1. Paediatric Brain Trauma Management: Moving towards evidence based practice Dr. T. Y. M. Lo Consultant Paediatric Intensivist Royal Hospital for Sick Children, Edinburgh

2. Demographics Head trauma – commonest cause for A&E attendants aged < 15 yrs old Brain trauma – Commonest cause of death – Commonest cause of newly acquired disability (> 100 per 100 000 population) Significant problem with memory & attention deficits Learning difficulties Disruptive behaviours / lack of inhibition (Frontal lobe syndrome)

3. Outcome Determinants Brain Trauma Primary Brain Injury Secondary Brain Insult Outcome

4. Secondary Insult Cerebral ischaemia / Inflammation / Energy failure Hypoxia Hypotension Low cerebral perfusion pressure Raised ICP Pyrexia Seizures Hypoglycaemia / hyperglycaemia Electrolytes abnormalities

5. Which Physiological Abnormalities Best Predict Outcome? Total duration of low CPP best predict outcome (p < 0.004). (Jones et al. British Journal Neurosurgery. 2003. 17:29-39) Best Treatment Option - Prevention of secondary physiological insults

6. Brain Trauma Treatment Goals Adults Treat if ICP > 20 mmHg Keep CPP > 70 mmHg & avoid < 50 mmHg J Neurotrauma, May 2007 (Thresholds not validated)

8. Brain Trauma Treatment Goals Children Treatment goals vary significntly between units Tilford et al. CCM, 2001. Treat if ICP > 20 mmHg CPP 40 - 65 mmHg, avoid < 40 mmHg Pediatric Critical Care Medicine, 2003. (Thresholds not validated)

9. Developing Age Specific Treatment Goals Limiting Factors Mostly adult studies Methodology to quantify ICP & CPP insult limited to single dimension Intracranial physiology changes with age (CPP = MAP - ICP) – Good age specific MAP data – Very little age specific ICP data – No age-specific CPP data

10. Hypothesized Age-specific Minimum CPP Levels Age (yrs) (mmHg) Jones et al. Br J Neurosurg. 2003 CPP = 5th percentile MAP level

11. Edinburgh - Newcastle TBI Study Prospective observational study 79 children – 52 boys, 27 girls Two regional centres

13. CPP Insult Quantification Cumulative pressure-time index (PTI) (Chambers, Jones, Lo et al. JNNP 2006)

14. PTI & Outcome OutcomeMean PTI Value Independent (GOS 4 & 5) 3228 (95% CI 1557, 4898) Poor (GOS 1 - 3) 32713 (95% CI 16168, 49258) Significant difference between the PTI area product and outcome (p<0.001) Chambers, Jones, Lo et al. JNNP 2006

15. ROC Curve for Different CPP Thresholds Sensitivity 1-specificity 0.2 0.4 0.6 0.8 1.0 AUC Threshold 0.890 Less 10% 0.883 Less 20% 0.886

16. Age-related CPP Insult Thresholds Aged 2 - 6 yrs - 48 mmHg Aged 7 - 10 yrs - 54 mmHg Age 11 - 16 yrs - 56 mmHg (Chambers, Jones, Lo et al JNNP 2006)

17. CPP Treatment Thresholds Treatment Thresholds Critical Insult Thresholds Aged 2 – 6 yrs Aged 7 – 10 yrs Aged 11 – 16 yrs 48 mmHg 54 mmHg 58 mmHg 55 mmHg 60 mmHg 65 mmHg

18. All individual characteristics of CPP affect brain trauma outcome Lo et al, PCCM 2011 (Suppl)

19. Clinical Importance To improve childhood brain trauma outcome, AVOID ANY significant reduction in CPP below the age-related insult threshold, of any duration

20. CPP Management in the Pre-ICU Setting Should we be thinking about optimizing CPP in the pre-ICU setting? Do you have targets for MAP (CPP)? What about age-related targets for MAP (CPP)?

21. Opening ICP + CPP in Childhood Brain Trauma N = 48 children with TBI Opening ICP > 20 mmHg = 18 (37.5%) Opening ICP > 15 mmHg = 26 (54%) Opening ICP > age-related norms = 33 (68.8%) Opening CPP below treatment thresholds = 19 (39.6%)

22. CPP Targets Pre-ICU Avoid reduction below age-related CPP insult thresholds Assume ICP 20 mmHg Keep MAP at least – Aged 2 – 6 yrs > 75 mmHg – Aged 7 – 10 yrs > 80 mmHg – Aged 11 – 16 yrs > 85 mmHg

23. Brain Trauma Inter-hospital Transfers Who should do it? – Primary hospital team vs Regional Retrieval Service What’s the ‘Power-that-be’ (NICE; SIGN; RCPCH) recommendation?? Can it be done???

24. Brain Trauma Primary Team Transfers Median distance from RHSC 35.2 miles (17.8 - 174.3 miles) Median stabilization time (Ts) 216.0 mins (60 - 390.0 mins) Median referral time (Tr) 62.0 mins (40.0 - 148.0 mins) Median journey time 56.0 mins (15.0 - 265.0 mins) Median time between injury to reaching neuro- surgical centre 5.3 hrs (1.8 - 9.8 hrs) (Dieppe, Lo et al. ICM 2010)

25. Edinburgh Retrieval Team Standards Median distance between RHSC and refering hospital 35.2 miles (7.5 - 211.5 miles) Median mobilization time (Tm) 60.0 mins (13.0 - 285.0 mins) Median ambulance response time 15.0 mins (5.0 - 135.0 mins) Median travel time 58.0 mins (17.0 - 240.0 mins) Median travel time per mile (Tt) 1.4 mins / mile (0.1 - 14.0 mins / mile) (Dieppe, Lo et al. ICM 2010)

26. Theoretical Maximum Distance (D) Brain Trauma Retrieval = 67 miles D = (Ts - Tr - Tm) / Tt (Dieppe, Lo et al. ICM 2010)

27. Summary CPP insult is the most significant outcome predictor in childhood brain trauma. To improve childhood brain trauma outcome, AVOID ANY reduction in CPP below age-related insult thresholds of any duration. Think about maintaining an adequate MAP (CPP) with an assumption of ICP > 20 mmHg in the pre- ICU setting (including during inter-hospital transfer).