For many prenatally diagnosed conditions, treatment is possible before birth. These fetal procedures can range from minimal invasive punctions to full open fetal surgery. Providing anesthesia for these procedures is a challenge, where care has to be taken for both mother and fetus. There are specific physiologic changes that occur with pregnancy that have an impact on the anesthetic management of the mother. When providing maternal anesthesia, there is also an impact on the fetus, with concerns for potential negative side effects of the anesthetic regimen used. The question whether the fetus is capable of feeling pain is difficult to answer, but there are indications that nociceptive stimuli have a physiologic reaction. This nociceptive stimulation of the fetus also has the potential for longer-term effects, so there is a need for fetal analgesic treatment. The extent to which a fetus is influenced by the maternal anesthesia depends on the type of anesthesia, with different needs for extra fetal anesthesia or analgesia. When providing fetal anesthesia, the potential negative consequences have to be balanced against the intended benefits of blocking the physiologic fetal responses to nociceptive stimulation.

Keywords:
Fetal surgery, Fetal pain, Fetal anesthesia, Obstetric anesthesia
1.
Deprest JA, Flake AW, Gratacos E, et al: The making of fetal surgery. Prenat Diagn 2010;30:653–667.
2.
Deprest JA, Devlieger R, Srisupundit K, et al: Fetal surgery is a clinical reality. Semin Fetal Neonatal Med 2010;15:58–67.
3.
Adzick NS: Open fetal surgery for life-threatening fetal anomalies. Semin Fetal Neonatal Med 2010;15:1–8.
4.
Adzick NS, Thom EA, Spong CY, et al: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011;364:993–1004.
5.
Clayton DB, Tanaka ST, Trusler L, et al: Long-term urological impact of fetal myelomeningocele closure. J Urol 2011;186:1581–1585.
6.
Ruano R, Duarte SA, Pimenta EJ de A, et al: Comparison between fetal endoscopic tracheal occlusion using a 1.0-mm fetoscope and prenatal expectant management in severe congenital diaphragmatic hernia. Fetal Diagn Ther 2011;29:64–70.
7.
Deprest J, Nicolaides K, Doné E, et al: Technical aspects of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia. J Pediatr Surg 2011;46:22–32.
8.
Chalouhi GE, Essaoui M, Stirnemann J, et al: Laser therapy for twin-to-twin transfusion syndrome (TTTS). Prenat Diagn 2011;31:637–646.
9.
Lombardo ML, Watson-Smith DJ, Muratore CS, Carr SR, O’Brien BM, Luks FI: Laser ablation of placental vessels in twin-to-twin transfusion syndrome: a paradigm for endoscopic fetal surgery. J Laparoendosc Adv Surg Tech A 2011;21:869–872.
10.
Lewi L, Gucciardo L, Van Mieghem T, et al: Monochorionic diamniotic twin pregnancies: natural history and risk stratification. Fetal Diagn Ther 2010;27:121–133.
11.
Paramasivam G, Wimalasundera R, Wiechec M, Zhang E, Saeed F, Kumar S: Radiofrequency ablation for selective reduction in complex monochorionic pregnancies. BJOG 2010;117:1294–1298.
12.
Hecher K, Lewi L, Gratacos E, Huber A, Ville Y, Deprest J: Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord. Ultrasound Obstet Gynecol 2006;28:688–691.
13.
Dighe MK, Peterson SE, Dubinsky TJ, Perkins J, Cheng E: EXIT procedure: technique and indications with prenatal imaging parameters for assessment of airway patency. Radiographics 2011;31:511–526.
14.
Abraham RJ, Sau A, Maxwell D: A review of the EXIT (Ex utero Intrapartum Treatment) procedure. J Obstet Gynaecol 2010;30:1–5.
15.
Cheek TG, Baird E: Anesthesia for nonobstetric surgery: maternal and fetal considerations. Clin Obstet Gynecol 2009;52:535–545.
16.
Biro P: Difficult intubation in pregnancy. Curr Opin Anaesthesiol 2011;24:249–254.
17.
Boutonnet M, Faitot V, Keïta H: Airway management in obstetrics. Ann Fr Anesth Reanim 2011;30:651–664.
18.
Carlin A, Alfirevic Z: Physiological changes of pregnancy and monitoring. Best Pract Res Clin Obstet Gynaecol 2008;22:801–823.
19.
Hignett R, Fernando R, McGlennan A, et al: A randomized crossover study to determine the effect of a 30° head-up versus a supine position on the functional residual capacity of term parturients. Anesth Analg 2011;113:1098–1102.
20.
Deprest JA, Doné E, Van Mieghem T, Gucciardo L: Fetal surgery for anesthesiologists. Curr Opin Anaesthesiol 2008;21:298–307.
21.
Hui C, Lili M, Libin C, et al: Changes in coagulation and hemodynamics during pregnancy: a prospective longitudinal study of 58 cases. Arch Gynecol Obstet 2011;DOI: 10.1007/s00404–011–2137-x.
22.
Paranjothy S, Griffiths JD, Broughton HK, Gyte GML, Brown HC, Thomas J: Interventions at caesarean section for reducing the risk of aspiration pneumonitis. Int J Obstet Anesth 2011;20:142–148.
23.
Zhan Q, Huang S, Geng G, Xie Y: Comparison of relative potency of intrathecal bupivacaine for motor block in pregnant versus non-pregnant women. Int J Obstet Anesth 2011;20:219–223.
24.
Higuchi H, Takagi S, Onuki E, Fujita N, Ozaki M: Distribution of epidural saline upon injection and the epidural volume effect in pregnant women. Anesthesiology 2011;114:1155–1161.
25.
Rosen MA: Management of anesthesia for the pregnant surgical patient. Anesthesiology 1999;91:1159.
26.
Rollins M, Lucero J: Overview of anesthetic considerations for Cesarean delivery. Br Med Bull 2012;101:105–125.
27.
Boat A, Mahmoud M, Michelfelder EC, et al: Supplementing desflurane with intravenous anesthesia reduces fetal cardiac dysfunction during open fetal surgery. Paediatr Anaesth 2010;20:748–756.
28.
Okutomi T, Saito M, Kuczkowski KM: The use of potent inhalational agents for the ex-utero intrapartum treatment (exit) procedures: what concentrations? Acta Anaesthesiol Belg 2007;58:97–99.
29.
Ioscovich A, Shen O, Sichel J-Y, et al: Remifentanil-nitroglycerin combination as an anesthetic support for ex utero intrapartum treatment (EXIT) procedure. J Clin Anesth 2011;23:142–144.
30.
Golombeck K, Ball RH, Lee H, et al: Maternal morbidity after maternal-fetal surgery. Am J Obstet Gynecol 2006;194:834–839.
31.
Santolaya-Forgas J, Romero R, Mehendale R: The effect of continuous morphine administration on maternal plasma oxytocin concentration and uterine contractions after open fetal surgery. J Matern Fetal Neonatal Med 2006;19:231–238.
32.
Ogunyemi D: Risk factors for acute pulmonary edema in preterm delivery. Eur J Obstet Gynecol Reprod Biol 2007;133:143-147.
33.
Quintero RA, Huhta J, Suh E, Chmait R, Romero R, Angel J: In utero cardiac fetal surgery: laser atrial septotomy in the treatment of hypoplastic left heart syndrome with intact atrial septum. YMOB 2005;193:1424–1428.
34.
Casella DP, Tomaszewski JJ, Ost MC: Posterior urethral valves: renal failure and prenatal treatment. Int J Nephrol 2012;2012:351067.
35.
Tran KM: Anesthesia for fetal surgery. Semin Fetal Neonatal Med 2010;15:40–45.
36.
Van de Velde M, De Buck F, Van Mieghem T, Gucciardo L, De Koninck P, Deprest J: Fetal anaesthesia: is this necessary for fetoscopic therapy? Fet Matern Med Rev 2010;21:24.
37.
Myers LB, Watcha MF: Epidural versus general anesthesia for twin-twin transfusion syndrome requiring fetal surgery. Fetal Diagn Ther 2004;19:286–291.
38.
Van de Velde M, Van Schoubroeck D, Lewi LE, et al: Remifentanil for fetal immobilization and maternal sedation during fetoscopic surgery: a randomized, double-blind comparison with diazepam. Anesth Analg 2005;101:251–258.
39.
Garcia PJ, Olutoye OO, Ivey RT, Olutoye OA: Case scenario: anesthesia for maternal-fetal surgery: the Ex Utero Intrapartum Therapy (EXIT) procedure. Anesthesiology 2011;114:1446–1452.
40.
Lee H, Ryu JW, Kim DY, Lee GY: Anesthetic management of the ex utero intrapartum treatment (EXIT) procedure. A case report. Korean J Anesthesiol 2010;59(suppl):S154–S157.
41.
Liechty KW: Ex-utero intrapartum therapy. Semin Fetal Neonatal Med 2010;15:34–39.
42.
Benonis JG, Habib AS: Ex utero intrapartum treatment procedure in a patient with arthrogryposis multiplex congenita, using continuous spinal anesthesia and intravenous nitroglycerin for uterine relaxation. Int J Obstet Anesth 2008;17:53–56.
43.
George RB, Melnick AH, Rose EC, Habib AS: Case series: combined spinal epidural anesthesia for Cesarean delivery and ex utero intrapartum treatment procedure. Can J Anaesth 2007;54:218–222.
44.
Marwan A, Crombleholme TM: The EXIT procedure: principles, pitfalls, and progress. Semin Pediatr Surg 2006;15:107–115.
45.
Stephanova E, Topouzova-Hristova T, Hazarosova R, Moskova V: Halothane-induced alterations in cellular structure and proliferation of A549 cells. Tissue Cell 2008;40:397–404.
46.
Nezvalová-Henriksen K, Spigset O, Nordeng H: Effects of codeine on pregnancy outcome: results from a large population-based cohort study. Eur J Clin Pharmacol 2011;67:1253–1261.
47.
Handal M, Engeland A, Rønning M, Skurtveit S, Furu K: Use of prescribed opioid analgesics and co-medication with benzodiazepines in women before, during, and after pregnancy: a population-based cohort study. Eur J Clin Pharmacol 2011;67:953–960.
48.
Safra MJ, Oakley GP: Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. Lancet 1975;ii:478–480.
49.
Wikner BN, Stiller CO, Bergman U, Asker C, Källén B: Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Safety 2007;16:1203–1210.
50.
Marinucci L, Balloni S, Carinci F, Locci P, Pezzetti F, Bodo M: Diazepam effects on non-syndromic cleft lip with or without palate: epidemiological studies, clinical findings, genes and extracellular matrix. Expert Opin Drug Saf 2011;10:23–33.
51.
Shepard TH, Lemire RJ: Catalog of Teratogenic Agents, ed 11. Baltimore, Johns Hopkins University Press, 2004.
52.
Kampe S, Krombach JW, Diefenbach C: Muscle relaxants. Best Pract Res Clin Anaesthesiol 2003;17:137–146.
53.
Fujinaga M: Assessment of teratogenic effects of lidocaine in rat embryos cultured in vitro. Anesthesiology 1998;89:1553–1558.
54.
Sanders RD, Weimann J, Maze M: Biologic effects of nitrous oxide. Anesthesiology 2008;109:707–722.
55.
Stratmann G: Neurotoxicity of anesthetic drugs in the developing brain. Anesth Analg 2011;113:1170–1179.
56.
Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al: Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23:876–882.
57.
Brambrink AM, Evers AS, Avidan MS, et al: Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010;112:834–841.
58.
Loepke AW, Soriano SG: An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesth Analg 2008;106:1681–1707.
59.
Briner A, Nikonenko I, De Roo M, Dayer A, Muller D, Vutskits L: Developmental Stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex. Anesthesiology 2011;115:282–293.
60.
Stratmann G, Sall JW, May LDV, et al: Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology 2009;110:834–848.
61.
Wilder RT, Flick RP, Sprung J, et al: Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009;110:796–804.
62.
Sprung J, Flick RP, Wilder RT, et al: Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort. Anesthesiology 2009;111:302–310.
63.
Habib AS: A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg 2012;114:377–390.
64.
O’Rourke N, Kodali B-S: Laparoscopic surgery during pregnancy. Curr Opin Anaesthesiol 2006;19:254–259.
65.
Okutomi T, Whittington RA, Stein DJ, Morishima HO: Comparison of the effects of sevoflurane and isoflurane anesthesia on the maternal-fetal unit in sheep. J Anesth 2009;23:392–398.
66.
Hill D: Remifentanil in obstetrics. Curr Opin Anaesthesiol 2008;21:270–274.
67.
Lee SJ, Ralston HJP, Drey EA, Partridge JC, Rosen MA: Fetal pain: a systematic multidisciplinary review of the evidence. JAMA 2005;294:947–954.
68.
Anand KJ, Maze M: Fetuses, fentanyl, and the stress response: signals from the beginnings of pain? Anesthesiology 2001;95:823–825.
69.
Anand KJ: Clinical importance of pain and stress in preterm neonates. Biol Neonate 1998;73:1–9.
70.
Smith RP, Gitau R, Glover V, Fisk NM: Pain and stress in the human fetus. Eur J Obstet Gynecol Reprod Biol 2000;92:161–165.
71.
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;95:828–835.
72.
Schenone MH, Mari G: The MCA Doppler and its role in the evaluation of fetal anemia and fetal growth restriction. Clin Perinatol 2011;38:83–102.
73.
Simons SHP, Tibboel D: Pain perception development and maturation. Semin Fetal Neonatal Med 2006;11:227–231.
74.
Fitzgerald M: The development of nociceptive circuits. Nat Rev Neurosci 2005;6:507–520.
75.
Ruda MA: Altered Nociceptive neuronal circuits after neonatal peripheral inflammation. Science 2000;289:628–630.
76.
Anand KJS, Celeste Johnston C, Oberlander TF, Taddio A, Tutag Lehr V, Walco GA: Analgesia and local anesthesia during invasive procedures in the neonate. Clin Ther 2005;27:844–876.
77.
Anand KJ, Coskun V, Thrivikraman KV, Nemeroff CB, Plotsky PM: Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav 1999;66:627–637.
78.
Heim C, Nemeroff CB: The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. Biol Psychiatry 1999;46:1509–1522.
79.
Taddio A, Katz J, Ilersich AL, Koren G: Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet 1997;349:599–603.
80.
Rychik J: Acute cardiovascular effects of fetal surgery in the human. Circulation 2004;110:1549–1556.
81.
Kaneko M, Tokunaga S, Mukai M, et al: Application of a fetal scalp electrode for continuous fetal heart rate monitoring during an ex utero intrapartum treatment. J Pediatr Surg 2011;46:e37–e40.
82.
Reed CA, Baker RS, Lam CT, et al: Application of near-infrared spectroscopy during fetal cardiac surgery. J Surg Res 2011;171:159–163.
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