The document discusses the management of a 7-year-old girl who presented to the emergency department after being hit by a taxi while crossing the road. On examination, she was crying and oriented but became agitated and drowsy. Her GCS score was assessed and she displayed abnormal flexion in response to pain. The document discusses various clinical decision rules for determining which pediatric patients with head injuries require CT imaging, including the CHALICE, PECARN, and CATCH rules. It considers the risks of radiation exposure from CT scans for children and how to balance these risks with clinical need.

1. PEDIATRIC HEAD INJURY
Dr Chong Shu-Ling
Department of Emergency Medicine

2. Objectives
Which head-injured child
requires a CT scan?
Hyperosmolar
agents
Analgesics,
Sedatives and
Neuromuscular
blockers
Hyperventilation
Prophylactic
Anti-epileptics
Glycemic
Control
Cooling heads
in pediatric TBI

3. You are on shift when…
A 7-year-old girl is brought into your Emergency
Department by paramedics with her head bandaged.
According to the paramedics, she was crossing the road
when she was hit by an oncoming taxi. She was flung
about 2 meters.

4. Case Scenario cont’d
According to the paramedics, the 7-year-old girl was crossing the road
when she was hit by an oncoming taxi. She was flung about 2 meters.
On physical examination, she is crying softly, but is able to
tell you her name, and lifts her right hand when asked to.
Vital signs: HR 140/min, RR 30/min BP 100/60mmHg
SaO2 96% on room air. Pupils are 3mm equal and reactive
bilaterally
Kept on hard cervical collar

5. According to the paramedics, the 7-year-old girl was crossing the road
when she was hit by an oncoming taxi. She was flung about 2 meters.
On physical examination, she is crying softly, but is able to tell you her
name, and lifts her right hand when asked to.
Vital signs: HR 140/min, RR 30/min BP 100/60mmHg SaO2 96% on
room air. Pupils are 3mm equal and reactive bilaterally
Kept on hard cervical collar
After removing her bandage – you notice a boggy
swelling over the right parietal region. There is no active
bleeding currently.

6. After you log roll, she complains of headache and
vomits once. She suddenly appears disoriented and
seems very agitated.
Which of the following clinical features is the greatest
indication for a CT brain?
A) Headache
B) Vomiting once
C) New onset agitation
D) Dangerous mechanism of injury
E) Presence of scalp hematoma

7. Before answering the question..

8. Is CT scan dangerous?
• Lethal malignancies occur between 1-in-1000 and
1-in-5000 paediatric cranial CT scans
• Risk increases with decreasing age
• ALARA
Brenner DJ. Estimating cancer risks from pediatric CT: going from the
qualitative to the quantitative. Pediatr Radiol 2002
Brenner DJ, Hall EJ. Computed tomography – An increasing source of
radiation exposure. N Engl J Med 2007
Shah NB, Platt SL. ALARA: Is there a cause for alarm? Reducing
radiation risks from computed tomography scanning in children.
Curr Opin Pediatr 2008

9. Is CT scan dangerous?
• Cancer risk in 680, 000 people exposed to computed
tomography scans in childhood or adolescence: data
linkage study of 11 million Australians
• Matthews JD et al. BMJ 2013; 346:f2360
• Cancer incidence was 24% greater for exposed than for unexposed
people, after accounting for age, sex and year of birth.
• Incidence Rate Ratio (IRR) increased significantly for many types
of solid cancers, leukemia or myelodysplasia
For brain cancer and all cancers combined –
IRR was greater at younger ages

10. Is CT scan dangerous?
•CT of the brain was significantly associated
with the risk of brain tumours (as was CT to
the red bone marrow, with the risk of
leukaemia)
• MS Pearce et al. Radiation exposure from CT scans in
childhood and subsequent risk of leukaemia and brain tumours: a
retrospective cohort study. Lancet 2012;380:499-505

11. 1999 Royal College of Surgeons of England
2001 Canadian CT head rule Stiell IG. Lancet 2001
National Collaborative Centre
for Acute Care. Published by NICE
guidelines
Implications of NICE guidelines on
management of children presenting
with head injury J Dunning Arch Dis Child
2004
CHALICE Clinical Prediction Rule
J Dunning. Arch Dis Child 2006
PECARN rule
Kupperman. Lancet 2009
2003
2006
2009
CATCH rule
Osmond. CMAJ 2010
Should a head-injured child
receive a head CT scan? A
systemic review of clinical
prediction rules. Macguire JL.
Pediatrics 2009
Comparing CATCH, CHALICE and
PECARN. Lyttle. Emerg Med J Jan 2012
2009
2010

12. CHALICE
Children’s Head injury
Algorithm for the prediction
of Important Clinical Events
J Dunning et al.
Arch Dis Child 2006;91:885-91
• Prospective Cohort study from
2000-2003 (n=22772)
• Outcome measure: composite
comprising death,
neurosurgical intervention, or
marked abnormalities on CT
• Safer than Canadian CT head
rule
• May increase rate of CT
scanning
History
-Witnessed LOC > 5 mins
-History of amnesia (either antegrade or
retrograde) > 5 mins
-Abnormal drowsiness
-≥ 3 vomits after HI
-Suspicion on NAI
-Seizure after HI
Examination
-GCS< 14, or < 15 if < 1 yr old
-Suspicion of penetrating or deprassed skull
fracture of tense fontanelle
-Signs of basal skull fracture
-≥Focal neurological deficit
-Presence of bruise, swelling or laceration > 5 cm if
< 1 yr old
Mechanism
-High-speed road traffic accident either as
pedestrian, cyclist or occupant (speed >40m/h)
-Fall of > 3m in height
-High speed injury from a projectile or an object

13. 1999 Royal College of Surgeons of England
2001 Canadian CT head rule Stiell IG. Lancet 2001
National Collaborative Centre
for Acute Care. Published by NICE
guidelines
Implications of NICE guidelines on
management of children presenting
with head injury J Dunning Arch Dis Child
2004
CHALICE Clinical Prediction Rule
J Dunning. Arch Dis Child 2006
PECARN rule
Kupperman. Lancet 2009
2003
2006
2009
CATCH rule
Osmond. CMAJ 2010
Should a head-injured child
receive a head CT scan? A
systemic review of clinical
prediction rules. Macguire JL.
Pediatrics 2009
Comparing CATCH, CHALICE and
PECARN. Lyttle. Emerg Med J Jan 2012
2009
2010

14. Identifying children with very low risk of
CITBI
• Large Prospective cohort study
• N=42,412 for derivation and validation populations
• Aim
• To derive and validate a prediction rules for ciTBI
• Sought to derive clinically important outcomes
• Death, Neurosurgery, Intubation > 24 hrs, Hospitalization ≥ 2 days
• To identify children at very low risk in whom CT heads may be
unnecessary
Kuppermann N.(PECARN) Lancet 2009; 374: 1160-1170

15. Children > 2 years
GCS = 14 or other signs of
altered mental status, or
Signs of basilar skull fracture
Yes
4.3% risk of ciTBI
CT
Recommended
No
History of LOC
History of Vomiting
Severe mechanism of injury
Severe headache
Yes
0.9% risk of ciTBI
Observation vs CT:
-Physician experience
-Multiple vs isolated findings
-Worsening symptoms and
signs
-Parental preference
No
CT Not Recommended
Kuppermann N. Lancet 2009; 374: 1160-1170

16. Children < 2 years
GCS = 14 or other signs
of altered mental status,
or Palpable skull
fracture
Yes
4.4% risk of ciTBI
CT
recommended
No
Occipital/Parietal/Temporal scalp
hematoma
History of LOC > 5s
Severe mechanisms of injury
Not acting normally as per parent
Yes
0.9% risk of ciTBI
Observation vs CT:
-Physician experience
-Multiple vs isolated
finding
-Worsening
symptoms or signs
-Age < 3 months
-Parental preference
No
CT Not Recommended
Kuppermann N. Lancet 2009; 374: 1160-1170

17. 1999 Royal College of Surgeons of England
2001 Canadian CT head rule Stiell IG. Lancet 2001
National Collaborative Centre
for Acute Care. Published by NICE
guidelines
Implications of NICE guidelines on
management of children presenting
with head injury J Dunning Arch Dis Child
2004
CHALICE Clinical Prediction Rule
J Dunning. Arch Dis Child 2006
PECARN rule
Kupperman. Lancet 2009
2003
2006
2009
CATCH rule
Osmond. CMAJ 2010
Should a head-injured child
receive a head CT scan? A
systemic review of clinical
prediction rules. Macguire JL.
Pediatrics 2009
Comparing CATCH, CHALICE and
PECARN. Lyttle. Emerg Med J Jan 2012
2009
2010

18. CATCH Rule
Osmond et al. (PERC) CMAJ 2010;182:341-8
• Prospectively derived Clinical Decision Rule
Classified as no ciTBI if they were well on telephone
follow up at 14 days
• N= 3866 patients (277 < 2 yrs old)
• 24 (0.6%) underwent a neurologic intervention
• 159 (4.1%) had any brain injury as demonstrated on CT

19. CATCH Rule
Osmond et al. (PERC) CMAJ 2010;182:341-8
CATCH RULE for Childhood Head Injury
CT of the head is required if:
HIGH RISK (need for neurologic intervention)
1. GCS < 15 - 2 hours after injury
2. Suspected open or depressed skull fracture
3. History of worsening headache
4. Irritability on examination
MEDIUM risk (brain injury on CT scan)
5. Any sign of basal skull fracture
6. Large, boggy hematoma of scalp
7. Dangerous mechanism of injury
-Sensitivity 100%
-Specificity 70.2%
-Require 30.2% to
undergo CT
-Sensitivity 98.1%
-Specificity 50.1%
-Require 51.9% to
undergo CT

20. Which
Clinical
Decision
Rule,
rules?
Comparing CATCH, CHALICE and PECARN
clinical decision rules for paediatric head injuries
Lyttle et al. Emerg Med J Feb 2012

21. Comparing Accuracy of Clinical Decision Rule
Lyttle et al. Emerg Med J. Feb 2012
Sensitivity Specificity NPV PPV
Need for Neurological intervention
CATCH 100% 70.2% 100% 2.1%
Clinically significant intracranial injury
CHALICE 98.6% 86.9% 99.9% 8.6%
Clinically significant intracranial injury in patients with GCS 13-15
CHALICE 97.6% 87.3% 99.9% 5.4%
Clinically important brain injury
PECARN < 2yrs 98.6% 53.7% 99.9% 1.8%
PECARN ≥ 2yrs 96.7% 58.5% 99.9% 2.0%
CT Visible brain injury
CATCH 98.1% 50.1% 99.8% 7.8%
CHALICE 98.6% - - -
PECARN < 2yrs Not possible to calculate – derivation group reported only ciTBI
PECARN ≥ 2yrs

22. Comparing Predictor Variables
Lyttle et al. Emerg Med J. Feb 2012

23. Which Clinical Decision rule, rules?
• PECARN rule was the only one prospectively validated
• PECARN rule divided those < 2 yrs old from those ≥ 2
yrs old
• Shift from identifying any lesion on CT to focusing on
clinically significant lesions makes results difficult to
compare
• 3 CDRs need to undergo process of
prospective validation and comparison in single
population

24. Conclusion
• Best Rule?
• ROLE OF OBSERVATION
• Nigrovic et al. (PECARN) Pediatrics June 2011
• The Effect of Observation on Cranial Computed
Tomography Utilization for Children After Blunt
Head Trauma
• 42,412 patients in prospective multicentre
observational study
• If patients were observed before making a decision
on CT, CT rate was lower (31% vs 35%)

25. What about us?
•Retrospective data
– N = 2380 (7 month retrospective series)
– 537 patients admitted (22.6%) , 49 patients had a CT brain (2.1%), while only
15 patients (0.6%) had a significant finding on CT (bleed, edema or fracture).
•Small prospective study on applicability of the CATCH, PECARN and CHALICE
rules in our local population
–N=77 (3 week period)
–We applied the above rules to our population but found that they would
increase the rate of CT in our centre from 2-3% to about 30%.

26. WHAT ABOUT US?

27. Back to the patient….
According to the paramedics, the 7-year-old girl was crossing the road when she
was hit by an oncoming taxi. She was flung about 2 meters.
Suddenly she turns drowsy. She opens her eyes only to
pain. On applying nail bed pressure she adopts a flexing
posture but is unable to withdraw her arm from the
stimulus. She moans intermittently.

28. 1 2 3 4 5 6
Eyes Does not
open eyes
Opens to
painful stimuli
Opens to
speech
Opens
spontaneously
N/A N/A
Verbal No verbal
response
Inconsolable,
agitated
Inconsistently
inconsolable,
moaning
Cries but
consolable,
inapproriate
interactions
Smiles,
interacts,
follows
objects
N/A
Motor No motor
response
Extension to
pain
(decerebrate
response)
Abnormal
flexion to pain
(decorticate
response)
Withdraws
from pain
Localizes
painful
stimuli
Obeys
commands
GCS scoring in children

29. 1 2 3 4 5 6
Eyes Does not
open eyes
Opens to
painful stimuli
Opens to
speech
Opens
spontaneously
N/A N/A
Verbal No verbal
response
Inconsolable,
agitated
Inconsistently
inconsolable,
moaning
Cries but
consolable,
inapproriate
interactions
Smiles,
interacts,
follows
objects
N/A
Motor No motor
response
Extension to
pain
(decerebrate
response)
Abnormal
flexion to pain
(decorticate
response)
Withdraws
from pain
Localizes
painful
stimuli
Obeys
commands
GCS scoring in children

30. 1 2 3 4 5 6
Eyes Does not
open eyes
Opens to
painful stimuli
Opens to
speech
Opens
spontaneously
N/A N/A
Verbal No verbal
response
Inconsolable,
agitated
Inconsistently
inconsolable,
moaning
Cries but
consolable,
inapproriate
interactions
Smiles,
interacts,
follows
objects
N/A
Motor No motor
response
Extension to
pain
(decerebrate
response)
Abnormal
flexion to pain
(decorticate
response)
Withdraws
from pain
Localizes
painful
stimuli
Obeys
commands
GCS scoring in children

31. 1 2 3 4 5 6
Eyes Does not
open eyes
Opens to
painful stimuli
Opens to
speech
Opens
spontaneously
N/A N/A
Verbal No verbal
response
Inconsolable,
agitated
Inconsistently
inconsolable,
moaning
Cries but
consolable,
inapproriate
interactions
Smiles,
interacts,
follows
objects
N/A
Motor No motor
response
Extension to
pain
(decerebrate
response)
Abnormal
flexion to pain
(decorticate
response)
Withdraws
from pain
Localizes
painful
stimuli
Obeys
commands
GCS scoring in children

32. What should you do next?
Vital signs: HR 138/min RR 30/min, BP 110/56 mmHg
SaO2 100% on 100% NRM
What should you do next?
Preparing for RSI…….

33. Analgesics, sedatives and neuromuscular
blockade
• Facilitate ability to maintain airway, vascular catheters and
other invasive interventions
• Anti-convulsant and anti-emetic properties
• Attenuate effects of pain and stress:
• Increased cerebral metabolic demands that increase cerebral blood
volume and raise ICP, increased metabolic rate with higher oxygen
requirements
• Raju et al. Intracranial pressure during intubation and anesthesia in infants. J
Pediatr 1980;96:860-862
• NM-blockers prevent shivering, posturing and breathing
against the ventilator
• Hsiang JK et al.Early, routine paralysis for intracranial pressure control in severe
head injuiry: is it necessary? Crit Care Med 1994;22:1471-1476
Analgesics, sedatives and NM blockers

34. Key Studies of Prospective trials of Ketamine and
Intracranial Pressure
CJEM 2010;12(2)154-7
Study Study
Type
Study Population ICP CPP
Bourgoin
2003
Prospective
double-blind
RCT
- 25 patients with severe head injury
- continuous infusion ketamine-midazolam
v sufentanil-midazolam
infusion
No significant
difference
between groups
No significant
difference
between groups
Bourgoin
2005
Prospective
double-blind
RCT
- 30 patients with TBI receiving
sufentanil-midazolam or ketamine-midazolam
using target controlled
infusion
No significant
difference
between groups
No significant
difference
between groups
Schmittner
2007
Randomized
prospective
trial
-24 patients with TBI
-Group 1: methohexitone + ketamine
sedation
Group 2: methohexitone + fentanyl
sedation
No significant
difference
between groups
No significant
difference
between groups
Bourgoin et al. Crit care Med 2003;31:711-7
Bourgoin et al. Crit Care Med 2005;33:1109-13
Schmittner et al. J Neurosurg Anesthesiol 2007;19:257-62 Analgesics, sedatives and NM blockers

35. Key Studies of Prospective trials of Ketamine and
Intracranial Pressure
Reference Study Description Data Quality
and Reasons
Results and
Conclusion
Bar-Joseph
et al
2009
Prospective series
N = 30 children with raised
ICP, 24 with non-penetrating
TBI
Protocol: Single dose of
ketamine (1-1.5mg/kg)
evaluated for ability to:
(1) Prevent further increase in
ICP during stressful
procedures
(2) Treat refractory intracranial
hypertension
No control for
confounders,
small sample
size, admission
GCS not
specified,
sample included
pathologies
other than
severe TBI
Ketamine reduced
ICP for both settings
Increase CPP
Bar-Joseph G et al. Effectiveness of ketamine in decreasing intracranial pressure in
children with intracranial hypertension J Neurosurg Pediatr 2009;4:40-46
Analgesics, sedatives and NM blockers

36. After intubation
Vital signs: HR 144/min, BP 100/50 mmHg SaO2 100% while
bagging
What should you do next?
A) Hyperventilation
B) Hyperosmolar agents
C) Give anti-epileptic therapy

37. Hyperventilation
• Reduces ICP by producing hypocapnia-induced cerebral
vasoconstriction
• Reduces cerebral blood flow (CBF) and cerebral blood
volume
• Studies in mixed adult and pediatric populations have
demonstrated that hyperventilation results in decreased
cerebral oxygenation and may induce brain ischemia
• Kiening KL et al. Brain tissue pO2-monitoring in comatose patients:
implication for therapy. Neurol Res 1997;19:233-240
• Schnieder GH et al. Continuous monitoring of jugular bulb oxygen
saturation in comatose patients – Therapeutic implications. Acta
Neurochir (Wien) 1995;134:71-75
Hyperventilation

38. Reference Study Description Data Quality
and Reasons
Results and
Conclusion
Skippen
et al 1997
Case series
N = 23
Mean age 11 yrs
Protocol: CBF measured by
xenon-enhanced CT during
partial pressure of arterial CO2
adjusted to > 35, 25-35, and <
25mmHg
Outcome: Ischemic threshold
defined as < 18 ml/100g/min
No control for
confounders
Areas of CBF below
ischemic threshold
28.9%, 59.4% and
73.1% respectively
Curry et al
2008
Retrospective cohort study
N = 464
Mean age 8 yrs
Outcome: incidence of severe
hypocarbia (pCO2 < 30mmHg)
during the initial 48 hours and
risk of inpatient mortality
Unclear if
outcome
assessment
methods
unbiased
Severe hypocarbia
60% before and 52%
after (p=0.19)
Mortality adjusted
odds ratio of 1.44
(For 1 episode), 4.18
(for 2 episodes) and
3.93 for 3 or more
episodes of severe
hypocarbia
Pediatr Crit Care Med 2012 Vol 13 Hyperventilation

39. Hyperventilation
• Avoid prophylactic severe hyperventilation to PaCO2 <
30mmHg in initial 48 hours after injury
• If hyperventilation is used in management of refractory
intracranial hypertension, advanced neuromonitoring for
evaluation of cerebral ischemia should be considered

40. HYPEROSMOLAR
AGENTS

41. Use of Hyperosmolar agents: Mannitol
• Uses: Reduces blood viscosity and has osmotic effect (moving water
from parenchyma into systemic circulation)
• Osmotic effects last up to 6 hours and requires intact blood brain
barrier (Bouma et al. J Neurotrauma 1992;9(Suppl 1): S333-348)
• Mannitol may accumulate in injured brain regions, where reverse
osmotic shift may occur with fluid moving from the intravascular
compartment into the brain parenchyma – worsening raised ICP.
• Kaieda R et al. Neurosurgery 1989;24:671-678
• Use of mannitol (excreted unchanged in the urine) may risk
development of acute tubular necrosis and renal failure
• The Brain Trauma Foundation. Use of Mannitol J Neurotrauma 2000;17:521-525
Hyperosmolar agents

42. Hyperosmolar agents: Hypertonic saline
• Low penetration of blood-brain barrier, shares favorable
osmolar gradient
• Treats hyponatremia (can cause cell swelling and
seizures)
• Result of cerebral salt wasting, SIADH, Na losses from CSF
drainage, iatrogenic causes
• Pediatr Crit Care Med 2012 Vol 13, No. 1(Suppl.)
• Side effects
• Rebound in ICP, central pontine myelinolysis, renal impairment,
natriuresis, masking of development of diabetes insipidus
• Qureshi AI et al. Crit Care Med 2000;28:3301-3313
Hyperosmolar agents

43. Hypertonic Saline
Reference Study Description Data Quality and
Reasons
Results and
Conclusion
Fisher et al
1992
Randomized
controlled crossover
trial
N = 18
Mean age 8.3 yr
Protocol: 3% saline
vs 0.9% saline
Randomization and
allocation concealment
methods not reported.
Crossover study lacking
reporting on first period
comparison of baseline
characteristics; small
sample size
During 2 hour trial,
hypertonic saline was
associated with lower
ICP and reduced need
for additional
interventions to treat
ICP
Simma et al
1998
Randomized
controlled trial
N=35
Mean age 87 months
Protocol: 1.7%
hypertonic saline vs
lactated Ringer’s
administered for 3
days
Not blinded, insufficient
power
No difference in
survival rates
Those with hypertonic
saline required fewer
interventions, had
shorter length of ICU
stay and shorter
mechanical ventilation
Fisher B et al. Hypertonic saline lowers raised intracranial pressure in children after head trauma. J Neurosurg Anesthesiol 1992;4:4-10
Simma B et al. A prospective, randomized and controlled study of fluid management in children with severe head injury: Lactated Ringer’s
solution versus hypertonic saline. Crit Care Med 1998;26:1265-1270

44. Hypertonic Saline
Reference Study Description Data Quality and
Reasons
Results and
Conclusion
Peterson
et al
2000
Retrospective chart
review
N =68
Mean age 7.8 years
Protocol : Use of
continuous infusion
of 3% hypertonic
saline to reduce ICP
Retrospective, no
control for confounders
Survival rate was
higher than expected
based on Trauma and
Injury Severity Score
None developed
central pontine
myelinolysis, SAH or
rebound increase in
ICP
Khanna et al
2000
Prospective
Observational Study
N = 10
Protocol: Use of 3%
hypertonic saline to
maintain ICP <
20mmHg in children
with raised ICP
resistant to
conventional therapy
Small study Mean duration of
treatment was 7.6 days
Reduction in ICP
spikes and increase in
cerebral perfusion
pressure were seen
during treatment with
3% hypertonic saline
Peterson B, et al. Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 2000;28:1136-1143
Khanna S et al. Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit
Care Med 2000;28:1144-1151

45. After intubation, while waiting for transfer, you wonder about
the use of phenytoin as a prophylactic anti-epileptic.

46. Post traumatic Seizures (PTS)
• Early: Within 7 days of injury
• Late: Beyond 8 days of injury
• Risk factors for PTS include: Age, intraparenchymal
hemorrhage, retained bone and metal fragments, depressed skull
fracture, focal neurological deficits, LOC, GCS < 10, severity of injury,
length of post-traumatic amnesia, subdural or epidural hematoma,
penetrating injury.
• Ates O et al. Post-traumatic early epilepsy in pediatric age group with emphasis on
influential factors. Childs Nerv Syst 2006;22:279-284
• Appleton RE et al. Post-traumatic epilepsy in children requiring inpatient
rehabilitation following head injury. J Neurol Neurosurg Psychiatry 2002;72:669-672

47. Post Traumatic Seizures
• Infants and children have lower seizure thresholds
• Holmes GL et al. Pediatr Neurol 2005;33:1-11
• Seizures may be subtle and challenging to diagnose in
critically head injured children
• Bratton SL et al. Guidelines for management of severe traumatic brain injury. XIII:
Antiseizure prophylaxis. J Neurotrauma 2007;24 (Suppl 1): S83-S86
• Adult guidelines recommend use of anticonvulsants to
decrease incidence of early PTS
• Temkin NR et al. A randomized, double-blind study of phenytoin for
the prevention of post-traumatic seizures. N Engl J Med
1990;323:497-502
• Incidence of early PTS was 3.6% in the phenytoin group vs 14.2%
in placebo group (RR 0.27 {95% CI 0.12-0.62}
Anti-epileptic Therapy

48. Citation Study Group Study
Type
Outcome Key Results Comments
Schierhout et
al
2001
6 controlled
trials, 1218
randomized
(both) adults
and children
System
-atic
review
Early
seizures (first
7 days), late
seizures,
mortality,
neurologic
disability
(GOS)
RR for early seizure
prevention 0.34
(CI0.21-0.54) NNT 10
No difference for
death, neurologic
disability and late
seizures
Early seizure
prevention
values
represent 4
studies with
phenytoin and
2 with other
agents
EA Hunt. Phenytoin in traumatic brain injury. Towards evidence based medicine for
paediatricians. Arch Dis Child 2002;86:59-63
Anti-epileptic Therapy

49. Reference Study Description Data Quality
and Reasons
Results and
Conclusion
Lewis et al
1993
Retrospective cohort study
N = 194 (31 with severe TBI)
Median age 6 yrs
Protocol: Phenytoin within 24
hours of hospital admission or
no prophylactic anticonvulsant
medication
Outcome: Any seizure during
hospitalization
Control for
confounders
only in analysis
of predictors of
seizure, not for
comparison of
groups based on
seizure
prophylaxis
Reduction in early
PTS rate in severe
TBI cases (GCS 3-8)
treated with
phenytoin (15% vs
53%)
Young et al
2004
Randomized, double-blinded,
placebo-controlled
N = 103
Age range: < 16 yrs
Protocol: Enrolled within 40
mins of presentation and drug
or placebo administered within
60 mins.
Limitations: Low
seizure rate,
small sample
size from loss to
follow up.
33% Lost at 48
hr follow up and
36% lost at 30
day follow up
No reduction in rate
of PTS within 48
hours of injury (7% in
phenytoin group vs
5% in placebo group)
Pediatr Crit Care Med 2012 Vol 13 Anti-epileptic Therapy

50. • The hypocount returns 15.6mmol/L
What should you do now?
A) Give subcutaneous insulin 0.1 units/kg
B) Start IV insulin at 0.1units/kg/hour
C) Repeat glucose in 2 hours

51. Study Design Inclusion criteria
(total n)
Results Comments
JRT Melo et al
[1], [2]
Retrospective
cross-sectional
Children < 17 years
old with severe TBI
as defined by GCS
≤ 8
(n = 315)
Hyperglycemia ≥11.1
mmol/L (≥200mg/dl)
is an independent
predictor for mortality
– OR 6.14 (95% CI
2.25-16.73)
A new scale was
proposed – this
included: age
group, GCS,
temperature,
blood glucose
levels and
prothrombin time
SM Seyed
Saadat et al
[3]
Retrospective
cross-sectional
Children < 18 years
old with severe TBI
as defined by GCS
≤ 8, admitted to ED
within 12 hours of
injury
(n=122)
Persistent
hyperglycemia during
the first 2-3 days had
adjusted ORs for
mortality of 2.84
(95% CI 0.89-9.06)
and 11.11 (95% CI
2.95-41.71)
respectively
Persistent
hyperglycemia is
an independent
predictor of
mortality
[1]Tude Melo JR, et al. Neurosurgery 2010;67:1542-1547
[2] Melo JR, et al. Acta Neurochir 2010;152(9):1559-1565
[3] Seyed Saadat SM et al. Childs Nerv Syst 2012;28(10):1773-1777 Glucose control

52. Study Design Inclusion criteria
(total n)
Results Comments
RL Smith
et al [4]
Retrospective
review of a
prospectively-collected
Pediatric
Neurotrauma
Registry
Children admitted
with severe TBI as
defined by GCS ≤
8. Mean age 81
months
(n=57)
Mean glucose
concentrations in the
Late period (49-168
hours) was associated
with unfavourable GOS
at 6 months
As part of the
protocol, glucose
administration
was avoided for
48 hours after
TBI
A Cochran
et al [5]
Retrospective
review
Children admitted
with a head
regional
Abbreviated Injury
Score (AIS) ≥3
(n=170)
Admission glucose had
adjusted OR for head-injury
related death of
1.01 (95% CI 1.003-
10.23)
On multivariate
analysis, GCS
was also an
independent
predictor for
head-injury
related death
[4] Smith RL, [4] Smith RL et al. Relationship Between Hyperglycemia and Outcome in Children with Severe Traumatic Brain Injury.
Pediatr Crit Care Med 2012;13(1):85-91
[5] Cochran A, et al. Hyperglycemia and outcomes from pediatric traumatic brain injury. J Trauma. 2003;55(6):1035-1038
Glucose control

53. Study Design Inclusion criteria
(total n)
Results Comments
Chong SL
et al
Retrospective
review
Children admitted
with moderate and
severe TBI as
defined by GCS <
14. Mean age
(n= 44)
Univariate analysis –
Hyperglycemia was a
predictor for
mortality, 14-day
ventilation free days
or 14-day PICU free
days.
But after stratifying to
patients with GCS <
7, this was no longer
statistically
significant
Initial
hyperglycemia
was associated
with prolonged
ICU stay,
mechanical
ventilation, and
increased
mortality

54. Does tight glucose control change
outcomes?
• A recent randomized trial among children admitted to the
PICU (not specific to TBI): No significant difference in the
number of days alive and free from mechanical ventilation
at 30 days post randomization
• The incidence of hypoglycemia being higher in the tight glucose
control group compared to that with conventional glucose control
• Macrae D, et al. A randomized trial of hyperglycemia control in
pediatric intensive care. N Engl J Med 2014 Jan 9;370 (2):107-118

55. • It is currently 2 hours post injury. The temperature is
36.4oC
What should you do now?
A) Give cold saline – target a temperature of 30-32oC
B) Surface cool – target 32-33oC
C) Keep the current temperature

56. Temperature Control: Does cooling help?
• Several small studies showed a positive effect of cooling on
intracranial hypertension
• Li H et al. Protective effect of moderate hypothermia on severe traumatic brain injury
in children. J Neurotrauma 2009;26:1905-1909
• Biswas AK et al. Treatent of acute traumatic brain injury in children with moderate
hyperthermia improves intracranial hypertension. Crit Care Med 2002;20:2742-2751
• Therapeutic hypothermia useful in newborn babies after hypoxic
ischaemic encephalopathy
• Shakaran S et al. Childhood Outcomes after Hypothermia for Neonatal
Encephalopathy N Engl J Med. 2012 May 31; 366(22): 2085–2092.
Cooling in TBI

57. Meta-analysis
Ma CK et al. Is therapeutic hypothermia beneficial for pediatric patients with
traumatic brain injury? A meta-analysis. Childs Nerv Syst 2013;29:979-984
Inclusion criteria: RCT, Pediatric TBI, hypothermia after TBI vs normothermia,
and primary outcome
Exclusion criteria: Non-RCT, TBI in adults, and no outcomes reported
Cooling in TBI

58. Meta-analysis
Ma CK et al. Is therapeutic hypothermia beneficial for pediatric patients with
traumatic brain injury? A meta-analysis. Childs Nerv Syst 2013;29:979-984
Cooling in TBI

59. Meta-analysis
Ma CK et al. Is therapeutic hypothermia beneficial for pediatric patients with
traumatic brain injury? A meta-analysis. Childs Nerv Syst 2013;29:979-984
Cooling in TBI

60. Reference Study Description Data Quality and
Reasons
Results and
Conclusion
Hutchison
et al 2008
Randomized controlled trial
N = 225
Protocol: Randomized to
cooling to 32-33 oC
within 8 hours of injury
for 24 hours, vs
normothermia. Patients
rewarmed at 0.5oC
every hour
Potential confounder
was that marked
hyperventilation
(PaCO2 <30mmHg)
was used as part of
standard
management in >
40% of patients and
use of hypertonic
saline was
significantly reduced
in the hypothermic
groups vs
normothermia group
Unfavourable
outcome at 6
months: 21% deaths
in hypothermia group
(vs 14% in
normothermia
group), more
hypotension and
more vasoactive
agents in the
hypothermia group
during the rewarming
period
Hutchison JS et al. Hypothermia therapy after traumatic brain injury in children. N
Engl J Med 2008;358:2447-2456
Cooling in TBI

61. Reference Study Description Data Quality and
Reasons
Results and
Conclusion
Adelson et
al 2005
Randomized controlled trial
N=75
Protocol: Cooled to 32-
33oC within 8 hours of
injury for 48 hours, vs
normothermia
Outcome: Mortality, 3- and
6-month Glasgow
Outcome Scale
Unclear reporting
of randomization
methods,
allocation
concealment
methods, and
attrition
Mortality 8%
(Hypothermia) vs 16%
(Normothermia)
{p=0.44} No difference
in 3- and 6-month
Glasgow Outcome
Scale. ICP was
significantly reduced in
initial 24 hours after
TBI in hypothermia vs
normothermia groups.
Adelson PD et al. Phase II clinical trial of moderate hypothermia after severe
traumatic brain injury in children. Neurosurgery 2005;56:740-754
Cooling in TBI

62. • Adelson et al. Comparison of hypothermia and normothermia after
severe traumatic brain injury in children (Cook Kids): A phase 3,
randomised controlled trial. Lancet Neurol 2013;12:546-53
• Children aged 0-17 were enrolled in the ED or ICU from 15 sites in
USA, NZ and Australia, within 6 hours of injury, GCS 3-8
• Randomized, investigators who assessed outcomes were masked
• Procedure for hypothermia group:
• Rapidly cooled initially using iced saline (4oC) to 34-35oC, then surface
cooled to 32-33oC.
• Maintained for the requisite 48h period
• Rewarming 0.5-1oC every 12-24 hours (slow rewarming)
• Outcome measures assessed by intention to treat analysis:
(Primary) mortality at 3 months (Secondary) GOS and GOS –E
Peds at 3 months after injury
Futility analysis was done after recruiting 77 patients and the trial was
stopped – they detected no significant difference in mortality at 3 months,
and no significant difference between the GOS or GOS-E Peds scores

63. Hutchison JS et al. Cooling of children with severe TBI. Lancet
Neurol 2013;12:527-529

64. What about the effect of hypothermia on
drugs in TBI?
• PE Empey et al. Therapeutic Hypothermia Decreases
Phenytoin Elimination in Children with Traumatic Brain
Injury. Crit Care Med 2013;41:2379-2387
• Pharmacokinetic study – retrospectively evaluated 19 children who
were randomized to 48 hours of cooling to 32-33oC
• Therapeutic hypothermia significantly reduces phenytoin elimination
in children with severe TBI leading to increased drug levels (and risk
for toxicity) for an extended period of time after cooling
Pharmacokinetic interactions between hypothermia and medications
should be considered when caring for children receiving this therapy.

65. • It is currently 2 hours post injury. The temperature is
36.4oC
What should you do now?
A) Give cold saline – target a temperature of 30-32oC
B) Surface cool – target 32-33oC
C) Keep the current temperature

66. Objectives
Which head-injured child
requires a CT scan?
Hyperosmolar
agents
Analgesics,
Sedatives and
Neuromuscular
blockers
Hyperventilation
Prophylactic
Anti-epileptics
Glycemic
Control
Cooling heads
in pediatric TBI

69. THANK YOU
Chong.Shu-Ling@kkh.com.sg

70. Lyttle et al. Emerg Med J. Feb 2012
Age
(yrs)
Primary
Outcome
Secondary
Outcome
Inclusion Criteria Exclusion criteria
CATCH < 17 Need for
neurological
intervention
Brain injury
on CT
Blunt trauma resulting in
LOC, amnesia, persistent
vomiting (2 or more 15
mins apart), initial GCS
13 or more, injury within
past 24 hrs
Obvious penetrating
injury or depressed
fracture, focal
neurological deficit,
chronic GDD, HI due to
NAI, return for
reassesment of
previous HI, pregnancy
CHALICE < 16 Clinically
significant
ICI
Presence of
skull fracture
Admission to
hospital
Any history or signs of
injury to the head
Refusal to consent
PECARN < 18 Clinically
important
TBI
- Present within 24hr of HI Trivial mechanism,
penetrating trauma,
known brain tumour,
previous neurological
disorder, prior
neuroimaging,
ventricular shunt,
bleeding disorder,
GCS < 14

71. ICP monitoring
• 4 lines of evidence support the use of ICP monitoring in
severe TBI
1. A frequently reported high incidence of intracranial hypertension
in children with severe TBI
2. A widely reported association of intracranial hypertension and
poor neurologic outcome
3. The concordance of protocol-based intracranial hypertension
therapy and best-reported clinical outcomes
4. Improved outcomes associated with successful ICP-lowering
therapies.
• All Class III evidence
• ICP monitoring of significant use in young children

72. Threshold for treatment of Intracranial Hypertension
• Level III evidence – treatment may be considered at a
threshold of 20mmHg
• Taking reference from adult studies
• While there are Class III studies that show sustained elevations in
ICP (>20mmHg) are associated with poor outcomes in children
after severe TBI, the absolute target for ICP-directed therapy has
not been well established
• Age-dependent values?
• Need to define the relative value of ICP versus CPP-directed
therapy in pediatric TBI

73. Phases of a clinical trial
• Phase 0 – Pharmacodynamics and Pharmacokinetics
• Phase 1 – Screening for safety
• Phase 2 – Establishing the testing protocol
• Phase 3 – Final Testing
• Phase 4 – Postapproval studies