Introductory Chapter: Traumatic Brain Injury

1. Introduction

Traumatic brain injury (TBI) is a global public health concern and one of the main causes of morbidity, disability, and mortality that has been associated as a risk factor for neurodegeneration and degenerative diseases. Brain injury, secondary to vehicular injury was the most common form of TBI [1]. Yearly, TBI costs the global economy approximately 400 billion US dollars, representing 0.5% of the gross world product [2]. Even with modern diagnosis and treatment, the prognosis for the patient with TBI remains poor. Severe TBI has mortality rates of 30–40% and can cause significant physical, psychosocial, and social deficits in up to 60% of cases [3, 4]. The highest rates of TBI are in children group (0–4 years old) as well as in young age group (15–24 y). There is another high incidence of TBI in old age group (>65 y). The 2 major causes of TBI are falls and motor vehicle accidents generally [5]. Because of the prevalence of TBI, an understanding of the management of this group of patients is vital to the modern health care provider. This introductory chapter based on the 4th edition of the Brain Trauma Foundation guidelines were published in 2016 [6].

2. Pathophysiology of TBI

The pathogenesis of TBI is a complex process, caused by primary and secondary injuries, resulting in temporary or permanent neurological deficits (Figure 1) [7]. Primary damage is directly related to the primary external influence on the brain. Secondary injury can occur minutes to days after the primary impact and consists of molecular, chemical, and inflammatory cascades that lead to further brain damage. This cascade involves depolarization of neurons and the release of excitatory neurotransmitters such as glutamate and aspartate, leading to an increase in intracellular calcium. Intracellular calcium activates a series of mechanisms by activating caspases, and free radicals, which lead to cellular degradation, directly or indirectly, through apoptotic processes. This degradation of neuronal cells is associated with an inflammatory response that further damages neuronal cells and triggers disruption of the blood-brain barrier (BBB) and further brain edema. The whole process is also up- and down-regulated through several mediators. The second injury phase is followed by a recovery phase that includes reorganization at the molecular, anatomical, and functional levels.

Figure 1.

Secondary injury from oxidative stress, disruption of the blood-brain-barrier (BBB), inflammation, excitotoxicity, and cell death and resulting factors involved in neuronal damage. MS: mitochondrial stress, CKS: cytokines, NO: nitric oxide, PGI: prostaglandins, Glue: glutamate, NMDA: N-methyl-D-aspartate receptor, Ca: calcium, CDP: caspase-dependent 3, CID: caspase-independent factor.

The volume of the intracranial compartment consists of 3 separate contents: brain parenchyma (83%), cerebrospinal fluid (CSF, 11%) and blood (6%). Each of these contents is interdependent on the homeostatic environment within the skull. However, when the intracranial volume exceeds its normal composition, a series of compensatory mechanisms occur. An increase in intracranial volume can occur in the traumatized brain through mass effects of hematoma, cytotoxic and vasogenic edema, and venous congestion. Because brain tissue is incompressible, edematous brain tissue initially causes CSF to squeeze into the spinal compartment. Eventually, blood, especially from venous channels, is also squeezed out of the brain. Without appropriate intervention, sometimes even the maximal intervention, compensatory mechanisms fail, and the end result is pathological brain compression and subsequent death.

3. Neurological exam in TBI

The Glasgow Coma Scale (GCS) is part of clinical practice guidelines and has been commonly used as a bedside neurological scale in routine office practice since its introduction in 1974 [8]. It helps neurosurgeons assess the patient's level of consciousness to determine the severity of TBI in patients. GCS measures eye-opening (4 points), verbal response (5 points), and optimal motor response (6 points), for a total of at least 3 to a maximum of 15 points. This score correlates with changes in pathophysiological changes after TBI and is reflected in the total score; it ranges from 13 to 15 (mild), 9 to 12 (moderate), and less than 8 (severe TBI) [8, 9].

4. Updated medical interventions for TBI

1. Bifrontal decompressive craniectomy is not recommended in severe TBI patients with diffuse injury (no mass lesions) and elevated ICP greater than 20 mmHg for more than 15 min within 1 h, which is not effective for first-line therapy, because it will not improve outcomes as measured by the Glasgow Outcome Score (GOS) at 6 months post-injury [6]. However, this procedure has been shown to reduce ICP and minimize ICU days. Compared with small frontotemporal parietal craniectomy, large frontotemporal parietal decompressive craniectomy (no smaller than 12 cm × 15 cm or 15 cm in diameter) is recommended to reduce mortality and improve neurological outcomes in patients with severe TBI.

2. Although hyperosmolar therapy may lower ICP, there was insufficient evidence about effects on clinical outcomes to support a specific recommendation or to support use of any specific hyperosmolar agent, for patients with severe TBI.

3. Current guidelines do not recommend the use of barbiturates to induce burst suppression measured by EEG to prevent the development of intracranial hypertension. High-dose barbiturates are recommended only to control ICP elevations that are refractory to standard medical and surgical treatment. It is important to maintain hemodynamic stability during barbiturate therapy because patients may develop hypotension.

4. Propofol sedation is recommended for the control of ICP but has failed to show improvement in mortality for 6-month outcomes.

5. The following agents, including Dexmedetomidine and Ketamine, have been shown to have a potential role in the management of TBI patients, although they are not included in the current Brain Trauma Foundation guidelines.

6. Prolonged prophylactic hyperventilation with PaCO2 of ≤ 25 mmHg is not recommended.

7. An EVD (extraventricular drainage) system, which zeroes at the midbrain and continuously drains CSF, can be considered to reduce the ICP burden more effectively than intermittent use. For patients with an initial GCS < 6, CSF drainage may be considered to reduce ICP within 12 h of injury.

8. The use of prophylactic hypothermia, early, within 2.5 h and short-term, 48 h post-injury, is not recommended to improve outcomes in patients with diffuse injury.

9. Once the intracranial hemorrhage has stabilized, low-dose unfractionated heparin or LMWH (low molecular weight heparin) may be used in combination with mechanical prophylaxis. There is a potential risk of intracranial hemorrhage expansion, so the appropriate timing to initiate anticoagulation will be based on clinical guidelines. There is insufficient evidence to support recommendations regarding the preferred drug, dose, or duration of drug prophylaxis for deep vein thrombosis. Other methods, such as compression stockings and maintenance of normovolemia, should be implemented to prevent deep vein thrombosis.

10. When the overall benefits outweigh the complications associated with tracheostomy, tracheostomy is recommended to reduce the number of days on mechanical ventilation to avoid ventilator dysfunction in the patient. Tracheostomy is also considered a potential method to reduce VAP (ventilator-associated pneumonia). However, there is no evidence that early tracheostomy reduces mortality or incidence of hospital-acquired pneumonia. The use of povidone-iodine in oral care to lower VAP is not recommended because it increases the risk of acute respiratory distress syndrome.

11. The use of antimicrobial-impregnated catheters may be considered to prevent catheter-related infections during extraventricular drainage.

12. Feeding patients to attain basal caloric replacement at least by the fifth day and, at most, by the seventh-day post-injury is recommended to decrease mortality. Trans-gastric jejunal feeding is recommended to reduce the incidence of ventilator-associated pneumonia.

13. Prophylactic use of phenytoin or valproate is not recommended for the prevention of advanced PTS (post-traumatic seizures). However, phenytoin is recommended to reduce the incidence of early PTS (within 7 days after injury) because the overall benefit of this treatment is thought to outweigh the complications associated with this treatment. However, early PTS was not associated with worse outcomes. There is insufficient evidence to suggest that levetiracetam is superior to phenytoin in preventing early PTS and toxicity.

14. Steroids are not recommended to improve results or reduce ICP. In patients with severe TBI, high-dose methylprednisolone is associated with increased mortality and is contraindicated.

5. Brain multi-modality monitoring

1. Management of severe TBI patients using information from ICP monitoring is recommended to reduce in-hospital and 2 weeks post-injury mortality.

2. Management of severe TBI patients using guideline-based recommendations for CPP (cerebral perfusion pressure monitoring) monitoring is recommended to decrease 2-week mortality.

3. Jugular bulb monitoring of AVDO₂ (Arteriovenous Oxygen Content Difference) may be considered to provide management decisions in TBI patients. Jugular venous saturation < 50% may be a threshold to avoid in order to reduce mortality and improve 3- and 6-month outcomes.

6. Blood pressure thresholds

1. Maintenance of SBP (systolic blood pressure) ≥ 100 mmHg for patients 50–69 years of age or ≥ 110 mmHg or more for patients aging 15–49 years or 70 years may be considered for reduced mortality and improved outcomes.

2. Recommend treatment for ICP > 22 mmHg, as values above this level are associated with increased mortality.

3. ICP values combined with clinical and brain CT results can be used to make management decisions.

4. The recommended CPP (cerebral perfusion pressure) target for survival and improved outcomes is 60–70 mmHg. Currently, it is unclear whether 60 or 70 mmHg is the minimum optimal CPP threshold and may depend on the patient's autoregulation status.

5. Avoid fluids and vasopressors for CPP > 70 mmHg due to increased risk of respiratory failure.

7. Potential new monitor

The use of brain tissue oxygen tension (PbtO₂) monitoring was originally proposed as a method to avoid cerebral ischemia to control ICP during therapeutic hyperventilation. The most common method for monitoring PbtO₂ is an invasive probe using a modified Clark electrode, with a typical pathological threshold of 20 mmHg [10]. In multivariate analysis, PbtO₂ was shown to have an impact on patient prognosis. This has led to prospective trials of PbtO₂-targeted therapy in addition to standard ICP-driven therapy. A phase II trial (BOOST-II, Brain Tissue Oxygen Monitoring, and Management in Severe Traumatic Brain Injury) demonstrated a significant reduction (74%) in the hypoxic burden during hospitalization in the PbtO₂-targeted group, with no substantial safety concerns. According to studies, direct intervention is used for ICP management (if >20 mmHg for >5 min), PbtO₂ control (if <20 mmHg for >5 min), or both [10]. The third phase of the randomized study (BOOST-III) will evaluate the clinical efficacy of “a treatment regimen based on PbtO₂ monitoring compared to a treatment based on ICP monitoring alone” and will enroll patients in the United States.

8. Deep brain stimulation

DBS (Deep Brain Stimulation) has been shown to be effective for cognitive and motor disorders and has the potential to treat other disorders such as depression [11]. These same clinical disorders (e.g., tremor, depression) are frequently present in patients with TBI due to direct structural brain injury or secondary damage from injury. DBS has shown efficacy in the treatment of subgroups of TBI patients with such comorbidities, but the effect of DBS on higher-order function is unclear.

9. Conclusions

TBI is a major global health challenge and priority. Despite the lack of effective treatments for TBI recovery today, continuous efforts have been made over the past few decades to develop therapeutic strategies for TBI recovery. Standard medical and surgical interventions have always played an important role in the acute management of patients with TBI. The number of TBI survivors has increased due to the emergence of better acute management guidelines in the acute phase of TBI, and the number of TBI survivors with various disabilities has increased.