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Maternal Epidural Fentanyl Administered for Labor Analgesia Is Found in Neonatal Urine 24 Hours After Birth

Authors:
Correspondence
Maternal Epidural Fentanyl Administered
for Labor Analgesia Is Found
in Neonatal Urine 24 Hours After Birth
Albert Moore, Aly el-Bahrawy, Roupen Hatzakorzian, and William Li-Pi-Shan
Dear Editor:
Fentanyl is an opioid medication that is given epidu-
rally for labor analgesia. Although fentanyl is commonly
used, there are reports of it interfering with breastfeeding
success.
1
We could find no information on whether fentanyl
would be found in a neonate more than 24 hours after delivery
and so decided to present this case.
The patient gave consent, and the research ethics board gave
approval for this study. A 34-year-old, 39-week gravida 1 para
0 woman presented in spontaneous labor. She was 162 cm tall,
weighed 75 kg, was healthy, took no medication other than
prenatal vitamins, and had enjoyed an uneventful pregnancy.
She requested and received an epidural at 4:45 h the day of her
admission. The epidural catheter placement was uncompli-
cated, and adequate analgesia was provided using a pump that
infused 0.06% bupivacaine with 2 lg/mL fentanyl at 10 mL/
hour with a patient-controlled 5-mL demand bolus and a
lockout time of 10 minutes. Throughout her labor the patient
received six extra boluses of this solution.
A 3,780-g baby boy was born at 14:08 h, with Apgar scores
of 9 and 9 at 1 and 5 minutes, respectively, and an umbilical
artery pH of 7.19. The epidural pump was stopped soon after
birth, with the patient receiving 140 mL of the epidural so-
lution (280 lg of fentanyl over 11 hours =25 lg/hour). The
patient recovered and was discharged to the postpartum ward
where she was assessed by us the next day. At that time she
had used no medications for pain.
The baby-dependent items on the LATCH score were as-
sessed, and the latching ability and audible swallowing were
rated at 2 (normal). Urine samples were collected from the
mother at 14:00 h. At the same time, a clean sponge was
placed in a new diaper, which provided a neonatal urine
sample that was collected at 17:00 h. The samples were sent
to a toxicology laboratory, where it was determined that the
maternal urinary fentanyl level was 2.0 ng/mL, whereas the
neonatal level was 2.4 ng/mL.
Although it is known that epidurally administered fentanyl
crosses the placenta, it is thought that this leads to clinically
unimportant levels in the neonate.
2
The measured half-life of
fentanyl administered intravenously to infants 1 day or less of age
is highly variable and ranges from 75 to 441 minutes,
3
making
the duration it would remain in the neonate unclear. Our case
demonstrates that fentanyl can persist in the neonate for at least
24 hours after delivery, at amounts that may have clinical effects.
The minimum effective analgesic level of fentanyl in plasma for
adults is 0.63 ng/mL.
4
Although the corresponding level is un-
known in neonates, a level of 1.1 ng/mL has necessitated pro-
longed intubation in neonates.
3
The urinary concentration seems
to have some correlation with fentanyl dosage and levels.
5
Although fentanyl is transferred in breastmilk, it is virtu-
ally undetectable in colostrum 10 hours after it has been given
maternally.
6
In addition, fentanyl’s limited oral bioavail-
ability makes us believe the majority of neonatal fentanyl was
from placental transfer and not through breastmilk. Although
our LATCH score was reported as normal, more subtle
markers of breastfeeding difficulty may have been found if
we had assessed the Widstrom stages of neonatal breast-
feeding,
7
or more severe problems may have occurred if the
patient had required higher fentanyl doses. Adequate initia-
tion is essential for the continued success of breastfeeding,
and it is possible that the presence of neonatal fentanyl could
interfere in the important first days of life.
In conclusion, we provide evidence that fentanyl admin-
istered through an epidural for less than 12 hours will remain
in the mother and neonate, even 24 hours after cessation of
the epidural infusion. The clinical implications of this should
be further investigated.
References
1. Beilin Y, Bodian CA, Weiser J, et al. Effect of labor epidural
analgesia with and without fentanyl on infant breast-feeding:
A prospective, randomized, double-blind study. Anesthe-
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2. Gambling DR, Huber CJ, Berkowitz J, et al. Patient-
controlled epidural analgesia in labour: Varying bolus dose
and lockout interval. Can J Anaesth 1993;40:211–217.
3. Koehntop DE, Rodman JH, Brundage DM, et al. Pharma-
cokinetics of fentanyl in neonates. Anesth Analg 1986;65:
227–232.
4. Gourlay GK, Kowalski SR, Plummer JL, et al. Fentanyl blood
concentration-analgesic response relationship in the treatment
of postoperative pain. Anesth Analg 1988;67:329–337.
5. Van Nimmen NF, Poels KL, Menten JJ, et al. Fentanyl trans-
dermal absorption linked to pharmacokinetic characteristics in
Department of Anesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada.
BREASTFEEDING MEDICINE
Volume 11, Number 1, 2016
ªMary Ann Liebert, Inc.
DOI: 10.1089/bfm.2015.0173
40
patients undergoing palliative care. J Clin Pharmacol
2010;50:667–678.
6. Steer PL, Biddle CJ, Marley WS, et al. Concentration of
fentanyl in colostrum after an analgesic dose. Can J Anaesth
1992;39:231–235.
7. Brimdyr K, Cadwell K, Widstrom AM, et al. The association
between common labor drugs and suckling when skin-to-
skin during the first hour after birth. Birth 2015 October 13
[Epub ahead of print]. doi: 10.1111/birt.12186.
Address correspondence to:
Albert Moore, MD
Department of Anesthesia
Royal Victoria Hospital
1001 Decaire Boulevard
Montreal, QC, H4A 3J1, Canada
E-mail: moore_albert@hotmail.com
CORRESPONDENCE 41
... They found that all three drugs can be detected in maternal and umbilical venous plasma at the time of delivery. In a case reported by Moore et al, [30] a 39week pregnant woman received epidural analgesia with a mixture of 0.06% bupivacaine and 2 mg/mL fentanyl for 11 h (280 mg fentanyl given). At 24 h after delivery, fentanyl could still be detected in the urine of both mother (2.0 ng/mL) and neonate (2.4 ng/mL). ...
... At 24 h after delivery, fentanyl could still be detected in the urine of both mother (2.0 ng/mL) and neonate (2.4 ng/mL). [30] Therefore, both local anesthetics and opioids administered for ELA can arrive neonates and produce effects. ...
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This review summarizes recent evidences regarding the potential influences of epidural labor analgesia (ELA) on the outcomes of neonates and children. Terms and relevant words including "ELA," "ELA and neonatal outcomes," "ELA and children's development," and "ELA and children's neurocognitive development" were used to search articles published in PubMed database up to October 2019.Original articles and reviews regarding potential influences of ELA on neonates and children were identified. Relevant references of the selected articles were also screened. The anesthetics used during ELA can be absorbed, enter the fetus, and produce neonatal depression; however, these effects are less severe than those during systematic opioid analgesia. The impact of anesthetic exposure during ELA on children's neurodevelopment has not been fully studied, but would be mild if any. ELA increases the risk of intrapartum maternal fever; the latter may be harmful to neonatal outcomes. The use of ELA may increase birth injury by increasing instrumental delivery, although long-term adverse events are rare. On the other hand, ELA may reduce maternal depression and, thus, produce favorable effects on neurocognitive development in childhood; but evidences are still lacking in this aspect. ELA may produce both favorable and unfavorable effects on neonates and children. These effects should be discussed with parturient women before making decisions. The potential harmful effects should be carefully managed. The overall impacts of ELA on neonatal and children's outcomes need to be studied further.
... Historically maternal fentanyl analgesia has been identified in fetal blood. Recently, a case report noted the presence of fentanyl in neonatal urine and raised concern that drug levels associated with detectable urine fentanyl may have unknown clinical consequences (19). Urine screening is typically performed using a fentanyl homogenous enzyme immunoassay (20). ...
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Background: Fentanyl is commonly given as an analgesic during labor and delivery. The extent of transplacental drug transfer and fetal exposure is not well studied. We analyzed the relationship between neonatal urine fentanyl results and various peripartum factors. Methods: A total of 96 neonates with urine toxicology screening between January 2017 and September 2018 were included in the study. Medical record review was used to obtain maternal, neonatal, and anesthesia parameters. A subset of 9 specimens were further tested for levels of fentanyl and norfentanyl by liquid chromatography-tandem mass spectrometry. Results: In 29% (n = 24) of cases associated with fentanyl-containing labor analgesia, neonatal toxicology screens were positive for the presence of fentanyl. Positive test results strongly correlated with the cumulative dose and duration of labor analgesia (P < 0.001). The odds of positive neonatal fentanyl screen results increased 4-fold for every 5 hours of maternal exposure to labor analgesia. Importantly, however, neonatal outcomes for infants with positive and negative urine fentanyl screens were the same. Conclusions: Our study establishes that maternal fentanyl analgesia is strongly associated with positive neonatal urine fentanyl screens and suggests that more judicious use of these laboratory tests may be warranted.
... A placental transfer of 90% has been measured by Moises (61). Fentanyl has been measured in the newborn infant's urine for at least 24 hours postpartum (62). Fentanyl exposure can depress the newborn infant's behaviour during the first hours after birth, especially the suckling behaviour in a dose-dependent manner (29). ...
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... По данным A. Moore и соавт. (2016), концентрация фентани- ла при его эпидуральном введении (280 мкг фен- танила = 25 мкг/ч) сохраняется у новорожденных в течение 24 часов послеродового периода в коли- честве, которое может давать клинические про- явления [23]. Однако в пилотном исследовании M. Kokki и соавт. ...
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Fentanyl transdermal absorption linked to pharmacokinetic characteristics in Department of Anesthesia, Royal Victoria Hospital
  • N F Van Nimmen
  • K L Poels
  • J J Menten
Van Nimmen NF, Poels KL, Menten JJ, et al. Fentanyl transdermal absorption linked to pharmacokinetic characteristics in Department of Anesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada. BREASTFEEDING MEDICINE Volume 11, Number 1, 2016
patients undergoing palliative care
  • Mary Ann Liebert
ª Mary Ann Liebert, Inc. DOI: 10.1089/bfm.2015.0173 patients undergoing palliative care. J Clin Pharmacol 2010;50:667-678.