GUIDELINES FOR THE
MANAGEMENT OF
PEDIATRIC SEVERE
TRAUMATIC BRAIN INJURY
THIRD EDITION: UPDATE OF THE BRAIN TRAUMA FOUNDATION GUIDELINES
THRESHOLDS FOR CPP
• Strength of Recommendation: Weak
• Level III:
• Treatment to maintain a CPP at a minimum of 40mmHg is suggested.
• A CPP target between 40-5-mmHg is suggested to ensure that the minimum value of 40 is not
breached
THRESHOLDS FOR CPP
• INTRODUCTION
• CPP – defined by MAP minus the mean ICP (28) – pressure gradient driving cerebral
blood flow (CBF)
• Normal state: autoregulated and coupled with cerebral metabolic rate for oxygen (CMRO)
• If autoregulation is disrupted after TBI, decrease CPP may induce cerebral ischemia
THRESHOLDS FOR CPP
• INTRODUCTION
• With continuous monitoring of MAP and ICP, CPP can be followed and manipulated by
interventions that attempt to avoid regional and global ischemia.
• The optimal therapy for CPP remains unkown
CEREBRAL PERFUSION PRESSURE: SUMMARY OF
EVIDENCE
• Pre-defined CPP thresholds by age group
• 40 and 30 mmHg for 0-5 years
• 50 and 35 mmHg for 6-11 years
• 60 and 50 for 12 years old and older
CEREBRAL PERFUSION PRESSURE: SUMMARY OF
EVIDENCE
• In the pediatric age range, there may be an age related threshold between 40 and 50
mmHg with infants at the lower end and adolescents at the upper end of this range.
• Studies specifically focused on assessment of the optimal upper limit for CPP
management in pediatric TBI were lacking.
TREATMENTS: HYPEROSMOLAR THERAPY
• Strength of Recommendation: Weak
• Level II - For ICP control
• 1. Bolus HTS (3%) is recommended in patients with intracranial hypertension. Recommended
effective doses for acute use range between 2-5ml/kg over 10-20 minutes
TREATMENTS: HYPEROSMOLAR THERAPY
• Strength of Recommendation: Weak
• Level III - For ICP control
1. Continuous infusion HTS is suggested in patients with intracranial hypertension. Suggested
effective doses as a continuous infusion of 3% saline range between 0.1-1.0 ml/kg of body
weight per hour, administered on a sliding scale.
The minimum dose needed to maintain ICP <20mmHg is suggested.
TREATMENTS: HYPEROSMOLAR THERAPY
• Strength of Recommendation: Weak
• Level III - For ICP control
• 2. Bolus of 23.4% HTS is suggested for refractory ICP. Suggested dose is 0.5ml/kg with a
maximum of 30 ml.
• Avoiding sustained >72hours serum Na >170mEq/L is suggested to avoid complications of
thrombocytopenia and anemia.
• Avoiding a sustained serum Na >160mEq/L is suggested to avoid DVT.
TREATMENTS: HYPEROSMOLAR THERAPY
• Introduction: Hyperosmolar Therapy for Intracranial Hypertension
• IV administration of hyperosmolar agents was shown to reduce ICP in 1919.
• Mannitol – introduced into clinical use in 1961. Agent of choice until the late 1970s
• HTS – introduced in 1990s. Usage had increase.
• Goal: euvolemia rather than dehydration as a therapeutic target is achieved by assessing:
• Fluid balance, central venous pressure, urine output, BUN, creatinine, clinical examination
• Foley catheter – used to quantify urine output and avoid potential bladder rupture.
TREATMENTS: HYPEROSMOLAR THERAPY
• Introduction: Mannitol - commonly used to manage raised ICP in pediatric TBI
• Can reduced ICP by 2 mechanisms:
• 1. reducing blood viscosity – effect is immediate. Results from viscosity-mediated reflex
vasoconstriction w/c allows CBF to be maintained despite a low cerebral blood volume. Effect on
blood viscosity – transient (<75min)
• 2. Reduces ICP by an osmotic effect – develops more slowly (15-30 mins) d/t gradual
movement of water from the brain parenchyma into systemic circulation . Effect persists for 6 hrs.
TREATMENTS: HYPEROSMOLAR THERAPY
• Introduction: Mannitol - commonly used to manage raised ICP in pediatric TBI
• May accumulate in injured brain regions – reverse osmotic shift may occur (fluid moving from
the vascular parenchyma to the brain), increasing ICP. Occurs when used for a long time.
• Excreted unchanged in urine
TREATMENTS: HYPEROSMOLAR THERAPY
• Introduction: HTS
• Theorectical beneficial effects: restoration of normal cellular RMP and cell volume, stimulation
of ANP release, inhibition of inflammation, and enhacement of cardiac output.
• Possible side effects: rebound in ICP, central pontine myelinosis, high urinary water losses,
hyperchloremic acidosis, masking diabetes insipidus
• Second use: treat hyponatremia d/t cerebral salt wasting if it develops in a pediatric patient
after TBI
TREATMENTS: HYPEROSMOLAR THERAPY
• Evidence Synthesis: Bolus administration of HTS to control ICP
• Recommendation II.1 Hypertonic saline vs. other drugs for Intracranial HPN
• Decrease in ICP, increase in CPP
• 2-fold faster resolution of intracranial HPN than fentanyl or phenobarbital
• HTS may be the 1st line tx given favorable hemodynamics and resolution of intracranial HPN
TREATMENTS: HYPEROSMOLAR THERAPY
• Evidence Synthesis: Bolus administration of HTS to control ICP
• Recommendation II.1- 3% saline vs. 0.9%
• HTS was associated with lower ICP and reduced need for additional interventions
• Serum Na concentration increased – 7mEq/L after 3% saline
TREATMENTS: HYPEROSMOLAR THERAPY
• Evidence Synthesis: Continuous Infusion Hypertonic Saline to control ICP
• Recommendation III.1- Hypertonic saline 1.7% vs. LR
• No difference between groups in survival rate and length of hospital stay
• Pxs treated with HTS required fewer interventions than those treated with LR to maintain
ICP control
• The HTS group had shorter ICU stay, shorter duration of mechanical ventilation
TREATMENTS: HYPEROSMOLAR THERAPY
• Use of Hyperosmolar Therapy to Improve Outcomes.
• There was insufficient evidence to support a recommendation for the use of HTS to improve
overall outcomes.
• The use of HTS or mannitol in the OR was associated with a favorable outcome vs. no
hyperosmolar therapy.
GUIDELINES FOR THE
MANAGEMENT OF
PEDIATRIC SEVERE
TRAUMATIC BRAIN INJURY
THIRD EDITION: UPDATE OF THE BRAIN TRAUMA FOUNDATION GUIDELINES
TREATMENTS: ANALGESICS, SEDATIVE, NMB
• LEVEL III: For ICP Control
• III.1. With use of multiple ICP related therapies as well as appropriate analgesia and sedation in
routine ICU care, avoiding bolus administration of midazolam and/or fentanyl during ICP
crises is suggested d/t risks of cerebral hypoperfusion.
• Based on guidance from US FDA, prolonged continuous infusion of Propofol for either
sedation or the management of refractory intracranial hypertension is not recommended.
TREATMENTS: ANALGESICS, SEDATIVE, NMB
• Pediatric severe TBI requiring tracheal intubation and mech. ventilation, analgesics and
sedatives are needed for comfort and tolerance
• NMB – not needed routinely except during RSI
• Pxs with mech. vent – prevent patient ventilator dyssynchrony which may result in rise in
CBV and raise ICP.
TREATMENTS: ANALGESICS, SEDATIVE, NMB
• Use of Fentanyl and Midazolam for ICP Control
• ICP crisis with absent analgesia and sedation. Additional fentanyl and midazolam may reduce
ICP.
• 2 agents – ineffective at reducing ICP in patients with adequate analgesia and sedation
• Use of NMB, etomidate and ketamine– no recommendation
• Ketamine – contraindicated in pxs w/ raised ICP ( increases CBF)
TREATMENTS: ANALGESICS, SEDATIVE, NMB
• Indications from Adult Guidelines
• Recommendations from the adult guidelines cannot be used to guide treatment decisions in
children
CSF DRAINAGE
• Strength of Recommendation: weak
• Level III - For ICP control
• CSF drainage through an External Ventricular Drain (EVD) is suggested to
manage increased ICP
• Introduction
• EVD – used to measure not only ICP, but also for CSF drainage (IVH and hydrocephalus)
CSF DRAINAGE
• Summary of evidence
• EVD to reduce ICP and Improve Outcomes – insufficient data to determine influence of EVD on
outcomes.
• LD to Reduced ICP and Improve Outcomes – the evidence is insufficient to support a
recommendation about LD
CSF DRAINAGE
• Indications from Adult Guidelines
• LEVEL III recommendations that might be additive to the pediatric recommendations
include the ff:
• The EVD system zeroed to the midbrain w/ continuous drainage of CSF may be more
effective in lowering the ICP burden than intermittent drainage
• The use of CSF drainage to lower ICP in patients w/ an initial GCS <6 during the 1st 12 hours
after injury may be considered
SEIZURE PROPHYLAXIS
• Strength of Recommendation: weak
• Level III – For Seizure Prevention (clinical and subclinical)
• III.1 prophylactic treatment is suggested to reduce the occurrence of early (within 7 days)
post-traumatic seizure (PTS)
• There is insufficient evidence to recommend Levetiracetam over phenytoin based on either efficacy
in preventing early PTS or toxicity
SEIZURE PROPHYLAXIS
• Introduction – PTS
• Post-traumatic seizure – occurs early, within 7 days of injury, or late, beyond 8 days of
recovery.
• Risk Factors - location of lesion, cerebral contusions, retained bone and metal fragments,
depressed skull fracture, focal neurologic deficits, loss of consciousness, GCS >10, severity of
injury, length of post-traumatic amnesia, subdural or epidural hematoma, penetrating injury,
and age.
SEIZURE PROPHYLAXIS
• Introduction – Post-traumatic Seizure
• The occurrence of electrographic seizures (seizures detected by continuous EEG recording)
following severe TBI is higher in children than adults, occurring up to 70% cases
• Evaluation of evidence
• Levetiracetam - indirect evidence from 1 treatment series and 1 phase 2 trial was insufficient
to support a recommendation
• Phenytoin – 2 class III retrospective studies provide a low-quality body of evidence to support
a recommendation
SEIZURE PROPHYLAXIS
• Evidence Synthesis
• Use of phenytoin to prevent PTSs – (older retrospective review with severe TBI) lower rate
on PTSs in pxs treated prophylactically with phenytoin than in those who were not treated.
• Direct and indirect evidence to support the Level III recommendation
• Use of Levetiracetam to prevent PTS – insufficient evidence to support a recommendation
• Indication from adult guidelines
• Recommendations about seizure prophylaxis from the adult guidelines cannot be used to
guide treatment decisions in children
VENTILATION THERAPIES
• Strength of Recommendation: weak
• Level III – To improve overall outcomes
• III.1 Prophylactic severe hyperventilation to a PaCO2 <30mmHg in the initial 48 hours after
injury is not suggested
• III.2 If hyperventilation is used in the management of refractory intracranial hypertension,
advance neuromonitoring for evaluation of cerebral ischemia is suggested
VENTILATION THERAPIES
• Introduction
• Patients w/ severe TBI are comatose and may lack both airway protective reflexes and normal
ventilatory drive –airway protection and controlled mechanical ventilation and oxygenation
are necessary.
• Hyperventilation – used in pxs w/ severe pediatric TBI for rapid reduction of ICP since 1970s
• Reduces ICP by producing hypocapnia induced cerebral vasoconstriction w/ a reduction in CBF and
CBV. Based on the assumption that hyperemia was common after pediatric TBI and was thought to
reduced ICP by reducing perfusion
VENTILATION THERAPIES
• Evidence Synthesis – Used of Hyperventilation to Manage Severe TBI in Children
• A relationship between the level of hypocarbia and and frequency of cerebral ischemia were
observed.
• The frequency of regional ischemia was 28.9 during normocapnia and increased to 59.4% and
73.1% for PaCO2 25-35 mmHg and < 25mmHg
• Evidence from this study is indirect, and the exact contribution of induced hyperventilation to
poor outcome cannot be clearly defined from this study
VENTILATION THERAPIES
• Introduction
• Hyperventilation – used in pxs w/ severe pediatric TBI for rapid reduction of ICP since 1970s
• Subsequent studies showed – hyperemia is uncommon, that low CBF is associated w/ unfavorable
outcomes, and that hyperventilation can produce hypoperfusion or ischemia
• Ventilation targeting normal arterial levels of CO2 (35-45 mmHg) is currently
recommended
TEMPERATURE CONTROL/HYPOTHERMIA
• Strength of Recommendation: MODERATE
• Level II – To improve overall outcomes
• 11.1 Prophylactic moderate 32-33C hypothermia is not recommended over normothermia to
improve overall outcomes
• Level III – For ICP control
• III.1 Moderate 32-33C hypothermia is suggested for ICP control
• Safety recommendation 1. If hypothermia is used and rewarming is initiated, it should be carried out
at a rate of 0.5 – 1.0 C every 12-24 hours or slower to avoid complication
TEMPERATURE CONTROL/HYPOTHERMIA
• III.1 Moderate 32-33C hypothermia is suggested for ICP control
• Safety recommendation
• 1. If hypothermia is used and rewarming is initiated, it should be carried out at a rate of 0.5 –
1.0 C every 12-24 hours or slower to avoid complication
• 2. If phenytoin is used during hypothermia, monitoring and dosing adjusted to minimize
toxicity especially during the rewarming period are suggested
TEMPERATURE CONTROL/HYPOTHERMIA
• Introduction
• Post-traumatic hypothermia – core body temperature of <35C
• Temperature >38-38.5C – fever/pyrexia (altered thermoregulatory set point), hyperthermia (normal
set point)
• Evidence Synthesis
• Influence of hypothermia on mortality and outcome - no significant difference in mortality between
hypothermia and normothermia groups
• Hypothermia on intracranial hypertension – Although the evidence does not suggest a long term
benefit for ICP control with hypothermia, it does suggest that hypothermia produces an
immediate decrease in ICP
