الفهرس 
Perinatal Pharmacology and Physiological ConsiderationsOnly 14 pages are availabe for public view
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Abstract
Developments and knowledge of the structure and dynamic function of the placenta during the last century as well as the appearance of various techniques to assess fetal evaluation; eventually encouraged physicians to acknowledge the potential fetal problems associated with administration of anesthetic drugs not only during delivery but a variety of obstetric and non-obstetric indications exist that lead to exposure of both the pregnant mother and her fetus to anesthesia. The anesthesiologist must consider the potential impact of surgery and anesthesia on fetal well-being, the potential for fetal exposure to teratogens among the anesthetic agents and other drugs administered perioperatively, the fetal risk for harmful alterations in uteroplacental perfusion and oxygenation, and risk of preterm delivery. Additional concerns are whether surgery and anesthesia during early gestation pose hazard to the developing fetus, by increasing the risk of congenital anomalies and spontaneous abortion.
Varieties of inhalational, intravenous as well as numerous adjuvant agents are used during general anesthesia and both their direct and indirect effects on the fetus have to be taken into consideration before their administration to the pregnant mother. Nitrous oxide readily crosses the placenta and has been hypothesized to be teratogenic as a result of the interference with DNA synthesis. After considerable years of extensive use, epidemiologic and outcome data does not support withholding nitrous oxide in clinical practice. The use of low-dose halogenated agents such as halothane, isoflurane, sevoflurane, desflurane and enflurane as supplements to nitrous oxide anesthesia is very common. Halothane has demonstrated teratogenicity and toxicity in some animal studies, but this occurred at maternally toxic doses. The anesthetic does not appear to be related to human structural anomalies or abortions. The safety of other halogenated inhalational agents during pregnancy is not backed by specific human studies directed to evaluate their teratogenicity. However, they are considered safe based on the notion that no teratogenic findings have been reported in humans despite worldwide use of these products. The association between operating room personnel exposure to anesthetic gases and increased rates of spontaneous abortions an important conflicting issue. Recent reviews and prospective studies have found no evidence of an association between occupational exposure and congenital anomalies. Intravenous agents are extensively used during anesthesia. The most common are thiopental, ketamine and to a lesser extent etomidate and propofol. Neither propofol, etomidate, thiopental nor ketamine are known to be a teratogen in clinically effective doses. Reproduction studies with propofol on rats and rabbits revealed no evidence of adverse fetal effects. Animal studies showed no birth defects after administration of etomidate and ketamine. However, there is lack of adequate and well-controlled studies in pregnant women to draw a final conclusion. Muscle relaxants are another group of intravenous agents used in general anesthesia for obstetrics. In clinical doses, muscle relaxants do not produce teratogenic effects. However, studies of muscle relaxants are lacking due to difficultly in design because of the need for mechanical ventilation and concomitant of other anesthetic drugs which may influence the results. Benzodiazepines (BDZS) are commonly used as sedatives/tranquilizers during anesthesia in pregnant women. BDZs did not affect Apgar scores or neonatal acid–base values in small doses. BZD were once feared to be associated with cleft lip and palate, based on poor epidemiologic studies of chronic use/abuse. More recent data contradicts these earlier flawed investigations, and BZD are likely safe, particularly in the small doses used in anesthesia. Literature review yields little information on analgesic agents used in human pregnancy. However, it is reassuring to note the lack of any clear association between common anesthetic agents, its adjuncts and congenital malformations but it is sensible to use any drug in pregnancy thoughtfully and conservatively. Regional anesthesia (RA) is popular in obstetric practice because it provides excellent analgesia, allows the mother and her partner to participate in the birth of their baby and the risks of serious complications are less than with general anesthesia. RA results in less neonatal exposure to drugs. For clinical concentrations of local anesthetics, there has been no indication of teratogenicity in humans. As for adjuvant drugs used by the anesthesiologist; the safest antibacterial agent during pregnancy are Penicillins. Sulfonamides, Tetracyclines, Aminoclycosides & Quinolones are preferred not to be used during pregnancy. Methyldopa and β-adrenoceptor antagonists have been used most extensively as antihypertensives during pregnancy. In acute severe hypertension, intravenous labetalol or oral nifedipine are reasonable choices. Methyldopa is considered the safest and most efficacious antihypertensive drug for use in pregnancy and is therefore recommended by all working groups. Prazosin (alpha-adenergic blocking agent) and Minoxidil (vasodilator) have been shown to adversely affect the fetus and ACEIs are absolutely contraindicated in pregnant women Antiepileptic drugs (AEDs) are essential to be administered during anesthesia in pregnant women. Considerable evidence has accumulated demonstrating that AED use is associated with an increased risk of congenital malformations and therefore the benefits must outweigh their adverse effects.None of the other commonly used adjuvant drugs used during anesthesia in pregnancy (H2 blockers, Antiemetics, tocolytics and uterotonic agents) have been shown to cause adverse fetal outcomes.
To date literature review suggests that there is no data to document an increase in congenital anomalies at birth following anesthesia exposure during pregnancy. Conclusive data can only be derived from well structured animal studies. Nevertheless these studies do not allow us to conclude that anesthetic agents are not teratogenic in humans. Furthermore, studies on the adverse effects of exposure to anesthesia are frequently deficient due to the lack of comparable control groups, lack of confirmation and verification of reported adverse outcomes, low response rates to questionnaires, lack of details on duration and amounts of actual exposure to anesthesia and lack of information on other factors associated with anesthetic exposure which are potentially teratogenic. Well structured randomized case-control human studies with limited confounding variables, are not implacable or expected to be conducted in the near future, due to the ethical barriers associated with exposure of pregnant females to a potential harmful anesthetic agent. Therefore large retrospective, epidemiological surveys of adverse reproductive outcomes either in women exposed to anesthetic agents during delivery or who underwent surgery during pregnancy are valuable tools in assessing the risk of anesthesia exposure on fetal outcome and to date none of these have incremented anesthetic agents as a cause of teratogenicity or abortions with only minor maternal effects that lead to adverse fetal outcomes.