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A Randomized Double-blinded Comparison of Ephedrine, Phenylephrine and Mephentermine Infusions to Maintain Blood Pressure During Spinal Anaesthesia for Cesarean Delivery: The Effects on Fetal Acid-base Status and Haemodynamic Control
Journal of Anaesthesiology Clinical Pharmacology, 10/13/09

Mahajan L et al. – Prophylactic intravenous infusion of ephedrine, mephentermine and phenylephrine was effective in controlling maternal hypotension; phenylephrine more closely meets the criteria for its use as a vasopressor in patients undergoing caesarean section under spinal anaesthesia.

Exclusive Author Commentary
Lakesh K Anand, 10/19/09

Anaesthesia to a parturient is not only unique but requires highest degree of care because the anaesthesiologist has to look after two individuals, the mother and fetus. Spinal anaesthesia, a frequently used technique for caesarean delivery associated with maternal hypotension, which is the most frequent complication of a spinal anaesthesia with an incidence approaching 100%. The maternal hypotension may have detrimental effects on both mother and fetus due to decrease in uteroplacental blood flow, impaired fetal oxygenation with asphyxial stress and fetal acidosis, and maternal symptoms of low cardiac output, such as nausea, vomiting, dizziness and decreased consciousness thus affecting maternal and fetal outcome. The cause of spinal hypotension is the inevitable preganglionic sympathetic blockade associated with the thoracic sensory levels required for caesarean delivery and the level of sympathetic blockade is several segments higher than the sensory level. This process is exacerbated in pregnant patients by the gravid uterus, which may further impede the venous return by inferior venacaval compression. Hypotension has been usually defined as a decrease in systolic arterial blood pressure (SBP) greater than 20% from the baseline value, or a systolic blood pressure less than 100 mmHg. A variety of different strategies have been employed to reduce the incidence and severity of maternal hypotension associated with spinal anaesthesia for caesarean delivery. The strategies like patient positioning to avoid aortocaval compression and promote cardiac preload, prehydration to expand blood volume, increase cardiac preload, and thereby avoid sudden decrease in cardiac preload and prophylactic or immediate use of appropriate vasopressors have been used and each has its own merits and demerits. The use of leg elevation and/ or compressive leg wrapping and colloid rather than crystalloid for prehydration are additional measures which are not currently practiced widely at present. Crystalloid administration by intravenous infusion shortly before inducing regional anaesthesia had been the mainstay of therapy to minimize the incidence and severity of hypotension but is not supported by recent reports. Various studies have shown that crystalloid administration and left uterine displacement may decrease but not completely eliminate the incidence of hypotension. The vasopressor of choice during spinal anaesthesia for caesarean section in obstetric patients is still unknown. Although it makes theoretical sense to restore both beta and alpha adrenergic tone after the induction of high sympathectomy from spinal anaesthesia by using drugs having such activity and limiting their dose to avoid reactive hypertension and possible fetal acidosis. Various vasopressors like ephedrine, mephentermine and phenylephrine have been used to manage hypotension under spinal anaesthesia in obstetric patients. Amongst the vasopressors ephedrine has a long history of use and has been considered to be the ‘gold standard’ for prophylaxis and treatment of maternal hypotension due to spinal anaesthesia in patients undergoing caesarean section. This is based on earlier animal studies which suggested that ephedrine’s combined ? and ? mimetic effects were better at increasing maternal blood pressure and preserving uterine blood flow when compared with other vasoconstrictors. In a quantitative systemic review by Lee et al reported that prophylactic ephedrine was an effective drug for preventing maternal hypotension but recently in 2004 another dose response meta-analysis by the same authors suggested that the use of higher dose of ephedrine does not eliminate hypotension but causes reactive hypertension and a minor decrease in umbilical arterial pH. Mephentermine, an indirect acting synthetic non-catecholamine ? and ? adrenergic receptor stimulant, has been found to increase maternal arterial pressure and preserve uteroplacental blood flow during spinal anaesthesia. Recent clinical trials have shown the effectiveness of phenylephrine for treatment of hypotension in parturient undergoing scheduled caesarean delivery with epidural or spinal anaesthesia and have found no deleterious effects either in mother or fetus. Phenylephrine, when used to maintain maternal BP at baseline during spinal anaesthesia for caesarean delivery has been shown to be associated with lower incidence of fetal acidosis and maternal nausea and vomiting in comparison to ephedrine. Phenylephrine has been found to be effective in maintaining maternal BP within 20% of baseline like ephedrine and mephentermine but has quicker onset effect quicker onset with a peak effect within one minute, whereas ephedrine has a peak effect at 2-5 minutes and mephentermine at 5 minutes. Ephedrine and mephentermine has been used as prophylactic infusion of 3mgml-1min-1 whereas phenylephrine 50- 100µgml-1min-1 to maintain maternal BP at baseline in patients undergoing caesarean delivery under spinal anaesthesia. Ngan Kee et al analysed the factors associated with umbilical arterial pH in women undergoing caesarean section under spinal anaesthesia and found that use of ephedrine was associated with lower umbilical artery pH compared with phenylephrine, and use of phenylephrine minimizes the magnitude and duration of hypotension and hence reducing the risk of fetal acidosis. Various studies have shown higher umbilical arterial pH with the use of phenylephrine as compared to ephedrine when used for maintaining maternal arterial pressure. Prolonged and marked maternal hypotension may decrease uteroplacental perfusion, reducing the gas exchange across the placenta and resulting first in acute fetal respiratory acidosis and then in fetal metabolic acidosis, both of which are reflected by umbilical artery pH and neonatal outcome by Apgar score at 1and 5 minutes. Apgar score (1952) has been used for the assessment of newborn for last 50 years, current evidence also supports that Apgar score is a better predictor of neonatal outcome; recently umbilical artery blood pH has been widely adopted as an adjunct to the Apgar score for assessing the condition of newborn infants. Uses of multimodal technique to minimize or prevent the maternal hypotension after spinal anaesthesia include ensuring proper maternal position with the uterus displaced off the vena cava, the infusion of fluids to increase effective blood volume as preload or coload , and the administration of ephedrine, and mephentermine to vasoconstrict the peripheral circulation and increase heart rate and phenylephrine or metaraminol, which act primarily by vasoconstriction. Physical interventions such as leg wrappings are also used and may act by minimising venous pooling of blood in the legs. All these methods aim to maintain blood pressure by increasing venous return to the heart or increasing the resistance of the peripheral circulation, or both. There is, however, no established ideal technique. Combination of technique, suitable to the particular patient should be used without spearing the vasopressors to prevent the maternal hypotension after spinal anaesthesia. Dr. Lakesh K Anand Associate Professor, Department of Anaesthesia and Intensive Care, Govt. Medical College & Hospital Chandigarh. India.

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