Pharmacogenetics of Remifentanil in Patients With Hypertension Undergoing Cesarean Delivery Under General Anesthesia

INTRODUCTION Even nowadays there is still a significant risk of insufficient depth of anesthesia during Cesarean delivery (CD) under general anesthesia (GA). The main reason in comparison to other surgeries is the lack of opioid administration due to risk of newborn respiratory depression.

Opioids easily cross the placental barrier to the fetus circulation and may cause depression of respiration and deteriorate the overall newborns postpartum adaptation. This presents the main reason why according to contemporary recommendation is the use of opioids in CD restricted until the time of fetus delivery, and are given as far as after the navel wort ligation. Not to cause any depression of the newborn the premedication to GA is usually also omitted. The beginning of GA in common surgical operation is usually accompanied by the decrease in systemic blood pressure (BP) and heart rate (HR). However, in CD the investigators face the increase of BP and HR due to stress reaction of mother during the period before the fetus delivery and before full anesthesia application, including opioids.

Generally, insufficient depth of anesthesia (assessed by patient's recollection) is reported in less than 1% of cases, but increases for up to 50% in GA during CD. However, this appraisal marginalized much more frequent cases when an insufficient depth of GA is accompanied by exaggerated autonomic reaction to the pain, especially the increase in systemic BP and heart rate as a reaction to the egestion of catecholamines, while total amnesia of the surgery is retained. In CD such type of anesthesia insufficiency was reported in 12-26% of patients! Current trend in CD anesthesia unequivocally prefers the use of regional techniques; GA remains indicated for emergency situations mainly and in those cases the stress reaction of mother tends to be much higher than in elective procedures.

An independent remarkable risk factor to the pregnant women is the hypertension, both chronic and gestational including preeclampsia. This condition of preoperatively mostly hardly and insufficiently controlled hypertension may get dramatically worse during the first phase of CD, when blood pressure due to uncontrolled stress reaction enormously rises and elevates intracranial pressure with high risk of hemorrhagic stroke - a life threatening complication.

Unfortunately there are only a few possibilities how to influence mother's stress response to intubation and laparotomy without increasing the risk of newborn depression. In absence of anesthetics not crossing placental barrier, the only possibility is the use of ultra-short acting anesthetics which should be eliminated from fetus circulation before his delivery. An important role might play remifentanil - µ-receptor agonist with rapid onset and ultra-short activity (biological half-life 3-10 min.). It's major advantage, beside fast onset, is also prompt and organs independent elimination.