presented”. This paper describes our mass spectrometer and presents the performance characteristics of the system using intravascular mass spectrometer catheters and skin-surface mass spectrometer probes.

maintained at operational vacuum. The gas sample passes from the catheter or probe via a cannula to the inlet of the analyser head. The vacuum system of the mass spectrometer, which creates the negative ressure diffusion gradient along the cannula l! om the catheter or probe, is maintained by a water-cooled, oil diffusion pump and rotary pump combination. This system has a base vacuum of 1O-g mbar which is well below the operational vacuum of around lo-’ mbar governed by the catheter or probe, membrane, cannula and inlet configuration. The catheters

and probes

a) Intravascular mass spectrometer catheter. The intraarterial mass spectrometer catheters used for the animal experiments are 45 cm lengths of 22-gauge annealed stainless steel needle tubing. The outside diameter is 0.7 mm and there are five to seven slots cut laterally into the distal 2.5 cm. The catheter attaches directly to the steel cannula of the mass spectrometer by means of a rubber compression seal and is sterilized by immersion in aqueous gluteraldehyde. Transcutaneous mass spectrometer probe. The skinsurface mass spectrometer probe4 is a I cm diameter, flat, electrically heated, brass gas collecting chamber with a perforated front to support the membrane. An outlet at the rear connects to the flexible double cannula (see next section) and the whole assembly can be sterilized before use by immersion in aqueous glutaraldehyde. Control of the heated circuit is by means of two thermistors in contact with the membrane through the front surface of the device lateral to the gas collecting chamber. A temperature of 43.5”C is used to induce dilation of the skin capillaries. The probe is attached to wet skin using tissue adhesive (Histoacryl, Braun) applied to a disposable polycarbonate fixation ring which fits b)

DESCRIPTION AND PERFORMANCE CHARACTERISTICS General

description

We have modified an industrial magnetic sector mass spectrometer+ so that two inlets can be Nuffkld

Department of Ostetrics and Gynaecology

and * Bioengineering Oxford, UK. Reprints from: Dr P. lohnson, Clinical Physiologist. Nuffield Department of Obsteks and Gynaecology, Johi dadcliffe Hospital, Oxford OX3 9DU, UK.

Unit, University of Oxford, John Radcliffe Hospital,

‘VC Gas Analysis. Winsford, Cheshire, UK, MC& MM.+.~o

0 1987 Butteworth & Co (Publishers) 0141-.5425/87/010161~8 $03.00

Ltd J.

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Mass spectrometer system J.A.D. Spencer et aL 10

8

Oxygen (mass 32)

02 /-

10%

-J-+-

L4 2

10r

4

;

i

4%

_-

0% -3 6

;

1’0

12

Carbon Dioxide

14

16

%

co2

1 minute

Linearity and response curves of the skin-surface mass spectrometer Figure 1 and carbon dioxide in vitro

tightly around the gas collecting chamber and is secured to the plastic body of the device by a double sided adhesive annulus. The membranes a) Intravascular catheter. The steel catheter is covered by silicone rubber tubing 0.55 mm thick* and the tip is sealed with silicone adhesive. Heparin impregnation of silicone rubber membranes for intravascular mass spectrometry has been describedI but we had few problems with thrombus formation with the probes inserted into major arteries and with the animals partially anticoagulated. Linearity of the readings in normal saline solution, saturated with different gas concentrations, is shown in Figure 2. The 90% response time of the intravascular system was measured in a specially constructed test rig which allowed two changes in the saturated saline solution flowing over the probe, at constant temperature, to produce step changes in the dissolved gas concentration. The results were similar to those of the skin-surface probe (Figures 1 and 2). Flow-dependency was also assessed in the test rig and this showed that the reading for a given concentration of dissolved gas remained stable with flows of 200 ml min-’ or more. The reading dropped 10% as the flow was reduced to 50 ml min-r below which the reading dropped by 80%. b) Transcutaneous probe. The material for the skinsurface mass spectrometer probe membrane is a high-density polyethylene (Barn@, 0.001 inches *SilastiP,

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probe to step-changes

in concentration

of dry oxygen

(25 pm) thick. This is cut to shape and fixed over the front of the perforated gas-collecting chamber by a double sided adhesive annulus. The time taken by the system to reach 90% of a step-change in gas concentration is influenced by the cannula and depends upon the diffusion coefficient of the membrane for the gas. The response time of our system for the gases nitrogen, oxygen, argon and carbon dioxide varies between 60 and 80 s, with carbon dioxide taking longest. Gas consumption from the skin by the system is known as the depletion or stirring effect and is related to the ratio of the membrane to skin permeability l3 . Gas throughput into the probe is reduced by using a low permeability membrane, but to provide the mass spectrometer with sufficient gas to measure reliably the membrane area is maximized by using large support orifices on the front of the probe. The depletion error was estimated by measuring the ratio of the readings obtained in humidified gas and then immersed in unstirred water at 43°C equilibrated with the same gas concentration. Table I shows the mean results for nitrogen, oxygen, argon and carbon dioxide expressed as the ratio of readings in gas and in unstirred water and expressed as a percentage of the gas reading. Thus oxygen has the highest depletion at approximately 11% and carbon dioxide the lowest at 2%. Humidification of a gas causes a reduction in the mass spectrometer reading proportional to the percentage of water vapour. Calibrations performed using dry gases had their partial pressures corrected for full saturation by water vapour at

Mass spectrometer sys&m J.A.D. Spencer et d lo-

p-

02

(Saturated

saline)

OZ > m

z

8P2

z,L 0; Eo

L z’;

6-

/-----‘ox

0

_-’

4-

x

m?

6

--

8

10%

co2

(Saturated

saline)

6%

MO%

1 minute

Linearity and response curves of the intravascular Figure 2 with different concentrations of oxygen and carbon dioxide

mass

43.5”C (66.5 mmHg). Exposure to water vapour or immersion in water caused a slow rise in the mass spectrometer reading for mass 18 (water) from 0.28 x lo-lo A to > 1 x lO+ A. This was accompanied by a small rise in pressure from 1.5 x lo-’ to 8.5 x IO-’ mbar, but the mass spectrometer readings for the other gases remained unchanged. During clinical studies the mass spectrometer water vapour reading was about 1.80 x lOWi A, and calibration gases were humidified by bubbling through water at 43°C. The effect of temperature change on the membrane was investigated by altering the probe heater power. The mass spectrometer reading changed by 4.6% (of the value at 43.5”C) per degree centigrade between 38.5 and 43.5”C.

Table 1 Depletion of the skin-surface mass spectrometer transducer expressed as a ratio (of the reading in humidified gas over the reading in unstirred saturated water) and a percentage (of the reading in humidified gas)

Nitrogen (mass 28) Oxygen (mws 52) Argon (mass 40) Carbon dioxide (mass 44) All values expressed

Pairs of readings

Ratio of readings (gas/unstirred water)

Depletion (% bf gas reading)

115 115 45

I. 10 (0.06)

8.5 (4.6) 11.0 (4.9) 7.4 (1.7)

94

1.02(0.01)

as mean (s.d.).

1.13 (0.07) 1.08 (0.02)

2.0

(i.3)

spectrometer

probe to step-changes

The cannula

in normal saline equilibrated

and inlet system

The gas sample passes to the mass spectrometer via a malleable annealed stainless steel cannula 2 m long and 1 mm inside diameter. The cannula has an outer polyethylene jacket for protection. Between the catheter or probe and the distal end of the steel cannula is a 15 cm length of flexible doublecannula which ensures some mobility for the mother and fetus whilst attached. The double cannula consists of an inner polyurethane-coated nylon tube and an outer high-density polyethylene tube which minimizes both oxygen and water vapour permeability during sterilization of the catheter or probe. The double cannula and the steel cannula are connected by a metal coupling around a rubber compression seal. Increasing the length of the cannula has the effect of slowing the response time4 and we are currently looking at the possibility of heating the steel cannula to reduce the water vapour further and improve molecular flow. The 90% response time of our cannula to a step change in dry gas with a capillary opening covered with the membrane material we use is about 20 s, with virtually no lag time**: The longer response time obtained with the skin-surface probe (see above) probably reflects interruptions to the molecular flow of the gas being sampled. The lag time of the sytem is 12-15 s. The proximal end of the steel cannula is soldered to a ceramic connector at the inlet system to isolate the probe and cannula from the mass spectro-

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Mass spectrometer system J.A.D. S@ncer et al

meter. The inlet system comprises a distal two-way ‘inlet’ solenoid valve which will shut off the cannula, and a proximal three-way ‘sample’ valve by which the inlet is connected to a rotary pump or to the mass spectrometer itself. The inlet rotary pump initially evacuates the cannula system after being connected and subsequently maintains the vacuum within the inlet system. A pirani gauge with a preset trip level (5 x lo-’ mbar) protects the vacuum of the mass spectrometer by preventing the ‘sample’ valve being opened until sufficient vacuum has been achieved in the inlet system by the rotary pump. Thus any significant leak in the cannula or at the probe which prevents the inlet system from pumping down will also prevent activation of the ‘sample’ valve. Should the membrane of the probe rupture then the ion gauge of the mass spectrometer will activate another trip (set at lOA mbar) and shut off the power supply to the inlet controls thereby closing the ‘sample’ valve. The inlet system has been modified to allow two cannulae to be evacuated by the inlet rotary pump. The pirani gauge registers the pressure of both inlets unless one ‘sample’ valve is open to connect that inlet to the mass spectrometer. Under these circumstances the operating inlet is closed off to the inlet rotary pump which continues to evacuate the second inlet. Once the vacuum of the second inlet has passed the pirani gauge trip level the two inlets can be opened alternately by first closing the ‘sample’ valve of the operating inlet and then opening the ‘sample’ valve of the other inlet.

Achievement of the initial operating vacuum of the mass spectrometer takes about 4 h. When using the skin-surface probes, at an operating vacuum of 1 x lo-’ mbar, switching between inlets results in a small loss of vacuum and the signals return to previous values within 30 s. When using intravascular catheters at an operation vacuum of 7 x lo-’ mbar, switching loses less vacuum and the signals return within 20 s. An alternative arrangement to maintain vacuum in the second inlet while it is not in use is to connect the inlet system to the vacuum pump of the mass spectrometer itselP5. The mass spectrometer After the gas sample enters the analyser it passes over a heated electric filament (the ion source) which ionizes the gas molecules. Under the influence of a 2 kV acceleration potential the ionized gas molecules enter the flight tube between the ion source and the collector. The flight path is curved to fit the arc of an 80 degree sector of 8 cm radius. An electromagnetic field deflects the beam of molecules which are focussed onto the collector according to mass/charge ratio (m/e). The four-to-one ratio of the peak heights of nitrogen and oxygen in air on the displayed mass spectrum are readily identified to enable mass alignment of peak positions with the electromagnet voltage. Programming of a microprocessor allows gases to be identified by selecting their atomic mass number and the microprocessors cycles between all

1 .oo

FiOp

400

Pa02 mmHg

I 40

PaC02 mmHg 35 FiCO2 1

1 Minute Figure 3 Simultaneous measurement of PO, and Pc,, using the mass spectrometer catheter in the arterial system of an anaesthetized lamb during hyperoxia. The arterial PC4 also rose because of inhibition of respiration

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Mass spectrometer system J.A.D. Spencer et at!

0.21&W

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0

__: __--

Pa02 mmHg

I

-e

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-_ -- ---_

---__

25

--

-_----

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PaCO 2 mmHg

1

1

3

Minute

Figure 4 Simultaneous measurement of PO, and Pco2 using the mass spectrometer lamb during hypoxia. The Pco, also fell secondary to the stimulation of respiration

channels selected. The speed with which the output is updated is governed by the number of channels in the operation cycle and the accuracy code selected. A typical cycle of readings from one source to obtain values for nitrogen (mass 28), oxygen (mass 32), argon (mass 40), carbon dioxide (mass 44) and water vapour (mass 18) takes = 4s. The ionized gas molecules pass through the collector to a Faraday detector. Readings for oxygen, argon and carbon dioxide in 100% nitrogen represent the ‘noise’ in 0% of each gas. Using the skin-surface mass spectrometer probe the reading for 100% nitrogen is 2.25 x lo-” A and zero values for oxygen, argon and carbon dioxide are 0.10, 0.01 and 0.02 x 10” A respectively. Readings in a mixture of 70% nitrogen with 10% each of oxygen, argon and carbon dioxide are 1.96, 0.67, 1.05 and 3.55 x lo-“A respectively and these values illustrate the selective permeability of the membrane to the various gases. Suitable amplification of the ion current converts the output to a scale of O-10 V. Accuracy and stability are maintained by focussing the beam of molecules through a collector slit before collection. As the spectrum is scanned each peak appears broad and flat-topped, and the accuracy codes govern the number of readings taken on the down slope of either side of the peak in order to determine the centre. Reference to the position of mass five acts as a zero reference. To calibrate the system the catheter or skin-surface probe was exposed to known concentrations of the gases to be measured. Linearity of the mass spectrometer to different concentrations of gases

catheter in the arterial system of an anaesthetized

was confirmed (see Figures I and 2) and stability was checked by taking repeated readings over many hours. Calibration readings were also stable over the duration of clinical studies with a drift of < 5 mmHg.

EXPERIMENTAL Intravascular

STUDIES

IN SHEEP

performance

Intra-arterial mass spectrometer catheters were calibrated for oxygen and carbon dioxide in u&o using conventional blood gas analysis*. Carotid arterial measurements were made during induced hypoxia and hyperoxia in two spontaneously breathing anaesthetized lambs and the response of the system is illustrated in Figures 3 and 4. The mass spectrometer followed the rapid change in arterial oxygen tension (Paq,) after the alteration in respired oxgyen concentrauon (Fio,) and simultaneously measured the changes in arterial carbon dioxide tension (Pace,) which resulted from the effect of the oxygen changes on respiration. Comparison between surface measurements

intravascular

and skin-

The skin-surface mass spectrometer probe on one inlet of the mass spectrometer was attached to the pinna of the ear of a one-day old anaesthetized lamb and an intravascular mass spectrometer catheter on the other inlet was inserted into the right carotid artery. Figure 5 illustrates the alternation between inlets during oxygen administration and shows the slightly longer response time of the skin-surface probe. Figure 6 “ABL-111,

Radiometer,

Copenhagen,

Denmark

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Mass spectrometersyxtnx J.A.D. Spencer et al.

-

Skin Surface

Probe (PsO2)

-

Intravascular

Probe

,

(Pa021

,

1 minute

Figure 5 Comparative responses of the intravascular mass spectrometer catheter (carotid artery) and skin-surface mass spectrometer probe (ear lobe) to hyperoxia in a lamb. The shin-surface level reached that of the carotid artery with a slightly longer response time

1.0

Fi Ar

I

“-’ L I

Inspired argon

10.0 b

. 2

Mlnr lnhaletion

76% Argon in Oxygen

Figure 6 Comparative responses of,the intravascular mass spectrometer probe (ear lobe) to 2 min inhalation of 75% argon in oxygen in a ewe

166

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.

,

. mhlut.0

catheter (carotid artery) and skin-surface mass spectrometer

Mass spectrometer system: J.A.D. Spencer et aL

cal

onto forearm

MS heater off

MS heater nn

MS heater on

calibration

PsO2 mmHg 0

PsN2 mmkfg

Heater Power Ill?

3nr

2nr

Comparative responses of mass spectrometer (ms) and electrochemical @ad) (TCM220, Radiometer) skin-surface blood Figure 7 gas measuring systems on the human forearm during 100% oxygen inhalation (0,), hyperventilation (Hy) and arterial cuff occlusion (Cuff). Note the downward drift of the Radiometer CO, reading after 90 min. Only the mass spectrometer was able to measure simultaneously the nitrogen and argon changes, seen particularly during the inhalation of 75% argon in oxygen (Ar). Pressure (Pr) on the mass spectrometer probe simulated to a small degree the effects of cuff occlusion

shows the responses of the skin-surface mass spectrometer probe and intravascular mass spectrometer catheter, similarly placed, to 2 min inhalation of 75% argon in oxygen in an adult sheep. The separate response curves have been superimposed for effective comparison of the response times. As the response times of the mass spectrometer catheter and probe are similar in vitro (figures I and 4, the delay in the skin-surface measurement represents the difference in time between the rise in intra-arterial and transcutaneous levels. This is presumably a result of diffusion time from the microcirculation to the skin surface. The steady-state correlation between skin-surface and intraarterial oxygen values in the absence of peripheral vasoconstriction in the fetus is well establishedi6-‘*. However there is little published on the dynamic relationships as shown in these studies. CLINICAL

STUDIES

The clinical performance of the skin-surface mass spectrometer probe was assessed by testing on the human forearm in parallel with a commercially available electrochemical PO, and Pco, transcutaneous monitoring system*. Figure 7 illustrates the similarity between the mass spectrometer system and the electrochemical system during hyperoxia, hyperventilation and arterial cuff occlusion of the arm. Lower mass spectrometer readings were obtained immediately after application before peripheral vasodilatation had been achieved by switching on the probe heater. Later when the probe heater was switched off the “TCM220, Radiometer,

Copenhagen,

Denmark

lower readings were expected because of the reduction in temperature of the membrane. A mixture of 75% argon in oxygen was inhaled for 2 min and the mass spectrometer showed that the intert gas rapidly displaced nitrogen from the blood and vasodilated tissues and was a good indication of perfusion of the vascular bed at the time. DISCUSSION One of the problems with skin-surface mass spectrometry is the balance between achieving a fast response time without significant depletion of the gas at the skin surfaceig. Features of the system described here are the low permeability of the membrane to all gases but especially water vapour whilst maintaining a sufficiently rapid response time to follow changes in blood gases as rapidly and as accurately as good production electrochemical techniques. Estimation of depletion has shown that such characteristics have been achieved without excessive consumption of gas by the system. The major advantage of mass spectrometry over the electrochemical technique is the ability to measure both respiratory and inert gases using the same probe. The mass spectrometer system described in this paper has sufficient stability and sensitivity for transcutaneous measurements of respiratory gases from the fetal scalp during laboulj. The use of two inlets to compare intra-arterial and transcutaneous responses has shown that skin-surface readings are closely and reproducibly related to intraarterial readings. On switching inlets the gases from the

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inlet which was closed are accurately measured within 30 s of opening. Thus this system is fast enough to examine many of the dynamic changes in the circulation, especially those between maternal and fetal circulations which are further ‘damped’ by the interposition of the placental circulations. Indeed our observations using this system confirm the recent suggestion that there can be large changes in both fetal and maternal perfusion of exchange areas within the placenta*O. These changes may be reciprocal or in parallel depending on the nature of the compromise. Maternal hypoxaemia, for example, increases the rate of rise in fetal argon whereas occlusion of the uterine artery reduces it and yet both cause fetal asphyxia *l . The placenta consumes much of the available energy before it is available to the fetus and so it is important that the mechanisms by which the placenta regulates gas transfer be studied in order to investigate the causes of fetal distress. The potential for one inlet to measure maternal blood gases and the other to measure fetal blood gases, using intravascular mass spectrometer catheters in pregnant ewes or skin-surface mass spectrometer probes during human labour, means that the relatively inaccessible fetal-placental unit can be studied in both chronic animal experiments (essential to the investigation of fetal physiology) and in the human during labour and possibly at fetoscopy. The ability of the mass spectrometer to measure inert as well as respiratory gases means that the system represents a powerful and unique method of studying the dynamic aspects of different parts of the cardiorespiratory system. We have shown that it is possible to measure simultaneously and continuously the movement of inert gases from mother to fetus”‘21. With the additional measurement of the respective maternal and fetal blood flows, transfer rates can be determined. Clearly other volatile and gaseous substances can also be measured, permitting specific investigation of feto-placental metabolism. The clinical usefulness of such a system as described here will depend upon whether a reasonably priced small and mobile mass spectrometer can be built with the same reliability and sensitivity as this large, expensive and immobile instrument.

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ACKNOWLEDGEMENTS We thank J.C. Wollner and D.C. Andrews for technical assistance. D. Murphy designed the data acquisition system used for Figure 7. The work was supported by a grant from the National Fund for Research into Crippling Diseases (Action Research A/;/;g$a.nd in part by the MRC (G/8315991)

REFERENCES 1

2

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Delpy, D. and Parker, D. Transcutaneous measurement of arterial blood-gas tensions by mass spectrometry. Lancet 1975, i, 1016 McIlroy, M.B., Simbruner, G. and Sonoda, Y. Transcutaneous blood gas measurements using a mass

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spectrometer. Acta. Anaesth. Scand. 1978, 69 Suppl, 128-133 Lundsgaard, J.S. and Gronlund, J. Transcutaneous measurement of arterialised capillary blood PC,, by a new mass spectrometer inlet system. Scat& J. Clin Lab. Invest 1981, 42, 199-202 Rolfe, P., Burton, P.J., Crowe, J.A., Basarab-Horwath, I., Goddard, P.J., Woolfson, J., Slevin, P. and Johnson, P. Foetal scalp mass spectrometer blood-gas transducer. Med. Biol. Erg. Cornput. 1982, 20, 375-382 Sykes, G.S., Molloy, P.M., Wollner, J.C., Burton, P.J., Wolton, B., Rolfe, P., Johnson, P. and Turnbull, A.C. Continuous noninvasive measurement of fetal oxygen and carbon dioxide levels in labour by use of mass spectrometry. Am. J. Obstet. Gynecol. 1985, 150, 847-858 Huch, A., Huch, R., Schneider, H. and Rooth, G. Continuous transcutaneous monitoring of fetal oxygen tension during labour. Br. J. Obstet Gynaecol. 1977, 78 Suppl 1 Weber, T. and Secher, N.J. Continuous measurement of transcutaneous fetal oxygen tension during labour. Br. J. Obstet. Gynaecol. 1980, 86, 954-958 Antoine, C., Young, B.K. and Silverman, F. Simultaneous measurement of fetal tissue pH and transcutaneous PO, during labour. Eur. J. Obstet. Gynecol Repod. Biol. 1984, 17, 69-76 Schmidt, S., Langner, K., Gesche, J., Dudenhausen, J.W. and Saling, E. Correlation between tramcutaneous PC,, and the corresponding values of fetal blood - a study at a measuring temperature of 39°C. Eur. J Obstet Gynecol. Reprod. Biol. 1984, 17, 387-395 Hansen, P.K., Thomsen, S.G., Secher, N.J. and Weber, T. Transcutaneous carbon dioxide measurements in the fetus during labour. Am. J. Obstet. Gynecol. 1984, 1.50, 47-51 Spencer, J.A.D., Andrews, D.C., Wollner, J.C., Wolton, R.S., Rolfe, P. and Johnson, P. The continuous measurement of maternal-fetal transfer using mass spectrometry: possible non-invasive intrapartum placental function testing. In: Physiologizal Deoelopment of Fetus and Newborn (Ed. C. Jones and P. Nathanielsz) Academic Press, London, 1985, 795-800 Brantigan, J.W., Gott, V.L., Vestal, M.L., Fergusson, G.J. and Johnston, W.H. A nonthrombogenic diision membrane for continuous in vivo measurement of blood gases by mass spectrometty. J. Appl. Physiol. 1970, 28, 375-377 Severinghaus, J.W. and Thunstrom, A. Problems of calibration and stabilization of tcp0, electrodes. Acta. Anaesth &and. 1978.68 Suppl, 68-72 Murphy, D. VG Gas Analysis Ltd. Unpublished observations, 1985 Severinghaus, J.W. Unpublished observations, 1985 Kunzel, W., Kastendieck, E. and Kurz, C.S. A comparative study of continuous intravascular 0, saturation and transcutaneous PO, measurements in the sheep fetus following the reduction of uterine blood flow. In: Continuous Transcutaneous Blood Gas Monitoring (Eds A. Huch, R. Huch and J.F. Lucey), Alan R. Liss, New York, 1979,591~597 Johnson, P., Wilkinson, A.R., Sloper, J. and Whyte, P.L. Continuous transcutaneous and intraarterial oxygen measurement during experimental hypoxia in infant monkeys. In: Continuous Transcutaneous Blood Gas Monitoring (Eds A. Huch, R. Huch and J.F. Lucey), Alan R. Liss, New York, 1979, 607614 Jansen, C.A.M., Bass, F.G., Lowe, K.C. and Nathanielsz, P.W. Comparison of continuous transcutaneous and continuous intravascular PO2 measurements in fetal sheep. Am. J. Obstet. Gynecol. 1980, 138, 679-676 Parker, D., Delpy, D. and Reynolds, E.O.R. Transcutaneous blood gas measurements by mass spectrometry. Acta. Anaesth. Stand. 1978, 68 Suppl, 131-136 Gu, W., Jones, C.T. and Parer, J.T. Metabolic and cardiovascular effects on fetal sheep of sustained reduction of uterine blood flow. J. Physiol. 1985, 368, 109-129 Spencer, J.A.D., Andrews, D.C. and Johnson, P. Continuous measurement of maternal-fetal argon transfer by mass spectrometry for assessment of fetal-placental reserve. Proc. Blair Bell Res. Sot. Br. J. Obstet. Gynaecol. 1986, 93, 289