PATHOPHYSIOLOGY OF ACUTE TRAUMATIC BRAIN INJURYDr Nick TaylorMBBS FACEM

The  Monro–Kellie  Doctrine

CPP=MAP-ICP

PRIMARY DAMAGE

• TBI is a heterogeneous disorder • Brain damage results from external

forces, as a consequence of direct impact, rapid acceleration or deceleration, penetration or blast waves• The nature, intensity, direction, and

duration of these forces determine the pattern and extent of damage.

MACROSCOPIC DAMAGE

•On the macroscopic level, damage includes shearing of white-matter tracts, focal contusions, haematomas and diffuse swelling

DAI

•DAI is characterised by multiple small lesions in white-matter tracts. • Patients with DAI are usually in

profound coma as a result of the injury, do not manifest high ICP, and often have a poor outcome.

BLEEDING

• Focal cerebral contusions are the most common traumatic lesion, are more frequent in older patients, and usually arise from contact impact. • Traumatic intracranial haematomas

occur in 25–35% of patients with severe TBI and in 5–10% of moderate injuries

CELLULAR LEVEL

• Early neurotrauma events include microporation of membranes, leaky ion channels, and stearic conformational changes in proteins. •At higher shear rates, blood vessels

can be torn, causing (micro)haemorrhages.

ISCHAEMIA

• Ischaemic brain damage is often superimposed on the primary damage and can be widespread or, more commonly, perilesional.• Impaired cerebral perfusion and oxygenation,

excitotoxic injury, and focal microvascular occlusion can be contributing factors.

ISCHAEMIA

•Although the total ischaemic brain volume may be less than 10% on average, the presence of cerebral ischaemia is associated with poor ultimate neurological outcome, that is, dead or vegetative state

SECONDARY INJURY

• Each type of head injury initiates different pathophysiological mechanisms, with variable extent and duration • Secondary processes develop over hours and

days, and include neurotransmitter release, free-radical generation, calcium-mediated damage, gene activation, mitochondrial dysfunction, and inflammatory responses.

EARLY SECONDARY INJURY

• The first stages of cerebral injury after TBI are characterized by direct tissue damage and impaired regulation of CBF and metabolism. This ‘ischaemia-like’ pattern leads to accumulation of lactic acid due to anaerobic glycolysis, increased membrane permeability, and consecutive oedema formation. • Since the anaerobic metabolism is inadequate to

maintain cellular energy states, the ATP-stores deplete and failure of energy-dependent membrane ion pumps occurs.

LATER INJURY

•Glutamate and other excitatory neurotransmitters exacerbate ion-channel leakage, worsen astrocyticswelling, and contribute to brain swelling and raised ICP. • Neurotransmitter release continues for

many days, paralleling the course of high ICP, and, with free-radical and calcium-mediated damage, is a major cause of early necrotic cell death

INFLAMMATION: 2 EDGED SWORD

• Inflammatory response is an important component of TBI, particularly around contusions and (micro) haemorrhages. • The maximum response occurs within a few days,

but cytokines are released within hours after TBI, leading to opening of the BBB, activation of cell death and apoptosis. • Although the inflammatory response can be

deleterious in excess, it is necessary in order to clean up cellular debris after injury

MITOCHONDRIA

• Recent research has raised new insights that challenge existing concepts of pathophysiology.•Mitochondrial dysfunction can cause

energy failure after TBI, with a decrease in production of ATP and consumption of oxygen by 40–50%. This can trigger apoptosis and necrosis.

MITOCHONDRIA

• Mitochondrial dysfunction might also lead to axonal disruption. The classical concept that DAI is due to mechanical rupture of axons, incompatible with regeneration or repair, has now been abandoned.• Neurons can at least partially regenerate their

axonal anatomy. This accords with clinical observations• Lab work has shown that DAI can take up to 48

hours to become fully established and is thus amenable to therapeutic interventions.

CEREBRAL BLOOD FLOW

•Whether decreased cerebral blood flow (CBF) after trauma is indicative of ischaemia or is secondary to metabolic depression remains the subject of debate.•Cerebral hemodynamics change

significantly post injury,and the pattern of these changes depends upon the type of injury and its severity

CBF

• The critical threshold of CBF for the development of irreversible tissue damage is 15 ml 100 g−1 min−1 in patients with TBI compared with 5–8.5 ml 100 g−1 min−1 in patients with ischaemic stroke.• This is likely because of the other brain

damage occurring in TBI vs CVA

CBF

• Patients with TBI may develop cerebral hyperperfusion (CBF >55 ml 100 g−1 min−1) in the early stages of injury. • Likewise, hyperaemia may follow immediate post-

traumatic ischaemia. • This pathology seems as detrimental as ischaemia

because increases in CBF beyond matching metabolic demand relate to vasoparalysis leading to increases in cerebral blood volume and in turn intracranial pressure (ICP).

CBF AUTOREGULATION

• After TBI, CBF autoregulation is impaired or abolished in most patients. • Defective CBF autoregulation may be present

immediately after trauma or may develop over time, and is transient or persistent in nature irrespective of the presence of mild, moderate, or severe damage. • Also, autoregulatory vasoconstriction seems to be

more resistant compared with autoregulatory vasodilation which indicates that patients are more sensitive to damage from low rather than high CPPs

CO2 RESPONSIVENESS

• Compared with CBF autoregulation, cerebrovascular CO2-reactivity seems to be a more robust phenomenon.• In patients with severe brain injury and poor

outcome, CO2-reactivity is impaired in the early stages after trauma. • In contrast, CO2-reactivity was intact or even

enhanced in most other patients offering this physiological principle as a target for ICP management in hyperaemic state

PRINCIPLES OF MX• Trauma renders the brain more

vulnerable to insults, and hypoxia and hypotension are strongly associated with poor outcome (hypoxia: odds ratio [OR] 2·1, 95% CI 1·7–2·6; hypotension: OR 2·7, 95% CI 2·1–3·4• Treat the patient (but consider the

impact this will have on their brain)

PRINCIPLES

• Protect the brain from secondary injury•Maintain CPP (by maintaining MAP

and reducing ICP)•Maintain oxygenation• Prevent complications•Arrange timely interventions

HOW DO WE SAFELY INTUBATE

• Protect the C-spine•Avoid hypotension• IVF load first • Judicious induction drug doses

based on patient characteristics• Eg • Propofol/Thio low dose (0.5-1mg/kg)• Fentanyl 3-5 mcg/kg • Ketamine (Theoretical raised ICP vs

absolute risk hypotension)• Combinations

• Have metaraminol drawn up and ready

HOW DO WE SAFELY INTUBATE

• Avoid hypertensive spikes• Avoid prolonged, multiple attempts

(experience)• Consider fentanyl• Paralyse for transport

• Avoid hypoxaemia• Pre O2•Maximise your first attempt success• Have a back up plan and rapidly use it

WHAT ELSE SHOULD WE DO

TREATING RAISED ICP

Crack  the  box

Assist  venous  outflow

Reduce  brain  water

Control  arterial  inflow

Drain  the  extra  blood

Reduce  the  CMR

DRAIN THE BLOOD, CRACK THE BOX

• Urgent CT scan is used to stratify patients who need emergency neurosurgery• Surgically drainable blood is a priority

for OT• Decompressive craniectomy is

controversial, (DECRA inconclusive) but used with high ICP and no drainable blood

CONTROL THE INFLOW

• Keep MAP >80 (ideally with ICP monitor in , keep CPP>60)

• Avoid SBP <90

• Keep PaCO2 low normal • CO2 is a cerebral vasodilator• Reducing CO2 below normal ranges causes

vasoconstriction and worsens secondary ischaemia

• Can acutely hyperventilate to a lower number if herniation suspected

ASSIST VENOUS OUTFLOW

•Head up 30 degrees (incline whole bed)•Avoid tight hard collars•Avoid tight tube ties

REDUCE BRAIN WATER• Avoid free water: N/Saline only (NOT

dextrose, NOT albumin)• Osmotherapy agents• Mannitol: Exact mechanism unknown;

multiple studies showing efficacy• Rebound phenomena exist• Hypotension may be worsened• Eg 0.5-1g/kg

• Hypertonic Saline:• Mobilises water across intact BBB via osmotic

effect; may increase local blood flow, may have anti inflammatory effect

• Good theory, used widely, solid evidence lacking

• Eg 100mL 3% saline , esp if hypotension

REDUCE THE CMR

• Hypothermia• Evidence for prophylactic hypothermia has

failed to find a mortality benefit despite early promise but may increase infection. The jury is still out

• Barbituate coma• Recommended for refractory ICP Mx in ICU• Assoc with signif increased VAP and K+

morbidity

OTHER STUFF

• Steroids• Unsurprisingly the CRASH study

showed patients did worse•Glutamate / Lipids/ anti free

radicals• Maybe

•Mg2+ the magic elixir• No

•Antifibrinolytic drugs• Need more info

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