Neuraxial opioids and the newborn Petter Kainu SOAT, Tartto

 Epidural analgesia in the latent phase of labor and the risk of cesarean delivery: a five-year randomized controlled trial. Epidural analgesia in the latent phase of labor and the risk of cesarean delivery: a five-year randomized controlled trial. Epidural analgesia in the latent phase of labor and the risk of cesarean delivery: a five-year randomized controlled trial.  Wang F. Shen X. Guo X. Peng Y. Gu X. Labor Analgesia Examining Group.  Anesthesiology (4):871-80

Labour analgesia and the baby: good news is no news Felicity Reynolds, IJOA 2011

Backround  newborn is very sensitive to opioids  newborn metabolizes opioids slowly  no balancing pain

Assessing newborn  Apgar-scores –are developed originally to assess drug- influence –unsensitive  Neonatal acid-base status –reflects the function of placenta –reflects poorly drug influences

Assessing newborn  NACS (Neurologic and Adaptive Capacity Scoring System) + and other scoring systems –muscular tone, reactivity,reaction to different stimuli  beginning of spontaneous breathing  pCO2  pulseoximetry  drug concentrations from blood samples

Kinetics of epidural opioid  epidurally administered opioids enter rapidly circulation  lipophilic opioids rapidly cross the placenta  ion trapping (acidotic fetus)

Kinetics of epidural opioid  if ≥ µg of fentanyl is used, the baby has measurable amouts of fentanyl in circulation –Epidural fentanyl in labour. Carrie LE. O'Sullivan GM. Seegobin R. Anaesthesia (10):965-9 Epidural fentanyl in labour.Epidural fentanyl in labour.  if epidural-infusions are used, fentanyl does not seem to accumulate –Maternal and neonatal fentanyl and bupivacaine concentrations after epidural infusion during labor. Bader AM. Fragneto R. Terui K. Arthur GR. Loferski B. Datta S. Anesthesia & Analgesia (4): Maternal and neonatal fentanyl and bupivacaine concentrations after epidural infusion during labor.Maternal and neonatal fentanyl and bupivacaine concentrations after epidural infusion during labor.

Epidural opioid & respiratory depression  case reports  Epidural Opioid Analgesia and Neonatal Respiratory Depression. Kumar M, Paes B. Journal of Perinatology (5):425-7 Epidural Opioid Analgesia and Neonatal Respiratory Depression. Epidural Opioid Analgesia and Neonatal Respiratory Depression.

Epidural opioid & NACS  with epid-/iv-opioid. vs no analgesic in some studies babies have had lower NACS –Maternal analgesia during labor disturbs newborn behavior: effects on breastfeeding, temperature, and crying. Ransjo-Arvidson AB. Matthiesen AS. Lilja G. Nissen E. Widstrom AM. Uvnas-Moberg K. Birth (1):5-12 Maternal analgesia during labor disturbs newborn behavior: effects on breastfeeding, temperature, and crying.Maternal analgesia during labor disturbs newborn behavior: effects on breastfeeding, temperature, and crying. –observational study (n=28) –unmedicated infants were more active (video recorded and analyzed by experts)

Epidural opioid & NACS  Effect of labor epidural analgesia with and without fentanyl on infant breast- feeding: a prospective, randomized, double-blind study. Beilin Y. Bodian CA. Weiser J. Hossain S. Arnold I. Feierman DE. Martin G. Holzman I. Anesthesiology 2005: 103(6): Effect of labor epidural analgesia with and without fentanyl on infant breast- feeding: a prospective, randomized, double-blind study. Effect of labor epidural analgesia with and without fentanyl on infant breast- feeding: a prospective, randomized, double-blind study.  when ≥ 150 μg fentanyl was used, NACS were slightly lower (p=0,03)

Breast feeding & epidural analgesia  the initiation of breast feeding is crucial for breast feeding to be succesfull  if infant is less active or ”tired” the interaction may become disturbed  opioid may supress activity of the infant

Breast feeding & epidural analgesia  Breast-feeding problems after epidural analgesia for labour: a retrospective cohort study of pain, obstetrical procedures and breast-feeding practices. Volmanen P. Valanne J. Alahuhta S. International Journal of Obstetric Anesthesia (1):25-9 Breast-feeding problems after epidural analgesia for labour: a retrospective cohort study of pain, obstetrical procedures and breast-feeding practices. Breast-feeding problems after epidural analgesia for labour: a retrospective cohort study of pain, obstetrical procedures and breast-feeding practices.

Volmanen et al.  only part of the epidurals had fentanyl  bupivacaine?

 The impact of intrapartum analgesia on infant feeding. The impact of intrapartum analgesia on infant feeding. The impact of intrapartum analgesia on infant feeding. Jordan S. Emery S. Bradshaw C.Watkins A. Friswell W. International Journal of Obstetrics & Gynaecology (7):  retrospective review, pts

 Intrapartum epidural analgesia and breastfeeding: a prospective cohort study Torvaldsen S. Roberts CL. Simpson JM. Thompson JF. Ellwood DA. International Breastfeeding Journal 2006, 1:24 Intrapartum epidural analgesia and breastfeeding: a prospective cohort study Intrapartum epidural analgesia and breastfeeding: a prospective cohort study  n=1280

 Epidural analgesia and breastfeeding: a randomised controlled trial of epidural techniques with and without fentanyl and a non-epidural comparison group. Epidural analgesia and breastfeeding: a randomised controlled trial of epidural techniques with and without fentanyl and a non-epidural comparison group. Epidural analgesia and breastfeeding: a randomised controlled trial of epidural techniques with and without fentanyl and a non-epidural comparison group. Wilson M. J. A. MacArthur C. Cooper G. M. Bick D. Moore P. A. S. Shennan A. Anaesthesia (2):

 n=1064  Study groups:  Low dose infusion-group (LDI group): bolus (30 µg fent +15 mg bupiv in 15 ml), followed by infusion (10 ml/h)  CSE-group: Spinal (Bup 5mg + Fent 25 µg) follwed by epidural infusion as in LDI-group  Control group: Epidural bolus (15 mg bup without fentanyl), infusion without fentanyl  Two comparison groups without epidural analgesia (pethidin/no pethidin- not randomized)  Rescue medication: –Control group: Epidural fentanyl 50µg  Results: –Epidural fentanyl did not affect breast feeding –Pethidine had negative influence on breast feeding

Conclusions  epidural labour analgesia/opioid can influence infant  serious influences are unlikely  breast feeding seems to be adversely affected  most studies are non-randomized cohort studies –except  Beilin et al 2005  Wang et al 2009  Wilson et al 2010

Conclusions  Editorial in Anesthesiology in regard to Beilin study: –”We should continue to use medications that are known to be effective and are satisfactory to patients, and provide the best obstetric outcome possible.”  Obstetric Anesthesia Diggest: –”As lower consentrations of local anesthetic are assosiated with many benefical effects for mother and baby, fentanyl should not be discarded based on weak links.”

 Reynolds F: Labour analgesia and the baby: good news is no news. International Journal of Obstetric Anesthesia (1):38-50 Labour analgesia and the baby: good news is no news. Labour analgesia and the baby: good news is no news. –” The effect on breast feeding has yet to be established, though it is certainly no worse than that of systemic opioid analgesia.”

However,  should we restrict larger doses of epidural opioids? –not > 150 µg of fentanyl?

 More studies are warranted!