BACKGROUND: The concept of fetal pain results from procedures conducted without anesthesia in preterm newborns and fetuses, which indicate that it is possible to examine fetal pain based on stress hormone, metabolic, and behavioral changes. Anatomical and physiological data suggest that fetuses become capable of processing nociceptive stimuli around midgestation, although the associated changes in fetal brain development remain unclear. What constitutes fetal pain remains controversial in the light of the definition of pain adopted by the International Association for the Study of Pain (IASP), which posits pain as an \"unpleasant sensory and emotional experience.\"
CONCLUSIONS: Here, we examine the notion that human fetuses cannot \"experience\" pain and potential implications of this claim. We highlight the key scientific evidence related to fetal pain, including clinical studies on pain in fetuses and preterm newborns. We argue that consistent patterns of stress hormones, metabolic changes, body movements, hemodynamic changes, and pain-related facial expressions in fetuses exposed to invasive procedures overcome the need for subjective proof of pain as articulated in the IASP definition. No study to date has conclusively proven the absence of fetal pain beyond the age of viability.
CONCLUSIONS: Based on the current evidence, we propose that all fetuses receive anesthesia regardless of the invasive procedures being performed to guarantee the least possible pain and physiological, behavioral, or hormonal responses without exposing the mother or her baby to unnecessary complications.

BACKGROUND: The aim of the study was to evaluate chemical stability and physical compatibility when combining fentanyl, rocuronium, and atropine in a fixed ratio to support intramuscular drug delivery during fetal intervention and surgery.
METHODS: A highly concentrated combination of fentanyl, rocuronium, and atropine was created based on common prescribing practices at a maternal-fetal care center. Chemical stability testing was completed using liquid chromatograph mass spectrometry-mass spectrometry (LC/MS-MS) to detect and quantitate atropine, rocuronium, and fentanyl, with fentanyl-d5 being an internal standard at 6, 12, 24, and 36 h following sample preparation. Physical compatibility testing was completed using United States Pharmacopeia (USP) <788> recommended analytical technique of light obscuration in addition to novel backgrounded membrane imaging at 6 and 24 h following sample preparation. Physical compatibility was determined using USP <788> particle count limits for both techniques.
RESULTS: Based on LC/MS-MS results, the samples retained expected medication concentrations at all time points tested. For physical compatibility testing, the particle counts met criteria to be considered compatible per USP <788> large-volume particle count thresholds at 6 h by both methods but exceeded tolerable thresholds at 24 h.
CONCLUSIONS: The combination of rocuronium, fentanyl, and atropine for intramuscular fetal administration is physically compatible and chemically stable for 6 h.

Controversy exists as to when conscious pain perception in the fetus may begin. According to the hypothesis of cortical necessity, thalamocortical connections, which do not form until after 24-28 weeks gestation, are necessary for conscious pain perception. However, anesthesiologists and neonatologists treat age-matched neonates as both conscious and pain-capable due to observable and measurable behavioral, hormonal, and physiologic indicators of pain. In preterm infants, these multimodal indicators of pain are uncontroversial, and their presence, despite occurring prior to functional thalamocortical connections, has guided the use of analgesics in neonatology and fetal surgery for decades. However, some medical groups state that below 24 weeks gestation, there is no pain capacity. Thus, a paradox exists in the disparate acknowledgment of pain capability in overlapping patient populations. Brain networks vary by age. During the first and second trimesters, the cortical subplate, a unique structure that is present only during fetal and early neonatal development, forms the first cortical network. In the third trimester, the cortical plate assumes this function. According to the subplate modulation hypothesis, a network of connections to the subplate and subcortical structures is sufficient to facilitate conscious pain perception in the fetus and the preterm neonate prior to 24 weeks gestation. Therefore, similar to other fetal and neonatal systems that have a transitional phase (i.e., circulatory system), there is now strong evidence for transitional developmental phases of fetal and neonatal pain circuitry.

Anesthesia for fetal and neonatal surgery requires subspecialized knowledge and expertise. Attention to important anatomic, physiologic, and metabolic differences seen in pregnancy and at birth are essential for the optimal care of these patients. Thorough preoperative evaluations tailored intraoperative strategies and careful postoperative management are critical when devising the anesthetic approach for each of these cases.

Fetal pain perception has important implications for fetal surgery, as well as for abortion. Current neuroscientific evidence indicates the possibility of fetal pain perception during the first trimester (<14 weeks gestation). Evidence for this conclusion is based on the following findings: (1) the neural pathways for pain perception via the cortical subplate are present as early as 12 weeks gestation, and via the thalamus as early as 7-8 weeks gestation; (2) the cortex is not necessary for pain to be experienced; (3) consciousness is mediated by subcortical structures, such as the thalamus and brainstem, which begin to develop during the first trimester; (4) the neurochemicals in utero do not cause fetal unconsciousness; and (5) the use of fetal analgesia suppresses the hormonal, physiologic, and behavioral responses to pain, avoiding the potential for both short- and long-term sequelae. As the medical evidence has shifted in acknowledging fetal pain perception prior to viability, there has been a gradual change in the fetal pain debate, from disputing the existence of fetal pain to debating the significance of fetal pain. The presence of fetal pain creates tension in the practice of medicine with respect to beneficence and nonmaleficence.

BACKGROUND: A wide range of fetal interventions are performed across fetal therapy centers (FTCs). We hypothesized that there is significant variability in anesthesia staffing and anesthetic techniques.
METHODS: We conducted an online survey of anesthesiology directors at every FTC within the North American Fetal Therapy Network (NAFTNet). The survey included details of fetal interventions performed in 2018, anesthesia staffing models, anesthetic techniques, fetal monitoring, and postoperative management.
RESULTS: There was a 92% response rate. Most FTCs are located within an adult hospital and employ a small team of anesthesiologists. There is heterogeneity when evaluating anesthesiology fellowship training and staffing, indicating there is a multidisciplinary specialty team-based approach even within anesthesiology. Minimally invasive fetal interventions were the most commonly performed. The majority of FTCs also performed ex utero intrapartum treatment (EXIT) and open mid-gestation procedures under general anesthesia (GA). Compared to FTCs only performing minimally invasive procedures, FTCs performing open fetal procedures were more likely to have a pediatric surgeon as director and performed more minimally invasive procedures.
CONCLUSIONS: There is considerable variability in anesthesia staffing, caseload, and anesthetic techniques among FTCs in NAFTNet. Most FTCs used maternal sedation for minimally invasive procedures and GA for EXIT and open fetal surgeries.

A wide range of fetal interventions are being performed worldwide to save the fetus\'s life, prevent permanent fetal organ damage, and allow a successful transition to extrauterine life. However, these are invasive procedures and can be associated with serious complications. This article focuses on promoting a culture of safety by highlighting five common error traps while anesthetizing patients for fetal interventions. They include failure to preserve uteroplacental perfusion and gas exchange, failure to achieve adequate uterine relaxation prior to hysterotomy, failure to monitor the fetus and prepare for fetal/neonatal resuscitation, failure to prepare for maternal hemorrhage, and failure to promptly treat uterine atony. Practical tips for avoiding these serious complications will also be discussed.

BACKGROUND: Open fetal repair of myelomeningocele (MMC) is an option for prenatally diagnosed spina bifida. Historically, high-dose volatile anesthetic was used for uterine relaxation but is associated with fetal cardiovascular depression. We examined the impact of administering a supplemental remifentanil infusion on the concentration of inhaled anesthetic required for intraoperative uterine relaxation.
METHODS: We retrospectively analyzed 22 consecutive patients who underwent open fetal MMC repair with desflurane anesthesia from 2014 to 2018. The anesthetic protocol was modified to include high-dose opioid with remifentanil in 2016. We examined intraoperative end-tidal desflurane concentrations, vasopressor use, incidence of umbilical artery Doppler abnormalities, and incidence of preterm labor and delivery.
RESULTS: Patients (n = 11) who received desflurane and remifentanil (Des/Remi) were compared to patients (n = 11) who received desflurane (Des) alone. Intraoperatively, the maximum end-tidal desflurane required to maintain uterine relaxation was lower in the Des/Remi group (7.9 ± 2.2% vs. 13.1 ± 1.2%, p < 0.001). The mean phenylephrine infusion rate was also lower in the Des/Remi group (36 ± 14 vs. 53 ± 10 mcg/min, p = 0.004).
CONCLUSIONS: Use of opioid with supplemental remifentanil was associated with lower volatile anesthetic dosing and decreased vasopressor use; fetal outcomes were not different. Remifentanil may allow for less volatile anesthetic use while maintaining adequate uterine relaxation.

Fetal anesthesia teams must understand the pathophysiology and rationale for the treatment of each disease process. Treatment can range from minimally invasive procedures to maternal laparotomy, hysterotomy, and major fetal surgery. Timing may be in early, mid-, or late gestation. Techniques continue to be refined, and the anesthetic plans must evolve to meet the needs of the procedures. Anesthetic plans range from moderate sedation to general anesthesia that includes monitoring of 2 patients simultaneously, fluid restriction, invasive blood pressure monitoring, vasopressor administration, and advanced medication choices to optimize fetal cardiac function.

Continuous fetal hemodynamic monitoring during in-utero surgery is desirable, but it is often not feasible without intermittent interruption. We report the use of a fetal spiral electrode for continuous heart rate monitoring during fetal myelomeningocele repair. Fetal echocardiography and a fetal spiral electrode were used to monitor fetal heart rate during in-utero repair at 25 weeks\' gestation. We observed good agreement between echocardiographic and spiral electrode heart rate measurements. Using the Bland-Altman approach, the mean (SD) difference between measurements was 1.8 (3.5) beats per minute with limits of agreement of -5.3 to 8.8 beats per minute. This case illuminates a potential role for a fetal spiral electrode as a real-time adjunct in fetal interventions.