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5: Documentation

5: For the purposes of surgery on unborn children, fetal anesthesia is routinely administered and is associated with a decrease in stress hormones compared to their level when painful stimuli are applied without such anesthesia.


a. For the purposes of surgery on unborn children, fetal anesthesia is routinely administered.

1.Giuntini, 2007, “It has also been shown that fetuses feel pain from week 18. This has given rise to the practice of using fetal anesthesia for surgery or invasive diagnostic procedures in utero.”

L. Giuntini & G. Amato, Analgesic Procedures in Newborns., in NEONATAL PAIN 73 (Giuseppe Buonocore & Carlo V. Bellieni ed., 2007).

2. Van de Velde, 2005, p.256, col.2, para.2, “Therefore, it has been suggested that pain relief has to be provided during in utero interventions on the fetus from mid-gestation (20 weeks) on.32-34

Van de Velde M, Van Schoubroeck DV, Lewi LE, Marcus MAE, Jani JC, Missant C, Teunkens A, Deprest J.  Remifentanil for Fetal Immobilization and Maternal Sedation During Fetoscopic Surgery: A Randomized, Double-Blind Comparison with Diazepam.  Anesthesia & Analgesia. 101 (2005) 251-258.

32Giannakoulopoulos X, Sepulveda W, Kourtis P, Glover V, Fisk NM. Fetal plasma cortisol and β-endorphin response to intrauterine needling Lancet. 344 (1994) 77-81.

33Giannakoulopoulos X, Teixeira J, Fisk N. Human fetal and maternal noradrenaline responses to invasive procedures. Pediatric Research. 45 (1999) 494-499.

34Anand KJS, Maze M. Fetuses, fentanyl, and the stress response. Anesthesiology.  95 (2001) 823-825.

3. Myers, 2004, p.236, para.3, “The anaesthesiologist is required to provide both maternal and fetal anaesthesia and analgesia while ensuring both maternal and fetal haemodynamic stability…Since substantial evidence exists demonstrating the ability of the second trimester fetus to mount a neuroendrocrine response to noxious stimuli…fetal pain management must be considered in every case.”

p.240, col.5, “A substantial amount of both animal and human research demonstrated that the fetus is able to mount a substantial neuroendocrine response to noxious stimuli as early as the second trimester of pregnancy. Fetal neuroanatomical development further substantiates this research. Evidence also exists that suggests that these responses to noxious stimuli may, in fact, alter the response to subsequent noxious stimuli long after the initial insult. This is the rationale behind providing fetal anaesthesia and analgesia whenever surgical intervention is thought to potentially provide a noxious insult to the fetus.”

Myers LB, Bulich LA, Hess, P, Miller, NM. Fetal endoscopic surgery: indications and anaesthetic management. Best Practice & Research Clinical Anaesthesiology. 18:2 (2004) 231-258.

4. Gupta, 2008, p.74, col.2, para.4, “As with any procedure, the provision of analgesia depends on the likely severity of pain associated with the intervention. However, analgesia is recommended for:

(i)   endoscopic, intrauterine surgery on placenta, cord, and membranes;

(ii)  late termination of pregnancy;

(iii) direct surgical trauma to the fetus.”

Gupta R, Kilby M, Cooper G. Fetal surgery and anaesthetic implications. Continuing Education in Anaesthesia, Critical Care & Pain. 8:2 (2008) 71-75.

5. Giannakoulopoulos, 1994, p.80, col.2, para.4, “Just as physicians now provide neonates with adequate analgesia, our findings suggest that those dealing with the fetus should consider making similar modifications to their practice.  This applies not just to diagnostic and therapeutic procedures on the fetus, but possibly also to termination of pregnancy, especially by surgical techniques involving dismemberment.”

Giannakoulopoulos X, Sepulveda W, Kourtis P, Glover V, Fisk NM. Fetal plasma cortisol and β-endorphin response to intrauterine needling. Lancet. 344 (1994) 77-81.

6. Van Scheltema, 2008, p.320, para.3, “Neuroanatomical, neurophysiological, hormonal, haemodynamic and behavioural data indicate that a fetus is capable of reacting to noxious stimuli, implying that the fetus can experience stress and possibly even pain… The changes described can be long-lasting, perhaps even life-long…We therefore think that when performing invasive intrauterine procedures it is important to accomplish fetal anaesthesia to protect the fetus from possible harmful effects on the developing neural system. It is difficult to determine from what gestation onwards fetal anaesthesia should be provided; however, we feel that it should be considered from at least mid-gestation.”

Van Scheltema PNA, Bakker S, Vandenbussche FPHA, Oepkes, D. Fetal Pain. Fetal and Maternal Medicine Review. 19:4  (2008) 311-324.

7.Rollins, 2012, p.466, “Despite ongoing debate regarding fetal capacity for pain perception, fetal anesthesia and analgesia are warranted for fetal surgical procedures.”

Mark D. Rollins, Mark A. Rosen, “Anesthesia for Fetal Intervention and Surgery”, in Gregory’s Pediatric Anesthesia, ed. George A. Gregory & Dean B. Adropoulos (West Sussex: Wiley-Blackwell, 2012), 444–474, 466.

8.Rosen, 2009, p131-132, “Although the link between the stress response and pain is not always predictable, the threshold for pain relief is typically below that for stress response ablation, and the stress response to noxious stimulation is clear evidence that the fetal nervous system is reactive. Administration of fetal anesthesia has been the standard practice since the inception of fetal surgery more than 25 years ago, and it is practiced worldwide. The importance of fetal immobility, cardiovascular homeostasis, analgesia, and perhaps, amnesia have always been emphasized in fetal surgery practice.”

Mark A. Rosen, “Anesthesia for Fetal Surgery and Other Intrauterine Procedures,” in Chesnut’s Obstetric Anesthesia: Principles and Practice, ed. David H. Chestnut et al (Philadelphia: Mosby, 2009), 131-132.

9.Danzer, 2011, “The objective of the trial was to determine if intrauterine surgery for MMC [one of the most common congenital malformations] between 19 and 25 weeks of gestation improves outcomes compared with standard postnatal neurosurgical repair…In addition to the anesthesia the fetus receives via the placental circulation, the fetus also receives an intramuscular injection of a narcotic and muscle relaxant just prior to the start of the fetal portion of the operation (see below)…. The initial clinical efforts succeeded based on careful and cautious application in a highly selected patient cohort and were recently confirmed in a properly controlled randomized clinical trial which has provided a definitive answer regarding the efficacy of fMMC surgery.”

Danzer, E., Johnson, M. P. and Adzick, N. S., Fetal surgery for myelomeningocele: progress and perspectives. Developmental Medicine & Child Neurology, 54 (2012) 8–14.

10.Sudhakaran, 2012, page 17, “Early fetal surgical repair helps avoid or minimise the secondary damage. Adzick, a doyen in this field, suggested that the timing for fetal surgical procedure is ideally between 19 and 25 weeks of gestation to minimise the length of time secondary damage can occur.”

N. Sudhakaran et al., “Best practice guidelines: Fetal surgery,” 88 Early Hum Dev (2012), 17.

b. Fetal anesthesia … is associated with a decrease in stress hormones compared to their level when painful stimuli is applied without such anesthesia.

1. Fisk, 2001, p.834, col.2, para.3, “This study provides the first evidence that direct fetal analgesia reduces stress responses to intervention in utero.”

Abstract, “The authors investigated whether fentanyl ablates the fetal stress response to needling using the model of delayed interval sampling during intrahepatic vein blood sampling and transfusion in alloimmunized fetuses undergoing intravascular transfusion between 20 and 35 weeks.

“Fentanyl reduced the β endorphin (mean difference in changes, -70.3 pg/ml; 95% confidence interval, -121 to -19.2;P = 0.02) and middle cerebral artery pulsatility index response (mean difference, 0.65; 95% confidence interval, 0.26-1.04;P = 0.03), but not the cortisol response (mean difference, -10.9 ng/ml, 95% confidence interval, -24.7 to 2.9;P = 0.11) in fetuses who had paired intrahepatic vein transfusions with and without fentanyl. Comparison with control fetuses transfused without fentanyl indicated that the β endorphin and cerebral Doppler response to intrahepatic vein transfusion with fentanyl approached that of nonstressful placental cord transfusions.

“Conclusions: The authors conclude that intravenous fentanyl attenuates the fetal stress response to intrahepatic vein needling.”

Fisk NM, Gitau R, Teixeira MD, Giannakoulopoulos, X, Cameron, AD, Glover VA.  Effect of Direct Fetal Opioid Analgesia on Fetal Hormonal and Hemodynamic Stress Response to Intrauterine Needling.  Anesthesiology.  95 (2001) 828-835.

2. De Buck, 2008, p.294, col.2, para.4, “The autonomic and endocrine responses to noxious stimuli, the stress response, consist of the activation of the hypothalamic, pituitary, and adrenal axis.15 Rises in blood levels of noradrenaline, cortisol and b-endorphin during invasive procedures in the human fetus are seen. Alterations in the brain blood flow have been seen as early as in the 18th week of pregnancy.15 These autonomic effects of noxious stimulation can be suppressed by the administration of analgesics.16

De Buck F, Deprest J, Van de Velde M. Anesthesia for fetal surgery. Current Opinion in Anaesthesiology. 21 (2008) 293-297.

15Rychik J, Tian Z, Cohen MS, Ewing SG, Cohen D, Howell LJ, Wilson RD, Johnson MP, Hedrick HL, Flake AW, Crombleholme TM, Adzick NS. Acute cardiovascular effects of fetal surgery in the human. Circulation. 110 (2004) 1549-1556.

16Smith RP, Gitau R, Glover V, Fisk NM. Pain and stress in the human fetus. European Journal of Obstetrics and Gynecology and Reproductive Biology. 92 (2000) 161-165.

3. Derbyshire, 2008, p.119, col.2, para.1-2, “Anand’s seminal work with neonates undergoing surgery demonstrated that fentanyl added to the anaesthetic regimen significantly reduces the stress response to invasive practice.4 Specifically, plasma adrenalin, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone and 11-deoxycortisol levels were significantly increased in the nonfentanyl group up to 24 hours after surgery. Reducing the normal stress response was considered to be responsible for the improved clinical outcome of the fentanyl group who required less post-surgical ventilator support and had reduced circulatory and metabolic complications.

“More recently, the stress response to invasive practice has been examined in the fetus to demonstrate increased cortisol and h-endorphin circulation following intrauterine needling of the fetus beyond 18 weeks gestation.25 Further studies have demonstrated that the fetal stress response includes haemodynamic changes in blood flow to protect essential organs, such as the brain, and blunting the stress response when providing opioid analgesia to the fetus.26,27

Note: Derbyshire believes pain requires subjective human experience, not possible until after birth; nonetheless, he acknowledges this finding.

Derbyshire SW. Fetal Pain: Do We Know Enough to Do the Right Thing? Reproductive Health Matters. 16: 31Supp. (2008) 117-126.

4 Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet. 329 (1987) 62-66.

25 Giannakoulopoulos X, Sepulveda W, Kourtis P, Glover V, Fisk NM. Fetal plasma cortisol and β-endorphin response to intrauterine needling. Lancet. 344 (1994) 77-81

26 Fisk NM, Gitau R, Teixeira MD, Giannakoulopoulos, X, Cameron, AD, Glover VA.  Effect of Direct Fetal Opioid Analgesia on Fetal Hormonal and Hemodynamic Stress Response to Intrauterine Needling.  Anesthesiology.  95 (2001) 828-835.

27Teixeira J, Fogliani R, Giannakoulopoulos X, Glover V, Fisk NM. Fetal haemodynamic stress response to invasive procedures. Lancet. 347 (1996) 624.

4.  Bellieni, 2012, pages 1-6, “Mellor et al92, discussed the importance of stress hormones increase as an affordable marker of fetal pain, and argued that the presence of hormonal responses to pain does not mean pain perception. But, anaesthetized patients do not show increases in stress hormones during surgery. According with Desborough et al106, “regional anaesthesia with local anaesthetic agents inhibits the stress response to surgery and can also influence postoperative outcome by beneficial effects on organ function” and the same is shown for general analgesia.”

Carlo V. Bellieni & Giuseppe Buonocore, “Is fetal pain a real evidence?,” The Journal of Maternal-Fetal and Neonatal Medicine (2012), 1–6.

92Leader LR, Fifer WP. The potential value of habituation in the prenate. In: Lecanuet JP, editor. Fetal development: a psychobiological perspective. Hillsdale, NJ: Lawrence Erlbaum Associates Publishers; 1995. pp 83–404.

106 Desborough JP. The stress response to trauma and surgery. Br J Anaesth 2000;85:109–117.

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