Norepinephrine vs. Phenylephrine for Hypotension in Low-Dose Spinal Anesthesia for Cesarean Delivery (NORPHE-CD)

Tam Anh Research Institute

Status and phase: Completed; Phase 4

Conditions: Cesarean Section; Hypotension, Controlled; Spinal; Anesthesia

Treatments: Drug: Phenylephrine; Drug: Norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT07327320

TA2.24.03

Details and patient eligibility

About

This clinical trial was conducted to compare the effectiveness and safety of two medications, norepinephrine and phenylephrine, in preventing hypotension during low-dose spinal anesthesia for cesarean delivery (CD). Although low-dose spinal anesthesia combined with opioids is widely used to mitigate hypotension, the incidence remains unacceptably high. Thus, vasopressors remain essential in maintaining maternal blood pressure during these procedures.

In this study, 100 women were initially assessed, with 2 excluded. The remaining 98 were randomly assigned to receive a continuous infusion of either norepinephrine or phenylephrine. During the follow-up process, 2 patients from each group were lost, resulting in 47 participants per group for final analysis.

The results showed that norepinephrine was significantly more effective, with a lower incidence of hypotension (14.9% vs. 42.6%). It also provided more stable heart rates with fewer episodes of bradycardia and less need for rescue medications. Both treatments were safe for the babies with comparable Apgar scores.

This study suggests that Norepinephrine infusion at 0.05 mcg/kg/min is more effective than phenylephrine at 0.25 mcg/kg/min in preventing hypotension during low-dose SA in CD, providing better hemodynamic stability and fewer episodes of bradycardia

Full description

Upon arrival in the operating room, the parturient was monitored using standard American Society of Anesthesiologists monitors, including electrocardiography, pulse oximetry, and invasive arterial BP measurement. A large peripheral vein was cannulated using an 18-gauge intravenous catheter for the administration of fluids and medications. Baseline BP was determined by averaging three measurements taken 2 minutes apart in the supine position before SA. Low-dose SA was performed with 8 mg of bupivacaine (Marcain) combined with 20 mcg of fentanyl and 100 mcg of morphine (Opiphine). At injection, patients received 15 ml/kg of 0.9% saline IV and group-specific vasopressors:

• P group: Continuous intravenous phenylephrine infusion was administered at 0.25 mcg/kg/min, prepared by diluting 500 mcg in 50 mL of 0.9% sodium chloride.
• N group: Continuous intravenous norepinephrine infusion was administered at 0.05 mcg/kg/min, prepared by diluting 100 mcg in 50 mL of 0.9% sodium chloride.

Following SA, patients were placed in a 15° left lateral tilt and administered 4 mg of ondansetron and 4 mg of dexamethasone intravenously. The sensory block was assessed at 10 minutes; a block at or above the xiphoid was considered effective. After placental delivery, uterotonics were administered as prescribed by the obstetrician. Vasopressor infusion was stopped 5 minutes after delivery.

BP and heart rate (HR) were recorded every 2 minutes during the first 30 minutes after SA, then every 5 minutes until the end of surgery. Neonatal HR was monitored continuously, and Apgar scores were assessed at 1 and 5 minutes by a neonatologist.

Management of Hemodynamic Events and Bradycardia Hypotension was defined as systolic blood pressure (SBP) < 90 mmHg or a drop of more than 20% from baseline. Management involved increasing the vasopressor infusion rate by 20%, followed by administration of phenylephrine 50 mcg intravenously if the HR was ≥ 75 bpm, or ephedrine 6 mg IV if HR was < 75 bpm. The infusion rate was returned to baseline once SBP recovered to the target range (80-120% of baseline).

Severe hypotension (SBP < 60% of baseline) was treated using the same approach but with a higher dose of rescue vasopressors: phenylephrine 100 mcg IV or ephedrine 12 mg IV, depending on HR.

In cases of hypertension (SBP > 120% of baseline), the vasopressor infusion was reduced by 50%. If the SBP exceeded 130%, the infusion was temporarily stopped and reinitiated at 50% of the original dose once the SBP returned to the target range.

Bradycardia was defined as a HR of less than 60 bpm. Management of bradycardia was based on the patient's hemodynamic status. If bradycardia occurred without hypotension, the vasopressor infusion was temporarily discontinued, and if the HR recovered to ≥ 60 bpm, the infusion was resumed at 50% of the original dose. Persistent bradycardia (>3 minutes) was treated with atropine 0.5 mg IV, up to 3 doses. If bradycardia was associated with hypotension, ephedrine 6 mg IV was administered.

Enrollment: 100 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Parturients aged ≥18 years
• Classified as American Society of Anesthesiologists physical status II
• Term singleton pregnancies
• Scheduled for elective CD under SA

Exclusion criteria

• Refusal to participate.
• Fetal anomalies or suspected fetal compromise
• Preeclampsia or eclampsia
• Conversion to general anesthesia or use of labor analgesia
• Contraindication to SA
• Preexisting cardiovascular or cerebrovascular disease; chronic hypertension
• Baseline bradycardia
• Current use of cardiovascular or antihypertensive medications
• Body mass index more than 40 kg/m²
• Body weight less than 50 kg or more than 100 kg

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups

Norepinephrine

Experimental group

Description:

Continuous intravenous norepinephrine infusion was administered at 0.05 mcg/kg/min, prepared by diluting 100 mcg in 50 mL of 0.9% sodium chloride

Treatment:

Drug: Norepinephrine

Phenylephrine

Experimental group

Description:

Continuous intravenous phenylephrine infusion was administered at 0.25 mcg/kg/min, prepared by diluting 500 mcg in 50 mL of 0.9% sodium chloride

Treatment:

Drug: Phenylephrine