Neurotrauma

Published in International Anesthesiology Clinics:Winter 2015 – Volume 53 – Issue 1 – p 23–38

Authors: Stippler, Martina MD et al

Epidemiology
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in developed nations and accounts for almost one-third of all trauma-related deaths. Currently, 50,000 Americans die of TBI-related complications annually, and about 5.3 million live with TBI-related disabilities. Among survivors of severe TBI, cognitive deficits are common, which poses a long-term societal burden, given its prevalence in the young. Only one-third of the patients can return to their prior occupation and engage in social activities. Elderly patients have the worst outcome; although accounting for only 10% of the TBI cases, they represent 50% of TBI-related deaths. Road traffic crashes account for 50% of the cases. Falls represent the most common cause in the elderly.

Whereas patients with mild TBI rarely seek medical attention, severe TBI requires rapid diagnosis and treatment to limit secondary injury and optimize outcome. Overall, mortality in patients with severe TBI is still poor. However, parallel improvements in the trauma response system and the development of subspecialization in neurocritical care have led to reductions in mortality.

Classification
TBI is classified according to mechanism, severity, and morphology. Blunt injury is the most common mechanism, with motor vehicle collisions and falls accounting for the majority of cases.

The frequency of penetrating injuries has increased with recent military conflicts, but are also seen in the civilian population. Gunshot wounds are the most lethal type of brain injury, with a 90% mortality rate. Although contamination is a concern in some penetrating injuries, gunshot wounds are considered sterile because of the exposure of the bullet fragment to the heat from the firearm. It is not advised to remove the fragments as doing so can cause more brain damage. Surgical management is mainly limited to local wound care, debridement of nonviable tissue, and water-tight scalp closure. Any further intervention is based on the neurological examination and whether the injury is survivable. Generally, routine surgical removal of the bone or missile fragments remote from the entry site or in the eloquent areas of the brain is not recommended.

In addition to serial neurological examinations and head computed tomographic (CT) scans, intracranial pressure (ICP) monitoring is often used to guide treatment. Although ICP monitoring is routinely used in severe nonpenetrating TBI, little evidence supports its use in penetrating brain injury. Vascular injury can occur with any type of TBI but is more common with penetrating trauma (25% to 36% incidence) than with blunt injuries (<1%). Traumatic aneurysms, or pseudoaneurysms, may present as delayed subarachnoid hemorrhage (SAH). Therefore, patients with penetrating injuries should undergo a screening cerebral angiogram.

Blast injury is rarely observed in civilians, but is common in combat. There are 3 types of blast injuries, all of which create damage as a result of the propagation of supersonic waves. The brain is understandably susceptible to blast injury. The threshold for brain injury from blast exposure is unclear.

Injury Severity
Although there are different methods to stratify TBI by severity, the Glasgow Coma Scale (GCS) is the most widely used. A GCS score of 13 to 15 is considered mild TBI, between 9 and 12 moderate, and <8 is severe. Mild TBI is 8 times more common than moderate and severe TBI. Mild TBI and concussion are often used interchangeably. Complicated mild TBI refers to a subgroup of patients with a GCS 13 to 15 and a positive finding on CT scan (contusions or traumatic SAH).

Evaluation
Rapid evaluation and intervention is essential for optimal outcome in TBI. This begins in the prehospital setting where the focus is on the prevention of secondary injury by limiting hypoxia and hypotension. A neurological examination is conducted immediately on arrival to the emergency room and helps to dictate the appropriate next steps. Patients with severe TBI are at high risk for mass lesions and must be evaluated with a head CT scan. Management (operative or nonoperative), depends on the clinical examination and CT findings.

Anticoagulation frequently complicates the management of patients with TBI. Patients who are anticoagulated with warfarin or antiplatelet medications have a 4-fold higher risk of death compared with a nonanticoagulated patient.  Factor Xa inhibitors and direct thrombin inhibitors pose a new challenge in the management of patients with complicated TBI, as no drug has been discovered to reverse this type of coagulopathy.

Management of Diffuse Injuries
Any patient with a positive CT finding, regardless of severity, should be admitted to an intensive care unit for serial neurological examinations. Complicated mild TBI is present in 6% to 12% of patients, with CT abnormalities such as contusion, traumatic SAH, subdural, or epidural hematomas (EDH). A second follow-up head CT scan is obtained within 12 to 24 hours as standard of care in many hospitals. Although mild TBI is common, neurosurgical intervention in these patients is uncommon, and required in <1%. Recent evidence suggests that the routine use of follow-up CT scans in this population may be unnecessary. A meta-analysis and more recent prospective study of mild TBI with a positive head CT showed that it is safe to not repeat a head CT for patients with mild TBI and a normal neurological examination. It is important to note that a routine repeat head CT scan does not replace the need for neurological examination. Most of these cases are nonoperative, and the patient can be discharged home after a short observation period. The exception to this is a patient with an EDH, which can present with a lucent interval after a brief loss of consciousness and then progress to coma and death.

Concussion is induced by biomechanical forces and results in a rapid and short-lived impairment with possible loss of consciousness. The role of pharmacological therapy is limited. Expert opinion supports the use of mild analgesics for headache, avoidance of narcotics, and meclizine, or promethazine, and vestibular exercise for dizziness.

Management of severe TBI is directed by the evidence-based Guidelines for the Management of Severe Traumatic Brain Injury published in 2007 by the Brain Trauma Foundation. Treatment for severe TBI is based on maintaining appropriate cerebral perfusion pressure, and guided by ICP monitoring, and more recently by brain-tissue oxygenation.

ICP measurement has been adopted as standard of care by most trauma centers in the United States. The recommendation to monitor ICP in severe TBI is based on limited data. In 2013, the first randomized trial examining the utility of ICP monitoring in severe TBI was published. The treatment arm received therapy based on ICP and the control group based on serial neurological exams and head CT scanning. While both groups received aggressive ICP treatment, the patients in the ICP monitoring arm received more treatment. The study failed to demonstrate an outcome difference. Despite the results of this study, patients with a GCS score ≤8 still warrant treatment based on ICP monitoring. This can be achieved through an external ventricular drain, which allows both ICP measurement and CSF drainage or fiberoptic or micro strain gauge devices, which are inserted into the brain parenchyma. The downside to parenchymal monitors is that they cannot be recalibrated during monitoring and have a negligible drift. No method of ICP monitoring has been demonstrated to be superior, although a greater number of device-related complications are seen with external ventricular drains.

The TBI Guidelines recommend maintaining a cerebral perfusion pressure above 60 mm Hg using a combination of methods to maintain mean arterial pressure and reduce ICP. A treatment strategy that includes sedation, hyperosmolar agents, and hyperventilation is effective in reducing ICP. Simple and effective (and often overlooked) treatments include elevating the head of the bed >30 degrees and ensuring that the head position is midline. If a cervical spine collar is present, ensure that it is correctly positioned.

Sedation and analgesia need to be optimized to prevent straining, bucking, and coughing. Providing optimal sedation is tricky because of the need to avoid hypotension and to perform frequent neurological examinations. A variety of sedation regimens can be used, but we tend to start with a propofol infusion.

For analgesia, fentanyl may be administered as a bolus or infusion. Care must be taken to avoid prolonged infusions of high-dose propofol on account of the risk of propofol infusion syndrome. In addition, bolus and infusion medications should be dose-adjusted when inducing hypothermia. Midazolam infusions can be used to replace or supplement propofol infusions for patients requiring high-dose propfol (>80 mcg/kg/min). To monitor the depth of sedation, some institutions use the BIS monitor. Neuromuscular blockade is used as a last resort, as its use impairs the ability to monitor neurological examinations.

Hyperventilation to induce hypocapnia (PaCO2 30 to 35 mm Hg) is not recommended in routine management. It can be effective as a temporizing measure to decrease ICP in patients who show signs of herniation, while other therapies are being considered. Otherwise, induced hypocapnia is thought to put the patient at risk for cerebral ischemia. Hypocapnia induces vasoconstriction, which has the effect of lowering ICP by decreasing cerebral blood volume. The current guidelines recommend maintaining eucapnia (PaCO2 35 to 40 mm Hg).

Hyperosmolar drugs such as mannitol or hypertonic saline are effective in reducing ICP. At present, there is no evidence to support the superiority of one particular agent. In general terms, both mannitol and hypertonic saline work to reduce ICP in similar ways. As the brain has a high water content, the formation of an osmotic gradient across the blood-brain barrier will drive water from the brain to the intravascular space. In addition, mannitol is thought to induce changes in the rheology of blood, which results in cerebral vasoconstriction. This concept has been recently challenged. Mannitol is dosed between 0.25 and 1 g/kg every 4 to 6 hours. As mannitol acts a diuretic, care should be taken when administering to a patient who is hypovolemic. Serum osmolarity should be measured and a ceiling of 320 mOsm/L is recommended as the upper limit for redosing. We calculate the osmolar gap to decide when to redose mannitol (gap<10). Hypertonic saline comes in a variety of concentrations (2% to 23.4%). The goal is to raise the serum sodium initially to 145 to 150 mmoL/L, and a step-wise increase in sodium in subsequent days if hyperosmolar therapy continues to be required. Hypertonic saline may be a good choice for patients who present hypovolemic as it acts as a volume expander. Care should be used in administering hypertonic saline in hyponatremic patients over concern for central pontine myelinolysis. In addition, a central line is required for the administration of concentrations greater than 3%. For both agents, the brain adapts to a hyperosmolar state by generating idiogenic osmoles. For this reason, stopping hyperosmolar therapy needs to be carried out gradually.

Persistently elevated ICP, despite maximal medical therapy, may be an indication for decompressive hemicraniectomy. Depending on the underlying pathology, one side of the skull or the frontal bone bilaterally (Kjellberg procedure) is removed. In 2011, the results of the randomized Decompressive Craniectomy trial were published.  Decompressive craniotomy did not improve functional outcome. The results of an ongoing trial of craniectomy for head injury called the Randomized Evaluation of Surgery with Craniectomy for uncontrollable Elevation of Intracranial Pressure (RESCUEicp) may provide further insight. Although a decompressive craniectomy may be a useful option for intractable ICP, it is not without risk. One study showed a 35% rate of complications that included subdural effusion, hydrocephalus, and infection. The incidence of posttraumatic hydrocephalus is higher in patients after decompressive craniectomy. This may be due to disturbance of CSF dynamics after decompressive craniectomy. Bilateral decompressive craniectomy is sometimes performed but is associated with an unfavorable outcome in 46% of cases.  Some patients suffer delayed neurological deterioration, described as “syndrome of the trephined.” It is thought that the brain function is impaired by the atmospheric pressure.

Temperature management in severe TBI is critical. It is postulated that most of the benefit seen with cooling is not from hypothermia but in the prevention of hyperthermia. This concept is known as therapeutic temperature modulation. Currently, aggressive treatment to maintain normothermia is recommended. A retrospective study found that maintaining normothermia decreased the ICP burden. To achieve and maintain normothermia advanced cooling methods, such as surface cooling or intravascular cooling, may be used. Conventional cooling methods, such as ice packs and acetaminophen are ineffective in modulating temperature. Intravascular cooling is the most effective method for maintaining normothermia. Hypothermia should be reserved for patients with refractory intracranial hypertension. A recent meta-analysis of all prospective TBI clinical trials found that therapeutic moderate hypothermia (32 to 34°C, 89.6 to 93.2°F) resulted in less mortality [relative risk (RR) 0.51; 95% confidence interval (CI), 0.33-0.79] and increased likelihood of a good outcome (RR 1.91; 95% CI, 1.28-2.85) compared with normothermia during acute care, but the risk of pneumonia increased (RR 2.37; 95% CI, 1.37-4.10). Problems associated with hypothermia include increased bleeding risk, arrhythmias, and increased susceptibility to infection and sepsis. Two large trials of hypothermia did not provide evidence to support hypothermia in severe TBI.

The Guidelines for the Management of Severe Traumatic Brain Injury recommend high-dose barbiturate to control elevated ICP only after maximum standard medical and surgical treatment have failed. High-dose barbiturate therapy has shown to be effective in lowering ICP but has never been proven to improve outcome. Barbiturate therapy has major side effects including myocardial depression, hypotension, and immunosuppression.

Multimodality monitoring is used in most centers specializing in TBI. Besides ICP, cerebral blood flow, partial brain-tissue oxygen tension (PbtO2), microdialysis variables, cerebral oximetry, and bispectral index are measured. Multimodal monitoring is discussed in more detail in this volume (see Neuromonitoring in the ICU). Multimodal monitoring increases the understanding of brain pathophysiology and may help to limit secondary brain injury by detecting changes to brain oxygenation and metabolic substrates.

PbtO2 is probably the most commonly applied and studied parameter. Numerous studies have examined the relationship between outcome and PbtO2. They found that likelihood of death increased with duration of time that PbtO2 was <15 mm Hg. The detrimental effects of hyperoxia have also been demonstrated. The brain-tissue oxygen monitoring in TBI (BOOST 2) trial is expected to complete enrollment by the end of 2014 and answer the question whether PbtO2-guided therapy improves outcome.

Microdialysis provides insight into the metabolic state of the brain by measuring substrates such as lactate, pyruvate, and glucose. A lactate/pyruvate ratio of 40 is considered an “energy crisis.” Microdialysis showed that tight systemic glucose control increased the prevalence of brain energy crisis: microdialysis glucose <0.7 mmoL/L with a lactate/pyruvate ratio >40. Including microdialysis and PbtO2 in severe TBI management was found to have the best predictive accuracy for outcome after severe TBI.

Autoregulation and compliance are other measures that help us to individualize management and set different thresholds for each patient. The healthy brain is able to maintain a constant cerebral blood flow across a range of mean arterial pressures (50 to 150 mm Hg). In severe TBI, autoregulation is often compromised. Surrogate measures to evaluate autoregulation have been developed. One such measure of autoregulation is the cerebrovascular pressure reactivity index (PRx). PRx is a linear correlation coefficient between the average arterial blood pressure and ICP. When the PRx is negative, autoregulation is intact. A positive PRx implies that ICP follows the mean arterial blood pressure, which indicates impaired autoregulation. To monitor compliance, ICP waveform analysis or derived indices such as the index of pressure-volume compensatory reserve (RAP) are used. RAP is defined as the correlation coefficient between the pulse amplitude and mean ICP.47 Higher values up to +1 indicate poor compliance. Compliance can be useful to interpret and find an individual ICP threshold. A patient with ICP<20 mm Hg and poor compliance might need treatment which a patient with good compliance and ICP>20 mm Hg might not.

Management of Focal Injuries
Patients with focal TBI and extra-axial bleeding with mass effect are treated surgically. A fronto-temporal or temporal-parietal craniotomy, with or without subtemporal decompressive craniectomy, is performed. In some cases, a prophylactic hemicraniectomy is performed at the same time if the brain appears swollen intraoperatively. The preoperative CT can help predict malignant brain swelling. More midline shift than one would expect from the extra-axial hematoma, effacement of basal cisterns and sulci, and loss of gray-white matter differentiation are warning signs.

A patient with an EDH can progress from having a normal neurological examination to coma rapidly. Most often, the patient becomes agitated and restless and may have an episode of emesis secondary to increased ICP. This is often followed by the development of focal neurological signs such as hemiparesis, seizures, pupillary dilation, decrease in consciousness, and, if the EDH is not evacuated within several hours, decortication. Any EDH>30 cm3 should be evacuated regardless of the GCS score. An EDH<30 cm3 in volume and <15 mm thick, with <5 mm midline shift in patients with a GCS score ≥8 without focal deficit can be managed nonoperatively. This should be done only with serial CT scans and frequent neurological examinations in a facility with neurosurgical coverage.

An acute SDH thicker than 10 mm or causing a midline shift >5 mm on CT scans should be surgically evacuated, regardless of the patient’s GCS score. A comatose patient (GCS score ≤8) with an SDH<10 mm thick and midline shift <5 mm should undergo surgical evacuation of the lesion if the GCS score decreased by 2 or more points between the time of injury and hospital admission, the pupils are asymmetric or fixed and dilated, or ICP exceeds 20 mm Hg.

The prognosis of SDH is worse compared with EDH. The magnitude of preoperative midline shift and age are independent predictors of unfavorable outcome.

Conclusions
Outcome after severe TBI remains poor; mortality is high and survivors are often left with severe disabilities. Several factors have been determined to be associated with worse outcome: low GCS score, pupillary response and size, older age, hyperthermia, hypoxia, and elevated ICP. A GCS score of 3 on presentation has been accepted as a poor prognostic factor. Mortality approaches 100% in the presence of bilateral fixed dilated pupils.

Age, most often a disregarded variable, is by itself an independent predictor of outcome. Outcome in the elderly is worse with or without surgery. Even with timely and satisfactory surgery, unexplained clinical deterioration occurs in patients older than 70 years of age.

The IMPACT and CRASH prognostic models take all these parameters into account when calculating the 6 month morbidity and mortality. They have been externally validated and demonstrated good generalizability. These models may provide some guidance when offering aggressive operative therapy such as decompressive craniectomy.

Finally, the facility where patients with TBI are treated affects outcome. Patient with severe TBI treated in American College of Surgeons-designated level-1 trauma centers have better survival rates and outcomes than those treated in American College of Surgeons-designated level-2 centers.