Traumatic brain injury is common and a major cause of morbidity and mortality
World wide. TBI is a heterogeneous condition in terms of aetiology, severity, and outcome. The most useful classification of severity is based on the level of consciousness as assessed by the Glasgow Coma Scale (GCS) after resuscitation.
TBI is classified as mild (GCS 15–13), moderate (GCS 13–9), and severe (GCS ≤ 8 ). However, factors such as hypoxia, hypotension, and alcohol intoxication can all affect GCS. Therefore the patient should be resuscitated and reversible causes corrected before  GCS assessment.
TBI can be divided into primary and secondary brain injury. The pattern and extent of damage in primary damage will depend on the nature, intensity, and duration of the impact. It  may result in skull fracture, contusions, intracranial haematoma, cerebral oedema, and diffuse brain  injury. Neurological injury progresses over hours and days, resulting in a secondary injury. Inflammatory and neurotoxic processes result in vasogenic fluid accumulation within the brain, contributing to raised intracranial pressure (ICP), hypoperfusion, and cerebral ischaemia . Hypoxia, hypotension, hyper- or hypocapnia, hyper- or hypoglycaemia have all been shown to increase the risk of secondary brain injury. Management is based on avoidance of   secondary injury, maintenance of cerebral perfusion pressure, and optimization of cerebral oxygenation.
Acute Management:
This is a crucial period when mortality and morbidity can be influenced by interventions to prevent secondary brain injury.1
Pre-hospital care & Management in the emergency department:
The priorities are to prevent hypoxia and hypotension.Early tracheal intubation  is advisable  for patients unable to maintain their own airway or achieve a target
SpO2 > 90% on supplemental oxygen.2 Adequate venous access with a minimum of two large bore(16 G or larger) is essential to manage the hypotensive and hypovolemic trauma patient. Simultaneously, a general survey  is to be performed to identify major extra-cranial injuries. Life–threatening injuries like Tension pneumo-thorax, cardiac tamponade  or major vascular injuries to be given preference to neurological injuries and treated first. Cervical spine injury is commonly associated with severe brain injury and hence, cervical immobilization is to be maintained until cervical injury is excluded.
Summary of Management goals in T.B.I:

 
-While the Brain Trauma Foundation (BTF) suggests targeting PaO2 > 8 kPa to avoid hypoxia, the European Brain Injury Consortium (EBIC) targets PaO2 > 10 kPa and the Association of Anaesthetists of Great Britain and Ireland (AAGBI) >13 kPa.3 Hyper and hypocapnia are both viewed as potentially avoidable secondary insults. UK guidelines suggest a PaCO2 value of 4.5–5.0 kPa4.
The BTF and EBIC advocate a mean blood pressure (MBP) of >90 mm Hg, while AAGBI targets > 80 mm Hg3,4
As the most common cause of hypotension after trauma is haemorrhage, the initial treatment is fluid resuscitation. For most patients an isotonic  fluid such as normal saline is suitable. There is some evidence that hypertonic saline may be useful as a resuscitation fluid , with one study showing increased survival in a subgroup of patients with TBI and GCS < 85. Hypotonic fluids must be avoided. Colloids confer no benefit, indeed the Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain Injury (SAFE)  study found an increased risk of death in patients who received Albumin rather than saline6 . After TBI there is a profound   catecholamine response, with cortisol release and glucose intolerance making hyperglycaemia common. Glucose-containing fluids should be avoided and blood sugar monitored. Sources of bleeding must be identified and controlled and blood products used early in the face of significant haemorrhage. Platelet infusions or Desmopressin may be useful in those patients on Aspirin and Clopidogrel who require urgent neurosurgical intervention.
IMAGING  :
The investigation of choice is CT scanning. Early imaging reduces time to detection of life-threatening complications and is associated with better outcomes. CT imaging of the cervical spine should be performed at the same time. MRI studies are rarely used in the acutely ill, as they are logistically more complex and take longer. MRI is useful if a penetrating injury with a wooden object is suspected.
Advanced MRI (diffusion tensor imaging) allows visualization of white matter tracts and quantification of axonal damage. Skull X-rays are useful only as part of a skeletal survey in children with non-accidental injury. As brain injury evolves over time, repeat imaging is commonly indicated and always necessary if there is clinical deterioration or an increase in ICP.
Transfer:
Initial resuscitation and stabilization of the patient should be completed before transfer. Patients who are persistently hypotensive despite resuscitation should not be transferred until the cause established and the patient stabilized. Patients with a GCS of < 8 should be intubated and ventilated, aiming for PaO2 >  13 kPa and a PaCO2 value of 4.5–5.0 kPa with adequate sedation, analgesia, and muscle relaxation.
Indications for Intubation & Ventilation while transferring Head-Injury Patient:  1) GCS ≤ 8
2) Significantly deteriorating conscious level (i.e. decrease in motor score > 2 points)
3)Loss of protective laryngeal reflexes
4)Hypoxaemia (PaO2 < 13 kPa on oxygen)
5)Hypercarbia (PaCO2 > 6 kPa)
6)Spontaneous hyperventilation causing PaCO2 <  4:0 kPa
7)Bilateral fractured mandible
8)Copious bleeding into the mouth (e.g. from skull base fracture)
9)Seizures
Anesthesia for Craniotomy in T.B.I:
About one-third of patients with severe TBI need neurosurgical intervention. Rapid treatment is crucial. Acute subdural haematomas in patients with a severe TBI have 90% mortality if surgical  evacuation occurs > 4 h after injury compared with 30% for those evacuated earlier. Essential monitoring includes ECG, SpO2 ; capnography, temperature, and urine output. Invasive arterial pressure allows beat-to-beat monitoring of ABP and regular assessment of arterial blood gases and glucose. Central venous access may be useful for resuscitation and administration of vasoactive drugs. ICP monitoring is recommended for patients with TBI who require non-neurosurgical intervention.
The goals of anaesthesia are:
- Optimization of cerebral perfusion pressure (CPP) and the prevention of intracranial hypertension;
-Adequate anaesthesia and analgesia;
-Prevention of secondary insults by adequate oxygenation, normocapnia, and avoidance of hyper- or hypoglycaemia and hyperthermia.
All volatile agents reduce CMRO2 and may produce cerebral vasodilation, resulting in increased CBF and ICP. They also impair CO2 reactivity.
However, at concentrations up to 1 MAC these effects are minimal. Sevoflurane appears to have the best profile. Nitrous oxide is best avoided. I.V. agents reduce CMRO2, CBF, and ICP. However, propofol can cause significant hypotension and reduce CPP. Neuromuscular drugs are recommended to prevent coughing or straining.
Ventilation should be controlled to maintain oxygenation and normocapnia as confirmed by ABG analysis. Intraoperative hypotension is associated with a three-fold increase in mortality. I.V fluids are the primary means to control ABP , but  administration of vasopressor agents may be necessary to maintain BP and CPP during periods of instability. Several studies have shown an association between hyperglycaemia and poor neurological outcome in patients with TBI. Currently, the literature supports targeting intermediate glucose levels in the range of 6–10.0 mmol7. Patients should have frequent glucose monitoring and hypoglycaemia must be prevented.
Management of I.C.P:
Intracranial hypertension reduces cerebral perfusion and results in Cerebral  ischaemia. Consensus guidelines recommend treatment of an ICP >20–25 mm Hg8.Measurement of ICP allows early detection of evolving mass lesions and enables the calculation of CPP from the relationship CPP = MAP - ICP. The primary goal of an adequate CPP is to maintain CBF and tissue oxygenation and its manipulation has become central to the management of TBI. Current consensus is CPP to be maintained > 60 mm Hg.
ICP can be controlled by a variety of methods.

1. Hyperventilation
2. Hyperosmolar therapy
3. Hypothermia
4. Barbiturates
5. Neurosurgical Interventions.

Hyperventilation:
A reduction in PaCO2 causes cerebral vasoconstriction, reducing CBV and ICP. Although once widely used, hyperventilation has been shown to exacerbate cerebral hypoperfusion and may result in ischaemia9. Moderate hyperventilation to a PaCO2 value of 4.0–4.5 kPa is reserved for those with intractable intracranial hypertension and should be guided by monitoring such as jugular venous oxygen saturation to ensure adequate cerebral oxygenation.
Hyperosmolar therapy:
This is particularly useful for acute increases in ICP. Mannitol remains the most commonly used agent. The effective dose is 0.25–1 g / kg, usually given as a 20% solution. Intermittent boluses appear to be more effective than continuous infusions. However, care must be taken to prevent serum osmolarity increasing
above 320 mOsm/ l, as this has been associated with neurological and renal complications. Other potential complications include hypotension, intravascular volume depletion, hyperkalaemia, and rebound intracranial hypertension10. The use of hypertonic saline is increasing. It has fewer side-effects and may control ICP refractory to mannitol. Hypertonic saline acts predominantly through the osmotic shift of fluid from the intracellular to the intravascular and interstitial space. It may also improve CBF and myocardial performance and may have immune-modulatory effects. The most recent clinical work in humans studied patients who were randomly assigned to receive 2 ml/kg of either 7.5% hypertonic saline solution or 20% mannitol. The mean number of intracranial hypertension episodes per day and the daily duration of intracranial hypertension episodes were significantly lower in the hypertonic saline solution group. The rate of clinical failure was also significantly lower in the hypertonic saline solution group11
Hypothermia:
Evidence from studies has failed to demonstrate that it is associated with a consistent and statistically significant reduction in mortality12. Moderate hypothermia effectively reduces ICP and is often included in management algorithms13.
Barbiturates:
I.V. barbiturates lower ICP but there is little evidence that they improve outcome. They are associated with significant cardiovascular instability and so are reserved for refractory intracranial hypertension. Dosage is titrated to produce burst suppression with EEG.
Neurosurgical Interventions:
Drainage of cerebrospinal fluid via an external ventricular drain is an effective method of reducing ICP. For intracranial hypertension refractory to medical therapy, decompressive craniectomy can be used. Decompressive craniectomy is currently reserved for those patients, when other methods of ICP control have failed.
Continuing Management:
The purpose of continuing care is to provide optimum opportunity for brain recovery. Maintenance of oxygenation, normocapnia, and haemodynamic stability is essential. Adequate sedation and analgesia reduces pain, anxiety, and agitation and facilitates mechanical ventilation. Multimodality monitoring of the injured brain is useful to tailor individual patient care. Advanced monitoring may include cerebral oxygenation, measurement of CBF, microdialysis, and electrophysiological monitoring14
Early nutritional support is associated with better outcomes and enteral administration is preferable. Appropriate metabolic monitoring is essential, as hyperglycaemia is associated with secondary ischaemic injury. Blood glucose should be monitored, but optimal targets for glycaemic control are yet to be defined. However, as with perioperative management, intermediate glucose levels in the range of 6–10.0 mmol/ l  are usually targeted. Hypoglycaemia must be avoided.
Seizure activity is relatively common, occurring both early and late after TBI. Seizures increase CMRO2 and are associated with increased ICP. Some advocate their use in high-risk groups such as those with depressed skull fractures.
Patients with TBI are at significant risk of thrombo-embolic events. Options for prevention include mechanical (graduated compression stockings or intermittent pneumatic compression), pharmacological (low-dose or low-molecular-weight heparin) prophylaxis,or a combination of both. Most would avoid pharmacological
thromboprophylaxis for 24 h after neurosurgical intervention. Additional care includes peptic ulcer prophylaxis, physiotherapy, and full hygiene care.
Newer Drugs & Strategies:
Dexanabinol:
Dexanabinol is a cannabinoid and a non-competitive NMDA receptor antagonist.
Initial studies were encouraging in stroke and TBI in limiting oedema formation and ischaemic damage15. It was not only shown to be safe, but the mean time
during which ICP exceeded 25 mm Hg and systolic blood pressure was less than 90 mm Hg was decreased.
Anti- inflammatory agents:
Investigators at University of Manchester are now studying the effects of interleukin-1 receptor antagonists as neuroprotective agents.
Corticosteroids are potent anti-inflammatory agents, and beneficial effects have been recognised if administered early in trauma, especially using high dose methylprednisolone in spinal trauma. A systematic review of trials concluded that
data were consistent with a 2% reduction in mortality16. This has initiated the ongoing, multicentre CRASH trial (Corticosteroid Randomisation After Significant Head Injury) which is being coordinated from the UK17.In this trial, treatment consists of a 2 g loading dose of methylprednisolone,followed by an infusion of 0.4 g/hour for 48 hours.

Lund Therapy:
This is a Swedish strategy from Lund University Hospital, based on principles for brain volume regulation and improved microcirculation. Interstitial fluid resorption is carried out by lowering intracapillary hydrostatic pressure, by preserving normal colloid osmotic pressure, and by maintaining a normovolaemic
(normal albumin/serum and haemoglobin) patient. Intracapillary pressure is reduced using low dose thiopental and dihydroergotamine to cause precapillary vasoconstriction. Mean arterial pressure is reduced with metoprolol and clonidine to reduce oedema caused by increased hydrostatic pressure. Clonidine, in combination with normovolaemia, also improves microcirculation by reducing catecholamines in plasma.
Biomarkers:
A number of biomarkers, including S110B, neuronspecific enolase and myelin basic protein, have been proposed as potentially prognostic but proven disappointing with only ubiquitin carboxyl-terminal hydroxylase L1 deemed worthy of further study18. A brain: serum glucose ratio less than 0.12 predicts
cerebral metabolic distress and mortality after severe TBI19.
Coagulopathy & Factor VII
Coagulation disorder is a common problem after TBI. Coagulation disorder could result from TBI and cause secondary brain injury. A recent review reported that the overall prevalence of coagulopathy was 32.7% after TBI and more than 60% in severe TBI and that the presence of coagulopathy was associated with an increased mortality and poor outcome20. Hemostatic drugs including antifibrinolytic agents such as tranexamic acid and pro-coagulant drugs such as recombinant activated factor VII (rFVIIa) are sometimes used in treatment of coagulopathy after TBI. The Clinical Randomization of Antifibrinolytics in Significant Hemorrhage (CRASH-2) trial, demonstrated that tranexamic acid was associated with a reduction of mortality. The risk of death from bleeding was also lower in tranexamic acid group21 .
Summary:
TBI is common and a major public health problem. Despite a progressive and significant reduction in mortality no single treatment has been shown to improve outcome. Management continues to be focused on prevention of secondary injuries and maintenance of CPP. While research focused specifically on the intraoperative and perioperative TBI management is awaited, clinical management will continue to be based on physiological optimization.
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