Pediatric Pain Measurement

Assessment and Management of Pain During Fetal Surgery and Intervention

By Linda A. Bulich, MD, FAAP

Despite steady advances in the care of fetuses undergoing surgical and minimally invasive/endoscopic procedures, the question as to if and when the fetus experiences pain remains unanswered.  Pain is believed to be a subjective experience.  Some may argue that to feel pain, one needs to be aware, or conscious - this is, of course, impossible to demonstrate in the fetus.

The fetus is a silent, often hidden patient - the fetus cannot tell us if it feels pain and there is no objective method available to measure pain in the fetus.  Hence, we are only able to record increases in fetal heart rate or see glimpses of fetal facial expressions1 and bodily movements resembling withdrawal responses using high-resolution ultrasound that may suggest either adequate or inadequate pain relief during such procedures. When the fetus experiences pain, there is clear hormonal and hemodynamic evidence that a stress response is elicited after a noxious stimulus is introduced in human fetuses as early as 18-20 weeks of gestation.2 Convincing evidence for the importance of providing analgesia to the fetus was presented in a landmark study by Fisk and colleagues in which intravenous fentanyl (10 mcg/kg) ablated both the B-endorphin and cerebrovascular response in fetuses undergoing invasive procedures.3 Regardless of whether stress equates with pain in the fetus, most practitioners would agree that a fetus is capable of experiencing pain somewhere between 20 - 30 weeks gestational age which is also the age range at which most fetal interventions occur.4 Most practitioners provide fetal analgesia and anesthesia if a fetus undergoes any open or minimally invasive/endoscopic procedure that is expected to elicit a pain response.

The administration of anesthesia and analgesia to many open fetal procedures is usually provided both through the transplacental route and by intravenous or intramuscular injection into the fetus. For most open surgical procedures, the mother is anesthetized under general endotracheal anesthesia using halogenated agents (usually desflurane or sevoflurane for optimal uterine relaxation) and as well as supplementation with a propofol infusion and intravenous narcotics. All inhaled anesthetics as well as most induction agents cross the placenta, but levels in the fetus remain below that of the mother.  Most commonly used opioid analgesics including fentanyl, sufentanil, remifentanil, hydromorphone and morphine also cross the placenta at varying rates of transfer and are delivered to the fetus in varying concentrations. Additional fetal analgesia may be provided with the intravenous or intramuscular injection of fentanyl (10-50 mcg/kg) along with vecuronium (0.2 mg/kg) or rocuronium (1-2 mg/kg) and atropine (20 mcg/kg).  Intravenous access may be obtainable by direct intravascular access on a fetal extremity (usually the hand) if available.

For most minimally invasive/endoscopic interventions, maternal general anesthesia is usually not required. The mother may receive a regional block with either a spinal or epidural anesthetic or may just have the procedure performed using either monitored anesthesia care or local anesthesia alone. Intravascular access to the fetus can be obtained via the non-innervated umbilical cord or through the large fetal hepatic veins or even directly into the cardiac chambers (during a planned cardiac intervention). Puncture of the umbilical vessels is not without significant risk and can lead to cord spasm, hematoma, embolism, and fetal death and is, therefore, usually avoided. More commonly, an intramuscular injection of fentanyl, a nondepolarizing muscle relaxant, and atropine in doses as noted above with be administered into the fetal thigh, deltoid or buttock using a 22-gauge spinal needle under ultrasound guidance. Fentanyl will provide analgesia to the fetus, the paralytic agent ensures an immobile fetus, and atropine blunts the vasovagal response that can be seen with some manipulations of the fetus (for example - intubation or balloon dilation of the aortic valve). Absorption of the fetal anesthetic into muscle tissue is not known and is probably variable, depending on the hemodynamic stability of the fetus. It is important to remember that in stressed fetuses, blood may be diverted away from the vessel-poor group (muscle) to the vessel-rich groups (brain and heart), and drug absorption will become even more unpredictable (brain-sparing effect) so it is crucial to provide the analgesia/anesthetic well before the intervention begins.

Fetal drug administration is also possible through the intra-amniotic route. Studies have shown that the intra-amniotic administration of vasopressin,5 steroids,6 thyroxine,7 digoxin,8 and sufentail,9 can be absorbed by the fetus. Although still in experimental stages, this may in the future, be the preferred approach to providing fetal analgesia without having any detrimental effects on the mother.

In summary, fetal analgesia is possible and justified for most fetuses during prenatal surgery, unless harmful collateral effects on the fetus or the mother are proven or suspected.10 Providing analgesia/anesthesia to a fetus is ethical and humane. As Glover and Fisk simply stated in the title of a 1996 editorial - “We don’t know; better to err on the safe side from mid-gestation.”11

References    

  1. Reissland N, Francis B, Mason J.  Can healthy fetuses show facial expressions of “pain” or “distress”? PLoS One 2013; 8: e65530.
  2. Giannakoulopoulos X, Glover V, Sepulveda W, et al.  Fetal plasma cortisol and B-endorphin response to intrauterine needling. Lancet 1994; 344:77-81.
  3. Fisk NM, Gitau r, Teixeira JM, et al.  Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology 2001; 95: 828-35.
  4. Lee SJ, Ralston HJ, Drey EA, et al.  Fetal pain:  a systematic multidisciplinary review of the evidence. JAMA 2005; 294: 947-54.
  5. Kullama K, Nijland MJ, Ervin MG, et al. Intraamniotic deamino(D-Arg8)-vasopressin:   Prolonged effects on ovine fetal urine flow and swallowing. Am J Obstet Gynec 1996; 174: 78-84.
  6. Murphy BE, The absorption by the human fetus of intra-amniotically injected cortisol. J Steroid Biochem1982;16:415-7.
  7. Kim MJ, Chae YH, Park SY, et al.  Intra-amniotic thyroxine in treat fetal goiter. Obstet Gynecol 2016; 59: 66-70.
  8. Hamamoto K, Iwamoto HS, Roman CM, et al.  Fetal uptake of intraamniotic digoxin in sheep.  Pediatr Res 1990; 27: 282-5.
  9. Stumper D, Durieux ME, Gogarten W, et al.  Plasma concentrations after intra-amniotic sufentanil in chronically instrumented pregnant sheep. Anesthesiology 2003; 98: 1400-6.
  10. Bellini C, Vannuccini S, Petraglia F.  Is fetal analgesia necessary during prenatal surgery? J Matern Fetal Neonatal Med2018; 31:1241-1245.
  11. Glover V1, Fisk N. Do fetuses feel pain? We don't know; better to err on the safe side from mid-gestation. BMJ 1996; 313: 796.