Title: A multi-site randomized controlled trial comparing regional and general anaesthesia for effects on neurodevelopmental outcome and apnoea in infants
Funder: Chief Scientist Office, Scotland

Abstract: Objectives: The primary objective of this trial is to determine whether different types of anaesthesia [regional versus general] given to infants undergoing inguinal hernia repair result in equivalent neurodevelopmental outcomes. Secondary objectives are to describe the frequency and characteristics of apnoea in the post-operative period after both regional and general anaesthesia for inguinal hernia repair in infants, and determine the factors associated with apnoea. Study population: 660 infants of postmenstrual age 60 weeks age or less, scheduled for inguinal hernia repair under anaesthesia. Exclusion criteria include recognised risk factors for adverse neurodevelopmental outcome or previous exposure to general anaesthesia. Infants born at less than 26 weeks gestation will be excluded. Design: Prospective, observer blind, multi-site, randomised, controlled, equivalence trial. Treatment groups: The general anaesthesia group will receive sevoflurane for maintenance and induction. The airway can be maintained with a face mask, laryngeal mask or endotracheal tube, with or without neuromuscular blocking agents. Analgesia can be supplied with a caudal or ilioinguinal nerve block with bupivacaine up to a maximum dose of 2.5 mg/kg. The regional group will have no sedative agents. The regional blockade may be with spinal block alone, spinal block with caudal block, spinal with ilioinguinal block or caudal alone. A maximum dose of 2.5 mg/kg of bupivacaine can be used. Outcome measure: Neurodevelopmental assessments will occur at 2 and 5 years with standard neuropsychological tools. Apnoea events and interventions for apnoea will also be recorded. Primary outcome: The primary outcome will be the WPPSI-III Full Scale IQ score at 5 years corrected age.

Lay abstract: It is quite common for up to 10% of babies to need a hernia repair in early life. Pre-term babies are more often surviving and so this operation is becoming more common. Small babies can have this surgery without any sedation or general anaesthetics if the area of the operation is blocked with local anaesthetic, especially if the local anaesthetic is given near to the spinal cord as a spinal or caudal block. This is a very skilled procedure and doesn't always work so general anaesthesia is an alternative. General anaesthesia is known to be very safe but recently, research on animals has suggested that general anaesthetic agents can in some way damage the developing brain and this has caused some parents to question whether their baby should have a general anaesthetic. To try to answer this question we propose to study two groups of babies, one having a general anaesthetic and the other a local anaesthetic and test their development over 5 years. We expect the two groups to develop similarly but will be monitoring for differences between the groups as they develop. The study will be carried out in specialist children's hospitals who are used to both general and local anaesthetic methods and also used to doing careful assessments of development. The main outcome we are testing is the development at age 5 years, but we also plan to do a general assessments of development and physical status at 2 and 5 years. Standard tools will be used to make these measurements. Awake regional and general anaesthesia are both accepted standards of care for inguinal hernia repair in children. Regional anaesthesia may be more technically demanding and preferences for one or the other may vary depending on the experience of the paediatric anaesthetist. In younger patients regional anaesthesia may be associated with less breathing upset than general anaesthesia but this may be less apparent with the newer general anaesthesia agents. Similarly although there is animal data for toxicity, the evidence for risk of general anaesthesia is sufficiently weak to accept general anaesthesia as an arm in the study. When recruiting patients the researcher approaching the patient must first ensure that both treating surgeon and anaesthetist are comfortable with randomisation. All sites will obtain approval from their local Human Research Ethics Committees. In all cases written informed consent will be obtained from parents or guardians. An independent Data Monitoring Committee and a Trial Steering Committee have been established to oversee the trial. The funding package is mainly for the long term follow up assessments by a specialist in child development.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH