Ephedrine vs Phenylephrine - ECG Changes

Pregnancy Clinical Trial

Official title:

Randomised, Double-blind, Phase IV Study to Compare the Incidence of ECG Changes During Elective Caesarean Section Under Spinal Anaesthesia When Using Phenylephrine or Ephedrine Infusion to Maintain Baseline Systolic Blood Pressure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01243970
• Other study ID #: 08/0182
• Status: Terminated
• Phase: Phase 4
• First received: November 18, 2010
• Last updated: October 25, 2016
• Start date: April 2012
• Est. completion date: January 2016

Study information

• Verified date: October 2016
• Source: University College London Hospitals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

ECG changes during caesarean section are common. Incidence of ST depression on the ECG is up to 81% in some studies. Although this may indicate inadequate oxygen supply to the heart muscle (myocardial ischaemia) many other theories have been suggested including air entering the circulation from the placental bed, high heart rate, hormone or nervous system influences and spasm of the coronary blood supply. Perioperative ST depression often reflects an imbalance between heart muscle oxygen supply and demand. At the time of delivery, high heart rate is common and there is a further increase in the amount of blood the heart has to pump every minute due to blood coming back to the circulation from the placental bed. This increases oxygen demand and most ST changes are seen at the time of delivery or within 30 minutes. The clinical significance of these changes is much debated, and apart from a few case reports do not appear to be associated with poor heart muscle function or ischaemia (lack of oxygen supply). Management of the mother's blood pressure during caesarean section has changed greatly in recent years. Intermittent boluses of ephedrine, given when blood pressure is low, have been replaced with prevention of low blood pressure and phenylephrine has become the drug of choice. Ephedrine increases heart rate and contractility of the heart muscle and is likely to increase oxygen demand. Phenylephrine reduces heart rate while maintaining blood pressure which may result in a more favorable oxygen supply demand ratio.

The investigators aim to compare the incidence of ECG changes if the mother's blood pressure is maintained with phenylephrine as compared to ephedrine. To see if these ECG changes are associated with myocardial ischaemia, the investigators will perform troponin T analysis after delivery. Troponin T is a molecule released by ischaemic heart muscle.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Able to give written informed consent

2. >37/40 weeks gestation

3. Singleton pregnancy

4. Elective caesarean section under spinal anaesthesia

5. In good general health (American Society of Anesthesiology Category 1 or 2, fit and well or with mild systemic disease that has no impact on physical activity )

Exclusion Criteria:

1. Circulatory disease (eg pre-existing hypertension)

2. Cardiac disease/medications (e.g. angina, cardiomyopathy, B Blocker medication)

3. Pregnancy related disease (eg pre-eclampsia)

4. Diabetes pre-existing the pregnancy

5. Hyperthyroidism

6. Renal Disease

7. Closed-angle glaucoma

8. Patients on monoamine oxidase inhibitors

9. In active labour

10. Emergency caesarean section

11. Fetal abnormalities

12. Contraindications to spinal anaesthesia

13. Height >6 feet/180cm / Height <5 feet/150cm

14. Body mass index (BMI) <19 or >35

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pregnancy
• Spinal Anesthesia

Intervention

Drug:
• Phenylephrine
Infusion dose 50 mcg / minute. On/off regimen in response to blood pressure (BP) readings every minute. Approximative 30 minutes treatment duration. Total dose 50 mcg - 1500 mcg * * We will start the infusion after the spinal anaesthetic (see trial design), and while we will monitor cardiac output and BP (for 20 minutes) the surgeons will prep the patient (surgery not started yet). Birth should occur more or less 10-15 minutes after beginning surgery, so this is approximatively 30 minutes after spinal anaesthetic. It is very unlikely that the infusion will run continuously and exceed 1500 mcg.
• Ephedrine
Infusion dose 4mg / minute. On/off regimen in response to blood pressure readings every minute. Approximative 30 minutes treatment duration. Total dose 4 mg - 120 mg. * * We will start the infusion after the spinal anaesthetic(see trial design), and while we will monitor cardiac output and BP (for 20 minutes) the surgeons will prep the patient (surgery not started yet). Birth should occur more or less 10-15 minutes after beginning surgery, so this is approximatively 30 minutes after spinal anaesthetic. It is very unlikely that the infusion will run continuously and exceed 120mg.

Locations

Country	Name	City	State
United Kingdom	University College London Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
University College London Hospitals	Obstetric Anaesthetists' Association

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ST segment changes on Holter monitoring		30 minutes pre spinal anaesthesia to 4 hours post delivery	No
Secondary	Troponin levels		24h post delivery	No
Secondary	Incidence of maternal low systolic blood pressure		20 minutes post spinal and 30 minutes post delivery	No
Secondary	Maternal cardiac output		20 minutes post spinal and one measure at 5 minutes post delivery	No