1. Pediatric Traumatic Brain Injury
Steven Kernie M.D.
Professor of Pediatrics (in Neurology)
Chief, Pediatric Critical Care Medicine
Columbia University Medical Center
Morgan Stanley Children’s Hospital/New York Presbyterian
September 29, 2017

2. Case Study -- 1999 12 y/o boy with autism
Hit by car while riding his bike
GCS 12 at scene and transported to ER
Agitated, not following commands, GCS 10
Decision to electively intubate for CT
Unable to secure airway for 30 minutes
Became hypoxic and hypotensive
Transferred to PICU unresponsive
Developed diffuse cerebral edema
Neurologic status did not improve
Family decided to withdraw support

3. Case Study
2 ½ y/o HF with h/o head on collision at highway speed (April, 2009)
Restrained in car seat in back
Mother died at scene
GCS 4 (3-15 scale), intubated and flown to CMC
CT with multiple skull fxs, poor gray-white differentiation, evolving edema
ICP monitor placed since GCS was not 3

4. Hospital course Remained unresponsive in coma
CT scan of brain progressed
Developed moderate intracranial hypertension
Conference with critical care, neurosurgery, neurology, and palliative care deemed prognosis extremely poor and family elected to withdraw support
Support withdrawn, could breathe and protect her airway so sent home comatose on tube feeds, anticonvulsants, and methadone

6. Subsequent course for LJ
4 weeks after injury, started to awake from coma, began visually following family and started vocalizing
9 weeks after injury admitted for inpatient rehabilitation
6 months after injury, following simple commands, vocalizing appropriately, walking with assistance, feeding herself
12 months after injury, following 3-step commands, has words, sitting unsupported, walking with support
Perot Center for Brain and Nerve Injury
D. Miles/A. Hernandez

7. Outcome 6 months after discharge in 307 children with moderate to severe TBI from 2002-2012
Slovis, et al (in review)

8. What’s special about the brain?
Alexander Monro (1783)
Brain enclosed in bone and incompressible
Inflow and outflow of blood needs to be balanced
George Kelli (1824)
Brain in hanging victims has constant blood volume
Monro-Kelli doctrine
Brain is incompressible and enclosed in a fixed space

9. “Modern” approaches to intracranial hypertension
Francois Magendie (19th century)
Discovered CSF
Cushing (1926)
Modern definition of Monro-Kelli doctrine
In an intact skull the volume of brain, blood, and cerebrospinal fluid is constant
Increase in one causes a reduction in other 2

10. Cerebrospinal fluid Production and absorption is dynamic
70% of CSF from choroid plexus
Transependymal movement of fluid from brain parenchyma accounts for rest
Average volume in children 4-13 is 90ml
Rate of formation is 500ml/dy
Hourly turnover of 14%
Rate of production is constant but rate of absorption varies
Increases linearly as ICP exceeds 15mm Hg to 40mm Hg where rate of absorption is triple rate of production

11. The obtunded child Etiologies Trauma Hypoxia-ischemia Seizures
Infection
Temperature
Ingestions
Metabolic
Vascular
Neoplasms
NEJM, 2001, 344:580

12. Pediatric Glasgow Coma Scale
Kernie and Lehman, Pediatric Critical Care Medicine, 2007

13. Acute brain-specific therapies for severe TBI
American Association of Neurological Surgeons (J. Neurotrauma, , updated 2000, 2007, 2016)
May be a role for:
Resuscitation of blood pressure and oxygenation
Electrolyte balance
Normoglycemia
Sedation and neuromuscular blockade
Intracranial pressure monitoring and treatment
No role for:
Steroids
Chronic hyperventilation
ICP monitoring increased from 32% to 78% from

14. Goals of Current Therapy
Maintain adequate blood pressure
Maintain adequate oxygenation
Prevent increases in intracranial pressure (ICP)
Preserve cerebral perfusion pressure (CPP = MAP-ICP)
Prevent brain death

15. Prevent Brain Death (tentorial herniation syndrome)
Kernie, Rudolph’s Pediatrics, 22nd Edition, 2011

16. Brain trauma foundation guidelines (2007)/Pediatric guidelines (2003)
Options
Osmotic agents
CPP
Steroids
ICP threshold
Blood pressure/oxygenation
Barbiturates
Hyperventilation
Nutrition
Anti-seizure prophylaxis
Outcome prediction
Hypoxemia
Hypotension
Pediatric trauma center

17. Airway protection Why intubate the obtunded child?
Historical animal data
Acute brain trauma linearly related to ventilatory pause (A. Polis, 1894)
Standard practice of GCS ≤ 8
1. Prevent aspiration
2. Improve oxygenation
3. Control ventilation

18. Reasons for airway protection
Prevent aspiration
Original studies in post-partum hemorrhage and follow-up in fatal TBI
Unclear whether early intubation prevents or facilitates aspiration
San Diego RSI trial showed more aspiration with RSI (Vadeboncoeur et al, 2006)
Prolonged intubation and paralytics increase risk of aspiration (numerous studies)
State of protective reflexes
If don’t need paralysis then intubate

19. Reasons for airway protection (cont)
Optimal oxygenation
Hypoxemia is bad (PaO2<60-65 mm Hg or sats <90%)
Clearest predictor for poor outcome in TBI (Chi, et al, 2005)
Intubation may exacerbate hypoxemia
Hyperoxia may not be good
2003 Pediatric TBI guidelines advocate for resuscitation with 100% oxygen (based on data suggesting children with PaO2>350 did best, Michaud, et al, 1992)
Numerous studies demonstrate production of increased oxygen radicals

20. Reasons for airway protection (cont)
Optimal ventilation
Hypercarbia is neuroprotective
Direct vasodilation
Improved cerebral blood flow (and increases ICP)
Acidosis improves oxygen delivery (Bohr effect)
Hypocarbia causes vasoconstriction
Decreases cerebral blood flow
Decreases intracranial hypertension
Optimal levels are unclear
Needs to be monitored with capnography

21. Conclusions about airway protection, ventilation, and oxygenation
Most data suggest common adverse outcomes with intubation
Total obtundation with inability to protect airway (don’t need paralysis) only absolute indication
Oxygenation
Optimal oxygenation unclear but hypoxemia is most harmful
PaO2 in normal range probably ideal
Ventilation
Optimal CO2 levels unclear but monitored normocapnia most safe

22. Circulation (Blood Pressure)
Early hypotension associated with poor outcome in severe TBI
Among 5 most powerful predictors of outcome (Traumatic Coma Databank, 1991, 1993)
Combination with hypoxia particularly bad (mortality > 50%)
Causes of hypotension
Hemorrhage
Shock
Therapy-related
Positive pressure ventilation
Intubating agents (midazolam, propofol, pentobarbital)
Anticonvulsants (lorazepam, phenobarbital)
ICP-directed therapy (mannitol)

23. Fluid resuscitation for blood pressure
Options
Colloid
Blood products
Albumin
Isotonic crystalloid
Saline
Lactated Ringer’s
Normosol
Hypertonic crystalloid
3% Saline
7.5% Saline (improved survival in TBI, Wade et al, 1997)

24. Fluid resuscitation for hypotension
Saline versus Albumin Fluid Evaluation Study (SAFE study)
RCT trial of 7000 patients requiring ICU admission (NEJM, 2004, 350)
Randomized to fluid resuscitation with saline or albumin
No difference at 28 days in mortality
Post hoc analysis for TBI (NEJM, 2007, 357)
Increased mortality (33%) in those receiving albumin than saline (20%)
Trend towards decreased mortality in septic patients who received albumin
Apparent difference in patients with increased ICP

25. Hypertonic saline Option for treatment of increased ICP (Level II-III)
Hypertonic saline (no data for mannitol) is effective for the control of increased ICP after severe head injury
Original description in 1919 used saline not mannitol (reemerged in 1988 from case report of 2 cases, Worthley, et al)
Mechanism
Similar to mannitol but some theoretical benefits
Stimulation of ANP
Inhibition of inflammation
Enhancement of cardiac output
Possible side effects have not been observed
ICP rebound
Central pontine myelinolysis
TBI Guidelines, 2012

26. Summary of treating hypotension during the resuscitation phase of brain injury
Hypotension is associated with increased morbidity and mortality
Resuscitation should occur with crystalloid and albumin should be avoided
Role of hypertonic saline unclear but 3% saline more justifiable than mannitol which can cause hypotension

27. Acute brain specific therapies for preventing severe intracranial hypertension
“Standard therapies”
Positioning
Surgical excision of discrete bleed
CSF drainage/monitoring
Sedation/Neuromuscular blockade
Modest hyperventilation
Osmotic agents
Hemodynamic support
Pharmacologic coma
“non-Standard therapies”
Jugular venous bulb monitoring
Tissue monitoring
Hypothermia
Decompressive craniectomy
What doesn’t work
Chronic hyperventilation
Steroids

28. Classification of data used for clinical guidelines
Level I (formerly Class 1 – standard)
Prospective randomized controlled trials
“gold standard”
Level II (formerly Class 2 – guidelines)
Moderate or poor-quality RCT
Good quality cohort
Good quality case control
Level III (formerly Class 3 – options)
Moderate or poor-quality RCT or cohort
Moderate or poor-quality case control
Case series databases or registries
TBI Guidelines, 2012

29. Cerebral perfusion pressure
2003 Guidelines
2012 Guidelines
Level II
CPP>40 should be maintained
Level III
CPP probably represents age-related continuum
Advanced monitoring may be useful to optimize CPP
Hypotension should be avoided
Level III
CPP of 40 can be considered minimum
CPP threshold of may be considered with infants at lower and adolescents at upper end of this range

30. Hyperosmolar Therapy 2003 Guidelines 2012 Guidelines Level III
Hypertonic saline effective at continuous infusion of 3% in range of 0.1-1cc/kg/hr
Mannitol is effective as bolus in range of g/kg
Euvolemia should be maintained
Serum osmolality <320 with mannitol and <360 with hypertonic saline
Level II
Hypertonic saline should be considered at doses of cc/kg
Level III
Hypertonic saline should be considered as infusion between 0.1-1cc/kg/hr for ICP<20 and osm <360
No mannitol studies met inclusion criteria

31. Temperature Control 2003 Guidelines 2012 Guidelines Level III Level II
Avoid hyperthermia
Consider hypothermia for refractory ICP elevation
Level II
Moderate hypothermia (32-33°C) for only 24 hours should be avoided
Moderate hypothermia for up to 48 hours should be considered
If hypothermia is induced rewarming should not occur at >0.5°C/per hour

32. Hyperventilation 2003 Guidelines 2012 Guidelines Level III Level III
Mild or prophylactic hyperventilation (PaCO2 < 35) should be avoided
Mild hyperventilation may be considered for refractory increased ICP
Aggressive hyperventilation (PaCO2<30) may be considered as second-tier option
Aggressive hyperventilation titrated to clinical effect may be briefly needed
Level III
Avoidance of prophylactic severe hyperventilation to PaCO2<30 may be considered in initial 48 hours
If hyperventilation is used, advanced neuromonitoring for evaluation of cerebral ischemia may be considered

33. Corticosteroids 2003 Guidelines 2012 Guidelines Level III Level II
Use of steroids not recommended for improving outcome or reducing ICP
Level II
Not recommended to improve outcome or reduce ICP

34. Analgesics, Sedatives, and Neuromuscular Blockade
2003 Guidelines
2012 Guidelines
Level III
In absence of outcome data, the choice of dosing and sedatives, analgesics, and neuromuscular blocking agents should be left to treating physician, however effect of individual sedatives and analgesics on ICP on children can be variable
Level III
Etomidate may be considered but risk from adrenal suppression must be considered
Thiopental may be considered
Propofol not recommended
Specifics on other agents left to treating physician

35. Glucose and Nutrition 2003 Guidelines 2012 Guidelines Level III
Replace 130% to 160% of resting metabolism expenditure
Level II
No support for use of immune-modulating diet

36. Antiseizure Prophylaxis
2003 Guidelines
2012 Guidelines
Level II
Prophylactic use of antiseizure therapy is not recommended for preventing late posttraumatic seizures
Level III
Prophylactic antiseizure therapy may be considered to prevent early posttraumatic seizures in those at high risk for seizures
Level III
Prophylactic treatment with phenytoin may be considered to reduce incidence of early posttraumatic seizures

37. Decompressive Craniectomy
Options – can be considered (Level IIb)
severe TBI
Bi-frontal not recommended
Should be large and bone flap should be removed
intracranial hypertension unresponsive to medical therapy
Does it improve outcome?
All level IIb data -- some pediatric-specific data
Some suggest improvement
2006 Cochrane review suggests benefit in children only
RESCUEicp (NEJM, 2016)
Improved survival, more vegetative survivors and those with severe disability
TBI Guidelines, 2016

38. Decompressive Craniectomy
2 hours after injury
7 hours after injury
30 hours after injury
Cappell and Kernie, Pediatric Clinics of North American, 2013

39. Hyperthermia is associated with poor outcome
Greer, et al, Stroke, 2008

40. Hypothermia in adults
Long recognized that cold-water drowning victims showed improved outcomes
Therapy pioneered in 1950s and 60s for cardiac and neurosurgical procedures
Simultaneous trials in Europe and Australia of therapeutic hypothermia
Comatose patients following cardiac arrest
Mild (32-34°C) hypothermia for hours
Hypothermia as standard of care recently questioned
“current practice supports “therapeutic normothermia” (Nielsen et al, NEJM, 2013)

41. Hypothermia and TBI (adults)
Death
2 meta-analyses
OR on mortality 0.81 ( )*
OR on poor neurologic outcome ( )*
OR on Glasgow Outcome Scale ( )**
OR for pneumonia favor normothermia)
Cochrane Review (2004)
OR for death 0.80 ( )
OR for death/severely disabled 0.75 ( )
OR for pneumonia 1.95 (1.18 – 3.23)
Cochrane Review (2009)
RR for good outcome 1.55 (1.22 – 1.96)
Death/Severe Disability
*Harris et al, Arch Neurol, 2002
**Henderson et al, Intensive Care Med, 2002

42. Results of Canadian trial 1999-2004
Hutchison, et al, NEJM, 2008

43. Hypothermia in children
Differences in children
Level II data for avoidance of moderate hypothermia early after TBI for 24 hours
Level II and III data for moderate hypothermia beginning early for up to 48 hours should be considered
Level II data for avoidance of rewarming at >0.5°C/hr

44. Is ICP monitoring effective?
Chesnut, et al, NEJM, 2012

46. Conclusions No Level I data (except steroids in adults with TBI)
Many opinions
Prevent herniation (and hypotension, hypoxemia, hyponatremia, hyperglycemia)
More (and better) investigation