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

Heart Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02481791
• Other study ID #: 146613
• Status: Recruiting
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: December 31, 2019

Study information

• Verified date: January 2019
• Source: Alder Hey Children's NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 7 Years

Eligibility

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

Related Conditions & MeSH terms

• Anaesthesia
• Children
• Heart Diseases
• Magnetic Resonance Imaging

Intervention

Drug:
• Remifentanil and/or propofol
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.
• Remifentanil and/or propofol
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.
• propofol
Equilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min

Locations

Country	Name	City	State
United Kingdom	Alder Hey Children's Hospital	Liverpool	Merseyside

Sponsors (1)

Lead Sponsor	Collaborator
Alder Hey Children's NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (10)

Chanavaz C, Tirel O, Wodey E, Bansard JY, Senhadji L, Robert JC, Ecoffey C. Haemodynamic effects of remifentanil in children with and without intravenous atropine. An echocardiographic study. Br J Anaesth. 2005 Jan;94(1):74-9. Epub 2004 Oct 14. — View Citation

Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005 Jun;100(6):1599-604. — View Citation

Hume-Smith H, McCormack J, Montgomery C, Brant R, Malherbe S, Mehta D, Ansermino JM. The effect of age on the dose of remifentanil for tracheal intubation in infants and children. Paediatr Anaesth. 2010 Jan;20(1):19-27. doi: 10.1111/j.1460-9592.2009.03190.x. Epub 2009 Nov 23. — View Citation

Min SK, Kwak YL, Park SY, Kim JS, Kim JY. The optimal dose of remifentanil for intubation during sevoflurane induction without neuromuscular blockade in children. Anaesthesia. 2007 May;62(5):446-50. — View Citation

R Core Team R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2013.

Ross AK, Davis PJ, Dear Gd GL, Ginsberg B, McGowan FX, Stiller RD, Henson LG, Huffman C, Muir KT. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg. 2001 Dec;93(6):1393-401, table of contents. — View Citation

Syed SK, Corry P. Cardiac Imaging under general anaesthesia for children with congenital heart disease. Our experience. Abstract presentation, APAGBI scientific meeting. 2012.

Whitehead J, Brunier H. Bayesian decision procedures for dose determining experiments. Stat Med. 1995 May 15-30;14(9-10):885-93; discussion 895-9. — View Citation

Whitehead J, Williamson D. Bayesian decision procedures based on logistic regression models for dose-finding studies. J Biopharm Stat. 1998 Jul;8(3):445-67. — View Citation

Zhou Y, Whitehead J. Practical Implementation of Bayesian Dose-Escalation Procedures. Drug Information Journal. 2003;37(1):45-59.

Outcome

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