1. CAMARADES: Bringing evidence to translational medicine The effect of anaesthetics on the developing neonatal brain: A systematic review and meta-analysis Robert Stewart (Neuroscience Honors Student) Christopher Ng, Gillian Currie, Marta Seretny, Emily Sena

2. CAMARADES: Bringing evidence to translational medicine Clinical background Animal Data suggests GA’s are neurotoxic in neonates Both histological and behavioural evidence Unclear how this translates to humans FDA suggests avoiding ALL elective surgery in < 3 yo RCOA + APAGBI no ‘set rules’ Ongoing human studies (SMARTTOTS, PANDA)

3. CAMARADES: Bringing evidence to translational medicine Why do we do meta-analysis of animal studies? Preclinical studies are performed to inform human health Used in preclinical research to: –assess the quality and range of evidence –identify gaps in the field –assess for publication bias –try to explain discrepancies between preclinical and clinical trial results –inform clinical trial design Used in clinical research to provide summary estimates to inform clinical practice

4. CAMARADES: Bringing evidence to translational medicine Aim: To identify all In vivo studies reporting the impact of clinically used anaesthetics on the developing brain (behavioural and/or histological measures) Assess the internal validity of existing animal data To provide an unbiased summary of the animal data

5. CAMARADES: Bringing evidence to translational medicine Methods Systematic literature search of PubMed, Embase and Web of Knowledge Screen the articles using a predetermined inclusion/exclusion criteria (2 reviewers) The publications were then assessed for quality using a modified CAMARADES checklist (MacLeod et al. 2004) Data extracted and meta analysis performed

6. CAMARADES: Bringing evidence to translational medicine Search Results

7. CAMARADES: Bringing evidence to translational medicine Search Results

8. CAMARADES: Bringing evidence to translational medicine Reported Study Quality Median score 3/7 (IQR 3-5) CRITERIA Number out of 66 (%) Blinding of outcome 26 (39%) Random Group allocation 39 (58%) Treatment Allocation Concealment 5 (7%) Sample Size Calculation 2 (3%) Report conflict of interest 19 (28%) Animal Welfare Report 65 (97%)

9. CAMARADES: Bringing evidence to translational medicine Results Outcome Specific outcome measure Effect size (95% CI) InterpretationComparisonsTotal animals Histological (NMD) Apoptosis 36.1% (30.6, 41.5) 2532530 (SMD) Neurodegeneration 0.16 SD (-0.014, 0.34) 43279 Behavioural (SMD) MWM - Memory 0.37 SD (0.21, 0.53) 27340 (SMD) MWM – Learning 0.06 (-0.07, 0.19) 17198 (SMD) Fear Conditioning0.92 (0.59, 1.27)9109

10. CAMARADES: Bringing evidence to translational medicine Conclusions Quality of reporting low (impacts on effect size estimate) Larger effects in apoptosis than in behavioural measures (how clinically relevant is this?) Very few non human primates (worse apoptosis in this group?) Amount of apoptosis appears to decreases with increase in age

11. CAMARADES: Bringing evidence to translational medicine Future Work Clear need for more human data Awaiting results of human trials Need for more robust approach to animal reporting Impact of surgery needs to be assessed More primate research

12. CAMARADES: Bringing evidence to translational medicine References