Headspace GC–MS Reveals Time-Dependent Placental Transfer of Sevoflurane During Cesarean Delivery

“General anesthesia for cesarean delivery” write the authors of a paper published in the International Journal of Obstetric Anaesthesia,¹ “requires balancing adequate maternal anesthetic depth against fetal drug exposure. The relationship between induction-to-delivery time, maternal anesthetic concentration, and fetal sevoflurane (a liquid that, when inhaled, is used to cause general anesthesia before and during surgery) exposure remains incompletely characterized.” The authors are part of a research group at the Ruhr-Universität Bochum (Germany) who conducted a prospective observational study where 16 women undergoing elective cesarean delivery under general anesthesia whose paired maternal and umbilical blood samples were analyzed by headspace gas chromatography-mass spectrometry at delivery, with the intent of determining correlation between induction-to-delivery time and feto-maternal ratio (the concentration of drugs or substances in fetal umbilical cord blood compared to maternal blood, indicating placental transfer).¹

General anesthesia is necessary for approximately 5–10% of caesarean deliveries, mostly as a result of contraindications to neuraxial anesthesia techniques, failed regional anesthesia, or emergency situations requiring rapid induction.² While a maintenance of sevoflurane at approximately 1.0 minimum alveolar concentration is commonly recommended in such deliveries, there are important uncertainties that remain, such as the extent to which end-tidal concentrations reflect fetal exposure, the degree to which transfer is influenced by time, and whether variability in exposure is clinically relevant.^3,4

The researchers reported thatthe average time from anesthesia induction to delivery was 3.3 minutes, with a range from 1.5 to 5.3 minutes. The average feto-maternal ratio was 0.2. The time between induction and delivery was strongly linked to this ratio, meaning that for each extra minute, the fetus was exposed to 52% more sevoflurane. However, the levels of sevoflurane in the mother's breath or blood didn't predict how much was in the fetus'blood. In further analysis, the amount of sevoflurane in the fetus didn’t show any significant impact on Apgar scores or the pH of the umbilical cord. All babies had an Apgar score of at least 8 at 10 minutes after birth, and no signs of acidosis were observed.¹

“Induction-to-delivery time,” write the study’s authors,¹ “was strongly associated with fetal sevoflurane exposure. End-tidal monitoring reflects maternal anesthetic depth but does not predict fetal drug levels. Given the limited sample size, the clinical implications for neonatal outcomes remain uncertain. Minimizing induction to delivery time may reduce fetal exposure, but this requires confirmation in larger studies.”

The authors admit to several limitations. First, only healthy, full-term pregnant women and their babies were included, excluding cases with complications like fetal distress or placental issues. While this was done to focus on the effects of sevoflurane without other factors getting in the way, the way sevoflurane transfers to the fetus might be different in high-risk pregnancies, and the results might not fully apply to those cases. Second, the babies' exposure to sevoflurane was short, which may not reflect longer exposures in real-world situations. Third, the 1-minute Apgar score, while useful for immediate newborn health, doesn't predict long-term developmental outcomes. Fourth, the study didn't track continuous blood pressure, so we couldn't analyze how anesthesia depth affected the mother’s health. Fifth, the small sample size limited the ability to find smaller effects, and it also meant the researchers were unable to run more detailed statistical tests. Lastly, the study was done at just one center and used a specific anesthetic, which might not apply to all settings.¹

References

1. Herzog-Niescery, J.; Botteck, N. M.; Kern, P. et al. Time-Dependent Placental Transfer of Sevoflurane During Cesarean Delivery Under General Anesthesia: A Prospective Observational Study. Int J Obstet Anesth. 2026, 67, 104928. DOI: 10.1016/j.ijoa.2026.104928
2. Mhyre, J.M.; Sultan, P. General Anesthesia for Cesarean Delivery: Occasionally Essential but Best Avoided. Anesthesiology 2019, 130, 1091-1093. DOI: 10.1097/ALN.0000000000002708
3. Jirasiritham, S.; Tantivitayatan, K.; Sirivararom, P. Over Half MAC Sevoflurane in Cesarean section. J Med Assoc Thai. 2005, 88 (7), 914-920.
4. Gambling, D. R.; Sharma, S. K.; White, P. F. et al. Use of Sevoflurane During Elective Cesarean Birth: A Comparison with Isoflurane and Spinal Anesthesia. Anesth Analg. 1995, 81 (1), 90-95. DOI: 10.1097/00000539-199507000-00018