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Influence of maternal remifentanil concentration on fetal-to-maternal ratio in pregnant ewes

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Abstract

Purpose

Maternal remifentanil infusion is used for minimally invasive fetal surgery or ex-utero intrapartum treatment. The fetal-to-maternal (F/M) ratio of remifentanil concentration at various dosing regimens is useful to manage remifentanil effects. The aim of this study was to investigate the F/M ratio of remifentanil at various concentrations.

Methods

Five pregnant ewes received continuous remifentanil infusion under propofol anesthesia. The remifentanil infusion rate was increased by 0.4 µg/kg/min every 15 min. The response to tail clamping in fetuses was assessed immediately before the change of infusion rate. Arterial remifentanil concentrations in the mother and fetus were determined at each tail clamp. After observing a loss of response to tail clamping, remifentanil infusion was terminated and the concentrations were assessed.

Results

The median remifentanil maximum infusion rate and maternal concentration were 3.0 µg/kg/min (range 2.4–3.6) and 21.6 (range 18.0–29.9) ng/mL, respectively. During continuous infusion, the F/M ratio was 0.15 (0.07–0.17), and the slope of the linear regression for the F/M ratio versus infusion rate in each individual was −0.001 ± 0.012/μg kg min (P = 0.876 vs hypothetical value of 0). The F/M ratio at the first sampling point in the elimination phase [0.33 (0.07–0.65)] was higher (P = 0.033) than at the last sampling point during continuous infusion [0.15 (0.06–0.17)].

Conclusion

The F/M ratio was constant at a steady state regardless of the remifentanil concentration up to 29.9 ng/mL, and increased in the elimination phase in pregnant ewes.

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References

  1. Harrison MR, Anderson J, Rosen MA, Ross NA, Hendrickx AG. Fetal surgery in the primate I. Anesthetic, surgical, and tocolytic management to maximize fetal-neonatal survival. J Pediatr Surg. 1982;17:115–22.

    Article  CAS  PubMed  Google Scholar 

  2. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS, Harrison MR. Operating on placental support: the ex utero intrapartum treatment procedure. J Pediatr Surg. 1997;32:227–30.

    Article  CAS  PubMed  Google Scholar 

  3. Chalouhi GE, Essaoui M, Stirnemann J, Quibel T, Deloison B, Salomon L, Ville Y. Laser therapy for twin-to-twin transfusion syndrome (TTTS). Prenatal Diagn. 2011;31:637–46.

    Article  CAS  Google Scholar 

  4. Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D’Alton ME, Farmer DL, Moms Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011;364:993–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Med. 1987;317:1321–9.

    Article  CAS  PubMed  Google Scholar 

  6. Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet. 1987;1:62–6.

    Article  CAS  PubMed  Google Scholar 

  7. Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA. Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. 2001;95:828–35.

    Article  CAS  PubMed  Google Scholar 

  8. Van de Velde M, Van Schoubroeck D, Lewi LE, Marcus MA, Jani JC, Missant C, Teunkens A, Deprest JA. Remifentanil for fetal immobilization and maternal sedation during fetoscopic surgery: a randomized, double-blind comparison with diazepam. Anesth Analg. 2005;101:251–8.

    Article  PubMed  Google Scholar 

  9. Fink RJ, Allen TK, Habib AS. Remifentanil for fetal immobilization and analgesia during the ex utero intrapartum treatment procedure under combined spinal-epidural anaesthesia. Br J Anaesth. 2011;106:851–5.

    Article  CAS  PubMed  Google Scholar 

  10. Coonen JB, Marcus MA, Joosten EA, van Kleef M, Neef C, van Aken H, Gogarten W. Transplacental transfer of remifentanil in the pregnant ewe. Br J Pharmacol. 2010;161:1472–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ouattara A, Boccara G, Kockler U, Lecomte P, Leprince P, Leger P, Riou B, Rama A, Coriat P. Remifentanil induces systemic arterial vasodilation in humans with a total artificial heart. Anesthesiology. 2004;100:602–7.

    Article  CAS  PubMed  Google Scholar 

  12. Kaye AD, Baluch A, Phelps J, Baber SR, Ibrahim IN, Hoover JM, Zhang C, Fields A. An analysis of remifentanil in the pulmonary vascular bed of the cat. Anesth Analg. 2006;102:118–23.

    Article  CAS  PubMed  Google Scholar 

  13. Laster MJ, Liu J, Eger EI 2nd, Taheri S. Electrical stimulation as a substitute for the tail clamp in the determination of minimum alveolar concentration. Anesth Analg. 1993;76:1310–2.

    Article  CAS  PubMed  Google Scholar 

  14. Masui K, Kira M, Kazama T, Hagihira S, Mortier EP, Struys MM. Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol infusion rate. Anesthesiology. 2009;111:805–17.

    Article  CAS  PubMed  Google Scholar 

  15. Ansari J, Carvalho B, Shafer SL, Flood P. Pharmacokinetics and pharmacodynamics of drugs commonly used in pregnancy and parturition. Anesth Analg. 2016;122:786–804.

    Article  CAS  PubMed  Google Scholar 

  16. Kan RE, Hughes SC, Rosen MA, Kessin C, Preston PG, Lobo EP. Intravenous remifentanil: placental transfer, maternal and neonatal effects. Anesthesiology. 1998;88:1467–74.

    Article  CAS  PubMed  Google Scholar 

  17. Ngan Kee WD, Khaw KS, Ma KC, Wong AS, Lee BB, Ng FF. Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery: a randomized, double-blind, controlled trial. Anesthesiology. 2006;104:14–20.

    Article  PubMed  Google Scholar 

  18. Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology. 1993;79:881–92.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Eiichi Inada, Department of Anesthesiology and Pain Medicine, Juntendo University, for his advice on conducting this study, and Dr. Futoshi Kimura, Tomoyuki Kudo, Tsuyoshi Kudo, and Mihoko Kudo, Department of Anesthesiology, Hirosaki University, for their advice on sample acquisition and handling.

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo, Japan

    Masaki Sato & Hiroyuki Sumikura

  2. Division of Obstetric Anesthesiology, National Center for Child Health and Development, Setagaya, Tokyo, Japan

    Masaki Sato

  3. Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan

    Kenichi Masui

  4. University Farm, Facility of Agriculture, Utsunomiya University, Utsunomiya, Tochigi, Japan

    Borjigin Sarentonglaga, Mio Yamaguchi, Rika Fukumori & Yoshikazu Nagao

  5. United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan

    Mio Yamaguchi, Rika Fukumori & Yoshikazu Nagao

  6. Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Setagaya, Tokyo, Japan

    Haruhiko Sago

Authors
  1. Masaki Sato
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  2. Kenichi Masui
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  3. Borjigin Sarentonglaga
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  4. Mio Yamaguchi
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  5. Rika Fukumori
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  6. Yoshikazu Nagao
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  7. Haruhiko Sago
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  8. Hiroyuki Sumikura
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Corresponding author

Correspondence to Kenichi Masui.

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Funding

This study was supported by the Grant from the National Center for Child Health and Development 24-2, Japan.

Conflict of interest

The authors declare no conflict of interests.

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Sato, M., Masui, K., Sarentonglaga, B. et al. Influence of maternal remifentanil concentration on fetal-to-maternal ratio in pregnant ewes . J Anesth 31, 517–522 (2017). https://doi.org/10.1007/s00540-017-2332-4

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  • DOI: https://doi.org/10.1007/s00540-017-2332-4

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