Placental Transfer Of Anaesthetic Drugs:

Mohamed Hamed Abdel-rahman

In an attempt to defme the risk to the fetus associated withanesthesia during pregnancy, this essay was performed. It includes ananatomical and physiological description of the maternal- placental- fetalunit with description of the placental functions:1- Nutritional function.2- Hormonal enzyme production.3- Blood placental barrier function.4- Placental transfer of respiratory gases.5- Immunological.Placental transfer of the drugs was found to depend upon:1- Lipid solubility of the drug.2- Degree of ionization of the drug.3- Protein binding.4- Molecular weight to the drug.5- Maternal- fetal concentration gradient.6- Placental factors as area and thickness of the membrane, maternal andfetal blood flow, and placental enzymes.Also, fetal uptake of the drugs depends on:I) Alteration in fetal circulation.2) Fetal PH.3) Plasma protein binding.4) Fetal metabolism.5) Tissue binding.Effects of anesthetic drugs on the fetus. It includes the effects of:1-Intravenous anesthetic agents e.g. thiopentone, methohexitione,barbiturates, ketamine, etomidate, althesin, propanidid, propofol,benzodiazepines, narcotic analgestic and narcotic antagonists.2- Neuromuscular blocking agents e.g. suxamethonium, tetrahydroamine,decamethonium, alcuronium, pancuronium, D-Tubocurarine,gallamine, rapacuronium, rocuronium, fazadinium, vecuronium andatracurium.3- The volatile and gaseous anesthetics e.g. nitrous oxide, halothane,methoxyflurane, fluroxene, trichloroethylene, ether, cyclopropone,enflurane isoflurane, and sevoflurane.4- Local anesthetics placental transfer of local anesthtic drugs dependsupon:a. Maternal factors1-Total dose of drug.2- Protein binding.3- The ionization constant.4- Metabolism and excretion.5- Injection site.6- Addition of adrenaline.7- Placental blood flow.b. Fetal/actors as protein binding, hepatic uptake and fetal’ pH.The local anesthetic drugs include lignocaine, prilaocaine,mepivacaine, buplvacaine, ropivacaine, procaine.All commonly used anesthetic agents and drugs undergo placentaltransfer. Understanding the placental transfer of anesthetic drugs and theireffects on the neonate is essential for optimal administration of bothregional and general anesthesia.Drug exposure before organogenesis usually causes all or noneffect, i.e. the embryo either doesn’t survive or develops withoutabnormalities, while use of drugs in late pregnancy may lead to multipleorgan involvement, developmental syndrome or intrauterine growthretardation. There is no overall increase in congenital abnormalities andno obvious relationship, between outcome and type of anesthesia.Elective surgery should not be performed in parturient as it canhave both immediate and long term undesirable effects on the fetus,hypertension, hypovolemia, hypoxemia and marked increase insympathetic tone can seriously compromise the transfer of oxygen andother nutrients across the uteroplacntal circulation and promoteintrauterine fetal asphyxia. The stress of surgery may also precipitatepreterm labor which often follows intra abdominal surgery. Secondtrimester procedures and those do not involve uterine manipulation carrythe lowest risk of preterm labor.Volatile anesthetics depress myometrial irritability andtheoretically are advantageous for abdominal procedures, however thereis no evidence that any specific technique influences the risk of pretermlabor. In any serious maternal condition the remote fetal risk of anesthesiaand operation are secondary to preserving the life of the mother.The choice of anesthesia. For cesarean section is determined bymultiple factors, including obstetric indication, its urgency, patient andobstetrician preferences and the skills of the anesthetist.SummaryThere is a world wide shift in obstetric practice in favor of regionalanesthesia. Both epidural and spinal anesthesia have advantages anddisadvantages for cesarean section compared to general anesthesia.Regional anesthesia offers reduced maternal mortality as it minimize theproblem of maternal aspiration, the ability to use fewer drugs, more directexperience of child birth and the capability to decrease blood loss, besideit provide excellent postoperative pain control and avoid neonataldepression associated with general anesthesia, recently the regionalanesthesia provides fewer modification of neonatal immune function.The disadvantage of the regional anesthesia include, hypotension,nausea, vomiting, intra operative discomfort, post lumbar headache andpotential for neurologic and cardiac toxicity from local anesthetics.Direct effects of local anesthetics: Although a diminution ofvariability of FHR has been reported after the beginning of an epiduralanesthesia using lidocaine, no significant modification of FHR afterepidural anesthesia using lidocine or bupicacaine with epinephrine hasbeen shown. Fetal neurologic toxicity is rare and there are very littlealterations of neurobehavioral scores, however the addition of opioids tothe epidural infusions may reintroduce the problem of neonatalrespiratory depression with systemic opioids. Although the addition ofopioids allow the reduction in the dose of local anesthetics withoutcompromising analgesia, lesser motor blockade, greater maternal mobilityand satisfaction. Sufentanil in doses up to 30~g in association withbupivacaine seems to be devoid of depressive effects on neonate.Indirect effects of local anesthetics: In high concentrations, localanesthetics entail a vasoconstriction of uterine vessels but the main fearedeffect is maternal hypotension that impedes directly the uteroplacentialSummaryblood flow (best prevented by 20-25 mL/kg crystalloid preload andprompt treatment with ephedrine) fetal consequences depend on theimportance and the duration of uteroplacental blood flow (UBF) decrease,the preliminary, state of uteroplacental circulation and hemodynamicadaptive capacities of the fetus when the former are exceeded, fetalhypoxia occurs and both myocardial and brain oxygenation can be rapidlyimpaired if the hemodynmics is not corrected.Ropivacaine (0.08%) in labor epidural analgesia produces goodlabor pain relief with no detectable adverse effects on the mother and the.neonate and without causing significant increase in cesarean section rate,also epidural 0.5% ropivacaine for CS do not compromise theuteroplacental circulation in healthy parturient and provides surgicalanesthesia as effective as 0.5% bupivacaine.In contrast to regional anesthesia for CS, general anesthesia has thefollowing advantages, less hypotension better control of airway andventilation. Pre- oxygenation is followed by rapid sequence induction,muscle relaxation and endotraceal intubation accompanied by cricoidpressure. Hyperventilation should be avoided, maintaining end- tidal CO2in the normal range for pregnancy (32- 34mmHg). Respiratory alkalosiscan compromise maternal-fetal oxygen transfer by causing umbilicalartery constriction and shifting the maternal hemoglobin dissociationcurve to the left. In addition positive pressure ventilation may reduceuterine blood flow and cause fetal acidosis as a consequence of increasedintra- thoracic pressure decreasing venous return and cardiac output.A technique employing a high concentration of oxygen, an opioidand moderate concentration of volatile agent with a muscle relaxant isoften used. In halation anesthetic diffuse readily but provided that the-U)6-induction- delivery is short. Neuromuscular blocking compounds andfully ionized cross the placenta very slowly, fetal maternal ratio atdelivery very low also bolus doses of succinylcholine are safe. Doses ofthiopental greater than 8mg/k- maternal weight produce neonataldepression. A dose of 4-7 mg/kg- maternal weight is commonlyadvocated for induction of general anesthesia as it ensuresunconsciousness beside wide clinical use testifies to the safety of thethiopental. On the other hand there is conflicting evidence concerning theeffect of propofol on the neonate, induction doses as 5mg/kg/h haveshown to cause significant neonatal depression. Neonatal elimination ofpropofol is slower than in adults unless thiopental is contraindicated.There seems little advantage in using propogol in cesarean section.The use of Benzodiazepines should be avoided if possible as theneonate may suffer from respiratory depression, hypotonia, poorthermoreguation and raised bilirubin concentrations. Opioids are mainlyweak bases bound to eel- glycoprotein, pethidine and its metabolitenormaperidine depress all neurobehavioral aspects of the neonate.Neonatal elimination is slower, resulting in prolongation of its effect.Neonatal elimination is slower, resulting in prolongation of its effect.Transfer of pethidine is increased in the presence of fetal acidosis,depressant effect are maximum when administration to delivery time is 2-3 hours (Elton and MacDonald, 2001). One the other hand Apgar andneurobehavioral scores are less affected after maternal IV administrationof fentanyl and alfentanil, while remifentanil is useful in obstetricsituation in which opioid based general anesthesia is desirable withexcellent fetal outcome.Maternal monitoring should include blood pressure measurement,EeG, pulse oximetry, cabnography, temperature monitoring and use ofnerve stimulator. FHR and uterine contractions should be monitored intraand post operatively when possible.Neonatal resuscitation is not without risk, iatrogenic laryngospasmtrauma to upper airway, pneumotheorax and tracheal perforation are allrecognized hazards. The administration of drug as oxygen naloxoneadrenaline and sodium bicarbonate are potentially dangerous particularlyif clinician is experienced. In addition, an infant who is depressedsecondary to anesthetic agents, will develop biochemical changes ofasphyxia if apnea persists for more than a few minutes or resuscitation isineffective.Finally, the skill and knowledge of the anesthesiologist are moreimportant than the type of the anesthesia administered, therefore whenproperly performed, both regional and general anesthesia are quite safe interms of neonatal outcome.