The aim of this double-blind randomised study will be to compare a fixed-rate prophylactic metaraminol infusion to a fixed-rate prophylactic norepinephrine infusion during elective cesarean section under combined spinal-epidural anaesthesia.

Spinal anaesthesia is the anaesthetic technique of choice for elective cesarean section.

Spinal anaesthesia can be complicated by hypotension, with incidence exceeding 80% occasionally. Hypotension can lead to nausea, emesis and a subjective feeling of discomfort due to cerebral hypoperfusion. If left untreated, severe or sustained hypotension can lead to decreased uteroplacental flow and fetal distress of premature or compromised fetuses while severe complications to the parturient might ensue, such as loss of consciousness, aspiration, apnea or cardiac arrest.

Prophylactic vasoconstrictor infusion is an effective strategy for preventing maternal hypotension during regional anaesthesia. Phenylephrine is widely used because it acts quickly and causes less neonatal acidosis than ephedrine, but high doses may reduce maternal cardiac output. Norepinephrine and metaraminol, a sympathomimetic amine that acts both directly and indirectly, mainly by stimulating alpha-1-adrenergic receptors, with a weak effect on beta-receptors, have emerged as potential alternatives. While the optimal norepinephrine infusion dose has been defined in several studies, research on metaraminol remains limited, with insufficient data on its ideal dosing and efficacy in obstetrics. Most comparative studies evaluate metaraminol against phenylephrine-some suggesting better fetal acid-base outcomes-but no studies directly compare metaraminol with norepinephrine. Further research is therefore needed before metaraminol can be routinely recommended in obstetric anaesthesia.

This study will include pregnant adults who are normotensive, without complications, with a single pregnancy, who are not in active labor, and who are scheduled to undergo an elective cesarean section at the Gynecology-Obstetrics Clinic of Aretaieion Hospital.The study will use randomized, concealed allocation to assign participants to receive either metaraminol or norepinephrine infusions. Study group allocation will take place according to a computer-generated sequence of random numbers. A non-involved healthcare professional will reveal each participant's assignment, and a nurse will prepare identical 50 mL syringes labeled "study infusion," containing the drug at concentrations that deliver either 100 µg/min (200 µg/mL at 30 mL/h) of metaraminol or 4 µg/min (8 µg/mL at 30 mL/h) of norepinephrine. The anaesthesiologist, patient, and data analyst will remain blinded to group allocation.

All parturients will receive standard pre-anesthetic evaluation and standard hemodynamic monitoring will be applied. Next, on the hand opposite the one with the cuff for measuring NIBP, a special finger cuff connected to the Edwards Lifesciences ClearSight system will be placed on the index, middle, or ring finger. The ClearSight system from Edwards Lifesciences is a non-invasive medical system that allows continuous monitoring of blood pressure (cBP), as well as a range of other hemodynamic parameters such as cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR).

Baseline systolic arterial pressure will be considered the average of three consecutive measurements that will not differ more than 10% among them.

All parturients will have a peripheral intravenous catheter placed in the upper extremity after baseline hemodynamic measurements are recorded. The peripheral venous catheter in the arm without the cuff will be connected via a three-way stopcock and a small-volume tube to an infusion syringe placed in an electronic infusion pump in standby mode. The syringe will contain the corresponding vasoactive drug "study infusion." At the same time, infusion of Ringer/Lactate solution at a dose of 3 mL/kg/h will begin through the study infusion line (pre-loading) before the regional procedure.

A standard spinal anaesthetic consisting of ropivacaine 0.75% 1.8 mL plus fentanyl 10 μg will be administered in the left lateraL position at the L3-4 or L4-5 vertebral interspace. The study infusion medication (either metaraminol or norepinephrine, depending on group allocation) will be started at the same time cerebrospinal fluid is obtained, immediately before injection of spinal medications. After the intrathecal injection, patients will placed in the supine position with a left lateral tilt to provide left uterine displacement and to prevent aortocaval compression. The spinal sensory level will be tested bilaterally to ensure a T4 dermatomal level before surgical incision.

Hemodynamic parameters [systolic blood pressure (SAP), diastolic blood pressure (DAP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR)] will be recorded by a specially trained, experienced anaesthesiologist at specific time points during the procedure: baseline (T0), initiation of the study drug infusion (T1), placement in the supine position after subarachnoid administration (T2), sympathetic blockade at the T4 level (T3), start of surgery (T4), delivery of the newborn (T5), 5 minutes after administration of the oxytocin bolus (T6), end of surgery (T7).

Requirements for additional vasoactive agents and any adverse effects and complications in the mother's health will also be recorded.

Hypotension will be defined as SAP < 80% of baseline, hypertension as SAP > 120% of baseline, and bradycardia as HR < 60 bpm. In case of hypotension combined with HR > 80/min, a dose of 50 μg of phenylephrine will be administered, while when hypotension is combined with HR < 80/min, a dose of 5 mg of ephedrine will be administered. Episodes of hypertension (SAP > 120% of baseline) will be treated by reducing the infusion of the "study drug" by half (15 ml/h) while if blood pressure rises to levels >130% of the baseline value, administration of the vasoconstrictor solution will be discontinued. In case of bradycardia (HR < 60 bpm) in combination with SAP within 80%-120% of baseline or hypertension, the infusion of the "study drug" will be discontinued without the administration of atropine. When HR < 55 bpm in combination with hypotension (SAP value < 80% of baseline) or in case of HR < 50 bpm regardless of the degree of hypotension, 0.6 mg of atropine will be administered.

Neonatal pH values in the first blood gas sample immediately after birth will be recorded, as well as the Apgar score at 1 and 5 minutes after birth.

The clinical interest of the study lies in determining whether the use of metaraminol is superior to the administration of norepinephrine as a vasoconstrictor during cesarean section and to what extent it ensures hemodynamic stability of the mother and a more favorable metabolic profile of the newborn.

Inclusion Criteria:

adult parturients, singleton gestation, elective cesarean section

Exclusion Criteria:

ASA >II, age <18 years, Body Mass Index (BMI) >40 kg/m2, body weight <50 kg, body weight>100 kg, height<150 cm, height>180 cm, multiple gestation, fetal abnormality, fetal distress, active labor, emergency CT, cardiovascular disease or cerebrovascular disease, pre-existing or pregnancy-induced hypertension, use of antihypertensive medication during pregnancy, preeclampsia, any contraindication for regional anesthesia, such as thrombocytopenia or coagulation disorder, communication or language barriers, lack of informed consent