Incidence of and Risk Factors for Neurological Complications of Cardiac Bypass Surgery in Children with Congenital Heart Disease Dr Neeraj Bhangu, Dr John Pappachan, Prof Fenella Kirkham, Dr Katharine Forrest

Background Children requiring surgery with cardio-pulmonary bypass (CPB) for palliation or correction of congenital heart disease (CHD) 80% survival rates into adulthood for those surviving beyond 1 year of age Knowles et al 2012 The decline in mortality is leading to a shift in emphasis towards reducing morbidity Well recognised that children with CHD often have neurological abnormalities Aetiology multifactorial Fallon et al 1995

Aetiology of Neurological abnormalities in children with CHD Pre-Operative – acidosis, hypoxia, pre existing neuro-dev abnormalities, low birth weight, co-morbidities, genetic diagnoses e.g. Di George SyndromeMaharasingam 2003 Intra-Operative - length of CPB, low perfusion pressures, pH management, depth of hypothermia, embolic events, inflammatory response due to blood exposed to bypass circuit Post-Operative - low perfusion pressures, haemodynamic instability

Post CPB Neurological Complications (NC) Fallon et al 1995 single centre UK study - acute NC in 6% of 523 procedures (411 involved CPB) Seizures are most common neurological complication Incidence 4-25% Usually on day 1-4 post operatively Choreoathetosis historically common NC post surgery Risk factors Prolonged deep hypothermic arrest (rare now) Duration of bypass Uneven cooling of the brain related to pCO2 and CBF ?Haematocrit: pre, intra, post operative

Background - Haematology Paediatric Intraoperative haemotocrit no difference to 1 year developmental score 25 vs 35% Newburger et al 2008 Adult Pre and post operative anaemia and low intra operative haematocrit may be associated with increased risk stroke increased risk of other morbidities mortality.

Objectives Case review conducted in an English centre currently providing paediatric cardiac surgery services (1 of 9) was designed to establish the current incidence of and risk factors for post-operative neurological complications (NC). Case control study to explore the secondary hypothesis that lower intra and post operative haematocrits in patients undergoing CPB lead to increased risk of NCs

Methods and Study Design All children (<16 years) with CHD undergoing CPB (including circulatory arrest) between 01/04/2003–31/03/2015 included. Patients identified from the electronic procedural database, and discharge summaries reviewed independently by 2 consultant paediatric neurologists, with case note review if information required clarification, and for all with NC. Cases: data on EEG and cerebral CT/MRI images reviewed Haematology Cases diagnosis, age & gender-matched controls

Definition of NC A NC was defined as an event occuring, regardless of cause, within 30 days of surgery or after 30 days during the same hospitalisation subsequent to the operation. In this time frame, both intra and post operative complications are included. This is according to consensus definitions of the Multi-Societal Database Committee for Paediatric and Congenital Heart Disease (6).

Neurological complications Results 1934 CPB operations in 1576 children 44 (2.2%) deaths Neurological Complications in 94 (4.9%) CNS Neurological Complications in 32/94 Death Neurological complications Odds ratio 95% CI p 95% CI Bypass time 1.006 1.002, 1.009 .001 1.004 1.002, 1.007 .002 Cross clamp time 0.998, 1010 .2 1.002 0.997, 1.007 .4 Circ arrest time 1.048 1.032, 1.063 1.014 0.996, 1.033 .1

Results – Neurological Complications N (total 94) Cerebrovascular disorders (AIS, SVT) 11 Chorea 1 Seizures 4 cardio-respiratory arrest 7 with hypocalcaemia (2 Di George) -Responded to electrolyte correction and/or a single load of anticovulsant medication -Typically transient 20 Phrenic Nerve Palsy 22 Miscellaneous 40

Results - Haematocrit Matched for date of birth, gender and diagnosis NC Controls p Intra-operative PCV 0.316+/-0.1 0.350+/-0.02 0.035 Post-operative PCV 0.357+/- 0.07 0.389+/-0.075 0.049

Discussion Range of observed NC following CPB may be changing ?Less CNS complications Previous lit did not include phrenic N. palsy CNS more long term impact Low intra & post-operative haematocrit may be associated with acute neurological complications and may be modifiable Examine pre-operative Hct