Fetal surgical pain

1. PAIN COLUMN
“It Will Not Hurt a Bit,” “What You Do Not
Know Cannot Hurt You,” and Other Myths
About Fetal Surgical Pain
Sharyn Gibbins, RN, PhD
Column Editor
Lisa Golec, RRT, BSc, MHSM
Advances in health care have made it possible to carry out a Myth One: Fetuses Do Not Feel Pain or
number of intrauterine procedures before birth in the hopes of
minimizing morbidity and mortality outcomes postnatally. Remember Pain
Surgery, ultrasound-guided and endoscopic therapies and Current data suggest that by 26 and even as early as 20
terminations1 exemplify some of the potentially painful ante- weeks' gestation, a rudimentary pain pathway may be present
natal therapies that can occur, with procedures ranging from for the perception of pain.2 “For analgesia to be effective, it is
blood sampling to thoracotomy, abdominal incision, and essential that the necessary receptors are present...there are
resection.2 Fetal surgery is routinely carried out between the abundant μ opioid receptors in the fetal brain and spinal cord
26th and 32nd weeks of gestation, with procedures occurring as from as early as 20 weeks gestation [making] opioids a good
early as 20 weeks and as late as 35 weeks.2 Pain is a serious option for fetal analgesia.”2 Neonatal data from extremely low-
concern in fetal surgery, both during the surgery itself as well as birth-weight and low-birth-weight infants confirm the presence
the long-term ramifications that may ensue. “The plasticity of of definitive pain responses in this gestational age group.5
the developing nervous system may allow for the greatest Where surgery itself is concerned, data regarding the long-term
impact of pain to occur in the least maturely born infants.”3 effects of surgery suggest the existence of “alterations in spinal
Although the use of fetal analgesia for fetal surgery has been cord connectivity, central sensitization, as well as more
considered,1,4 few infants receive direct analgesia during these generalized changes in stress reactivity.”3 These data represent
potentially painful procedures. Why? Three main arguments a portion of the plethora of research on perinatal pain done over
(myths) may be postulated to explain why fetal analgesia has not the past decade, which dispels the common misconceptions
evolved in line with fetal surgery: first, the fetus does not feel that preterm infants do not have the same “physiologic response
pain or remember pain, and therefore, analgesia is unnecessary; to painful stimuli” as adults and that what pain experience they
second, the use of fetal analgesia is not possible or safe, nor are do have “doesn't count” because they do not remember pain.6
there data to support it; and third, the fetus' pain management Where these data do become problematic, however, relates to
needs are covered by maternal analgesia delivered transplacen- the second myth: that the use of fetal analgesia is not possible or
tally during the procedure. Herein, we discuss each of these safe, nor are there data to support it.
myths and give reasons why we believe them to be problematic.
It is our belief that our moral responsibility as caregivers
demands that we value the fetus in itself, not simply as a means,
and as such, direct pain control consideration ought to be given Myth Two: The Use of Fetal Analgesia Is
to the fetus undergoing procedures suspected to cause pain. Not Possible or Safe, Nor Are There Data
to Support It
In 2001, Fisk et al,7 published some preliminary research in
From the NICU, Sunnybrook Health Sciences Centre, Toronto, Ontario, support of the use of fetal analgesia. They administered fentanyl
Canada M5S-1B2; Interdisciplinary Research, Sunnybrook Health Sciences
directly to the fetus through the intrahepatic vein during
Centre, Toronto, Ontario, Canada M5S-1B2.
intrauterine transfusion. Their data showed a significant
Address correspondences to Lisa Golec, RRT, BSc, MHSM, NICU,
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M5S-1B2. decrease in stress response as measured by a reduction in β-
E-mail: lisa.golec@sunnybrook.ca. endorphin levels and the prevention of change in the middle
© 2007 Elsevier Inc. All rights reserved. cerebral artery pulsatile index. In addition, they noted that
1527-3369/07/0704-0220$10.00/0 cortisol levels were reduced by 50%; however, these differences
doi:10.1053/j.nainr.2007.09.005 were not statistically significant. These data provide the “first

2. evidence that direct analgesia reduces stress responses to Despite a cornucopia of previously dispelled arguments
invasive procedures in utero.” Opponents of fetal analgesia against neonatal sedation, preterm infants undergoing surgical
might argue that little is known about appropriate fetal dosing to procedures usually receive analgesia. In their book chapter
support fetal analgesic use. It is known, however, that the half- “Ethical issues in the treatment of neonatal and infant pain,”
life of a drug given to a fetus is shorter that of a neonate, resulting Lantos and Meadow6 ask, “can pain be worse than death?” They
in the need to give 25% more of the drug than would normally forward that, “in most clinical situations involving adults,
be given to the fetus.2 This knowledge, coupled with valid patients are willing to take some gamble on the risk of mortality
neonatal dosing guidelines, provides a solid starting point for in order to achieve better pain relief…most people prefer the
determining appropriate fetal dose. Although it may be true that pain relief associated with general anaesthesia, even though it
there is a paucity of data regarding fetal analgesia, these data may be associated with slightly higher risks of side effects and
suggest that it is both possible and safe to administer fetal morbidity.” As in the case of any intervention, treatment, or
analgesia during fetal surgical procedures. That being said, therapy, attention must be paid to balancing risk against benefit.
current neonatal data may complicate the case for fetal analgesia Outcome concerns notwithstanding, the effectiveness of opioids
because findings showed that “treatments that work well enough for the relief of infant pain has been demonstrated.6 In a
to relieve pain seem to worsen other outcomes.”6 Further studies systematic review of 13 studies examining the safety and efficacy
to examine the effects of treatment are therefore required. of opioids, pain scores using the Premature Infant Pain Profile
The Neurologic Outcomes and Pre-emptive Analgesia in (PIPP) were significantly reduced.12 If a 26-week infant having
Neonates (NEOPAIN) study8 randomized 900 infants to thoracic surgery is given analgesia during surgery despite the
either morphine or placebo infusion. Infants who did not potential risks associated with its administration, why, then,
receive open-label morphine in the morphine infusion group does a 26-week fetus not receive the same treatment? What
had higher rates of composite outcome (P = .0338) and differentiates the two other than a little bit of geography?
severe intraventricular hemorrhage (IVH) (P = .0209) than
those in the placebo group. Infants given open-label
morphine in the morphine infusion group were more likely Myth Three: The Fetus' Pain Needs Are
to develop severe IVH (P = .0024), and infants receiving Covered by Maternal Analgesia Delivered
open-label morphine in the placebo control group had worse
rates of composite outcome than those who did not receive
During the Procedure
open-label morphine (P b .0001). These data appear to How does the in utero locale of a fetus influence
provide strong support against the use of continuous consideration of pain? Cultural perceptions of pregnancy are
analgesia in preterm infants. It is important to note, however, deeply rooted in a tradition of folklore that views the body of a
that these data predominantly deal with the extended woman as a sacred metaphor13, the womb, a sacred space
treatment of ventilated infants in the Neonatal Intensive protecting and providing for the developing fetus. Does our
Care Unit (NICU) setting, not the short-term administration adherence to this ideology cause us to naively support a belief
to infants undergoing surgical procedures. that the womb will protect and provide even during instances of
With regard to infants undergoing surgical procedures, ingression? During fetal surgery, the mother is anesthetized, and
studies have shown that term infants who received deep analgesia given to her flows transplacentally. 2 Although
anesthesia (with sufentanil) during cardiac surgery had maternal analgesia crosses the placenta, assuming it sufficient
significantly reduced postoperative stress responses as measured for fetal coverage may prove problematic. A trend away from
by levels of β-endorphins, norepinephrine, epinephrine, general anesthetic in obstetrics2 notwithstanding, inhaled
glucagon, aldosterone, and cortisol. Infants who received light anesthetics take longer to elicit their effect in the fetus than in
anesthesia had more hyperglycemia and lactic academia as well the mother.1 In addition, Desprats et al14 demonstrated that
as greater likelihood of sepsis, acidosis, disseminated intravas- transplacental anesthesia may be insufficient. In their study,
cular coagulation, and postoperative death.9,10 Studies with umbilical cord data sampled for maternal fentanyl at the time of
preterm infants undergoing surgery11 have shown that stress- surgery showed that, on average, less than 50% of the drug
related hormonal changes precipitate a catabolic state character- reached the fetus. It is not known whether this decreased
ized by glycogenolysis, gluconeogenesis, lipolysis, and mobiliza- amount of analgesia is sufficient to meet the pain needs of a fetus
tion of gluconeogenic substrates in the postoperative period. during a surgical procedure. Moreover, these data showed
Prevention of these metabolic derangements by anesthesia has “considerable individual variation.”2 Evidently, we cannot
been suggested as a method of improving postoperative clinical naively assume that maternal analgesia will cover the needs of
outcomes for preterm infants. These data support the belief that the fetus as well.
pain management during and after surgery is important for both Sadly, the generalized lack of consideration of perinatal pain
the immediate well-being of the patient as well as the long-term is not a myth. “One might wonder how intelligent, dedicated
outcomes that may prevail. Although no studies have critically individuals who care deeply for their patients could continue to
examined fetal pain behaviors or the safety and efficacy of fetal ignore pain in infants and neonates that they are caring for.”15 In
pain management on immediate and long-term outcomes, it is the case of the fetus, fetal pain control and research need to
plausible that the responses mimic those observed in the evolve in tandem with fetal surgery. Without wading into a
extremely low-birth-weight infant. contentious personhood debate, consideration ought to be given
VOLUME 7, NUMBER 4, DECEMBER 2007 225

3. to the fetus undergoing procedures suspected to cause pain. McGrath PJ, editors. Pain in neonates and infants. 3rd ed.
Indeed, it could be argued that fetal analgesia ought to be used New York: Elsevier; 2007. p. xiv. [329 p].
for termination procedures as well. “In Britain, most surgical 7. Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X,
terminations take place under general anaesthesia, which is Cameron AD, Glover VA. Effect of direct fetal opioid
believed to affect the fetus, though evidence for this is sparse.”2 analgesia on fetal hormonal and hemodynamic stress
Although an in-depth discussion about pain management for response to intrauterine needling. Anesthesiology. 2001;95:
pregnancy termination is beyond the scope of this editorial, 828-835.
surely, in instances such as these, it would be reasonable, even 8. Anand KJ, Hall RW, Desai N, et al. Effects of morphine
humane, to administer analgesia directly to the fetus, for which analgesia in ventilated preterm neonates: primary outcomes
morbidity and mortality issues are moot. Fetal surgery, with its from the NEOPAIN randomised trial. Lancet. 2004;363:
intent to minimize morbidity and mortality, in effect enhances 1673-1682.
the value of the fetus. Although the law within our society does 9. Anand KJ, Hickey PR. Halothane-morphine compared with
not predominantly recognize fetal rights, there is a general high-dose sufentanil for anesthesia and postoperative
recognition of “fetal interests.”16 In failing to consider the analgesia in neonatal cardiac surgery. N Engl J Med. 1992;
interests of the fetus where pain is concerned, we fail to value the 326:1-9.
fetus in itself. Our moral responsibility as caregivers demands 10. Anand KJ, Aynsley-Green A. Measuring the severity of
that we value the fetus in itself, not simply as a means, and as surgical stress in newborn infants. J Pediatr Surg. 1988;23:
such, direct pain control consideration ought to be given to the 297-305.
fetus undergoing procedures suspected to cause pain. 11. Anand KJ, Brown MJ, Bloom SR, Aynsley-Green A. Studies
on the hormonal regulation of fuel metabolism in the
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