A randomised study to see if two drugs that increase blood pressure, namely phenylephrine and metaraminol, are equally effective to preventing blood pressure falls and in resulting in a healthy baby, at the time of spinal anaesthesia for elective caesarean section

Caesarean section is one of the most commonly performed procedures in Australia and many other countries. Approximately 80-90% of all caesarean sections performed in developed countries are conducted under regional anaesthesia. Due to the high incidence of maternal hypotension after spinal anaesthesia for elective caesarean delivery (approximately 70-80% in the absence of prophylaxis with sympathomimetic drugs), it has become routine practice in many centres worldwide to administer a sympathomimetic drug to support the blood pressure, either prophylactically, which is more effective, or as treatment. Phenylephrine has been extensively investigated and has become the first-line sympathomimetic drug for prophylactic continuous infusion. Spinal anaesthesia induces systemic vasodilation and a mild fall in arterial pressure, accompanied initially by a compensatory rise in heart rate and cardiac output. Preventing reduced maternal cardiac output and a substantial fall in maternal arterial pressure (and possibly prevention of even minor reductions in blood pressure of less than 10% from baseline values) is considered fundamental to avoiding maternal nausea, vomiting, syncope and neonatal hypoxaemia and acidosis. Phenylephrine, which has almost no beta-agonist activity, and in higher doses causes a baroreceptor mediated reflex bradycardia, reduction in stroke volume because of increased afterload, shift of blood into the splanchnic venous circulation decreasing venous return and thus a dose-dependent fall in cardiac output. These factors may, if severe, be detrimental to placental perfusion. An alternative sympathomimetic drug and alpha-adrenergic agonist is metaraminol. This drug differs from phenylephrine in having mixed direct and indirect alpha- and beta-agonist effects (although direct alpha- effects predominate at clinical doses). It is more effective than ephedrine in maintaining arterial pressure and its pharmacological properties suggest it might have advantages over phenylephrine, by maintaining cardiac output more effectively. Limited evaluation shows it is associated with excellent neonatal outcomes and metaraminol is widely used in non-obstetric clinical practice. There are no human data comparing phenylephrine and metaraminol in pregnancy. We have established that the potency ratio between these drugs is approximately 1:4-5, so infusions will be commenced at equipotency, based on a well supported dose of phenylephrine. The rate of metaraminol will be consistent with the only previous human trials, in which it was used at 250 mcg/min initially and maximum rates approached 500 mcg/min. This non-inferiority study will compare these two well-known sympathomimetic drugs with respect to neonatal and maternal outcome. Should metaraminol be found to compare favourably with phenyephrine, it would provide good evidence that it is a suitable option in this setting.