A new microdialysis probe for continuous lactate measurement during fetal monitoring: Proof of concept in an animal model

Abstract

Introduction: Cardiotocography (CTG) is currently the most commonly used method for intrapartum fetal monitoring during labor. However, a high false-positive rate of fetal acidosis indicated by CTG leads to an increase in obstetric interventions. We developed a microdialysis probe that is integrated into a fetal scalp electrode allowing continuous measurement of lactate subcutaneously, thus giving instant information about the oxygenation status of the fetus. Our aim was to establish proof of concept in an animal model using a microdialysis probe to monitor lactate subcutaneously.

Material and methods: We performed an in vivo study in adult male wild-type Wistar rats. We modified electrodes used for CTG monitoring in human fetuses to incorporate a microdialysis membrane. Optimum flow rates for microdialysis were determined in vitro. For the in vivo experiment, a microdialysis probe was inserted into the skin on the back of the animal. De-oxygenation and acidosis were induced by lowering the inspiratory oxygen pressure. Oxygenation and heart rate were monitored. A jugular vein cannula was inserted to draw blood samples for analysis of lactate, pH, pco₂ , and saturation. Lactate levels in dialysate were compared with plasma lactate levels.

Results: Baseline blood lactate levels were around 1 mmol/L. Upon de-oxygenation, oxygen saturation fell to below 40% for 1 h and blood lactate levels increased 2.5-fold. Correlation of dialysate lactate levels with plasma lactate levels was 0.89 resulting in an R² of .78 in the corresponding linear regression.

Conclusions: In this animal model, lactate levels in subcutaneous fluid collected by microdialysis closely reflected blood lactate levels upon transient de-oxygenation, indicating that our device is suitable for subcutaneous measurement of lactate. Microdialysis probe technology allows the measurement of multiple compounds in the dialysate, such as glucose, albumin, or inflammatory mediators, so this technique may offer the unique possibility to shed light on fetal physiology during the intrapartum period.

Keywords: cardiotocography; cesarean; delivery; fetal acidosis; fetal monitoring; fetal scalp electrode; lactate; prenatal care.

Figure 1

A, A schematic representation of a cardiotochography (CTG) electrode modified to incorporate a needle‐type microdialysis setup. The arrow denotes the positioning of the needle. B, A semi open needle (2), in which a microdialysis membrane is inserted (3), in which thin fused silica tubing is inserted (1). When dialysis fluid is pushed through the fused silica (4), the flow will leave the fused silica at the other end and be forced back (6), because the membrane is blocked by glue (7). While running back along the microdialysis membrane, exchange (5) of small molecules will occur between the dialysis fluid and the external fluid space. Fluid can be collected for analysis when leaving the dialysis membrane (8)

Figure 2

Oxygen saturation and blood lactate levels upon de‐oxygenation for 60 min. Red lines depict saturation levels in 3 animals (percentage, right y‐axis), green lines represent corresponding blood lactate levels (mmol/L, left y‐axis). Red squares represent average oxygen saturation, green circles represent average blood lactate

Figure 3

Oxygenation, pCO₂ and pH upon de‐oxygenation for 60 min. Red lines depict saturation in 2 animals (percentage, right y‐axis), blue lines depict corresponding pCO₂ levels (mm Hg, right y‐axis) and green lines represent corresponding pH values (left y‐axis). Red squares depict average saturation, blue circles depict average pCO₂ values and green diamonds depict average pH

Figure 4

Blood and dialysis lactate levels upon de‐oxygenation for 60 min. Red lines depict blood lactate levels in 3 animals, blue lines represent corresponding dialysis lactate levels (mmol/L). Red triangles depict average blood lactate, blue squares represent average lactate in dialysate