Ephedrine vs Phenylephrine - ECG Changes

NCT01243970 | Terminated Phase 4 DMC

• 1 other identifier: 08/0182
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spinal Anesthesia; Pregnancy

Keywords

Spinal anaesthesia; phenylephrine; ephedrine; ECG changes; Caesarean delivery; Myocardial ischaemia; Cardiac output; hypotension

Outcome Measures

Primary Outcomes (1)

• ST segment changes on Holter monitoring

  30 minutes pre spinal anaesthesia to 4 hours post delivery

Secondary Outcomes (3)

• Troponin levels

  24h post delivery

• Incidence of maternal low systolic blood pressure

  20 minutes post spinal and 30 minutes post delivery

• Maternal cardiac output

  20 minutes post spinal and one measure at 5 minutes post delivery

Study Arms (2)

phenylephrine infusion

ACTIVE COMPARATOR

Drug: Phenylephrine

Ephedrine infusion

ACTIVE COMPARATOR

Drug: Ephedrine

Interventions

Phenylephrine DRUG

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.

phenylephrine infusion

Ephedrine DRUG

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.

Ephedrine infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give written informed consent
• \>37/40 weeks gestation
• Singleton pregnancy
• Elective caesarean section under spinal anaesthesia
• 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 )

You may not qualify if:

• Circulatory disease (eg pre-existing hypertension)
• Cardiac disease/medications (e.g. angina, cardiomyopathy, B Blocker medication)
• Pregnancy related disease (eg pre-eclampsia)
• Diabetes pre-existing the pregnancy
• Hyperthyroidism
• Renal Disease
• Closed-angle glaucoma
• Patients on monoamine oxidase inhibitors
• In active labour
• Emergency caesarean section
• Fetal abnormalities
• Contraindications to spinal anaesthesia
• Height \>6 feet/180cm / Height \<5 feet/150cm
• Body mass index (BMI) \<19 or \>35

Sponsors & Collaborators

• University College London Hospitals: lead
• Obstetric Anaesthetists' Association United Kingdom: collaborator

Study Sites (1)

University College London Hospital

London, NW1 2BU, United Kingdom

Location

MeSH Terms

Conditions

Coronary Artery Disease; Hypotension

Interventions

Phenylephrine; Ephedrine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Propanolamines; Propanols; Phenethylamines; Ethylamines

Study Officials

• Roshan Fernando, FRCA

  University College London Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief investigator

Study Record Dates

• First Submitted: November 18, 2010
• First Posted: November 19, 2010
• Study Start: April 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

GB (1)