Jul. 05, 2023
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Intracerebral hemorrhage is a common complication of traumatic brain injury. Traumatic brain injuries can be classified into three major groups: closed head injury, penetrating injury, and explosive blast injury. Blast injuries appear to have a high risk for traumatic pseudoaneurysm formation. Differentiation between an intracerebral hemorrhage and a hemorrhagic contusion is difficult. Glasgow Coma Scale is the most valuable tool to assess the level of consciousness after traumatic brain injury. Intracranial hemorrhage in patients with traumatic brain injury results in poor neurologic outcomes and high mortality. In severe head injury, a hematoma of more than 50 mL is associated with higher mortality. Brain edema is a very significant independent prognostic variable across all categories of traumatic brain injury severity. Traumatic intracerebral hemorrhage, like spontaneous hemorrhage, often expands over time. The contrast extravasation, on multidetector CT angiography, is a strong and independent predictor of hematoma expansion, poor outcome, and increased risk of in-hospital mortality. Intraventricular hemorrhage on initial CT predicts lesions of diffuse axonal injury in the corpus callosum. Coagulopathies are common in patients with severe head injuries and contribute to hematoma formation. Approximately, 10% of patients with traumatic brain injury are likely to develop acute kidney injury, and many of them require kidney replacement therapy. Acute kidney injury adversely affects the outcome. The patients taking antiplatelet and anticoagulant drugs are at greater risk of intracranial hemorrhage, and treatment should include immediate withdrawal of these drugs. Effective neurocritical care coupled with timely and appropriate neurosurgical intervention can significantly improve outcomes. Bilateral fixed dilated pupils generally indicate a grave prognosis. Aggressive decompressive craniectomy in some of these patients improves the chances of a favorable outcome. Many patients, even with a Glasgow Coma Scale of 3, may have a good outcome at 6 months. Tranexamic acid is a promising drug that can be used to lower mortality. Genetic abnormities have been identified as a risk factor for hematoma expansion in patients with traumatic brain injury. Trials targeting these genes are currently ongoing, and they may open avenues for targeted treatment. In this article, the author discusses the pathophysiology, clinical presentation, impact on outcomes, and available treatments for traumatic intracerebral hemorrhage.
• Traumatic intracerebral hemorrhages result from either nonpenetrating or penetrating trauma to the head.
• A contusion consists of blood intermixed with brain tissue.
• Data have shown that traumatic intracerebral hemorrhages often expand over time.
• Delayed posttraumatic hemorrhages may sometimes result from coalesced blood within contusions.
• Therapeutic interventions that are frequently used include the administration of hypertonic saline, hyperoxygenation, decompressive craniectomy, and hypothermia.
• Mortality rates in severe traumatic brain injury are very high.
• Use of helmets, seat belts, and airbags has been shown to reduce fatal and serious head injuries.
Traumatic head injury has been noted in human civilization for 3000 years. Descriptions of head injuries are available in ancient Sumerian, Egyptian, and Greek medicine. Hippocrates suggested that head injury in which the cranium was perforated might be followed by serious consequences, such as the extravasation of blood. Hippocrates’ treatise On Wounds in the Head represents an excellent classical source of information about head injury (65). The first description of gunshot wounds to the head was by Brunschwig, a German surgeon (11; 55). Cushing in his classical article of 1917 described varieties of missile injuries (19). Surgical treatment of traumatic intracerebral lesions was advanced in the late 19th and 20th centuries by several pioneer neurosurgeons, including Victor Horsley, Harvey Cushing, W H Jacobson, Hugh Cairns, and Walter Dandy. In 1974, the Glasgow Coma Scale (GCS) was first used as a functional scale for the assessment of coma and impaired consciousness (Teasdale and Jennet 1974). The development of brain CT allowed improvements in the diagnosis and characterization of traumatic intracerebral hemorrhage, and the traumatic brain injury field is being further revolutionized by the development and refinement of brain MRI (54).
Traumatic brain injury is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force (57). The Department of Defense and the Department of Veterans Affairs in the United States, by consensus, have defined traumatic brain injury as any traumatically induced structural injury or physiological disruption of brain function as a result of an external force that is indicated by new onset or worsening of at least one of the following clinical signs, immediately following the event (81):
(1) Any period of loss of or a decreased level of consciousness
Traumatic brain injury can produce various types of intracranial hemorrhage, including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, intracerebral hemorrhage, intraventricular hemorrhage, and cortical contusion. Cortical contusions result from direct trauma to the brain parenchyma from impact with boney prominences of the skull. Typical cerebral areas of contusions are the frontal, orbital frontal, anterior temporal, and lateral temporal areas. Differentiation between an intracerebral hemorrhage and a hemorrhagic contusion is difficult. A contusion consists of blood intermixed with brain tissue. Intracerebral hemorrhages are composed of hemorrhagic areas within the cerebral parenchyma, which may be as small as 1 mm or large enough to involve the majority of a cerebral hemisphere. Traumatic intracerebral hemorrhages frequently coexist with extracerebral hemorrhages. Frequently, clinical manifestations of traumatic intracerebral hemorrhage depend on the severity of traumatic brain injury.
Nonenhanced CT scan of two patients showing coup injury and contrecoup injury on the opposite side. (Contributed by Dr. Ravindra Kumar Garg.)
The Glasgow Coma Scale, a clinical scale that assesses the level of consciousness after traumatic brain injury is shown in Table 1.
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Patients are typically divided into the broad categories of mild, moderate, and severe injury.
Mild injury. Patients with traumatic brain injury who have a normal neurologic examination, GCS of 15, no risk factors (such as abnormal coagulation parameters, drug or alcohol intoxication, or CSF rhinorrhea and posttraumatic seizure), and a normal CT are much less likely to develop an intracerebral hematoma (83). Children with blunt head trauma, initial GCS scores of 14 or 15, and normal cranial CT scan results are at very low risk for subsequent traumatic findings on neuroimaging and extremely low risk of requiring neurosurgical intervention (32).
Moderate injury. The presence of a state of altered consciousness (GCS 9 to 12), confusional state, behavioral changes, severe vertigo, or focal neurologic deficit, such as hemiparesis, indicates the presence of cerebral contusion or a hematoma.
Severe injury. Patients who are comatose (GCS 8 or lower, preferably after resuscitation) immediately after injury may indicate the presence of an extensive cerebral contusion, epidural or subdural hematoma, or a large intracerebral hemorrhage.
Brain edema is a very significant independent prognostic variable across all categories of traumatic brain injury severity. Brain edema predicted an 8-fold greater mortality rate in all patients and a 5-fold greater mortality rate for patients with mild traumatic brain injury (79). In patients with severe head injury, a traumatic hematoma of more than 50 ml was associated was higher mortality (87). In addition to age and GCS score, the CT patterns of bilateral hematoma, temporal hematoma, and associated subdural hematoma were suggestive of death or poor outcome in survivors. A meta-analysis assessed the 6-month prognosis of moderate and severe traumatic brain injury. Studies used the GCS at 6 months postinjury as an outcome measure. Determinants were assessed within the first month postinjury. Factors that predicted outcome were GCS, motor score, midline shift, subdural hematoma, and pulsatility index. Strong evidence of no association was found for gender and intraventricular hemorrhage (35). A sizable number of patients (14.5%) even with a Glasgow Coma Scale of 3 may have a good outcome at 6 months (71).
In traumatic brain injury, intraventricular hemorrhage on initial CT predicts lesions of diffuse axonal injury in the corpus callosum (52). Midline traumatic subarachnoid hemorrhage also indicates diffuse axonal injury (53). In the majority of patients, traumatic parenchymal hemorrhages are present in the frontal and temporal lobes. Significant residual blood products are present even after 6 months postinjury and are a potential source of ongoing secondary brain injury. Larger temporal lobe hematomas are associated with more brain atrophy and more severe cognitive decline (51).
A disorder of consciousness is initially seen in a majority of patients with traumatic brain injury and in most of these patients with persisting unconsciousness, altered sensorium eventually gets reversed and patients regain consciousness during rehabilitation. In a study, 17,470 patients with traumatic brain injury were analyzed (41). Of these, 7547 (57%) patients had early loss of consciousness. In 2058 patients (12%), loss of consciousness persisted during rehabilitation. Factors associated with persisting loss of consciousness were high-velocity injuries, intracranial mass effect, intraventricular hemorrhage, subcortical contusion, and long acute care. Eighty-two percent (n=1674) of comatose patients regained consciousness during inpatient rehabilitation. Young age, male sex, absence of intraventricular hemorrhage, mass effect, and subcortical contusion predicted better functional outcomes (41).
Traumatic brain injuries can be classified into three major groups: closed head injury, penetrating injury, and explosive blast injury. Traumatic brain injury caused by explosive or blast events is known as “blast-induced traumatic brain injury.” A typical blast wave consists of a lead shockwave followed by supersonic flow. The resultant tissue injury includes hematoma formation, edema, pseudo-aneurysm development, vasoconstriction, and induction of apoptosis (60).
Most traumatic intracerebral hemorrhages result from nonpenetrating head trauma. A “coup” injury occurs within areas of brain underlying the skull at the site of direct impact. They can occur at the coup site when a depressed skull fracture or transient calvarial deformity from a blow to the stationary head affects the underlying brain. Subsequent to impact, the brain is accelerated within the calvaria, and areas of brain opposite the direct impact contact the skull when head motion is suddenly stopped, resulting in a “contrecoup” injury.
Nonenhanced CT scan of two patients showing coup injury and contrecoup injury on the opposite side. (Contributed by Dr. Ravindra Kumar Garg.)
This mechanism results in cerebral contusions, although vascular lacerations leading to frank intracerebral hemorrhage can also occur in this manner. These contrecoup contusions are frequently of greater severity than the injuries at the coup site. Contrecoup injuries are especially severe when the blow occurs to the occiput, allowing the rough, irregular surfaces of the anterior and central skull base to bruise the undersurface of the brain, resulting in the characteristic hemorrhagic contusions seen in the inferior frontal and temporal lobes (39). Blast injuries can produce several types of vascular effects on both arteries and veins, such as sagittal sinus injury and lacerated cortical arteries. Blast injuries appear to have a high risk for traumatic pseudoaneurysm formation. All these vascular complications can lead to hematoma formation in the brain (46; 31; 50).
The damage to the brain from traumatic brain injury is divided into primary and secondary injuries. Primary injuries, such as hematomas and traumatic axonal injury, occur as a direct result of the trauma itself. Secondary injuries, which develop minutes to days after the primary trauma, include bimolecular and cellular changes that occur after the primary injury. Molecular and cellular changes lead to alterations in cell function and propagation of injury through processes such as depolarization, excitotoxicity, disruption of calcium homeostasis, free-radical generation, blood-brain barrier disruption, ischemic injury, edema formation, and intracranial hypertension (30; 39).
Traumatic intracerebral hemorrhage is often associated with increased intracranial pressure, ischemia, oxidative damage, vasogenic edema, and cytotoxic edema. These processes produce mitochondrial dysfunctions and, subsequently, lead to neuronal death. Heme-toxicity, iron-toxicity, and activation of coagulation are some of the key mechanisms in the pathogenesis of intracerebral hemorrhage. Coagulopathy after traumatic brain injury includes hypercoagulable and hypocoagulable states that can lead to secondary injury by either microthrombosis or the further progression of hemorrhagic brain lesions. The exact mechanisms responsible for coagulopathies are poorly understood. Multiple hypotheses have been proposed to explain this phenomenon, including the release of tissue factor, disseminated intravascular coagulation, hyperfibrinolysis, hypoperfusion with protein C activation, and platelet dysfunction (43).
Secondary hemorrhages of the brainstem in traumatic brain injury occur at a later stage as a result of descending transtentorial herniation. These are known as Duret hemorrhages. Duret hemorrhages are delayed, secondary brainstem hemorrhages. They occur in patients with rapidly evolving descending transtentorial herniation. Diagnosis is made on CT of the brain (66).
Progression of hemorrhagic lesion. An increase in the hematoma volume in traumatic intracerebral hemorrhage adversely affects prognosis. When head trauma results in a cerebral contusion, the hemorrhagic lesion often progresses during the first several hours after impact, either expanding or developing new, noncontiguous hemorrhagic lesions, a phenomenon termed hemorrhagic progression of a contusion (42). Intracerebral hematomas may also develop in a delayed fashion in a part of the brain that was previously seen to be radiographically normal, an entity known as the “delayed traumatic intracerebral hematoma.” It has been estimated that approximately 51% of the subjects demonstrate an increase in traumatic intracerebral hemorrhage volume. Most of the increase occurs early in the course of disease. Larger hematomas exhibit a greater amount of expansion (62). Expansion of hemorrhagic contusions is common after decompressive hemicraniectomy. The volume of hemorrhagic contusion expansion following hemicraniectomy is strongly associated with mortality and poor outcome. The severity of initial CT findings may predict the risk of contusion expansion following hemicraniectomy. In a study, CT scans of 40 consecutive patients with nonpenetrating traumatic brain injury who underwent decompressive hemicraniectomy, were analyzed. Hemorrhagic contusions of any size were present on the initial head CT scan in 48% of patients, but hemorrhagic contusions with a total volume of greater than 5 cc were present in only 10%. New or expanded hemorrhagic contusions of equal or greater than 5 cc were observed after hemicraniectomy in 58% of the patients (26). Another study analyzed the early CT signs of progressive hemorrhagic injury following acute traumatic brain injury and explored their clinical significance. A cohort of 630 patients with traumatic brain injury was evaluated, and there were 189 (30%) patients who suffered from progressive hemorrhagic injury. For patients with their first CT scan obtained as early as 2 hours post-injury, there were 116 (77.3%) cases who suffered from progressive hemorrhagic injury. The differences between patients with progressive hemorrhagic injury and those with nonprogressive hemorrhagic injury were frequency of skull fracture, subarachnoid hemorrhage, brain contusion, epidural hematoma, subdural hematoma, and multiple hematoma as well as the times from injury to the first CT scan. Logistic regression analysis showed that early CT scans showing epidural hematoma, subdural hematoma, subarachnoid hemorrhage, fracture, and brain contusion were predictors of progressive hemorrhagic injury (78). Another study noted that traumatic intracerebral hemorrhage progression occurred in 63% of patients (13). The factors that were significantly associated with traumatic intracerebral hemorrhage growth included multiple traumatic intracerebral hemorrhages, a lower initial volume, acute subdural hematoma, cisternal compression, older patient age, hypoxia, falls, and decompressive craniectomy. The contrast extravasation, on multidetector CT angiography, was also a strong and independent predictor of hematoma expansion, poor outcome, and increased risk of in-hospital mortality in patients with traumatic brain contusions (70; 03). A multivariate logistic regression analysis identified several factors like age, Injury Severity Score, blood alcohol level, initial scan volume, concomitant epidural hematoma, presence of subarachnoid hemorrhage, transfusion of platelets, and ventriculostomy as predictors of volumetric expansion of traumatic hematoma. Among these variables, traumatic hematoma volume proved to be the factor most predictive of hemorrhagic progression contusion (12). Wan and coworkers identified that APOE ε4, an elevated international normalized ratio, and higher glucose level (greater than or equal to 10 mmol/L) also act as independent risk factors for traumatic intracerebral hematoma expansion (85).
Coagulopathy triggered by traumatic brain injury leads to hematoma expansion and, subsequently, enhanced mortality (49). Bohm and colleagues noted a distinct pattern of coagulation factor abnormalities following traumatic brain injury (06). The activity of coagulation factors V, VIII, IX, and XIII and protein C and S levels dropped to around 15% to 20%. Plasminogen activity significantly decreased. In addition, D-dimer levels significantly increased. Coagulopathies also resulted in an increased international normalized ratio in many patients. Low-molecular-weight heparin may lead to hematoma expansion in approximately 6% of patients with traumatic brain injury, and half of these patients need a change in clinical management. Subdural hematoma, pupillary reflex abnormalities, and preexisting dementia predicted hematoma expansion following low-molecular-weight heparin initiation (76). Low serum calcium level was associated with hematoma expansion in patients with traumatic cerebral hemorrhage. It has been hypothesized that hypocalcemia triggers coagulopathy (92).
Approximately, 10% of patients with traumatic brain injury are likely to develop acute kidney injury, and many of them require kidney replacement therapy. Acute kidney injury adversely affects the outcome among patients with traumatic brain injury admitted to the intensive care unit. The precise reasons for kidney damage in patients with traumatic brain injury are not known. Circulating molecules that are released on tissue damage, inflammatory cytokines, catecholamine release, fluid resuscitation, vasoactive drugs, or hyperosmolar agents are all known to adversely affect kidney function in these patients. In addition, several other factors associated with trauma, like hypovolemic shock, rhabdomyolysis, renal trauma, blood transfusion, use of nephrotoxic agents, and abdominal compartment syndrome, can contribute to kidney injury. Proper type and dose of fluids and vasoactive drugs to optimize the hemodynamic state are key to reducing the risk of kidney damage (21).
Jha and colleagues identified genetic abnormities as a risk factor for hematoma expansion in patients with traumatic brain injury (37). Sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) cation channel gene abnormalities were associated with hematoma progression. A phase 2 trial of SUR1-TRPM4 inhibition in patients with traumatic brain injury is currently ongoing. Such trials may open avenues for targeted treatment in patients with traumatic brain injury.
About 1.3 million people die each year on the world's roads, and between 20 and 50 million people sustain nonfatal injuries. Road traffic injuries are the leading cause of death among young people 15 to 29 years of age (89). Corrigan and coworkers analyzed the estimates of the incidence and prevalence of traumatic brain injury (18). This review observed that each year 235,000 Americans are hospitalized for nonfatal traumatic brain injury, 1.1 million are treated in emergency departments, and 50,000 die. The northern Finland birth cohort found that 3.8% of the population had experienced at least one hospitalization due to traumatic brain injury by 35 years of age. The Christchurch New Zealand birth cohort found that by 25 years of age, 31.6% of the population had experienced at least one traumatic brain injury requiring medical attention. An estimated 43.3% of Americans have a residual disability 1 year after injury. The most recent estimate of the prevalence of United States civilian residents living with disability following hospitalization with traumatic brain injury is 3.2 million.
In the CRASH (Corticoid Randomization After Significant Head injury) trial, which included 10,008 adults with head injury and a GCS score of 14 or less, 56% of trial participants had at least one intracranial bleed (epidural, subdural, subarachnoid, or intraparenchymal) (22). In New Zealand, the total incidence of traumatic brain injury per 100,000 person-years was 790 cases; the incidence per 100,000 person-years of mild traumatic brain injury was 749 cases (709 to 790), and incidence of moderate to severe traumatic brain injury was 41 cases (31-51). Children, adolescents, and young adults constituted almost 70% of all cases (24).
Globally, falls and road injuries are the most important cause of nonfatal traumatic brain injury. The incidence of traumatic brain injury continues to increase because of increasing population density, population aging, and increasing use of motor vehicles, motorcycles, and bicycles. According to an estimate, the age-standardized prevalence of traumatic brain injury from 1990 to 2016 increased by 8.4%. In 2016, globally there were approximately 27.08 million new cases of traumatic brain injury, and the prevalence of traumatic brain injury was approximately 55.50 million (28).
For a bicycle or motorcycle rider, wearing a helmet is the most effective strategy for preventing injuries from a crash or fall. Use of helmets has been shown to reduce fatal and serious head injuries by between 20% and 45% among motorized 2-wheeler users. For automobile divers, prevention can be accomplished by advocating seat belts and air bags (88).
In addition to traumatic brain injury, several nontraumatic diseases can produce intracerebral hemorrhage. Spontaneous intracerebral hemorrhage most commonly results from hypertensive damage to blood vessel walls. Aneurysm, arteriovenous malformation, cerebral amyloid angiopathy, moyamoya disease, coagulopathies, and cerebral venous thrombosis are other commonly encountered causes of nontraumatic intracerebral hemorrhage. There are certain differences in traumatic intracerebral hemorrhage in comparison with spontaneous intracerebral hemorrhage. In traumatic intracerebral hemorrhage, various other types of hemorrhage (subdural, subarachnoid, intraparenchymal, or intraventricular) may be associated. In addition, traumatic intracerebral hemorrhage may be associated with larger and faster hemorrhage progression, more increase in intracranial pressure, and the presence of blood beneath the subarachnoid matter (47).
Although CT is the most valuable imaging modality in patients with acute traumatic brain injury, MRI has better diagnostic sensitivity for certain types of traumatic brain injuries that are not hemorrhagic, including cortical contusions and nonhemorrhagic traumatic axonal injuries. CT readily identifies the progression of hemorrhage, cerebral edema, herniation, and the development of hydrocephalus (39). For this reason, serial CT scans and close clinical monitoring of patients with traumatic brain injury are important. Intracerebral hemorrhage is best detected with gradient-echo (GRE) T2-weighted MR sequences because their magnetic susceptibility effects the blood (39).
Effective neurocritical care along with timely and appropriate neurosurgery can produce significant improvements in patient outcomes. Prehospital management of these patients should be initiated as early as possible with the objectives of preventing and limiting secondary brain injury while facilitating rapid transport to a medical facility. Key points in management include the assessment of oxygenation, blood pressure, and extended alteration in sensorium and the pupillary examination. Treatment strategies should be directed toward maintaining adequate brain oxygenation and perfusion and treating herniation (58). Initial neurocritical care goals of therapy depend largely on the GCS scores at the time of admission. Patients with GCS scores of greater than 8 and no emergent surgical indications may be observed in the intensive care unit without the placement of an intracranial pressure monitoring device, as the neurologic exam can be readily followed. Coagulopathies and electrolyte disorders should be corrected; specifically, pCO2, and sodium should be in the normal range unless the patient has increased intracranial pressure. Normothermia and normoglycemia should be maintained.
Intracranial pressure is important in traumatic brain injury because of its effect on cerebral perfusion pressure and reflection of local mass effect and impending herniation. The goal of intracranial pressure treatment is the maintenance of adequate cerebral perfusion pressure and the reduction of the likelihood of herniation. Sustained intracranial pressure greater than 25 mmHg portends higher mortality or poor neurologic outcome; therefore, intracranial pressure treatment generally starts between 20 and 25 mmHg (08). The numerical threshold should not be the only determinant; clinical examination and imaging data should also be used to establish the clinical intracranial pressure threshold in any patient. Patients can herniate with intracranial pressure lower than 20 mmHg, depending on the location of the mass lesion.
The appropriate cerebral perfusion pressure threshold has not been rigorously prospectively validated (08). In general, cerebral perfusion pressure higher than 70 mmHg is used as a target in adult patients, given the likelihood that it is beneficial to the neurologic outcome and carries a relatively low risk. Continuous display of cerebral perfusion pressure in the intensive care unit setting is associated with better neurologic outcomes in traumatic brain injury, possibly by increasing the chance of nurse or clinician intervention for cerebral perfusion pressure below goal (40). Data have become available suggesting that a cerebral perfusion pressure goal lower than 70 mmHg may be appropriate in adults, but more research is necessary before the change can be recommended (63). In children, data on proper cerebral perfusion pressure goals are sparse, but cerebral perfusion pressure higher than 40 mmHg is probably reasonable (01).
Cerebral perfusion pressure is related to the mean arterial pressure and intracranial pressure, as illustrated by the following equation: CPP = MAP-ICP. Thus, cerebral perfusion pressure can be augmented not only by lowering the intracranial pressure but also by increasing the mean arterial pressure. The risks associated with augmenting cerebral perfusion pressure by elevating mean arterial pressure (by increasing intravascular volume or pharmacologically) include worsening cerebral edema, heart failure, arrhythmias, pulmonary congestion, and acute respiratory distress syndrome.
The following are suggested means for medically controlling intracranial pressure (05; 82).
Avoidance of shivering and agitation. Short-acting sedating agents should be used as needed. Paralysis should be avoided as it prevents the evaluation of the neurologic exam. Fever should be controlled using pharmacologic and other cooling means, including cooling blankets, gastric lavage, or central venous cooling systems.
Maintenance of cerebral venous outflow. The head should be midline and elevated at 30 degrees. Tight tape across the neck, internal jugular venous catheters, or endotracheal tube- or tracheostomy-securing devices that may potentially compress the jugular venous system should not be used.
Hyperventilation. The contents of the rigid skull include the brain, CSF, and venous and arterial blood. An increase in these components will increase intracranial pressure, eventually causing brain herniation through the path of least resistance, usually the foramen magnum. Hyperventilation decreases intracranial pressure by vasoconstricting and, thus, attenuating the volume of the cerebral vascular compartment. The goal pCO2 is 25 to 30 mmHg. Hyperventilation is one of the quickest means of controlling intracranial pressure and should only be used in the short term for acute intracranial pressure elevations. Prophylactic use correlates with a worse neurologic outcome (08). In addition, aggressive hyperventilation to pCO2 below the above goal may cause severe vasoconstriction and decreased cerebral blood flow.
Osmotic therapy. Osmotic therapy is the mainstay of intracranial pressure management. The agent used most frequently is mannitol. Mannitol can be administered through peripheral intravenous lines through an in-line filter at a dose of 1 gm/kg. The goal serum osmolality is 300 to 320 mOsm/L (08). Alternatively, hypertonic saline (2 mL/kg body weight of 7.5% saline, approximately 480 mOsm/70 kg body weight) can be used (82). Hypertonic saline is preferred after brain injury because it is not associated with hypervolemia. The available literature suggests that hypertonic saline solution with sodium chloride concentration greater than the physiologic 0.9% can be useful in controlling intracranial pressure and as a resuscitative agent in patients with traumatic brain injury (27). Several studies have compared the use of hypertonic saline and mannitol in brain-injured populations. These studies have shown that not only is hypertonic saline a safe drug, but it also is more effective in reducing intracranial pressure. In one study, authors observed that in patients with severe traumatic brain injury and elevated intracranial pressure refractory to previous mannitol treatment, 7.5% hypertonic saline is associated with a significant increase of brain oxygenation as well as improved cerebral and systemic hemodynamics (64). Hypertonic saline infusion in hypotensive traumatic brain injury reduces intracranial pressure and raises cerebral perfusion pressure, and brain tissue oxygenation tends to improve after hypertonic saline infusion (67). A Cochrane review suggested that mannitol may have a beneficial effect on mortality when compared to pentobarbital but may have a detrimental effect when compared to hypertonic saline (84). Even highly concentrated hypertonic saline (such as 23.4%) provides an effective small-volume solution with low cost with an over 50% reduction effect in situations of raised intracranial pressure crises. Side effects reported are also minor (45).
Traumatic brain injury is often associated with hemorrhage and hypotension, which can contribute significantly to morbidity and mortality. Various types of resuscitation fluid have been evaluated in these patients, such as fresh blood, normal saline, hypertonic saline, and albumin fluid. Hypertonic saline solution with sodium chloride concentration greater than the physiologic 0.9% is considered more useful in controlling increased intracranial pressure. A large-scale randomized controlled trial, “the Saline versus Albumin Fluid Evaluation (SAFE) study,” demonstrated that albumin and saline were clinically equivalent treatments for intravascular volume resuscitation in critically ill patients. However, in the traumatic brain injury subgroup of patients, it was associated with a trend toward increased mortality (25; 59). In a post hoc study of these critically ill patients in the SAFE study, fluid resuscitation with albumin was found to be associated with higher mortality rates in comparison to resuscitation with saline (72). Authors in this analysis followed 460 patients, of whom 231 (50.2%) received albumin and 229 (49.8%) received saline. At 24 months, 71 of 214 patients in the albumin group (33.2%) had died, as compared with 42 of 206 in the saline group (20.4%). Among patients with severe brain injury, 61 of 146 patients in the albumin group (41.8%) died, as compared with 32 of 144 in the saline group (22.2%); among patients with GCS scores of 9 to 12, death occurred in 8 of 50 patients in the albumin group (16%) and 8 of 37 in the saline group (21.6%).
Hypothermia. Hypothermia is a widely used method by which the body can protect the brain in patients with severe traumatic brain injury admitted to the emergency department and intensive care unit. Rapid cooling to 33°C for 24 hours is considered the standard of care for minimizing neurologic injury. Mild-to-moderate hypothermia (33°C to 35°C) can be used as an effective form of therapy for patients with elevated intracranial pressure (16). Patients with refractory elevated intracranial pressure may respond better to hypothermia therapy than those with diffuse injury. Randomized controlled trials are underway to evaluate the impact of hypothermia on neurologic outcomes in patients with severe traumatic brain injury (80).
A multicentric, randomized controlled trial assessed the safety and efficacy of long-term hypothermia (34-35 °C for 5 days) in adults versus normothermia (34). Hypothermia did not decrease the risk of mortality. Some marginal benefit of hypothermia was noted in patients who had initial intracranial pressure equal to or greater than 30 mm Hg.
Corticosteroids. There is no evidence that steroids decrease intracranial pressure or improve outcomes in traumatic brain injury. Steroids can worsen hyperglycemia and cause immunosuppression, which can adversely affect outcomes. A Cochrane review found increased mortality and disability with steroids and, therefore, offered no support for the routine use of steroids in traumatic brain injury (02).
Correction of traumatic coagulopathy. The greatest risk factor for progression of a hemorrhagic lesion was coagulopathy within the first 24 hours after traumatic brain injury. The highest risk was in those with elevated PTT, with a 100% progression rate. Thrombocytopenia (platelets, 100,000) was associated with a 90% progression rate, and increased prothrombin time was associated with a 75% progression rate. Patients taking antiplatelet and anticoagulant drugs are at greater risk of intracranial hemorrhage following traumatic brain injury and treatment should include immediate withdrawal of anticoagulant and antiplatelet drugs (48).
In a prospective, randomized, placebo-controlled, dose-escalation study, authors evaluated the safety and effectiveness of rFVIIa to prevent expansion of traumatic intracerebral hemorrhage. Patients were enrolled if they had traumatic intracerebral hemorrhage lesions of at least 2 ml on a baseline CT scan obtained within 6 hours of injury. Recombinant factor VIIa or placebo was administered within 2.5 hours of the baseline CT scan but no later than 7 hours after injury. Five escalating dose tiers were tried (40, 80, 120, 160, and 200 microg/kg). No significant differences were detected in mortality rate or number and type of adverse events among various treatment groups (61). In addition, the use of rFVIIa is associated with decreased transfusion of packed red blood cells in patients with traumatic brain injury undergoing emergent craniotomy (10). A platelet count lower than 100,000/mm3 is associated with a 9-fold adjusted risk of death, and a platelet count lower than 175,000/mm3 is a significant predictor of intracerebral hematoma progression (73). High platelet ratio was associated with improved survival in massively transfused (high or low ratios of platelets or plasma to red blood cell units) trauma patients with and without severe brain injury (09).
Seizure prophylaxis. The American Academy of Neurology recommends seizure prophylaxis to reduce the incidence of early (within the first 7 days) seizures (15). Seizure prophylaxis does not affect the incidence of late posttraumatic seizures. Thus, the continuation of prophylactic antiepileptic agents after the first 7 days in patients with severe traumatic brain injury is patient- and situation-specific (15). Current standard therapy for seizure prophylaxis in neurosurgical patients involves the use of phenytoin. However, the drug levetiracetam is emerging as a new treatment choice. A meta-analysis revealed that levetiracetam and phenytoin demonstrate equal efficacy in seizure prevention after brain injury (91).
Control of blood glucose. Hyperglycemia may have harmful effects on cerebral function. Intensive blood glucose control dramatically reduces morbidity and mortality in a heterogeneous population of intensive care unit patients (82). These results can probably be extrapolated to critically ill neurologic patients, including those with traumatic brain injury and intracerebral hemorrhage.
Nutrition. Patients with traumatic brain injury have increased energy expenditure. Early nutritional replacement to 140% of energy expenditure in nonparalyzed patients is recommended (08).
Fever. Hyperpyrexia (core temperature of higher than 38°C) should be aggressively treated as it increases cellular metabolism and vasodilatation. Antipyretic drugs and cooling blankets may be used to effect cooling. Paracetamol, a frequently employed antipyretic agent in patients with traumatic brain injury, may cause hypotension. Paracetamol-induced hypotension must be recognized and treated promptly to prevent further damage to an already injured brain (68).
Tranexamic acid. Tranexamic acid reduces bleeding by inhibiting the breakdown of fibrin. A published meta-analysis revealed that tranexamic acid statistically significantly reduces the intracerebral hematoma progression with a nonstatistically significant improvement of clinical outcomes in patients with traumatic brain injury (44). It was concluded by the authors of this meta-analysis that more evidence is needed to support its routine use in traumatic brain injury. However, data from 651 patients revealed that on logistic regression analysis, low Glasgow Coma Scale on admission, renal impairment, and warfarin were identified as independent factors associated with higher mortality. Tranexamic acid emerged as an independent factor associated with lower mortality (14).
Amantadine. Amantadine hydrochloride is a commonly prescribed drug in patients with prolonged disorders of consciousness after traumatic brain injury. A placebo-controlled trial of amantadine for severe traumatic brain injury has suggested that amantadine may promote functional recovery (29).
Barbiturates. There is no evidence that barbiturate therapy in patients with acute severe head injury improves outcomes; instead, barbiturate therapy results in a fall in blood pressure in some patients (69).
Deferoxamine mesylate. In a nonrandomized trial, deferoxamine mesylate, an iron-chelating agent, was found to accelerate hematoma absorption and inhibit edema after traumatic intracerebral hemorrhage (90).
Intracranial pressure monitoring. One study noted that in patients with severe traumatic brain injury treated for intracranial hypertension, the use of an intracranial pressure monitor is associated with significantly lower mortality when compared with patients treated without an intracranial pressure monitor (23). In this study of 2134 patients with severe traumatic brain injury (GCS lower than 9), 1446 patients were treated with intracranial pressure-lowering therapies. Of those, 1202 had an intracranial pressure monitor inserted, and 244 were treated without monitoring. Age, initial GCS score, hypotension, and CT findings were associated with 2-week mortality. In addition, patients of all ages treated with an intracranial pressure monitor in place had lower mortality at 2 weeks than those treated without an intracranial pressure monitor, after adjusting for parameters that independently affect mortality (23). In another prospective, observational study, the overall in-hospital mortality was significantly higher in patients who did not undergo intracranial pressure monitoring (53.9% vs. 32.7%) (74). Similarly, mortality due to brain herniation was higher for the group not undergoing intracranial pressure monitoring (21.7% vs. 12.9%). Earlier, The Brain Trauma Foundation guidelines recommended that patients with a GCS score of less than 8 and an abnormal CT scan should undergo intracranial pressure monitoring (08). Patients with a GCS of less than 8 and a normal head CT should undergo intracranial pressure monitoring if two or more of the following are present on admission: age greater than 40 years, systolic blood pressure lower than 90 mmHg, or motor posturing (08). Intraventricular catheter placement remains the standard method of monitoring intracranial pressure.
Hematoma evacuation. The specific indications for craniotomy and surgical evacuation in patients with contusion or hematoma have not been established. Generally, a combination of clinical and radiologic factors is felt to be important, including hemorrhage location and volume, the extent of mass effect on CT (cisternal effacement or midline shift), GCS score, intracranial pressure, and neurologic deterioration. Patients with contusions or hematoma and progressive neurologic decline, medically refractory increased intracranial pressure, or radiographic evidence of mass effect tend to have poor outcomes without surgical treatment (39). During surgery, resection of the adjacent contused brain and removal of extracerebral hemorrhages are often necessary, and a large craniectomy may be preferable. In a study of traumatic brain-injured patients with increased intracranial pressure, due mostly to contusions and hemorrhages, a standard trauma craniectomy resulted in better functional outcomes than a limited craniectomy (38). Bedside catheter evacuation has proven to be a quick and easy-to-apply technique to evacuate predominantly isolated traumatic supratentorial hemorrhage (20).
A published multi-center, patient-randomized, parallel-group trial suggested that early surgery (hematoma evacuation within 12 hours of randomization) led to significantly fewer deaths. A total of 170 patients were randomized worldwide. Of 82 patients randomized to early surgery, 30 (37%) had an unfavorable outcome. Of 85 patients randomized to initial conservative treatment, 40 (47%) had an unfavorable outcome, with an absolute benefit of 10.5%. There were fewer deaths in the surgical treatment group (33% vs. 15%). The trial was prematurely terminated because of a failure to recruit sufficient patients from the United Kingdom (56).
Decompressive craniectomy. Decompressive craniectomy is the removal of skull bone segments to reduce intracranial pressure. Decompressive craniectomy is a useful method for the treatment of traumatic brain injuries with intracranial hypertension resistant to medical treatment. Several studies have shown that decompressive craniectomy can consistently reduce intracranial pressure, and patients can achieve a good long-term functional recovery. Decompressive craniectomy can also result in increased cerebral perfusion pressure in patients with traumatic brain injury and refractory elevated intracranial pressure (07). A group of surgeons assessed the safety and feasibility of decompressive craniectomy and duraplasty versus traditional craniotomy with hematoma evacuation as the primary surgical procedure in 54 patients with a severe head injury. In this study, 16 patients underwent traditional craniotomy with hematoma evacuation, and the remaining 38 patients underwent craniectomy. Mortality, reoperation rate, Glasgow Outcome Scale-Extended scores, and length of hospital stay were compared. Mortality (13.2% vs. 25.0%) and reoperation rate (7.9% vs. 37.5%) were significantly lower in the craniectomy group, whereas the length of stay in both the acute care setting and the rehabilitation phase were similar (33). A randomized controlled study assessed the value of decompressive craniectomy for improving the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure. An early bifronto-temporo-parietal decompressive craniectomy decreased intracranial pressure and the length of stay in the intensive care unit but was associated with more unfavorable outcomes; however, the rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%) (17). Postoperative care involves aggressive management of intracranial hypertension, correction of metabolic abnormalities, and management of infectious complications. A randomized trial observed that at 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, and lower severe disability and upper severe disability than medical care. However, the rates of moderate disability and good recovery were similar in the two groups (36). Bilateral fixed dilated pupils generally indicate a grave prognosis. Aggressive and early decompressive craniectomy in some of these patients improves the chances of a favorable outcome (77).
The incidence of intracerebral hemorrhage does not appear to be influenced by pregnancy. However, increased plasma volume, physiologic anemia, decreased respiratory functional residual capacity, and hypotension may exacerbate associated cerebral edema and ischemia in pregnant traumatic brain injury patients with intracerebral hemorrhage. Severe traumatic brain injury in pregnant women can result in devastating outcomes for both the mother and the fetus. However, a study revealed that pregnant patients with moderate to severe traumatic brain injury showed no statistically significant difference in mortality compared with their nonpregnant counterparts (04). A group of authors presented a case of a young woman 21 weeks pregnant with a severe traumatic brain injury (GCS score 3) in whom safe medical intracranial pressure management became ineffective. A decompressive craniectomy was performed to obviate the need for aggressive medical management of elevated intracranial pressure using fetal-toxic medications, and, thus, providing the fetus the best chance of continued in utero development until a viable gestational age was reached (86).
In a patient with traumatic brain injury, an anesthetist is frequently involved in initial stabilization, airway management, intra-operative mechanical ventilation, hemodynamic support, administration of blood and blood products, positioning, and providing appropriate anesthetic techniques during surgery.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Ravindra Kumar Garg MD
Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.See Profile
Steven R Levine MD
Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.See Profile
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