Traumatic brain injury (TBI) is the leading cause of death in the early decades of life. The estimated number of deaths is 50,000 with 40% of survivors with disability after the injury.1 The estimated incidence is 17.5 to 24.6 deaths per 100,000 population.2,3 Men are more likely to suffer TBI compared to women and the majority of injuries are due to falls.
In TBI injuries are classified as primary and secondary. Primary injury (Table 50–1) happens at the time of impact and secondary injury occurs later due to oxygen deprivation to the brain and the cascade of events set off by ischemia and reperfusion leading to further injury. The target of management focuses more on prevention and treatment of secondary brain injury.
Table 50–1Primary brain injury. |Favorite Table|Download (.pdf) Table 50–1 Primary brain injury.
|Primary Injury (Direct Impact) |
Depressed skull fracture
|Diffuse axonal injury |
In primary injury, depending upon the mechanism of trauma, fractures of the skull can be open or closed, depressed or nondepressed, and linear or comminuted. Most of these fractures are evident on clinical exam but radiography is required for accurate diagnosis. Both plain skull X-ray and computed tomography (CT) scan can be used for skull fractures, although plain radiologic films are better for linear calvarial fractures tangential to the axial plane. Multislice CT, alternatively, can delineate skull fractures better than plain CT scans. Fractures can result in neurologic deficits related to underlying brain injury, cerebral spinal fluid (CSF) leak (suggesting dural laceration) such as otorrhea or rhinorrhea, pituitary gland shearing injuries, and cranial nerve (CN) injuries. Depending on the fracture location, different CNs can be involved. Temporal bone fractures cause facial or acoustic nerve injuries, anterior fossa basal skull fracture can cause olfactory and optic nerve injuries, and clival fractures can cause abducens nerve injuries. Postauricular ecchymosis (Battle's sign) and periorbital ecchymosis (raccoon's eye) may be seen in basal skull fractures.
Most skull fractures are managed conservatively and prophylactic antibiotic use is controversial. Operative or endovascular treatment is indicated in traumatic aneurysms, carotid-cavernous fistula, CSF fistula, abscess management and for CN decompression.
Depending on the type of injury, different types of hemorrhage can occur in TBI as follows:
Epidural: Bleeding between dura and skull, usually from disrupted meningeal artery laceration. The mean age of patients with epidural hemorrhage (EDH) is between 20 and 30 years. About 70% to 90% of EDH is associated with skull fracture and in 36% of cases there was found to be a bleeding artery. Diffuse bone bleeding and venous bleeding (middle meningeal vein, diploic veins and dural venous sinuses) also cause EDH. The most common location is temporal because the bone is relatively thin and more vulnerable to fracture. It appears as a lentiform shape on CT scan and usually stops at the suture lines where the dura is adherent (Figure 50–1).
Subdural: Occurs between the dura and the arachnoid space and is caused by disruption of bridging veins due to acceleration, deceleration, and rotational shearing forces. Frontal and parietal convexities are common places for subdural hemorrhage (SDH). The skull suture lines do not limit the bleeding, so on CT scan it can appear as crescent shape, conforming to the brain surface and traversing suture lines. Acute SDH appears hyperdense on CT scan but can have low-attenuation areas representing hyperacute or active hemorrhage. The incidence of SDH after TBI is approximately 11% with most due to motor vehicle accidents (MVAs) in young people and falls in the elderly. Up to 80% of patients with acute SDH may present with a Glasgow Coma Scale (GCS) less than 8 and pupillary abnormalities are seen in 50% of these patients (Figure 50–2).
Subarachnoid: Occurs in the space surrounding the brain and blood vessels. Trauma is the most common reason and occurs due to crushed or ruptured small vessels. Bleeding is common on the cortical surface but occasionally in the basal cisterns. Complications of SAH include hydrocephalus, seizures, and cerebral vasospasm, the latter an independent predictor of mortality in severe TBI (Figure 50–3).4
Intraparenchymal or intracerebral: Bleeding occurs in the parenchyma of the brain. This can vary from contusions to large hematomas in superficial or deep brain areas. Coup injuries are contusions present at the site of impact. For example, an occipital impact may cause frontal contusions. The coup/countercoup phenomenon can also be seen with subdural hematomas, indicating acceleration–deceleration forces. The inferior frontal and temporal areas are most vulnerable to contusion formation due to ridging of the orbital roof and floor of the temporal fossa.4
Epidural hematoma. Patient with significant head injury resulting in a comminuted right temporal bone fracture and underlying large epidural hematoma with pneumocephalus causing midline shift. This hematoma required surgical evacuation.
Subdural hematoma. Patient who fell and sustained an occipital laceration with staples noted in the soft tissues. He has a left frontoparietal subdural hematoma which is less than 1 cm in thickness causing only minimal midline shift. This patient underwent observation in the hospital.
Subarachnoid hemorrhage. Patient fell after syncope, hit the back of his head, and sustained smaller bilateral subdural hematomas and diffuse subarachnoid blood in both sylvian fissures. There is also subdural hemorrhage along the midline falx cerebri.
Primary injury causes direct trauma to tissue leading to symptoms. Primary injury to the brain can be due to acceleration, deceleration, or rotational forces. Linear forces cause more superficial grey-matter injuries, while rotational forces cause deeper white-matter injuries leading to diffuse axonal injuries.
Secondary injury occurs due to deprivation of oxygen to the brain, which in turn sets off a cascade of biochemical/molecular events leading to further damage to brain. There are complex cellular and molecular changes including glutamate excitotoxic effects, oxidative stress, metabolic derangements, and inflammatory changes that play a major role in its pathogenesis.5 Progressive neuronal necrosis and apoptosis may result.
At the beginning of the injury, huge depolarization of neurons and glial cells lead to influx of calcium into the brain cells. This increases oxygen-free radical reactions producing nitric oxide and excitatory amino acids such as glutamate. Glutamate is believed to promote cell death and dysfunction. Mitochondrial influx of calcium causes swelling and loss of ATP generation. As cellular membranes depend on ATP for their integrity, the inability to produce ATP leads to cell wall disruption and cell death.
Apart from the direct compromise of the cranium and outer layers of brain in TBI, disruption of blood brain barrier (BBB) contributes to loss of cerebral autoregulation. Cerebral autoregulation is the maintenance of cerebral blood flow (CBF) over a wide range of blood pressures of which cerebral perfusion pressure (CPP) is an important component. CPP is defined as the difference between mean arterial pressure (MAP) and intracranial pressure (ICP). In TBI, loss of autoregulation results in the inability to maintain adequate cerebral perfusion at CPP below 50. Loss of the BBB causes vasogenic edema from leaking, dilated blood vessels. In the brain, the edema resulting from cellular swelling is called cytotoxic edema.
According to the Monroe–Kellie principle, the cranium has fixed space and is occupied predominantly by brain tissue, CSF, and blood. Any increase in the volume in the cranium will lead to an increase in ICP, unless it is offset by a decrease in the volume of any one of the contents of the cranium. Therefore, intracranial hemorrhage and brain swelling, which increase intracranial mass, cause ICP increase and further brain damage.
In conclusion, production of oxygen-free radicals and calcium ion influx leads to widespread neuronal injury due to oxidation and enhanced enzymatic activity. Shearing of axons causes neurofilament disruption and increases permeability to calcium ions. Calpains are enzymes, which target the cytoskeleton of axons. Apoptosis ensues during TBI and there is proliferation of glial cells and astrocytes.6
Diffuse axonal injury is an acceleration–deceleration and rotational injury leading to shearing and disruption of the white-matter axonal transport system pathways. Both functional and anatomic injury can lead to unconsciousness in a patient not explained by other primary injuries (Figures 50–4a and 50–4b).
Diffuse axonal injury. Patient with a significant diffuse injury after TBI resulting in (A) small right temporal and medial frontal intraparenchymal hemorrhages and (B) compressed/effaced perimesencephalic cisterns resulting in severe diffuse brain swelling. There is also bilateral frontal subarachnoid blood.
The severity of injury determines the outcome of patients with TBI. The GCS (Table 50–2) is the most common tool used to grade severity of TBI at the time of initial injury. It uses 3 parameters—eye opening, motor response, and verbal response—for injury assessment.
Table 50–2Glasgow coma scale (GCS). |Favorite Table|Download (.pdf) Table 50–2 Glasgow coma scale (GCS).
| ||Score |
|Eye Opening || |
|Spontaneous ||4 |
|Response to verbal command ||3 |
|Response to pain ||2 |
|No eye opening ||1 |
|Best Verbal Response || |
|Oriented ||5 |
|Confused ||4 |
|Inappropriate words ||3 |
|Incomprehensible ||2 |
|No verbal response ||1 |
|Best Motor Response || |
|Obeys commands ||6 |
|Localizes to pain ||5 |
|Withdraws to pain ||4 |
|Flexion response to pain ||3 |
|Extensor response to pain ||2 |
|No motor response ||1 |
A GCS score of 13 to 15 is considered mild TBI, 9 to 12 is moderate TBI, and 3 to 8 is severe TBI (patient in coma). About 70% to 90% of TBI cases are in the mild category. The GCS scoring system is limited when patients are intubated, aphasic, or aphonic as the verbal and eye variables are hard to measure. Other scales have been developed to account for respiratory or pupillary abnormalities.7 These scales are not as widely used as the GCS.
Neuroimaging can also be used to predict injury severity. Presence of midline shifts, Intracerebral hemorrhage (ICH), SAH, and extra-axial hematomas on CT scan are poor prognostic markers. CT scan grading systems have been used for grading injury on initial presentation. The Marshall (Table 50–3) score is an example.8,9
Table 50–3Marshall's CT classification of brain injuries. |Favorite Table|Download (.pdf) Table 50–3 Marshall's CT classification of brain injuries.
|Class ||Definition ||Mortality |
|Diffuse injury type 1 ||No visible intracranial abnormality ||10% |
|Diffuse injury type 2 ||0-5 mm midline shift/cisterns present/and or lesion density present ||14% |
|Diffuse injury type 3 ||0-5 mm midline shift/cisterns compressed or absent/no lesion density > 25 cm3 ||34% |
|Diffuse injury type 4 ||Midline shift >5 mm/no lesion density > 25 cm3 ||56% |
Imaging can provide important information regarding severity of injury. The goal of initial imaging is to rapidly diagnose life-threatening injuries in TBI and to treat them in a timely manner.
CT scan is a widely used modality and often the first one to be used in TBI, as it is fast and sensitive. Newer multi-row-detector CT is even faster and can scan a head within seconds. CT scan provides either 2D or 3D reformatted images. CT scans are useful for diagnosing and differentiating different types of brain hemorrhage, hydrocephalus, and mass effect.
In SDH, as mentioned earlier, the bleed can spread beyond skull suture lines and on CT scan blood can appear as crescent-shaped hyperdense in acute stage. Epidural hematomas appear as a lens-shaped hyperdensity not extending beyond suture margins. Subarachnoid hemorrhage usually conforms to the sulcal space of the brain and CT angiography helps in determining aneurysm or vascular malformation as the cause of the bleed.
If hemorrhagic, contusions can be seen on CT scan and if these small hemorrhages coalesce, they can appear as a hematoma. Small hemorrhages (also called Duret hemorrhages) can be seen in the central pons as a consequence of severe uncal herniation and brainstem compression.
CT angiography is useful for assessing vascular injuries such as aneurysm, pseudoaneurysm, dissection, or thrombus, especially in the face of basilar skull fracture or those crossing a venous sinus. CT perfusion scanning evaluates time to peak (contrast) density, mean transit time, cerebral blood volume, and CBF. Normal CBF is 50 mL/100 g/min (of brain tissue). This modality helps in differentiating between ischemia and infarction, CBF measure 10 to 22 mL/100 g/min and less than 10 mL/100 g/min, respectively.
Magnetic resonance imaging (MRI) evaluates the movement of protons in the tissue when a magnetic field is applied. MR is sensitive in detecting subacute hemorrhage and depending on the appearance of blood on T1 and T2 weighted images, it can detect the timeline of the bleed. Gradient Recalled Echo is a modality of MR that provides information about blood or its degradation products, which appears as a low-intensity signal.
MR angiography is an alternative to CT angiography for characterizing major arterial or venous vascular injuries and can be done with or without contrast. Catheter angiography is the gold standard for diagnosing and treating vascular injuries. Due to long acquisition times, MR imaging may be problematic in critically ill, intubated trauma patients.10
Management of TBI starts with basic resuscitation efforts. Supplemental oxygen to correct hypoxemia is essential. Hypoxemia should be avoided as it leads to an increase in severe disability and mortality.11 If needed, the airway should be secured in the field. Volume resuscitation should begin prior to reaching the hospital. Hypertonic solutions such as hypertonic saline (HS) solutions are anti-inflammatory and immunomodulatory.12 They can be used in case of suspected high ICP.
There is no role for prophylactic hyperventilation that should only be used as a brief temporizing measure when there are visible signs of herniation such as dilated and unreactive pupils, asymmetric pupils, extensor posturing, or no response or decline of 2 or more points from the baseline GCS.
Care should be taken to avoid hypoxemia and hypotension at all costs in TBI patients. Patients with oxygen saturations less than 60% have a 50% incidence of mortality or severe disability. Correction of hypotension improves outcomes. Although a systolic blood pressure value cutoff of 90 is normally targeted, the best systolic blood pressure for optimal outcomes is unknown.
Patients with concussion should be managed based on the severity of the concussion. Patients with mild TBI may be discharged home after a brief observation without any follow-up CT scan or imaging. The only exception is EDH as these patients may have a lucid interval and then rapidly progress to coma and death. Normally, analgesics (avoiding opioids) for headache and meclizine or vestibular exercises for dizziness are sufficient, along with appropriate rest. Some may have a seizure that may be mistaken for a more severe brain injury.
For severe TBI, management is based mainly on treatment of ICP/CPP derangements. Both mannitol and HS can be used to lower ICP. If patients have signs of high ICP such as transtentorial herniation or deteriorating mental status, ICP monitoring is advised for goal directed ICP treatment. Mannitol expands plasma volume and improves blood viscosity and improves oxygen delivery often reducing ICP within a few minutes. The osmotic effect starts within a few minutes and may last for a few hours as a gradient is established between plasma and cells. Mannitol can be given as an intravenous infusion or as a bolus in dosages of 0.25 g/kg to 1 g/kg. HS acts by mobilization of water from the brain across the BBB due to its high osmolality. It also improves plasma volume and hence blood flow. As with mannitol, it can also be given as intravenous infusion or bolus. HS comes in different concentrations ranging from 1.5% to 23.4%. As of this writing, there has been no consensus on the dosing and method of administration. Serum osmolality and serum sodium (Na) levels should be periodically checked, with a goal of not exceeding 320 mOsm/kg and Na of 155, respectively; there is potential for acute kidney injury if these levels are exceeded.
Hyperventilation reduces CO2 and causes cerebral vasoconstriction, decreasing ICP. Hyperventilation is to be avoided in patients with TBI in the first hours (24-48 hours) as the CBF is decreased. It should only be used as a short-term temporizing measure to delay impending herniation.13
Currently, the indications for measuring ICP are GCS less than 8, an abnormal CT scan showing evidence of mass effect in the presence of SDH, EDH, or brain swelling. If the CT scan is normal but injury is severe then monitoring is indicated in patients who have 2 or more of the following:
Age above 40 years of age
Systolic blood pressure below 90
Unilateral or bilateral posturing
Measurement of ICP is useful for prognosis and helpful in guiding therapy. Patients in whom ICP responds to treatment do better than patients who fail to respond, while ICP elevations have been associated with poorer outcomes. The currently proposed threshold to initiate treatment for ICP is 20 to 25 mm Hg.
The devices to monitor ICP range from invasive to less invasive. The gold standard and most accurate ICP monitor is an external ventricular drain (EVD) attached to an external strain gauge pressure transducer. Although being most invasive, EVD confers the benefit of CSF drainage to manage ICP. The risk of hemorrhage is about 0.5% and infection is about 8% with these catheters. Internal transducer devices consisting of a fiber-optic cable or strain-gauge wire can be placed in the brain parenchyma. They are largely accurate but unable to be calibrated once inserted in the parenchyma and are subject to varying degrees of drift after several days of monitoring. Parenchymal devices are also helpful in cases where intraventricular drain insertion is unsuccessful or when the ventricles are collapsed around the catheter. Subdural, subarachnoid, or epidural space transducers are fluid-coupled systems placed through a hollow bolt in the cranium but are less accurate and are now rarely used.
CPP, the difference between MAP and ICP, is a primary determinant of CBF (along with cerebrovascular resistance). Patients with TBI should be targeted for CPP between 60 and 70 mm Hg. CPP less than 50 mm Hg should be avoided and aggressively treated as patient outcomes are poor. In the same manner, higher CPP should be avoided, as there is an increased risk of acute lung injury, which is thought to be due to increased fluid and inotrope usage.
Besides monitoring and treating ICP/CPP, there are other parameters that can be monitored. These include brain tissue oxygen tension (PtiO2), jugular venous oximetry, near infrared spectroscopy, cerebral microdialysis, CBF assessment, and continuous electroencephalography. Among these parameters, PiO2 is the most commonly used due to wider commercial availability. TBI patients with optimal ICP/CPP may still have cerebral hypoxia in pericontusional areas according to PtiO2 measurements. Patients who have PtiO2 less than 15 for increased duration have been shown to have poor outcomes and increased mortality. Use of PtiO2 along with use of ICP-based treatment/CPP-based treatment may improve outcomes as compared to only ICP-based management/CPP-based management.14
TBI patients may need sedation or analgesia or both for comfort and pain relief. Analgesics such as morphine, fentanyl, or sufentanil provide pain relief, but have minimal effect on ICP. Sedative agents commonly used include propofol and midazolam. The long-term use of propofol or midazolam does not result in significant differences in ICP, CPP, or MAP. In general, sedation decreases ICP in patients with TBI. Propofol infusion may have some side effects such as hypertriglyceridemia (if patients are on TPN, the lipid should be reduced) and the propofol infusion syndrome (rare but usually fatal), especially if used in doses of more than 4 mg/kg/h for more than 48 hours. Barbiturates such as pentobarbital can be used in patients with elevated ICP. For pentobarbital, the following dosing regimen can be used: loading dose 10 mg/kg over 30 min; 5 mg/kg/h for 3 doses; and maintenance of 1 mg/kg/h (see Table 50–4).
Table 50–4Analgesic and sedative dosing.
Other medications that are used include ketamine and etomidate. The use of any specific analgesics or sedatives, however, has not shown to improve outcome after TBI.15
Use of prophylactic hypothermia in patients with TBI has not shown statistically significant mortality benefit,13 although hypothermia can be used for the management of high ICP.
Patients with TBI and spinal cord injury are at high risk of venous thromboembolism (VTE). The risk ranges from 5% to 6% in patients with spinal cord injury and 3% to 5% in TBI.16 Currently, the recommendations are to add mechanical thromboprophylaxis to pharmacologic thromboprophylaxis in patients with TBI. When the decision to employ pharmacologic thromboprophylaxis is made after TBI or spinal injury, intravenous unfractionated heparin is the first choice due to the short half-life and rapid reversibility. Low-molecular-weight heparin (LMWH) is an option if the bleeding risks are assessed to be low, but LMWH is avoided in renal failure due to bioaccumulation. There is no data about the timing of VTE prophylaxis, but the sooner it can be safely started, the better. Our protocol is to commence chemoprophylaxis 24 hours after the last stable (no increase in hemorrhage) CT.
Patients with TBI should be started early on nutritional support. Early nutrition support may reduce infectious complications and mortality. If possible enteral nutrition should be started 24 to 48 hours following admission with the aim of reaching goal within 5-7 days.
Post-traumatic seizures (PTS) can occur in patients with TBI with an incidence of 4% to 25% within the first 7 days of injury. Risk factors for PTS after TBI are as follows: GCS less than 10; epidural, subdural, or intracerebral hematoma; cerebral contusion; depressed skull fracture; penetrating head injury; and seizures within the first 24 hours of injury.
Anticonvulsants can be used to decrease the incidence of early PTS during the first week of TBI. They are not recommended for long-term use to prevent late onset PTS. Phenytoin or valproate can be used for seizure prophylaxis. The use of steroids in TBI is not recommended and may be even harmful.
Surgical options are considered using the following criteria.
Epidural—If EDH volume is more than 30 cm3, it should be evacuated regardless of the GCS score. Patients with anisocoria and coma should undergo hematoma evacuation as soon as possible. Patients can be managed nonoperatively, if they meet all of the following criteria: EDH volume is less than 30 cm3; thickness is less than 15 mm; midline shift is less than 5 mm; GCS is more than 8; and no focal neurologic deficit.17
Subdural—Patients with acute traumatic SDH with GCS less than 9 should have ICP monitoring. These patients can be watched nonoperatively if the SDH thickness is less than 10 mm and midline shift is less than 5. If the GCS decreases by 2 points from the time of admission and/or they have asymmetrical or fixed and dilated pupils and/or their ICP rises above 20, they should be taken to operating room (OR). Patients with a hematoma thickness more than 10 mm or midline shift more than 5 mm should be operated upon irrespective of the GCS score. Surgery should be conducted sooner rather than later to improve outcomes.18
Parenchymal Lesions—Patients with TBI can have either focal or diffuse parenchymal lesions. Diffuse or nonfocal injuries include cerebral edema or diffuse injury. Focal lesions include contusions, ICH, delayed traumatic ICH (DTICH), and infarctions. DTICH is defined as ICH, which was not initially present on admission CT scan but developed subsequently, mostly in the region of contusions.
Patients with parenchymal lesions should be operated on in the following situations: deteriorating neurologic exam as evidenced by a decrease in GCS by 2 points; refractory ICP; signs of mass effect on CT scan such as basal cistern obliteration; GCS of 6 to 8 and fronto-temporal lesion of more than 20 cm3 with midline shift more than 5 mm and/or cisternal obliteration on CT scan; any patient with a lesion volume more than 50 cm3.
Patients who do not meet the aforementioned criteria and who have their ICP controlled medically can be monitored with serial exams and CT scans. Patients who have diffuse cerebral swelling and difficult to control ICP, can undergo decompressive craniectomy. Others may have focal decompression and lesion resection.19
Traumatic Posterior Fossa Mass Lesions—Patients with lesions in the posterior fossa leading to neurologic dysfunction or deterioration require emergent craniotomy as they have a tendency to worsen rapidly. If CT scans show signs of a mass effect such as distortion or compression of the fourth ventricle or hydrocephalus, suboccipital craniotomy should be performed.20
Depressed Skull Fractures—Patients with depressed skull fractures may have dural penetration, hematoma formation, and wound contamination. The fracture can involve frontal sinuses and also major cosmetic defects. Surgery may be warranted if any of the aforementioned is present. It is also recommended to operate if the bone is depressed the full thickness of the cranium, or if CSF leak or brain parenchyma is present in the open fractures.21
Patients after TBI may follow basic functions of emergence of consciousness, recovery of neuropsychologic functions, and return of functional capacity, or they can progress to coma and further deterioration leading to brain death (Table 50–5).22
Table 50–5Clinical features of various TBI outcomes. |Favorite Table|Download (.pdf) Table 50–5 Clinical features of various TBI outcomes.
| ||Brain Death ||Coma ||Vegetative State ||Minimally Conscious State ||Emergence From Minimally Conscious State |
|Eye Opening ||None ||None ||Occasional ||Occasional but inconsistent ||Present |
|Visual Fixation or Pursuit ||None ||None ||None ||Occasional but inconsistent ||Present |
|Spontaneous Movement ||None ||None ||Purposeless ||Present ||Purposeful |
|Response to Pain ||None ||None, flexion or extension ||Variable ||Variable ||Variable |
|Vocalization ||None ||None ||None ||Occasional but inconsistent ||Present |
|Functional Communication ||None ||None ||None ||Occasional but inconsistent ||Consistent |