Maternal and neonatal effects of remifentanil in women undergoing ceasarean section in relation to multidrug resistance protein 1 (MDR1) and mu-opioid receptor (OPRM) polymorphisms

Opioids are considered as the gold standard for achieving good anesthetic action. However, opioids are usually avoided at the induction of general anesthesia for caesarean delivery until the delivery of newborn because of the risk of placental transfer and neonatal respiratory depression. The absence of opioids can cause a lack of analgesia. Moreover, insufficient anesthesia is manifested by exaggerated response to painful stimulus with increased catecholamine levels in the blood resulting in increased blood pressure, heart rate, intracranial pressure and decreased uteroplacental blood flow. This effect may be particularly risky in pregnant women with hypertension, chronic or gestational, including preeclampsia for a high risk of cerebrovascular accident. Consequences of hypertension can results even in malignant arythmia, pulmonary edema and hypoxia of the newborn One of the best suited opioid for providing labor analgesia using a systemic approach could be remifentanil. Remifentanil has a small volume of distribution with a rapid redistribution phase , and a short elimination half-life. Remifentanil quickly transfers across the placenta with a mean umbilical vein to maternal artery concentration ratio, but it is metabolized rapidly by nonspecific plasma and tissue esterases in the fetus and thus should not produce neonatal depression. This pharmacokinetic profile gives remifentanil an advantage over other opioids. P-glycoprotein (P-gp), which is highly expressed in the maternal-facing apical membrane of the syncytiotrophoblast, plays an important role in drug transfer across the placental barrier icluding opioids. Genetic polymorphisms are believed to be a major cause of the varaibility of its activity. Of particular interest are three SNPs C3435T in exon 26, and G2677T/A in exon 21 and the linkage between them. Another possible source of interindividual variability in the reaction to opioids including remifentanil are polymorphisms of OPRM1 gene coding mu-opioid receptor. There is great interest in one common polymorphism of OPRM1, p. A118G.