What are the guidelines for using fentanyl (synthetic opioid) in pregnancy?

Guidelines for Using Fentanyl in Pregnancy

Fentanyl should be used with extreme caution during pregnancy, reserved only for severe pain unresponsive to other treatments, using the lowest effective dose for the shortest duration possible, due to potential risks to both mother and fetus. 1

Safety Profile and Risks

Fentanyl use during pregnancy is associated with several potential risks:

• Possible association with stillbirth, poor fetal growth, preterm delivery, and birth defects 2
• Risk of neonatal opioid withdrawal syndrome 2
• Potential for maternal respiratory depression and sedation
• Risk of opioid dependence (approximately 1 in 300 women may become dependent after treatment) 1

Clinical Decision Algorithm for Fentanyl Use in Pregnancy

First-line Approach

• Use non-pharmacological interventions first (physical therapy, proper postural hygiene, rest periods, heat or cold therapy, acupuncture) 1
• If medication is needed, acetaminophen is the preferred first-line agent (650 mg every 6 hours or 975 mg every 8 hours) 1

Second-line Approach (Second Trimester Only)

• NSAIDs may be used for short-term (7-10 days) in the second trimester only 1
• Avoid NSAIDs in first trimester (risk of congenital malformations) and third trimester (risk of premature closure of ductus arteriosus) 1

Third-line Approach (Severe Pain Only)

• Fentanyl should be considered only when:
  1. Pain is severe and unresponsive to other treatments
  2. Benefits clearly outweigh risks
  3. No alternatives are available or effective 2, 1

Administration Guidelines When Fentanyl Is Necessary

If fentanyl must be used during pregnancy:

1. Dosing: Use the lowest effective dose for the shortest possible duration 1
2. Monitoring: Implement close maternal and fetal monitoring during administration 2
3. Delivery Planning: Arrange for delivery at a facility prepared to monitor, evaluate, and treat neonatal opioid withdrawal syndrome 2
4. Route of Administration:
   • IV administration appears to be safe when properly dosed 3, 4
   • Epidural administration is commonly used for labor pain 5
   • Subcutaneous administration has been studied with promising results 6

Special Considerations for Procedural Use

When fentanyl is used for procedural sedation during pregnancy (e.g., endoscopy):

• Fentanyl appears to be safe for humans during pregnancy when used for procedural sedation 2
• Position patients with a left pelvic tilt or left lateral position to avoid vascular compression 2
• Avoid positioning patients on their backs to prevent compression of the aorta or inferior vena cava 2
• Consider periprocedural fetal monitoring in consultation with an obstetrician 2
• If benzodiazepines are required for sedation, midazolam is preferred, though benzodiazepines should generally be avoided in the first trimester 2

Maternal-Fetal Transfer

• Fentanyl readily crosses the placenta to the fetus 7
• Studies show extensive fetal exposure to fentanyl, with median fetal/maternal concentration ratios of 0.63-0.69 8
• Despite concerns about ion trapping in acidemic fetuses, significant accumulation of fentanyl in the fetus has not been observed even with fetal acidosis 8

Neonatal Effects

• Short-term use of fentanyl during labor has shown minimal adverse effects on neonates 3, 4
• Studies have found normal neonatal neurological and adaptive capacities at two and 24 hours after birth 3, 4
• However, chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures characteristic of neonatal abstinence syndrome 7

Breastfeeding Considerations

• Fentanyl is excreted in human milk 7
• Not recommended for use in nursing women because of the possibility of effects on infants 7
• If used during labor, monitor the infant for potential sedation and respiratory depression

Key Pitfalls to Avoid

1. Prolonged use increasing the risk of neonatal opioid withdrawal syndrome
2. Failure to arrange appropriate neonatal monitoring after delivery
3. Concurrent use with benzodiazepines, which increases risk of respiratory depression
4. Inadequate maternal monitoring for signs of respiratory depression or sedation
5. Failure to consider the impact on breastfeeding

Remember that for pregnant women with opioid use disorder, medication-assisted therapy with buprenorphine or methadone is preferred over withdrawal management and should be offered 2.