1. Effects ofmaternal analgesia and anesthesia on the fetus and newborn BY MAGED ZAKARIA NICU Resident

2. PART I:ANALGESIA FOR LABOUR Nonpharmacologic methods Continuous labour support The use of baths, even if membranes were ruptured. Touch/massage Intradermal water blocks Maternal movement and positioning Systemic opioids Nitrous oxide (N2O) Paracervical block Neuraxial analgesia

3. Potential Adverse Effects of Untreated Maternal Pain on the Fetus Compensatory MA VC of uterine vessels Left shift of oxyhemoglobin dissociation curve with  O2 release to tissues  Placental perfusion Lipolysis Increased FFA  Ketosis

5. Opioids may affect the fetus directly, as a result of placental transfer, and/or indirectly, by affecting maternal ventilation or uterine tone. These effects are largely dose rather than drug dependent.

7. Naloxone (Narcan® 0.4 mg / mL) Narcotics given to the mother inhibit respiratory drive and activity in the newborn. In such cases, administration of naloxone(a narcotic antagonist) to the newborn will reverse the effect of narcotics on the baby. Note Giving a narcotic antagonist is not the correct first therapy for a baby who is not breathing. The first corrective action is PPV. Dose0.1 mg/kg IV push or IM, if adequate perfusion (equal to 0.25 mL/kg of the 0.4 mg/mL concentration). Onset of action is within minutes after IV dose and within 1 hour, if given IM. Tracheal administration is not recommended. MonitorRespiratory effort, Neurologic status. No short-term toxicity reported. Narcan® is contraindicated for infants of narcotic-dependent mothers, as it may precipitate acute withdrawal and convulsions.

8. Indications of narcan® : 1. Continued respiratory depression after PPV has restored a normal HR and color. And 2. A history of maternal narcotic administration within the past 4 hours. After Narcan® administration, continue to administer PPV until the baby is breathing normally. The duration of action of the narcotic often exceeds that of Narcan®. Therefore, observe the baby closely for recurrent respiratory depression, necessitating repeated doses.

9. Caution: Other drugs given to the mother, such as MgSO4 or non-narcotic analgesics or general anesthetics, also can depress respirations in the newborn and will not respond to Narcan®. If maternal narcotics were not given to the mother or if Narcan® does not result in restoring spontaneous respirations, transport the baby to the NICU for further evaluation and management while continuing to administer PPV.

10. 2. Nitrous oxide (N2O) N2O readily crosses the placenta but it has no effect on uterine contractions or FHR. It is not metabolized, and is eliminated quickly and entirely by the lungs with the onset of respiration at birth whether the mother inhales N2O for 5 minutes or 5 hours. N2O does not affect Apgar scores or sucking behaviour.

11. Paracervical block (PCB) Transvaginal injection of LA on either side of the cervix in order to interrupt pain transmission at the level of the uterine and cervical plexuses (located at the base of the broad ligament). It’s relatively easy to perform and, when effective, it provides good to excellent analgesia that lasts 1-2 hours. Since its introduction in the 1940’s, reports of serious adverse sequelae, including injection of LA directly into the uterine arteries or fetal head, fetal death, and profound bradycardia, have resulted in modification of the injection technique and changes to the concentration and type of LA used. Overall, in current practice, the incidence of fetal bradycardia post-block is about 15%, with the onset beginning 2-10 minutes after injection and the bradycardia lasting 15-30 min. The exact etiology may be an increase in uterine artery tone, (vasoconstriction). However, this doesn’t affect Apgar scores, umbilical arterial and venous pH.

12. Neuraxial analgesia Spinal, epidural and combined spinal-epidural (CSE) techniques are used to administer opioids, LA, and other pain-modulating adjuvants. 1. NEURAXIAL OPIOIDS Fetal bradycardia may develop following administration of intrathecalopioid, although its occurrence can follow any type of effective labour analgesia. While technique-specific etiologies can occur (for example, maternal hypotension or fetal LA toxicity), uterine hypertonus as the mechanism inciting the transient but profound drop in heart rate was first reported in 1994. Bilateral lumbar sympathetic block for first stage labour pain caused abnormal uterine contraction patterns to normalize and previously normal patterns to become hyperactive. The etiology is thought to be related to a change in the balance of circulating catecholamines, favouring α- over ß-activation of smooth muscle receptors as a result of the contraction inducing norepinephrine predominating over the contraction-relaxing epinephrine effect. FHR decreases because of a reduction in uteroplacental blood flow.

13. The effect may be more pronounced with the use of oxytocin. Bradycardia occurs faster with spinal analgesia (<10 minutes) and more slowly with epidural analgesia (15–30 min). The hypertonus usually lasts < 10 minutes and can be relieved by administration of a nitric oxidedonor such as nitroglycerin (50–100 μgiv), or a ß2 agonist such as terbutaline (125–250 μgiv), in cases of prolonged fetal bradycardia. The observed changes in FHR have not correlated with observable clinical differences in neonatal outcome, including Apgar scores, cord pH, or admission rate to a NICU.

14. 2. NEURAXIAL LA In general, when LA are used alone, concentrated solutions are required to afford pain relief. Since block density is dose dependent, the more concentrated the solution used, the greater the degree of motor block expected; this has been implicated in pelvic muscle relaxation-induced fetal malposition, maternal inability to push, and need for instrumental delivery.

15. 3. COMBINING OPIOIDS, LA, AND PAIN-RELIEVING ADJUVANTS When spinal, epidural, and CSE techniques involve combinations of pain-modulating drugs (sodium channel blocking agents, opioid-receptor agonists, α- adrenergic agonists and/or acetylcholinesterase inhibitors) acting by different mechanisms, there is potential to afford analgesia with minimal motor blockade and other relevant side effects.

16. Labour epidurals and outcome Epidural analgesia was associated with: Longer second stage labour (~ 14 min). More fetal malposition (occiput posterior). A higher rate of instrumental vaginal deliveries. (Vacuum extraction or forceps) put the baby at risk of injury, including hemorrhagic morbidities such as subgaleal hematomacephalohematoma and cerebral hemorrhage. Forceps use is also associated with facial nerve and brachial plexus injury. Maternal fever. Increased use of oxytocin augmentation.

17. PART II: ANESTHESIA FOR LABOUR Types: General anesthesia Regional anesthesia (spinal, epidural or combined spinal and epidural anesthesia) In Urgent CS (such as cases with heavy, rapid bleeding or other haemodynamic compromise), RA may not be appropriate and GA is considered.

18. 1. Regional anesthesia (RA) Regional anesthesia (95% of CS) is preferred as it allows the mother to be awake and react immediately with her baby. It is different to the analgesia (pain relief) used in labor and vaginal delivery. The pain that is experienced because of surgery is greater than that of labor and therefore requires a more intense nerve block. The dermatomal level of anesthesia required for CS is also higher than that required for labor analgesia.

21. The routine measures used to maintain uteroplacental perfusion and prevention of hypotension includeiv fluid loading,lower leg compressive stockings and left lateral tilt position. Vasopressor therapy is reserved for the treatment rather than prevention of hypotension. Ephedrine (a mixed αß agonist) use was associated with lower umbilical arterial pH values when compared with phenylephrine (pure α agonist). Fetal acidemia may be due to the metabolic effects of ß-stimulation in the fetus or insufficient maintenance of uteroplacental perfusion by failure to reclaim sequestered blood from the splanchnic bed in order to augment preload. Regardless, the choice of a vasopressor drug is perhaps less important than the avoidance of hypotension.

22. 2. General anesthesia (GA) An important factor affecting neonatal outcome is the elapsed time between the induction of anesthesia and clamping of the umbilical cord, as this represents the time of fetal exposure to maternally administered medication. A second factor is the time from uterine incision to delivery of the baby. A long incision to delivery time is associated with an  incidence of fetal acidosis, caused by uteroplacental vasoconstriction. If possible, induction to clamp time should be <10 minutes and uterine incision to delivery time < 3 minutes.

23. induction agents used to initiate GA Sodium thiopental (Intraval®) Following IV injection, it rapidly reaches the brain and causes unconsciousness within 30-45 seconds. At 1 minute, it reaches a peak concentration of about 60% of the total dose in the brain. Thereafter, the drug distributes to the rest of the body and in ~ 5–10 minutes the concentration is low enough in the brain such that consciousness returns. It peaks in umbilical arterial plasma at 3-5 minutes and declines rapidly until 11 min. Induction to umbilical cord clamp times of approximately 10 minutes coincide with declining fetal levels of this agent and therefore little neonatal depression. Thiopental is not used to maintain anesthesia because, in infusion, it displays zero-order elimination kinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an inhaled anesthetic agent.

24. Ketamine (Ketalar®) is usually reserved for situations involving maternal hemodynamic instability because it preserves sympathetic outflow. Ketalartends to increase HR and BP. Because ketamine tends to increase or maintain cardiac output, it is sometimes used in anesthesia for emergency surgery when the patient's state of fluid volume status is unknown.

25. Midazolam(Dormicum®) and Propofol (Diprivan®) have been associated with longer induction times, a lighter plane of maternal anesthesia (as measured by EEG), and lower Apgar scores.

26. The inhalation agents Desflurane and sevoflurane would be expected to cross the placenta and equilibrate in fetal tissues more rapidly than their more soluble counterparts (for example, isoflurane), potentially resulting in a more depressed neonate. However, once the newborn establishes ventilation the lungs would excrete ("blow off") these relatively insoluble drugs more quickly. Desflurane is more pungent and irritating to the airway and may result in laryngospasm. This should be considered when suctioning the neonate whose mother has received desflurane.

27. Neuromuscular blocking drugs They share a structural similarity, a quaternary ammonium ion, which slows but does not eliminate transfer of these drugs across the placenta. Succinylcholine (Sux) is degraded so rapidly by plasma cholinesterase that virtually none reaches the fetus, whereas the percentage of Nondepolarizing neuromuscular blocking drug (for example rocuronium, pancuronium = Pavulon®, and atracurium = Tracrium®) that crosses the placenta ranges from 7 to 22%, depending on the drug. In the setting of high-dose nondepolarizing neuromuscular blockade, it may be necessary to support neonatal ventilation for a period of time or to administer reversal agents.

28. PART III: Postpartum pain management Breastfeeding calls for use of analgesic agents that are transferred minimally into breast milk and have little effect on the neonate. Drug exposure can be minimized if the mother takes medication immediately after nursing or just before the baby is due to have a lengthy sleep, and uses short-acting medications. The neonatal dose of most medications obtained through breastfeeding is 1 to 2% of the maternal dose. Lipid soluble drugs are less likely to accumulate in colostrum, which contains little fat. Only small amounts of colostrum are secreted during the 1st few postpartum days (10–120 mL/day) so newborn exposure from volume is limited.

29. PART III: Postpartum pain management Milk composition continues to change over the 1st 10 days after birth. There is a gradual  in fat and lactose content and  in protein and pH. By day 10 postpartum, factors such as high lipid solubility, low molecular weight, minimal protein binding, and the un-ionized state facilitate secretion of medications into mature breast milk. Women who breastfeed and require GA for surgery are usually counseled to feed their baby before the surgery and temporarily interrupt feeding postoperatively by wasting the first milk sample (express with a breast pump and discard). After that, if the mother feels well enough and there are no surgical contraindications, she is encouraged to resume feeding. Most anesthetics are rapidly cleared from the mother; some authors argue that no portion of human milk need be wasted. The AAP considers paracetamol, most NSAIDs, and morphine compatible with breastfeeding.