Human Reproduction, Vol. 14, No. 11, 2901-2904,
November 1999
© 1999 European Society of Human Reproduction and Embryology
In-vivo measurement of intrauterine gases and acid–base values early in human pregnancy
1 Academic Departments of Obstetrics and Gynaecology, and 2 Anaesthetics, University College London (UCL), London and 3 Department of Anatomy, University of Cambridge, Cambridge, UK
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Abstract |
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A new multiparameter sensor that combines electrochemical and fibre-optic technology was used for continuous in-vivo investigation of pH, carbon dioxide partial pressure (PCO2), oxygen partial pressure (PO2), bicarbonate concentration (HCO3–), base excess, and oxygen saturation (O2Sat) early in human pregnancy. The sensor was inserted into the amniotic cavity and the placental bed of 16 pregnancies at 10–15 weeks gestation, before termination under general anaesthesia. Amniotic fluid and retroplacental blood from the same site were also aspirated and analysed by means of cartridges and a portable blood gas analyser. Eleven series of measurements were obtained. The variation in measurements over the 5 min of monitoring was
10% for all parameters. The sensor was damaged during insertion into the amniotic cavity in one case and in the placental bed in four cases. Measurements of PO2 in both the amniotic cavity and the placental bed and of pH in the placental bed were higher using the cartridges than in vivo. The results indicated that in-vivo monitoring of fetoplacental gas and acid–base with a sensor is stable and accurate. Such technology will be helpful in improving our understanding of the fetoplacental metabolism in normal and complicated pregnancies.
Key words: acid–base balance/gases/in-vivo measurements/placenta/pregnancy
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Introduction |
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Many techniques to monitor fetal blood gas and acid–base values in normal and abnormal pregnancies have been evaluated. During the 1960s and 1970s, investigators used amniotic fluid samples, collected by means of amniocentesis between 8 weeks and term, which were tested in vitro using a pH meter and a gas analyser (Sjostedt et al., 1961
; Quilligan, 1962; Seeds and Hellegers, 1968; Bejar et al., 1971; Johnell and Nilsson, 1971; Fadel et al., 1979). More recently, fetal blood, obtained in utero from 16 weeks gestation by means of ultrasound-guided cordocentesis has become available for gas analysis and other acid–base parameters, and tested similarly (Daffos et al., 1983, Soothill et al., 1986).
The aim of most of the early studies was to find amniotic fluid parameters that would reflect intrauterine fetal acid–base balance and could be used as an indicator of fetal asphyxia in utero (Vasika and Hutchinson, 1964; Johnson and Ojo, 1967; Corson and Bolognese, 1968). Often, until multipurpose automatic analysers were developed, only one parameter could be investigated at a time. We have used a multiparameter sensor and a monitor which can simultaneously measure in-vivo pH, carbon dioxide partial pressure (PCO2), oxygen partial pressure (PO2), bicarbonate concentration (HCO3–), base excess, and oxygen saturation (O2Sat) and compared these data with those obtained by means of aspiration.
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Materials and methods |
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The Paratrend multiparameter sensor was used to measure amniotic and retroplacental gases and acid–base values in 16 healthy women who underwent surgical termination of pregnancy under general anaesthesia for psychosocial reasons at 10–15 weeks gestation. All the women gave their written informed consent to participate in this study which had been approved by the University College London Hospitals Committee on the Ethics of Human Research.
The Paratrend 7 (Diametrics Medical Inc., St Paul, MN, USA) is a monitoring system with automated sensor calibration. The Paratrend sensor (Figure 1) is a single, compact, 0.5 mm multiparameter sensor that combines electrochemical technology (Clark electrode) for PO2 measurement and fibre-optic technology to monitor pH and PCO2 (Clutton-Brock et al., 1994; Hoffman et al., 1996). Changes in hydrogen ion concentration produce colour changes in phenol red, which are detected by the pH fibre-optic elements. The CO2 sensor includes an ion impermeable barrier that excludes the movement of hydrogen ions but allows movement of CO2, which alters the local pH, producing a colour change in phenol red. The sensor also contains a thermocouple for determining temperature, and all measured gas and pH variables are corrected for temperature. The Paratrend monitoring system incorporates an alarm to inform the operator if the sensor is damaged.
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The sterile sensor is packaged with a tonometer containing buffer solution that serves as a calibrating medium. The sensor is calibrated with three precision gases supplied with the monitor. The range and 95% confidence intervals for each sensor are determined in vitro by the manufacturer (pH, range 6.80–7.80, 95% CI 0.03; PCO2, range 10–80 mmHg, 95% CI 3 mmHg; PO2, range 0–120 mmHg, 95% CI 1 mmHg). The 0–90% response time for each of the electrodes was <150 s. Bicarbonate concentration (HCO3–) is calculated using pH and PCO2 from the Henderson–Hasselbalch equation (Driscoll et al., 1997
). O2Sat was calculated using pre-operative maternal haemoglobin concentration and the base excess was automatically calculated using HCO3– values. After insertion of the calibrated sensor, the Paratrend monitor provided continuous graphical and numerical display of the measured pH, PCO2, and PO2. Calculated values of HCO3–, base excess, and O2Sat were displayed numerically (Figure 2).
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The values obtained with the sensor were compared with those obtained in amniotic fluid or blood aspirated from the same sites and immediately measured on the portable immunoradiometric assay (IRMA) blood gas analyser using multiparameter (pH, PCO2, PO2, HCO3–, base excess, and O2S) cartridges (Diametrics Medical Inc.). The IRMA analyser was calibrated using a reusable calibration cartridge set-up at the temperature obtained in vivo.
In each case, an 18 gauge needle was first introduced under ultrasound guidance into the amniotic cavity, near the placental edge. Amniotic fluid was aspirated in a 2 ml gas-tight syringe and immediately measured on the IRMA analyser. A calibrated multiparameter sensor was subsequently inserted through the needle into the amniotic cavity and measurements were started after 150 s. Gas and acid–base values were monitored for 5 min. The needle and the sensor were then removed from the amniotic cavity and reinserted within the decidua of the placental bed, in its central part, near the uterine muscle. The needle and sensor were kept in exactly the same position as assessed by continuous ultrasound guidance. Similar measurements were obtained as above. After 5 min the sensor was removed and 2 ml of uterine blood were aspirated through the needle and immediately analysed on the IRMA analyser.
The data were analysed with a biomedical processing statistics package (Statgraphics, Manugistics, Rockville, MA, USA). Standardized kurtosis was used to determine whether the samples derived from a normal distribution; as they were normally distributed, the data are presented as the mean and SEM. The difference in mean gas and acid–base values obtained with the sensors and with the cartridges was tested using Student's t-test. Results were considered statistically significant at P < 0.05.
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Results |
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One sensor was damaged during the initial insertion within the amniotic cavity and no measurements could be obtained. Four sensors were damaged during insertion inside the placental bed. None of these data were included in subsequent analyses. No acute complication was associated with the use of the Paratrend sensor in the amniotic cavity or the placenta. In particular, insertion of the needle and sensor did not appear to damage the tissues, as shown by an absence of bleeding and/or any echographic signs of haematoma.
Eleven series of matched measurements were available for evaluation. These measurements are presented and compared in Table I. The PO2 of the amniotic cavity and the PO2 and O2Sat in the placental bed measured by the cartridges were significantly higher than with the sensors. Significantly higher pH (P < 0.005) and lower PCO2 were also found in the placental bed with the cartridge system as compared with the Paratrend sensor system. The mean maximum variation in measurements over the 5 min of monitoring was 0.5 and 1% for pH, 2 and 6% for PCO2, and 8 and 10% for PO2 in the amniotic cavity and placental bed respectively.
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Discussion |
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Laboratory gas measurements are fraught with a variety of pitfalls, due mainly to the presence of air bubbles in the sample, diffusion of gases through the plastic wall of syringes and delays in analysis with samples stored at room temperature (Biswas et al., 1982
; Harsten et al., 1988). This explains why it has been suggested that amniotic fluid acid–base and gas measurements may not relate to those of the fetus (Economides et al., 1992). It also explains the wide variation in amniotic fluid PO2 measurements previously reported in the literature (Table II).
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Our study shows that the Paratrend 7 sensor can be inserted easily into the amniotic cavity or into the placenta early in pregnancy and can provide quantitative information about the metabolic status of the corresponding fluid and tissues. Measurement of amniotic fluid gases revealed a 2.4-fold increase in the PO2 when measured with the cartridges compared with the sensors (Table I
). All other measurements were similar using both systems and comparable to those reported by other authors having also investigated amniotic fluid samples from early pregnancies in humans (Table II). In the placental bed, the increase in PO2 with the change from sensor to cartridge systems was less pronounced, but there was also an increase in pH and a decrease in PCO2 (Table I). This may be due to the fact that the blood aspirated from the placental bed was probably a mixture of arterial and venous blood.
There is little information on in-vivo fetal tissue or fluid gas measurements in the literature. The PO2 of amniotic fluid has been measured at term by inserting a PO2 needle electrode into the amniotic cavity (Vasika and Hutchinson, 1964). More recently, we have measured placental and endometrial PO2 in the first trimester of pregnancy using an umbilical artery polarographic electrode introduced transcervically into the uterine cavity under ultrasound guidance (Rodesch et al., 1992). Using these electrodes, a wider range of PO2 measurements was obtained than in the present study.
The multipurpose Paratrend sensor has been validated and used mainly for continuous intra-arterial monitoring in intensive care units (Venkatesh et al., 1994). Recently this sensor has been evaluated in direct tissue measurements in order to provide information on the adequacy of brain tissue oxygenation in neurological patients at risk of ischaemia (Hoffman et al., 1996). In human pregnancy, the adequacy of placental perfusion and fetal oxygenation has been indirectly evaluated using ultrasound Doppler investigation (Bower et al., 1993) and directly by fetal blood sampling (Soothill et al., 1986).
Measurement of amniotic or placental PO2, PCO2, pH, and bicarbonate may allow better assessment of substrate delivery, clearance, and metabolism than has hitherto been possible with any other method. However, due to the size of the sensor we do not anticipate that it will find many applications in fetal monitoring in utero. For practical reasons, we have evaluated this instrument early in pregnancy when there is limited direct access to the fetal circulation. A shorter and thinner version (Neotrend; Diametrics Medical, Inc.) of the original sensor, which can be introduced via an umbilical artery catheter, is currently being evaluated in neonatology. This new sensor, which can be inserted through a 20-gauge needle, could be placed in the placenta and eventually in late gestation into the umbilical vein, where it can remain in place for several hours and be used to monitor continuing pregnancies. This may improve the management of fetal hypoxia and our understanding of the pathophysiology of placental-related disorders of pregnancy, such as fetal growth restriction and pregnancy-induced hypertension. As a research tool, we are currently investigating other applications using an animal model.
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Acknowledgments |
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This work was supported by a grant from UCLH Special Trustees and the Medical Research Council (G9701485), London, UK
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Notes |
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4 To whom correspondence should be addressed at: The Academic Department of Obstetrics and Gynaecology, University College London Medical School, 86–96 Chenies Mews, LondonWC1E 6HX, UK
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Submitted on June 2, 1999; accepted on August 13, 1999.
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