Can pethidine (meperidine) be used in pregnancy?

Pethidine Use in Pregnancy

Pethidine (meperidine) can be used during pregnancy for labor analgesia, but timing of administration is critical—it should be avoided in the 1-4 hour window before anticipated delivery to minimize neonatal respiratory depression. 1, 2

Evidence-Based Timing Guidelines

Optimal Administration Windows

• Less than 1 hour before delivery: Associated with shorter time to sustained neonatal respiration, likely because insufficient drug has transferred to the fetus 1
• 1-4 hours before delivery: Avoid this window—this is when maximal neonatal depression occurs due to peak fetal drug accumulation 1, 2
• More than 4 hours before delivery: Safer window as maternal-to-fetal transfer begins to plateau, though some neonatal effects may still occur 1, 2

Pharmacokinetic Rationale

• Continuous net transfer of pethidine from mother to fetus occurs for approximately 2 hours after maternal injection 1
• Fetal pethidine concentration reaches peak-plateau between 1-5 hours after maternal dose 2
• The feto-maternal drug ratio varies between 0.35 and 1.5, with positive correlation to the injection-delivery time interval 2
• Maternal plasma half-life is 3.4 hours, with peak maternal concentrations of 300-650 ng/ml after 1.5 mg/kg intramuscular dose 2

Clinical Efficacy and Safety

Labor Duration Benefits

• Pethidine significantly shortens the active phase of labor (odds ratio 2.906), particularly when combined with multiparity 3
• Effective for both nulliparous and multiparous women in reducing active phase duration 3
• No significant effect on second stage of labor duration 3

Neonatal Safety Profile

• No significant differences in mechanical ventilation requirements, Apgar scores, or NICU admissions when used appropriately 3
• Neonatal depression is related to unmetabolized pethidine transferred from mother to fetus, not to the metabolite norpethidine 1
• Norpethidine concentrations increase with longer injection-delivery intervals but remain too low to affect the newborn 1

Practical Management Algorithm

Dosing

• Standard dose: 100 mg intramuscularly 1 or 0.8 mg/kg 4
• Alternative: 1.5 mg/kg intramuscular produces predictable plasma levels 2

Monitoring Requirements

• Naloxone should be immediately available for neonatal resuscitation 1, 5
• Naloxone reverses respiratory depression in approximately 40% of cases, particularly when intrauterine pethidine exposure exceeds 1 hour 1
• Naloxone can be administered to the neonate before delivery or injected into the umbilical vein after delivery 5

Alternative Considerations

• Nalbuphine (0.1 mg/kg) may be preferable due to its "ceiling effect" on respiratory depression, providing longer analgesic duration (6 hours) with better safety profile for both mother and newborn 4
• Nalbuphine produces more sedation but fewer overall side effects compared to pethidine 4

Critical Pitfalls to Avoid

• Never administer pethidine 1-4 hours before anticipated delivery—this is the window of maximal neonatal risk 1, 2
• Do not assume norpethidine metabolite causes neonatal depression; the parent compound is responsible 1
• Ensure naloxone is immediately available regardless of timing, as approximately 40% of neonates may require reversal 1
• Do not use pethidine as sole analgesic without considering epidural anesthesia or other regional techniques for patients who can access them 3

Clinical Context

Pethidine remains a reasonable option for labor analgesia, particularly for patients who cannot receive or afford epidural anesthesia 3. The key to safe use is strict attention to timing relative to anticipated delivery and immediate availability of neonatal resuscitation with naloxone 1, 5.