01Approach to the Critical Patient/attcp60

Immediate priorities

›Airway and breathing

›GCS <= 8 mandates immediate endotracheal intubation

›Rapid sequence intubation preferred

›Cervical spine precautions until cleared

›Oxygenation target SpO2 >= 94%

›Hypoxia is a primary secondary injury driver

›Avoid SpO2 < 90% at all times

›Ventilation target PaCO2 35 to 38 mmHg

›Avoid aggressive hyperventilation

›PaCO2 < 30 mmHg causes cerebral vasoconstriction and ischemia

›Circulation and hemodynamics

›SBP target >= 110 mmHg for age 15 to 49 years

›Hypotension doubles mortality risk in TBI

›Single episode of SBP < 90 mmHg associated with worse outcomes

›SBP target >= 100 mmHg for age >= 50 years

›Brain Trauma Foundation guideline recommendation

›Avoid hypotension from sedation boluses

›If hypotension, consider polytrauma hemorrhage as cause

›DAI itself does not cause hemodynamic instability

›FAST exam and trauma survey mandatory

›Head and ICP management

›Head of bed elevation 30 to 45 degrees

›Head midline to facilitate venous drainage

›Avoid jugular compression from cervical collar

›ICP monitoring if GCS <= 8 with abnormal CT

›Also indicated for GCS <= 8 with normal CT plus two of: age > 40, posturing, SBP < 90 mmHg

›Target ICP < 22 mmHg

02History/hx69

Mechanism and event

›Mechanism of injury

›High-speed motor vehicle collision

›Most common mechanism, approximately 70 percent of DAI cases

›Ejection from vehicle increases severity

›Motorcycle or bicycle crash

›Rotational force component critical

›Helmet use and type

›Fall from height

›Head impact angle

›Surface characteristics

›Blast injury

›Military and civilian blast exposure

›Overpressure wave mechanism

›Sports-related impact

›Contact sport, repeated subconcussive impacts

›Prior concussion history

›Loss of consciousness

›Immediate onset at time of injury

›Distinguishes DAI from expanding mass lesion

›Absence of lucid interval is key feature

›Duration of unconsciousness

›Correlates with DAI severity grade

›Immediate coma with high-energy mechanism suggests severe DAI

›Post-traumatic amnesia duration

›PTA > 24 hours suggests significant injury

›Correlates with long-term functional outcome

03Physical Exam/exam64

Vitals and general

›Hemodynamic assessment

›Blood pressure

›Hypertension from sympathetic surge

›Hypotension suggests polytrauma hemorrhage not DAI

›Heart rate

›Tachycardia from sympathetic activation

›Bradycardia with Cushing reflex is late herniation sign

›Temperature

›Fever > 38 degrees C worsens secondary injury

›Hyperthermia episodes may indicate paroxysmal sympathetic hyperactivity

›Oxygen saturation

›Continuous monitoring mandatory

›Desaturation events associated with worse outcome

Neurologic exam

›Consciousness assessment

›GCS total and components separately

›Eye opening: 1 to 4

›Verbal response: 1 to 5

›Motor response: 1 to 6

›GCS <= 8 defines severe TBI

›Coma with immediate onset after trauma

›No lucid interval characteristic of DAI

›Pupillary assessment

›Size, reactivity, and symmetry bilaterally

›Fixed dilated pupils suggest brainstem DAI or herniation

›Asymmetric pupils suggest focal compression

›Quantitative pupillometry preferred

04Differential Diagnosis/ddx47

Life-threatening conditions

›Mass lesions requiring surgery

›Epidural hematoma

›ICD-10 S06.4

›Lucid interval may occur; lenticular hyperdensity on CT; surgical emergency

›Acute subdural hematoma

›ICD-10 S06.5

›Crescent-shaped hyperdensity; may coexist with DAI

›Intracerebral hemorrhage traumatic

›ICD-10 S06.3

›Focal hyperdensity on CT; may be amenable to surgery if large

›Diffuse injury patterns

›Diffuse cerebral edema

›ICD-10 S06.1

›Loss of gray-white differentiation on CT; often from prolonged hypoxia or hypotension

›Hypoxic-ischemic injury

›Bilateral cerebral involvement

›Associated with prolonged cardiac arrest or respiratory failure

›Status epilepticus non-convulsive

›Continuous EEG required to detect

›Causes persistent coma without motor convulsions

Close mimics

›Cerebral contusions

›Focal hemorrhagic lesions at gray-white junction

›ICD-10 S06.3

›Frequently frontal and temporal

›Frequently coexist with DAI

›Coup and contrecoup pattern

05Laboratory Tests/lt62

Trauma and resuscitation labs

›Standard trauma panel

›Complete blood count

›Hemoglobin target > 7 g per dL in TBI

›Thrombocytopenia increases hemorrhage risk

›Coagulation profile

›PT, INR, PTT, fibrinogen

›Trauma-induced coagulopathy common with severe TBI

›Emergent reversal if on warfarin or DOACs with intracranial hemorrhage

›Type and screen

›Anticipate transfusion needs in polytrauma

›Massive transfusion protocol activation criteria

›Metabolic panel

›Electrolytes and renal function

›Sodium monitoring for DI and SIADH risk

›Glucose control avoids secondary injury

›Glucose point-of-care

›Hypoglycemia causes secondary brain injury

›Hyperglycemia also worsens outcomes; target < 10 mmol/l

›Blood alcohol level

›Contribution to GCS depression

›Medicolegal documentation

›Urine drug screen

›Confounding substance identification

›Opiates, benzodiazepines, stimulants

›Arterial blood gas

›PaO2 target > 80 mmHg

›Hypoxia threshold < 60 mmHg worsens secondary injury

06Diagnostic Tests/dt111

Scoring Systems

›DAI severity classification

›Adams grading system

›Grade 1: lobar white matter injury at gray-white junction

›Grade 2: corpus callosum involvement added

›Grade 3: brainstem dorsolateral involvement added

›Grade 1 prognosis

›Fastest recovery trajectory

›Mean time to follow commands approximately 9 days

›Grade 2 prognosis

›Intermediate prognosis

›Mean time to follow commands approximately 17 days

›Grade 3 prognosis

›Worst prognosis

›GOSE 4 median outcome; approximately 8-fold increased risk of poor outcome

›TBI severity scoring

›Glasgow Coma Scale

›Severe TBI GCS 3 to 8

›Moderate TBI GCS 9 to 12

›Mild TBI GCS 13 to 15

›IMPACT prognostic model

›Age, motor score, pupillary reactivity inputs

›CT characteristics and lab values included

›Predicts 6-month functional outcome

›Paroxysmal Sympathetic Hyperactivity Assessment

›PSH-AM clinical feature scale

›Heart rate, respiratory rate, temperature, blood pressure, diaphoresis, posturing scored

›Diagnosis likelihood tool component

›PSH-AM score >= 8 supports diagnosis

›Occurs in approximately 10 to 15 percent of severe TBI

›DAI is strongest risk factor

MRI

›MRI brain indications for DAI

›Gold standard for DAI detection

›Superior to CT for white matter and axonal injury

›Indicated when clinical severity disproportionate to CT findings

›Timing considerations

›Early MRI within 24 to 72 hours for prognostication

›Repeat at 6 weeks for subacute changes and further grading

›Recommended MRI sequences

›SWI or T2 GRE susceptibility

›Most sensitive for hemorrhagic microbleeds

›Detects hemosiderin deposits at gray-white junction, corpus callosum, brainstem

›FLAIR

›Detects non-hemorrhagic white matter lesions

›Hyperintense signal in injured white matter tracts

›DWI and ADC map

›Identifies acute cytotoxic edema in injured axons

›Restricted diffusion in white matter tracts

›T1 and T2 conventional sequences

›Anatomic reference

›Hemorrhage characterization by chronicity

›Advanced MRI techniques

›Diffusion tensor imaging DTI

›Most sensitive for quantifying axonal injury

›Fractional anisotropy reduction indicates tract injury

›Can detect injury even with normal conventional MRI

›MR spectroscopy

›NAA reduction reflects neuronal loss

›Choline elevation reflects membrane disruption

›ACR Appropriateness Criteria support MRI for suspected DAI with normal CT

›2021 update recommendation

›SWI and DTI preferred sequences

CT

›CT head indications

›First-line emergent imaging in all moderate to severe TBI

›Rapid acquisition and wide availability

›Identifies surgical lesions requiring immediate intervention

›CT limitations for DAI

›Low sensitivity for axonal injury at cellular level

›Often normal or near-normal despite severe clinical presentation

›Discrepancy between CT appearance and clinical severity is hallmark of DAI

›CT findings in DAI

›Punctate hemorrhages

›At gray-white junction in lobar white matter

›In corpus callosum

›In dorsolateral brainstem

›Surrogate markers of severe DAI

›Traumatic midline subarachnoid hemorrhage

›Intraventricular hemorrhage

›Sensitivity approximately 30 to 50 percent for DAI diagnosis

›Coexisting lesions to exclude

›Epidural or subdural hematoma

›Cerebral contusions

›Midline shift

›CT C-spine

›Mandatory in obtunded patients

›Cannot clinically clear in GCS < 15

›Concurrent cervical injury in 5 to 10 percent of TBI

›CT angiography considerations

›Cervical vascular injury screening if neck trauma

›Denver criteria or expanded criteria screening

Ultrasound

›Point-of-care ultrasound roles

›FAST exam for polytrauma

›Free fluid in abdomen and pelvis

›Pericardial effusion

›Lung ultrasound for pulmonary complications

›Pneumothorax detection

›Pulmonary edema B-line pattern

›Neurogenic pulmonary edema assessment

›Hemodynamic POCUS

›Cardiac function estimation

›LV function gross estimate

›Cardiac tamponade exclusion

›Volume status assessment

›IVC collapsibility index

›Integrate with clinical exam and invasive monitoring

›Optic nerve sheath diameter

›ONSD > 5.0 to 5.9 mm correlates with elevated ICP

›Sensitivity approximately 74 to 95 percent

›Specificity approximately 79 to 100 percent

›Non-invasive surrogate for ICP elevation

›Adjunct to clinical assessment

›Does not replace formal ICP monitoring

07Disposition/dispo39

Level of care selection

›ICU admission indications

›GCS <= 8 with DAI diagnosis or concern

›Airway protection required

›ICP monitoring candidacy

›Moderate TBI GCS 9 to 12 with MRI-confirmed DAI

›Serial neurologic monitoring

›Rapid deterioration risk

›Abnormal CT with mass effect or shift

›Neurosurgical accessibility

›Hemodynamic instability

›Paroxysmal sympathetic hyperactivity

›Requires intensive monitoring and titrated pharmacotherapy

›High nursing care burden

›Transfer criteria

›Transfer to Level 1 trauma center if neurosurgery unavailable

›World Society of Emergency Surgery recommendation

›Do not delay transfer for non-emergent imaging

›Transfer when ICP management not available

›Specialized TBI center

›Neuro-critical care expertise

Rehabilitation and follow-up disposition

›Inpatient rehabilitation

›Transfer from acute care when medically stable

›Specialized inpatient brain injury rehabilitation

›Higher probability of functional independence with specialized care

›Rehabilitation team composition

›Physical therapy

08Treatment/t128

Resuscitation and stabilization

›Airway management

›Endotracheal intubation for GCS <= 8

›Rapid sequence intubation with appropriate agents

›Avoid succinylcholine if concerns about hyperkalemia from denervation injury

›Post-intubation ventilation targets

›SpO2 >= 94 percent

›PaCO2 35 to 38 mmHg

›Tidal volume 6 to 8 mL per kg ideal body weight

›Hemodynamic resuscitation

›SBP target >= 110 mmHg age 15 to 49 years

›Brain Trauma Foundation 2016 guideline

›Isotonic crystalloid or blood products

›SBP target >= 100 mmHg age >= 50 years

›Avoid hypotension at all costs

›Vasopressors if fluid-refractory hypotension

›Norepinephrine for vasodilatory shock

›Starting dose 0.05 to 0.1 mcg/kg/minute

›Titrate to MAP target maintaining CPP >= 60 mmHg

ICP management

›Osmotherapy

›Mannitol 20 percent

›Dose 0.25 to 1.0 g per kg IV bolus

›Repeat every 4 to 6 hours as needed

›Hold if serum osmolality > 320 mOsm/kg

›Hypertonic saline

›3 percent NaCl 250 mL bolus for acute ICP elevation

›23.4 percent NaCl 30 mL via central line for herniation

›Serum sodium target 145 to 155 mmol/l

›Indication ICP > 22 mmHg

›Brain Trauma Foundation guideline threshold

›Both agents are Class IIa recommendation

›Sedation and analgesia

›Propofol IV infusion

›Starting dose 5 to 10 mcg/kg/minute

›Titrate to ICP target

›Propofol infusion syndrome monitoring with prolonged high doses

›Midazolam IV

›0.02 to 0.1 mg/kg/hour infusion

›Alternative when propofol not suitable

›Fentanyl IV

›25 to 100 mcg/hour infusion

›Analgesia-first approach minimizes sedation requirements

›Neuromuscular blockade

›Vecuronium or cisatracurium for refractory ICP

›Vecuronium 0.1 mg/kg IV loading then infusion

›Facilitates controlled ventilation

›Reserve for ICP refractory to other measures

Seizure prophylaxis

›Early post-traumatic seizure prevention

›Levetiracetam preferred agent

›500 to 1500 mg IV every 12 hours

›Duration 7 days only

›Class IIa recommendation; Brain Trauma Foundation guideline

›Phenytoin alternative

›15 to 20 mg per kg IV loading dose over 30 minutes

›Maintenance 100 mg IV every 8 hours

›Cardiac monitoring during loading

›Valproic acid not recommended

›Associated with increased mortality risk in TBI

›Avoid in acute severe TBI

›Do not continue beyond 7 days without seizure activity

›No benefit for late seizure prevention

›Prolonged use increases side effect burden

Temperature and metabolic management

›Fever management

›Treat fever > 38 degrees C aggressively

›Fever worsens secondary brain injury

›Acetaminophen 650 mg IV or PO every 6 hours

›Cooling devices if pharmacotherapy insufficient

›Surface cooling blankets

›Intravascular cooling catheters for refractory hyperthermia

›Therapeutic hypothermia not routinely recommended

›Not proven to improve outcomes in adult DAI

›May be considered in specific research protocols

›Glucose management

›Target glucose 6 to 10 mmol/l

›Avoid hypoglycemia which causes secondary brain injury

›Avoid marked hyperglycemia > 10 mmol/l

›Continuous glucose monitoring in ICU

›Insulin infusion if required

›Frequent point-of-care glucose checks

Paroxysmal sympathetic hyperactivity treatment

›Pharmacologic management of PSH

›Opioids for acute paroxysmal episodes

›Morphine 2 to 4 mg IV per episode

›Blunts sympathetic surges

›Propranolol oral or IV

›10 to 80 mg orally 3 to 4 times daily

›Beta-1 and beta-2 blockade

›Gabapentin

›100 to 300 mg PO three times daily titrated

›Reduces paroxysmal frequency and severity

›Bromocriptine

›2.5 mg orally twice daily

›Dopamine agonist for autonomic modulation

›Dantrolene

›25 to 100 mg orally 4 times daily

›For muscle rigidity component

›Benzodiazepines

›Clonazepam or diazepam for acute episodes

›Lorazepam 0.5 to 2 mg IV per episode

Nutrition and prophylaxis

›Nutritional support

›Early enteral nutrition within 24 to 72 hours

›Nasogastric or post-pyloric tube in intubated patients

›Reduces catabolism and improves outcomes

›Caloric targets

›25 to 30 kcal per kg per day

›Protein 1.5 to 2 g per kg per day for hypermetabolic state

›Avoid hyperglycemia from nutritional delivery

›Tight glucose protocol required

›Enteral preferred over parenteral nutrition

›Prophylaxis bundle

›Deep vein thrombosis prophylaxis

›Mechanical compression devices immediately

›Pharmacologic prophylaxis when hemorrhagic lesion stable typically 24 to 72 hours

›Stress ulcer prophylaxis

›Proton pump inhibitor while mechanically ventilated

›H2 blocker alternative

›Corticosteroids contraindicated in TBI

›CRASH trial showed increased mortality

›Absolute contraindication in severe TBI

Rehabilitation

›Early rehabilitation

›Multidisciplinary team from day of admission

›Physical therapy mobilization

›Occupational therapy cognitive and ADL assessment

›Speech-language pathology for swallow and communication

›Cognitive rehabilitation for memory and attention deficits

›Neuropsychology involvement early

›Structured stimulation programs

›Graded physical exercise when medically stable

›Progressive mobilization program

›Prevents deconditioning

09Special Populations/sp66

Pregnancy

›Pregnancy-specific considerations

›Physiologic changes affecting management

›Increased blood volume alters hemodynamic targets

›Gravid uterus displaces aorta; left lateral tilt when supine

›Fetal monitoring when viable gestation

›Obstetrics consultation immediately

›Continuous fetal heart monitoring

›Imaging considerations

›CT head with abdominal shielding when indicated

›MRI preferred when time allows and patient stable

›Benefits of imaging outweigh radiation risk in severe TBI

›Medication considerations in pregnancy

›Levetiracetam preferred over phenytoin for seizure prophylaxis

›Phenytoin is Category D teratogen

›Levetiracetam data more favorable

›Mannitol use with caution

›Fetal dehydration risk

›Hypertonic saline alternative considerations

›Corticosteroids for fetal lung maturity if preterm delivery anticipated

›Separate from TBI management; consult obstetrics

›Betamethasone 12 mg IM two doses 24 hours apart

Geriatric

›Geriatric-specific risk profile

›Higher mortality for equivalent injury severity

›Less physiologic reserve

›Blunted sympathetic response may mask severity

›Anticoagulant and antiplatelet use prevalent

10Background/b90

Epidemiology

›Incidence and demographics

›DAI found in all TBI severity grades

›Predominant pathologic mechanism in concussion through severe TBI

›Approximately 50 percent of all severe TBI cases have DAI

›Age and sex distribution

›Median age 31 to 41 years

›Approximately 79 percent male

›Bimodal age distribution: young adults and elderly fallers

›Mechanism distribution

›Motor vehicle collisions approximately 70 percent of DAI cases

›Falls more common in elderly population

›Sports-related increasing recognition

›Mortality and outcomes

›Overall 51 percent of DAI patients achieve favorable long-term functional outcome (GOSE 6 to 8)

›Even Grade 3 patients can recover favorably

›van Eijck et al 2018 Journal of Neurotrauma data

›Independent prognostic factors

›Age

›Pupillary reaction at admission

›Hemoglobin level

›DAI grade on MRI

›Return of consciousness within 7 days

Pathophysiology

›Primary injury mechanism

›Rotational acceleration-deceleration forces

›Shear strain on white matter axons at moment of impact

›Differential motion between gray and white matter at interface

›Stretch-induced axonal injury

›Sodium channel disruption causing axonal swelling

›Cytoskeletal protein breakdown including neurofilament and MAP2

›Axonal retraction balls

›Pathologic hallmark seen on microscopy

›Represent disconnected proximal axon segments

›Secondary injury cascade

›Calcium influx and excitotoxicity

›Glutamate release from injured axons

›Mitochondrial dysfunction

›Wallerian degeneration

›Progressive distal axon degeneration over days to weeks

›Explains delayed MRI findings and progressive atrophy

›Neuroinflammation

›Microglial activation

›Astrocyte reactivity (GFAP release)

›Graded anatomic distribution

›Grade 1 lobar white matter

›Gray-white junction involvement

›Parasagittal white matter and corona radiata

›Grade 2 corpus callosum

›Splenium more vulnerable than genu

›Intraventricular hemorrhage from callosal vein disruption

›Grade 3 brainstem

›Dorsolateral midbrain and upper pons

›Responsible for autonomic dysregulation and PSH

›Chronic consequences

›Progressive neurodegeneration documented beyond 5 years

›Brain atrophy on serial MRI

›Serum NfL remains elevated reflecting ongoing degeneration

›Chronic traumatic encephalopathy risk

›Repeated injuries amplify tau pathology risk

›Contact sports athletes with multiple DAI events

›Alzheimer-like pathology association

›Amyloid precursor protein accumulation at injury sites

›Accelerated amyloid deposition post-TBI

Therapeutic Considerations

›Neuroprotection evidence base

›No proven neuroprotective pharmacotherapy for DAI exists

›Progesterone: multiple Phase 3 trials negative (ProTECT III, SyNAPSe)

›Ciclosporin A: Phase 2 data inconclusive; no Phase 3 trial positive

›Erythropoietin: no definitive clinical benefit in TBI trials

›Secondary injury prevention is the primary therapeutic target

›Avoid hypoxia, hypotension, hyperglycemia, fever, hyponatremia

›These secondary insults are modifiable and cause additional axonal death

›Rehabilitation evidence

›Early multidisciplinary rehabilitation improves outcomes

›Cochrane review supports specialized inpatient rehabilitation

›Turner-Stokes et al 2015 Cochrane Database of Systematic Reviews

›Cognitive rehabilitation for attention and memory deficits

›Evidence-based cognitive training protocols

›Starting in ICU with environmental modifications

›Neuroplasticity window

›Greatest in first 3 to 6 months post-injury

›Intensive early intervention maximizes recovery

›Emerging and future therapies

›Stem cell therapies under investigation

›No current clinical recommendations

›Phase 1 and 2 trials ongoing

›Serum biomarker-guided therapy

›NfL and GFAP may guide intensity of monitoring and rehabilitation

›Emerging role in clinical trial stratification

›Hyperbaric oxygen therapy

›Inconclusive evidence in TBI

›Not currently standard of care

11Patient Discharge Instructions/pdi55

copy discharge instructions

›Brain injury home care

›Rest is the cornerstone of early recovery

›Physical rest and cognitive rest

›Avoid screens, reading, and mentally demanding tasks initially

›Gradual return to activity

›Only when completely symptom-free at rest

›Follow return-to-sport or return-to-work protocol from your doctor

›Medications as prescribed

›Take all anti-seizure medications exactly as directed

›Do not stop seizure medications without physician guidance

›No alcohol or recreational drugs during recovery

›Impairs brain healing

›Increases seizure risk

›No driving until cleared by physician

›Seizure precaution period applies

›Cognitive function must be assessed first

›Warning signs to return to ER immediately

›Worsening headache

›Especially if severe or thunderclap

›Not responding to acetaminophen

›Vomiting

›New onset or repeated vomiting

›Sign of elevated intracranial pressure

›Seizure

›Any shaking episode with loss of awareness

›Call 911 immediately

›Weakness or numbness

12References/r36

Guidelines and key sources

›Society guidelines

›Brain Trauma Foundation Guidelines for Management of Severe TBI

›Fourth edition thresholds for ICP, CPP, oxygenation, and blood pressure

›Stocchetti et al Lancet Neurology 2017

›American College of Surgeons Best Practices in Management of TBI 2024

›Manley et al; comprehensive institutional guidance

›ACR Appropriateness Criteria Head Trauma 2021 Update

›Shih et al Journal of the American College of Radiology 2021

›World Society of Emergency Surgery WSES Consensus 2023

›Picetti et al World Journal of Emergency Surgery 2023

›Key clinical studies

›El-Abtah et al World Neurosurgery 2023

›DAI pattern predicts timing of in-hospital neurologic recovery

›Retrospective case series with grading correlation

›van Eijck et al Journal of Neurotrauma 2018

›DAI patients can recover to favorable long-term functional and quality of life outcome

›Skandsen et al Journal of Neurosurgery 2010

›Prevalence and impact of DAI in moderate and severe head injury

›MRI findings and 1-year outcome cohort study

›Graham et al Science Translational Medicine 2021

›Neurofilament light predicts long-term outcomes and progressive neurodegeneration

›Ferrazzano et al JAMA Network Open 2024

›MRI and clinical variables for prediction of outcomes in pediatric severe TBI

›Biomarker and pathophysiology references

›Shahim et al Neurology 2020

›Time course and diagnostic utility of NfL, Tau, GFAP, and UCH-L1 in TBI

›Helmrich et al Lancet Neurology 2022 CENTER-TBI

Evidence & Review