Study to Evaluate the Optimal Dose of Remifentanil During MRI of the Heart Under General Anaesthesia

Study Overview
=================
Brief Summary
-----------------
What is the optimal maintenance dose of remifentanil to ensure apnoea, during breath hold episodes in children having cardiac MR imaging with general anaesthesia?

Detailed Description
-----------------
The management of congenital heart disease depends upon accurate imaging of the heart to define anatomical abnormalities. The use of magnetic resonance imaging has grown in response to this need. Young children, however, are unable to cooperate sufficiently to allow the scan to occur; this necessitates the use of general anaesthesia. The optimal anaesthetic management of children in this situation is complex. Imaging of an acceptable quality depends on a low (normal) heart rate which is relatively constant during the scan and frequent breath holds to avoid respiratory artefacts. Children undergoing such scans commonly have significant cardiac and non-cardiac disease. A technique, currently used at Alder Hey Hospital, is to use intravenous agents to provide anaesthesia: commonly a mixture of the intravenous anaesthetic propofol and the potent opiate remifentanil. The patient's own ventilation is suppressed by the use of remifentanil which also reduces heart rate and heart rate variability. Controlled ventilation is provided via a ventilator and endotracheal tube. Adequate doses of remifentanil are required to ensure suppression of the patient's ventilation whilst excess doses are avoided to reduce the risk of adverse effects (primarily arterial hypotension) and ensure rapid recovery. Remifentanil dose has been studied during surgery(3-6), however this is a unique indication and optimal dosage has not been formally studied. In particular the absence of any stimulation from surgery is likely to mean that substantially lower doses of remifentanil will be required.

Official Title
-----------------
Study to Evaluate the Optimal Dose of Remifentanil Required to Ensure Apnoea During Magnetic Resonance Imaging of the Heart Under General Anaesthesia

Conditions
-----------------
Children, Heart Diseases, Anaesthesia, Magnetic Resonance Imaging

Intervention / Treatment
-----------------
* Drug: Remifentanil and/or propofol
* Drug: Remifentanil and/or propofol
* Drug: propofol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children of one year (of age) or older and younger than 7 years of age. Scheduled for cardiac MR imaging under general anaesthesia at Alder Hey Children's Hospital. Parental Consent Exclusion Criteria: Hypersensitivity to any study drug Known abnormal response to opiate analgesics or co-morbidity associated with abnormal central control of breathing Families unable to understand or complete consent Any other contraindication to proposed anaesthetic technique: at the discretion of the responsible anaesthetist. Documented significant renal or hepatic dysfunction

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 7 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanil<br>Induction Phase: A dose of remifentanil 1mcg/kg by slow bolus, will be given to facilitate endotracheal intubation. Further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given to ensure an anaesthetised patient. Settling Period: An infusion of the test dose of remifentanil will be commenced from an infusion prepared prior to the patient being anaesthetised. 1mg of Remifentanil (one vial) will be diluted to a volume of 50mls in normal saline 0.9% in a 50ml syringe. Maintenance dose of propofol 130 mcg/Kg/min for the first 5 minutes reduced to 100 mcg/kg/min thereafter. 40mls of propofol 1% (10mg/ml) will be drawn undiluted into a 50ml syringe. During the settling period further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given. Equilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min. | Drug: Remifentanil and/or propofol<br>* Induction Phase: A dose of remifentanil 1mcg/kg by slow bolus, will be given to facilitate endotracheal intubation. Further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given to ensure an anaesthetised patient.<br>Drug: Remifentanil and/or propofol<br>* Settling Period: An infusion of the test dose of remifentanil will be commenced from an infusion prepared prior to the patient being anaesthetised. 1mg of Remifentanil (one vial) will be diluted to a volume of 50mls in normal saline 0.9% in a 50ml syringe. Maintenance dose of propofol 130 mcg/Kg/min for the first 5 minutes reduced to 100 mcg/kg/min thereafter. 40mls of propofol 1% (10mg/ml) will be drawn undiluted into a 50ml syringe. During the settling period further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given.<br>Drug: propofol<br>* Equilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diaphragm movement | The primary outcome will be movement of the diaphragm during the single test apnoea. The dose of remifentanil will be judged: A success. If no movement of the diaphragm is detected by MRI imaging during a 30 second test apnoea. A failure. If movement of the diaphragm is detected during the test apnoea. | 30 seconds | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scan Quality | • quality of the scan from the respiratory gated sequence (graded by the radiologist who will be blinded to the dose) | 1 hour | 
| Heart Rate | • highest and lowest heart rate (during equilibrium and study period) | 1 hour | 
| Blood pressure | • lowest blood pressure (during equilibrium and study period) | 1 hour | 
| Emergence time | • time to emergence (waking up) at end of scan | 1 hour |