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

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
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.
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,
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.
Although the corresponding level is un-
known in neonates, a level of 1.1 ng/mL has necessitated pro-
longed intubation in neonates.
The urinary concentration seems
to have some correlation with fentanyl dosage and levels.
Although fentanyl is transferred in breastmilk, it is virtu-
ally undetectable in colostrum 10 hours after it has been given
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-
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.
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Department of Anesthesia, Royal Victoria Hospital, Montreal, Quebec, Canada.
Volume 11, Number 1, 2016
ªMary Ann Liebert, Inc.
DOI: 10.1089/bfm.2015.0173
patients undergoing palliative care. J Clin Pharmacol
6. Steer PL, Biddle CJ, Marley WS, et al. Concentration of
fentanyl in colostrum after an analgesic dose. Can J Anaesth
7. Brimdyr K, Cadwell K, Widstrom AM, et al. The association
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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
... 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. ...
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). ...
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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Aim This paper integrates clinical expertise to earlier research about the behaviors of the healthy, alert, full‐term infant placed skin‐to‐skin with the mother during the first hour after birth following a non‐instrumental vaginal birth. Method This state‐of‐the‐art article forms a link within the knowledge‐to‐action cycle, integrating clinical observations and practice with evidence‐based findings to guide clinicians in their work to implement safe uninterrupted skin‐to‐skin contact the first hours after birth. Results Strong scientific research exists about the importance of skin‐to‐skin in the first hour after birth. This unique time for both mother and infant, individually and in relation to each other, provides vital advantages to short‐ and long‐term health, regulation and bonding. However, worldwide, clinical practice lags. A deeper understanding of the implications for clinical practice, through review of the scientific research, has been integrated with enhanced understanding of the infant's instinctive behavior and maternal responses while in skin‐to‐skin contact. Conclusion The first hour after birth is a sensitive period for both the infant and the mother. Through an enhanced understanding of the newborn infant's instinctive behavior, practical, evidence‐informed suggestions strive to overcome barriers and facilitate enablers of knowledge translation. This time must be protected by evidence‐based routines of staff.
... 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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Labor analgesia is an important aspect of obstetrics, because it significantly influences the process, quality, result and costs of medical management of labor and delivery. From this perspective, one of the most urgent and not fully resolved issues, that requires further studies, is the efficacy and safety of anesthesiological management of spontaneous vaginal delivery. The review presents detailed information on the effects of labor pain on the fetus and on pathophysiological characteristics of the mother giving spontaneous vaginal birth. The authors discuss the influence of narcotic analgesics, neuroaxial analgesia and inhalation analgesia on perinatal and obstetric outcomes, duration of labor and delivery, rates of surgical delivery, with assessment of their side effects, patient's satisfaction with the quality of analgesia, as well as fetal status at birth, neurological status and umbilical blood gases. The use of narcotic analgesics is associated with the risks of inadequate analgesia and such adverse reactions as nausea, vomiting, dizziness in the mother and respiratory suppression in the newborn. Regional analgesia with highly concentrated analgesic solution is associated with pelvic muscle relaxation that may result in the fetus malposition and an increase in duration of delivery. Inhalation of nitrogen monoxide for labor analgesia is no longer used due to its low effectiveness and frequent side effects. The analysis of few publications on the use of inhalation anesthesia with flurane derivatives shows an absence of papers with detailed description of its safety, maternal and fetal effects of an inhalational anesthetic and its influence on perinatal and obstetric outcomes. Thus, the apparent well-doing of the methods used for labor analgesia and anesthesia is rather relative, and we believe that many issues of anesthesiological management have not been unequivocally resolved from the perspective of their effects on the mother, fetus and the newborn.
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The objective of the paper was to describe the concept Early Breastfeeding Initiation (EBFI). Early breastfeeding initiation (EBFI) is recommended within the first hour following giving birth as a simple strategy in enhancing neonatal health and survival. Despite the clear definition by [WHO] on EBFI, some variations still exists across board on what exactly EBFI initiation is. The variations have compounded negatively on neonatal outcomes hence the need to describe EBFI by assigning measurable attributes for standardisation of operations in maternity units. A literature review of 39 articles was conducted between the years 1999 to 2016 in a period of two weeks from the 1st to the 15th of July 2016. The following search engines were used: Cochrane data base, Journal of human Lactation, Pub- med and MEDLINE. EBFI has been inconsistently described within the same health profession. Taking into cognisant the attributes of EBFI and applying them in the maternity units has a potential of averting neonatal deaths by a significant percentage. Key words: Early breastfeeding initiation.
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Background: Intrapartum drugs, including fentanyl administered via epidural and synthetic oxytocin, have been previously studied in relation to neonatal outcomes, especially breastfeeding, with conflicting results. We examined the normal neonatal behavior of suckling within the first hour after a vaginal birth while in skin-to-skin contact with mother in relation to these commonly used drugs. Suckling in the first hour after birth has been shown in other studies to increase desirable breastfeeding outcomes. Method: Prospective comparative design. Sixty-three low-risk mothers self-selected to labor with intrapartum analgesia/anesthesia or not. Video recordings of infants during the first hour after birth while being held skin-to-skin with their mother were coded and analyzed to ascertain whether or not they achieved Stage 8 (suckling) of Widström's 9 Stages of newborn behavior during the first hour after birth. Results: A strong inverse correlation was found between the amount and duration of exposure to epidural fentanyl and the amount of synthetic oxytocin against the likelihood of achieving suckling during the first hour after a vaginal birth. Conclusions: Results suggest that intrapartum exposure to the drugs fentanyl and synthetic oxytocin significantly decreased the likelihood of the baby suckling while skin-to-skin with its mother during the first hour after birth.
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This double-blind prospective study was designed to determine the best dose variables for patient-controlled epidural analgesia (PCEA) and to compare bolus-only PCEA with continuous infusion epidural analgesia (CIEA) during the first stage of labour. Five groups of parturients self-administered 0.125% bupivacaine with 1:400,000 epinephrine and fentanyl 2.5 μg·ml-1 using PCA pumps programmed as follows: Group A, 2 ml bolus/10 min lockout interval (LI); Group B, 3 ml bolus/15 min LI; Group C, 4 ml bolus/20 min LI; Group D, 6 ml bolus/30 min LI; Group E, 8 ml·hr-1 continuous infusion. Hourly assessments included: VAS scores for pain and satisfaction, sensory and motor block, bupivacaine and fentanyl consumption. Blood samples were collected at birth for maternal and fetal fentanyl concentrations. Data from 68 patients showed no differences among groups in pain relief or maternal satisfaction. Most patients received excellent analgesia and those requiring extra epidural supplements were evenly distributed across groups. There was higher consumption of bupivacaine and fentanyl in Group E than in any of the other four groups: bupivacaine mg·hr-1, mean (SD), 9.4 (2.7) in Group E vs 5.2 (1.7) in Groups A-D inclusive (P<0.0001); fentanyl μg·hr-1, 19.6 (4.6) in Group E vs 12.6 (7.5) in Groups A-D inclusive (P<0.05). Motor block was minimal, whereas sensory levels were higher at the 3- and 4-hour assessments in Groups D and E than in all other groups (P<0.05). Plasma fentanyl concentrations were <0.5 ng·ml-1 in all samples and no sequelae from fentanyl were observed, apart from mild pruritus. Bolus-only PCEA is a safe and effective alternative to CIEA during the first stage of labour irrespective of the initial dose variables selected.
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The purpose of this study was to measure the concentration of fentanyl in human colostrum after intravenous administration of an analgesic dose. Thirteen healthy women were given fentanyl 2 for analgesic supplementation during either Caesarean section or postpartum tubal ligation. Serum and colostrum were collected for 45 min, two, four, six, eight, and ten hours following administration of the drug. Radioimmunoassay showed that colostrum fentanyl concentrations were greatest at 45 min, the initial sampling time, reaching 0.40 +/- 0.059, but were virtually undetectable ten hours later. Fentanyl concentrations were always higher in colostrum than in serum. This concluded that with these small concentrations and fentanyl's low oral bioavailability, intravenous fentanyl analgesia may be used safely in breast-feeding women.
Delivery rates and plasma concentrations vary among patients treated with fentanyl patches. Absorption and urinary excretion characteristics of fentanyl were studied in patients undergoing palliative care. Almost 500 patches were analyzed for residual fentanyl content. Fentanyl and norfentanyl levels were determined in the urine of 50 patients. General and mixed effects linear regression models were established for the relationship between fentanyl dose rate and urinary excretion and to incorporate influencing factors. For different patch nominal dose strengths, wide but comparable variability in estimated dose rate and delivery efficiency was observed (coefficients of variation of 15% to 17%). Fentanyl delivery efficiency was 8.5% higher for patches of 25 microg/h as compared to 75 microg/h and, accordingly, 7.5% for patch application on the arm as compared to the leg. Urinary fentanyl and norfentanyl concentrations varied considerably. The general linear model revealed a positive effect of the calculated transdermal dose rate on urinary fentanyl levels, explaining 34% of the variability (P < .0001). In addition, gender (P = .04) and type of cancer pathology (P = .03) exerted significant effects on the linear model, explaining 40% and 64% of the variability, respectively. Delivery efficiency of fentanyl patches can vary substantially, possibly leading to either underdosing or overdosing.
The pharmacokinetics of fentanyl were studied in fourteen neonates undergoing major surgical procedures. Five patients were less than 1 day of age, seven were 1-4 days old, and two were 7-14 days old. Fentanyl was given intravenously, 10 micrograms/kg (n = 1), 25 micrograms/kg (n = 4), or 50 micrograms/kg (n = 9), and plasma concentrations measured at intervals of up to 18 hr. Average weight was 2.9 kg. The injection of 25 or 50 micrograms/kg of fentanyl over 1-3 min was hemodynamically well-tolerated by all patients. Four newborns without respiratory impairment secondary to surgery or disease needed ventilatory support for an average of 24 hr (range 11-40 hr). Plasma concentrations of fentanyl were most appropriately described by a two-compartment model. The mean +/- SEM values of selected model parameters were volume of the central compartment, 1.45 +/- 0.34 L/kg; volume of distribution at steady state, 5.1 +/- 1 L/kg; clearance, 17.94 +/- 4.38 ml X kg-1 X min-1; and terminal elimination half-life (t 1/2 beta), 317 +/- 70 min. In seven patients transient rebound in plasma fentanyl concentrations of 0.5 ng/ml or greater occurred. In three patients with markedly increased intraabdominal pressure, the t 1/2 beta was 1.5-3 times the population mean. Thus fentanyl disposition in neonates is highly variable, but the t 1/2 beta is predictably prolonged in the presence of increased abdominal pressure.
The influence of labor epidural fentanyl on the neonate is controversial. The purpose of this study was to determine whether epidural fentanyl has an impact on breast-feeding. Women who previously breast-fed a child and who requested labor epidural analgesia were randomly assigned in a double-blinded manner to one of three groups: (1) no fentanyl group, (2) intermediate-dose fentanyl group (intent to administer between 1 and 150 microg epidural fentanyl), or (3) high-dose epidural fentanyl group (intent to administer > 150 microg epidural fentanyl). On postpartum day 1, the mother and a lactation consultant separately assessed whether the infant was experiencing difficulty breast-feeding, and a pediatrician assessed infant neurobehavior. All women were contacted 6 weeks postpartum to determine whether they were still breast-feeding. Sixty women were randomly assigned to receive no fentanyl, 59 were randomly assigned to receive an intermediate dose, and 58 were randomly assigned to receive high-dose fentanyl. On postpartum day 1, women who were randomly assigned to receive high-dose fentanyl reported difficulty breast-feeding (n = 12, 21%) more often than women who were randomly assigned to receive an intermediate fentanyl dose (n = 6, 10%), or no fentanyl (n = 6, 10%), although this did not reach statistical significance (P = 0.09). There was also no significant difference among groups in breast-feeding difficulty based on the lactation consultant's evaluation (40% difficulty in each group; P = 1.0). Neurobehavior scores were lowest in the infants of women who were randomly assigned to receive more than 150 microg fentanyl (P = 0.03). At 6 weeks postpartum, more women who were randomly assigned to high-dose epidural fentanyl were not breast-feeding (n = 10, 17%) than women who were randomly assigned to receive either an intermediate fentanyl dose (n = 3, 5%) or no fentanyl (n = 1, 2%) (P = 0.005). Among women who breast-fed previously, those who were randomly assigned to receive high-dose labor epidural fentanyl were more likely to have stopped breast-feeding 6 weeks postpartum than woman who were randomly assigned to receive less fentanyl or no fentanyl.
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.