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Numerous guidelines based on critical evaluation of the pertinent literature have been created and disseminated. Best-known among these is the Guidelines for the Management of Severe Traumatic Brain Injury.24 Subsequent companion guidelines have been created for prehospital management of TBI,25 pediatric TBI,26 surgical management of TBI,18 penetrating TBI,27 and field management of combat-related head trauma.28 The reader is referred to these documents for further background about creation of treatment recommendations.
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Interventions for TBI may be initiated in series or in parallel. Some treatments can be started in the field. Others may be added as more advanced equipment or qualified personnel become available in the emergency department, operating room, or intensive care unit.
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Basic measures should be implemented in all TBI patients undergoing monitoring. These patients often require a setting with the capability for careful assessment of vital signs, fluid balance, and neurological status. Initial goals are normothermia and euvolemia, with administration of isotonic fluids (ie, 0.9% NaCl + 20 mEq KCl/L). Many practitioners avoid dextrose-containing intravenous fluids because of concerns about exacerbating the deleterious effects of potential ischemia and cerebral edema. Patients usually receive prophylaxis against Cushing’s (stress) gastric ulcers, which are frequently seen in patients with severe TBI and elevated ICP. The head of bed is usually elevated to 30°C, the neck should be kept midline, and the fit of the patient’s cervical collar and endotracheal tube stabilizer should be assessed to prevent compression of the jugular veins. Most important is frequent assessment of the patient’s condition, evaluation of responses to therapies, and willingness of providers to modify care strategies in a timely manner to help ensure optimal patient outcome.
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Another basic measure is maintenance of hemoglobin concentration (Hgb) above a specified minimum level. Historically, this level has been commonly set at 10 g/dL, which was felt to represent the optimal trade-off between blood viscosity and oxygen-carrying capacity. Numerous reports have questioned the benefit of such a high threshold, and most practitioners came to accept a Hgb as low as 7 g/dL. The question remained whether the exquisite sensitivity of the injured brain to hypoxia made TBI patients a special subgroup in which the traditional higher Hgb level was still required. A prospective trial failed to confirm this hypothesis,29 leading many clinicians to accept the lower Hgb of 7 g/dL as the minimum acceptable value even in TBI patients—assuming, of course, that there exists no other indication to target a higher goal.
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Over the past two decades, it has become common to advocate for systematic, evidence-based treatment of TBI patients by dedicated neurosurgeons, neurologists, intensivists, surgical trauma and critical care teams, nurses, and allied health care workers. Several publications claim to demonstrate improved outcomes as a direct result of the arrival of an intensivist to a specific ICU. More likely, however, is that the very process of standardizing care and eliminating unwarranted excessive variation in care was the real driver behind improvement in outcomes compared to historical controls. The exact background or specialty of the clinician driving that standardization is less important.
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Blood Pressure and Oxygenation
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Medical practitioners cannot undo the events surrounding a primary brain injury. However, every effort must be made to mitigate or eliminate secondary injuries, which may be even more devastating than the primary injury. Prior to, or during, transport to a hospital setting, a significant portion of patients may experience periods of hypoxemia or hypotension.30 These are among the most common and most deleterious secondary insults. Occurrence of a single episode of hypoxemia or hypotension is an independent predictor of worse outcome after TBI.31,32
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Oxygen saturation and blood pressure monitoring should start in the field and continue in the hospital setting. The goal is to prevent hypoxemia and hypotension, or if they occur, to identify and treat them as rapidly as possible. Crystalloid, colloid, blood products, or even intravenous pressors may be required to avoid hypotension.24 Empiric oxygen administration should start as early as possible. Endotracheal intubation may be required. Of interest, several studies have demonstrated worse outcomes in TBI patients who are intubated in the field. One possible reason is that the frequently chaotic prehospital environments surrounding TBI patients and the relative inexperience of some first responders in performing difficult intubations may combine to cause prolonged hypoxemia during attempts at endotracheal intubation. Another factor may be unintentional hyperventilation of intubated patients (and consequent cerebral vasoconstriction and reduction in cerebral blood flow [CBF]) from excessively rapid and forceful squeezing of the bag/valve system if patients are manually ventilated. Consequently, for many TBI patients, careful oxygenation and ventilation via a face mask may be preferred over prehospital endotracheal intubation.
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TBI patients usually exhibit an increase in basal energy expenditure (BEE). Patients who are sedated and paralyzed may show BEE increases to 120–130% of baseline. Comatose patients (GCS score ≤8) with isolated TBI may have BEE approximately 140% of baseline (range 120–250%).33 Mortality is reduced in patients who receive full caloric replacement by 1 week postinjury.34 At least 15% of calories should be supplied as protein. Since it may take 2 or 3 days to ramp up feedings to desired levels, nutritional replacement should begin as soon after injury as possible.
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Enteral feeding is preferred over parenteral nutrition because it enhances immunocompetence and reduces risk profile.35 If a patient has diminished gastric motility, a jejunal feeding tube can be placed since patients with severe TBI can tolerate early jejunal feeding even in the presence of gastric dysfunction and limited small bowel activity. Total parenteral nutrition can be considered if enteral feeding is not possible or if higher nitrogen intake is required.
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Post-traumatic seizures (PTS) are potentially harmful in TBI patients for many reasons, including increased ICP and elevated metabolic demand that may exacerbate the effects of ischemia. TBI patients at increased risk for PTS include those with GCS score below 10 and those with depressed skull fractures, cortical contusions or intracranial hemorrhage, and penetrating injury or seizure within 24 hours of brain injury. Anticonvulsants have been shown to effectively reduce the risk of PTS during the first 8 days of injury, but not later.24,36. Despite absence of high-quality studies showing equivalent efficacy for early PTS prevention, many centers are now using levetiracetam because of ease of administration and a perceived lower rate of adverse reactions.
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Trauma patients may develop infections from grossly contaminated wounds, from immunosuppression following the stress of severe trauma or other causes, or from such necessary interventions as open surgical procedures, intubation for mechanical ventilation, and use of invasive monitoring equipment, as well as other causes. In general, antibiotic coverage should be targeted toward specific organisms and stopped as soon as possible to minimize the risk of development of drug-resistant strains of bacteria or alterations in normal floral patterns.
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Perioperative antibiotics are generally recommended only for a single dose preoperatively or at most for the first 24 hours after surgery. This same principle applies to insertion of external ventricular drains (EVDs). Maintaining patients on prophylactic antibiotics for the entire period that an EVD is in place is not recommended. Routine flushing or exchange of ventricular catheters is also not recommended.24 Use of antibiotic-impregnated or coated ventriculostomy catheters may result in an overall decrease in infection rate.37
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Most critically ill trauma patients have decreased levels of plasma antithrombin (AT) activity. TBI patients, however, tend to have increased rates of coagulopathy, with supranormal AT activity that can progress to disseminated intravascular coagulation and fibrinolysis (DICF), as well as expansion of existing cerebral contusions and delayed development of additional hemorrhages.38 Coagulopathy may be especially severe after penetrating brain injury.
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For all trauma patients, medical history and review of systems should specifically inquire about history of excessive bleeding or clot formation, use of specific antiplatelet or anticoagulant medication (such as aspirin, warfarin, or low-molecular-weight heparin), medications that have antiplatelet compounds as a component, and medical disorders that pose an increased risk of bleeding. Measurements of prothrombin time, activated partial thromboplastin time, international normalized ratio, platelet count, and possibly bleeding time, platelet function assay, or thromboelastography are often helpful in guiding the management of hemorrhage.
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Effects of warfarin anticoagulation may be reversed by administration of vitamin K, fresh frozen plasma, or prothrombin complex concentrate; effects of heparin may be reversed with protamine sulfate; and thrombocytopenia or platelet dysfunction may be treated with donor platelet transfusion. Unfortunately, these interventions require time for preparation and administration, which may limit their usefulness in patients with life-threatening intracranial hemorrhage and rising ICP.
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Recombinant activated coagulation factor VII (rFVIIa) rapidly forms a complex with tissue factor to produce thrombin and, separately, converts factor X to its active form, factor Xa, resulting in a “thrombin burst” at the site of tissue damage. It is FDA-approved for use in hemophiliacs and in patients with antibodies to factor VIII or IX, and it has been studied off-label in intracerebral hemorrhage and TBI patients requiring rapid craniotomy in the face of coagulopathy. Its effects on neurological outcome and mortality, as well as its cost burden, are currently under investigation and have not been fully defined.39
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Deep Venous Thrombosis
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Trauma patients in general, and TBI patients in particular, are at risk for venous thromboembolic complications like deep venous thrombosis (DVT) and pulmonary embolus (PE). Risk factors for DVT and PE include stroke or spinal cord injury, prolonged surgery or prolonged bed rest, SAH or TBI causing altered coagulation or dehydration, and increased blood viscosity from cerebral salt wasting and treatment of cerebral edema.40 Low-risk, prophylactic measures against DVT include passive range of motion, early ambulation, rotating beds, and electrical stimulation of calf muscles. If DVTs are not already present, pneumatic compression boots (PCBs) and sequential compression devices may be safely used and can reduce the incidence of DVT and PE.
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Pharmacologic anticoagulation can increase the effectiveness of DVT prophylaxis, but with the risk of additional hemorrhagic complications. Low-molecular-weight heparins have a higher ratio of anti-factor Xa to anti-factor IIa activity versus unfractionated heparin, have greater bioavailability after subcutaneous injection, and have more predictability in terms of plasma levels. They can be added to use of PCBs without significantly increased risk of hemorrhage,41 and their use has been recommended in postoperative neurosurgery patients.24 Because there are no universally accepted recommendations for the method and timing of postoperative anticoagulation, this decision should be tailored individually to each patient. One study reported no increased incidence of hemorrhagic complications if full anticoagulation was resumed 3 days after craniotomy.21
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Cerebral Metabolism and Pathophysiology
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Intracranial Pressure
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To understand the rationale behind ICP management, one must start with understanding how pressure in the intracranial space differs from that in other body compartments. If a patient sustains an injury to an arm or leg, the surrounding soft tissue may expand outwards from the humerus or femur. By contrast, in cases of TBI, the brain is unable to expand because it is confined within the rigid skull.
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The modified Monro–Kellie hypothesis assumes that the skull is completely inelastic, that the ventricular space is confluent, and that pressures are equally and readily transmitted throughout the intracranial space. This hypothesis states that there is a balance between the brain, intravascular blood, and CSF contained in the intracranial space. Increases in the volume of one constituent (eg, cerebral edema, hyperemia) or addition of new components (eg, tumor, hemorrhage) mandate compensatory decreases in other constituents in order to maintain constant ICP.
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Mildly increased localized pressure in part of the brain may cause neurological dysfunction confined to the affected area. More severe increases in pressure may cause local tissue compression as well as shift of intracranial structures, subfalcine and transtentorial herniation, and both local and distant neurological dysfunction. In the most severe cases, transtentorial herniation causes compression at the level of the brainstem, with direct tissue damage to the midbrain, occlusion of arteries, infarction, and death.
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Normal ICP varies by age. Normal values probably lie below 10–15 mm Hg in adults and older children and in the range of 3–7 mm Hg in younger children, 1.5–6 mm Hg in infants, and possibly even at subatmospheric levels in neonates. Intracranial hypertension (IC-HTN) has been reported in 13% of trauma patients with a normal head CT, 60% of patients with an abnormal head CT (demonstrating hemorrhage, contusion, edema, herniation, or compressed basal cisterns), and ~60% of patients with a normal head CT plus two or more of the following criteria: age > 40 years, SBP > 90 mm Hg, and unilateral or bilateral abnormal motor posturing (flexing or extending to a noxious stimulus).42 Therefore, ICP monitoring is often recommended in patients with severe TBI (GCS score of 3–8) and an abnormal CT scan or with severe TBI, a normal CT scan, and two or more of the select criteria listed earlier. ICP monitoring may also be considered in patients in whom a reliable neurological examination cannot be performed because of sedatives, paralytics, or general anesthesia required for other reasons, such as difficult ventilator management, extreme agitation, or need for non-neurological surgery.
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Higher mortality and worse outcomes have been described in patients with ICP persistently above 20 mm Hg.43 Therefore, most centers consider ICP to be elevated when it exceeds 20–25 mm Hg, and ICP reduction measures are often recommended to bring values below this range.24
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The most accurate, reliable, and lowest-cost ICP monitoring technology is the fluid-coupled ventriculostomy catheter, or EVD, connected to an external strain gauge.24 Another advantage of EVDs is that CSF drainage can be performed as a therapeutic measure to control ICP. Parenchymal ICP monitors based on fiberoptics or miniaturized strain gauge transduction require less tissue penetration and do not require the ability to localize the ventricle. They are roughly as accurate as EVDs but carry a higher cost. They cannot be recalibrated in situ and may be subject to measurement drift, although this is currently not as significant a concern as it was with earlier versions of these monitors. Parenchymal monitors do not allow for therapeutic drainage of CSF. Placement of these devices in the subdural or epidural spaces renders their data less accurate.
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Of interest, a recent prospective trial found no difference in outcome between severe TBI patients managed with ICP monitoring and patients in whom elevated ICP was inferred and treated based on clinical and imaging findings.44 This trial is often incorrectly interpreted as indicating that ICP monitoring is of no benefit in severe TBI patients. A more appropriate interpretation is that ICP was monitored, and elevated ICP was treated, in both groups, with the difference being invasive monitoring versus noninvasive monitoring based on examination and imaging. This trial did not compare a monitored to an unmonitored group.
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Cerebral Perfusion Pressure
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The recently injured brain is highly vulnerable to ischemia both regionally, near contused or otherwise damaged tissue, and also globally, from more diffuse impairment of CBF regulation. In addition, brief periods of hypotension or hypoxia that might be well-tolerated by an uninjured brain may have significant deleterious consequences in a brain that has just received a traumatic insult. Neurological dysfunction may result from direct disruption of tissue or from impaired metabolism of a structurally intact brain. For neural tissue to function normally, CBF must be adequate to meet metabolic demand. CBF depends on cerebral perfusion pressure (CPP), calculated by subtracting ICP from mean arterial pressure (MAP – ICP). Studies have shown that the injured adult brain is more susceptible to ischemia if the CPP trends below 50 mm Hg.45 Children have been demonstrated to show improved survival when CPP is sustained above 40 mm Hg.46 In adults, artificially maintaining CPP above 70 mm Hg results in unacceptably higher rates of adult respiratory distress syndrome without significant improvement in functional outcome.47,48 Collectively, these data suggest that there exists a “floor” below which CPP should not drop (the exact value varies with age), but above this floor, there is no benefit from driving CPP to higher levels. There is likely an age-dependent continuum of optimal CPP values. Current recommendations support avoidance of CPP <40 mm Hg in children, <50 mm Hg in adults, and artificial elevation >70 mm Hg in either population.24
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Monitoring of Cerebral Blood Flow and Metabolism
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CT perfusion scanning can measure relative cerebral blood volume, CBF, and mean transit time after injection of iodinated contrast. It has been used extensively in stroke patients and has been investigated in TBI patients to determine the potential viability of contusional and pericontusional tissue, and also to help guide judicious use of other therapeutic strategies, such as hyperventilation (HV).
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Intermittent measurements of cerebral arteriovenous difference in oxygen content or of oxygen saturation in the jugular bulb (SjvO2) can also be used to assess global cerebral perfusion. Normal venous saturation of oxygen is approximately 50–69%. The occurrence of multiple episodes of venous desaturation (<50%) or of a sustained and profound single such episode is associated with poor outcome.49 In addition, excessively high SjvO2 (>75%) is associated with poor outcome, perhaps because such measurements reflect cerebral hyperemia or possibly the existence of significant areas of infarcted tissue which will not extract oxygen.
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More focal techniques to measure CBF include transcranial Doppler ultrasonography and parenchymal CBF monitoring. Thermal diffusion probes provide local CBF measurements based on the temperature difference between two points on a probe, the relative conductive properties of cerebral tissue, and convective properties of blood flow.
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Cerebral microdialysis requires intraparenchymal placement of a fine catheter. Specific chemicals diffuse into dialysate through a semipermeable membrane at or near the tip of these catheters. The dialysate is collected and subsequently analyzed. Neurochemical changes indicative of primary and secondary brain injury may be detected. TBI patients with poor clinical outcome have been shown to have elevated levels of specific neurotransmitters, as well as elevated lactate/pyruvate ratios and abnormal lactate and glutamate levels.
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Brain tissue oxygen tension (PbtO2) monitoring allows direct measurement of oxygen level in a specific region of the brain. In most cases, PbtO2 mirrors oxygen delivery, but it may also increase if the tissue surrounding the catheter is infarcted and incapable of metabolizing oxygen. Normal PbtO2 has been reported as approximately 32 mm Hg. Patients with multiple or prolonged episodes of PbtO2 below 10–15 mm Hg have been shown to have increased morbidity and mortality.50 Probes are often placed in penumbral tissue that is thought to be “at risk” but still salvageable. Others prefer to place such probes in brain that appears “normal,” with the thought that monitors in this area provide data about global cerebral metabolism, as opposed to the local metabolic environment near a contusion or other visible lesion.
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Therapies are commonly targeted to keep SjvO2 above 50% and PbtO2 above 15 mm Hg or higher.24 A multicenter trial is currently testing the value of this approach. At the present time, SjvO2 and PbtO2 monitoring are best viewed as adjuncts to ICP and CPP monitoring.
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Management of Elevated ICP
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Analgesics and Sedatives
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TBI patients will likely have increased levels of stress, agitation, and discomfort. These may cause increases in sympathetic tone, temperature, and blood pressure and produced increased ICP, metabolic demand, and resistance to controlled ventilation.
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The medications used to treat pain and agitation and their doses must be carefully monitored and administered to achieve a balance between their beneficial effects in reducing pain and anxiety and their potentially adverse effects of hypotension, alteration or masking of the neurological examination, and rebound ICP elevation when they are discontinued. If heavy sedation or pharmacological paralysis is needed and a neurological examination becomes unobtainable, consideration should be given to placement of an ICP monitor.
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Short-acting agents are preferred in order to facilitate frequent neurological examinations. Continuous infusion is often used instead of bolus administration to avoid potential transient ICP increases between doses. Fentanyl and its derivatives (remifentanil and sufentanil) are used increasingly for both acute and longer-term analgesia. They are short-acting, reversible, and suitable for administration by continuous infusion.
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Midazolam and propofol are two commonly used sedatives. Midazolam is a short-acting benzodiazepine that is effective for sedation of the ventilated TBI patient. Propofol is a hypnotic anesthetic with rapid onset and a very short half-life that facilitates rapid neurological assessment. It should be limited in both concentration and duration to avoid propofol infusion syndrome.51 First described in children, and later in adults, this syndrome has generally been reported after use of excessively high doses or extensive durations of use of propofol. Features can include hyperkalemia, hepatomegaly, metabolic acidosis, rhabdomyolysis, renal failure, and death. Caution should be exercised if doses exceed 5 mg/kg/h or if duration of treatment exceeds 48 hours.
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While the exact mechanism of mannitol’s beneficial effects is unclear, two primary actions have been postulated. In the first few minutes, it produces immediate plasma expansion with reduced hematocrit and blood viscosity, improved rheology, and increased CBF and O2 delivery. This reduces ICP and is most notable in patients with CPP below 70 mm Hg.52,53 Over the next 15–30 minutes, and perhaps lasting 90 minutes to 6 hours, mannitol creates an osmotic gradient, with increased serum tonicity and withdrawal of edema fluid from the cerebral parenchyma.
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When given as a bolus, mannitol begins to reduce ICP after 1–5 minutes. This effect peaks at 20–60 minutes. For acute ICP reduction in cases of neurological worsening or herniation, an initial bolus of mannitol is often given at 1 g/kg, with subsequent administration at smaller doses and longer intervals, such as 0.25–0.5 g/kg every 6 hours. Mannitol opens the blood–brain barrier (BBB). It may cross the BBB itself, drawing water into the brain and transiently exacerbating vasogenic cerebral edema. Furosemide may also be used synergistically with mannitol to reduce cerebral edema through increased serum tonicity and reduced production of CSF.
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There has been concern that continuous mannitol infusions lead to elevated serum levels of mannitol, sequestering of mannitol within brain tissue, rebound shifts of water back into the brain, and worsening outcomes. It was thought that bolus administration reduced this effect and was more effective than continuous mannitol infusion for ICP reduction, with the added benefit of maximized rheologic increase in CBF. More recent investigations suggest that there are no good data to support this.54 The significant water shifts caused by mannitol suggest that it may be wise to replace fluids to maintain euvolemia.
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Acute renal tubular necrosis may be seen when mannitol is used in high doses in patients with preexisting renal disease or when other potentially nephrotoxic drugs are administered. Use of mannitol is often restricted when serum osmolality exceeds 320 mOsm/L.55 Urine output should be followed to help minimize the likelihood of hypotension and hypovolemia.
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Although TBI patients usually receive mannitol in conjunction with ICP monitoring, some clinicians employ high-level empiric dosing.25 No strong evidence supports empiric prehospital administration of mannitol to TBI patients,56 but in principle, mannitol may be of benefit in patients with signs of rapidly expanding mass lesions, such as decreasing level of consciousness with unilateral pupillary dilatation and contralateral hemiparesis. In such cases, mannitol may be used as a bridge toward definitive therapy, such as operative evacuation of mass lesions.
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As with mannitol, hypertonic saline (HTS) is thought to lower ICP through two mechanisms. First, hypernatremia produces an oncotic pressure gradient across the BBB and mobilizes water from brain tissue. Second, rapid plasma dilution and volume expansion, endothelial cell and erythrocyte dehydration, and increased erythrocyte deformability lead to improvements in rheology, CBF, and oxygen delivery. HTS is often administered as a continuous infusion of 25–50 mL/h of 3% saline (replacing the patient’s isotonic IV fluid) or bolus infusions of 10–30 mL of 7.2%, 10%, or 23.4% saline solution. Clinical response can begin within minutes and may last for hours, making HTS a potentially useful intervention in cases of severe ICP elevation or acute herniation syndrome.
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A common target for serum sodium concentration is 145–160 mEq/L, and even higher serum sodium levels may be chosen. However, it is unclear if deliberately driving up the serum sodium concentration to supranormal levels can prevent IC-HTN. Instead, high sodium levels are better viewed as a reason to stop administering HTS, rather than as a desired goal. Serum sodium and osmolality levels are often followed serially because excessively rapid increases in sodium, which may occur during HTS administration, may result in central pontine myelinolysis. This occurs most commonly in patients with preexisting chronic hyponatremia and is rarely seen in the chronically normonatremic patient who receives HTS. HTS may also induce or exacerbate pulmonary edema in patients with underlying cardiac or pulmonary deficits.
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By lowering PCO2, HV induces vasoconstriction, reduction of cerebral blood volume, and reduction in ICP. Time of onset of effect ranges from 30 seconds to 1 hour. Peak effect may be seen at 8 minutes and may last up to 15–20 minutes. This rapid onset of action makes HV particularly effective in the treatment of an IC-HTN crisis and as a bridge to more definitive therapy, such as surgical decompression, or as a temporizing measure while other ICP-lowering therapies take effect.
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Although HV was once used as a first-line therapy, concerns subsequently grew regarding prophylactic or prolonged use in TBI patients. During the first 24 hours after injury, perhaps as many as 50% of patients with severe TBI exhibit cerebral ischemia.57 Induced vasoconstriction from HV may lower CBF even further. Depending on the degree of functional autoregulation, the brain may undergo increases in the oxygen extraction fraction or shunting of blood to ischemic areas, with the net result being an increase in the total ischemic volume.
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Severe TBI patients should be kept normocarbic (PCO2 = 35–45 mm Hg). If HV becomes necessary, brief periods of mild HV (PCO2 = 30–35 mm Hg) may be effective for bringing ICP down while other treatment strategies are initiated. Prophylactic HV is contraindicated because it has been associated with worse outcomes.58 If HV is used, consideration should be given to tracking cerebral oxygenation via monitoring of jugular venous oxygen saturation or brain tissue oxygen tension.
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Decompressive Craniectomy
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If the above therapies fail to provide adequate control of ICP, additional therapies that may be considered include decompressive craniectomy (DC), barbiturate coma, and hypothermia.
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Some patients with TBI require emergency craniotomies to evacuate focal hemorrhagic lesions. The bone is removed, the lesion resected, dura closed, and bone replaced. More severe cases of TBI may develop diffuse cerebral edema, contusions of large size in eloquent areas, or multiple, coalesced contusions. In these cases, it may be preferable to leave the bone flap off. Additionally, when ICP is refractory to the previously mentioned management techniques, DC effectively expands the intracranial space to lower the ICP.
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The most common DC technique is a unilateral hemispheric decompression. Bifrontal and bilateral hemispheric craniectomies (Fig. 19-8) have also been described and may be more appropriate in some cases. The dura is opened widely, and areas of noneloquent contused or devitalized brain can be removed if required. The larger the size of the decompression, the better. The brain is then contained only by the augmented dural covering and the more compliant scalp.
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DC is most commonly used in patients with IC-HTN refractory to maximal medical management. Ideally, operative intervention should occur before ICP has been dangerously elevated for sustained periods of time. Success depends largely on patient selection. Regardless of the preoperative indications or patient profile, continuing postoperative IC-HTN greater than 35 mm Hg has been associated with very high mortality rates.59
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Early surgical intervention may be an option for potentially salvageable patients presenting with severe unilateral or bilateral cerebral edema, parenchymal lesions resistant to initial medical management of ICP, or other injuries whose management conflicts with standard ICP control measures (eg, patients with acute respiratory distress syndrome requiring elevated ventilatory pressures).
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DC can be effective for reducing ICP, but improvement in outcome has been difficult to demonstrate because most reports describing this practice consist only of case series, lack appropriate control subjects, and/or do not achieve statistical significance with regard to all end points.60 The prospective, randomized, controlled DECRA trial of bifrontal DC in patients with diffuse TBI who exhibited increasing ICP found that DC not only failed to improve outcome, but was actually associated with worse outcomes.61 RESCUE-ICP is another trial investigating the role of DC as a salvage procedure after other interventions have failed to control elevated ICP.62 Results are not available at the time of this writing.
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DC is not a benign procedure. Complications are common. These include infection, subdural hygroma, hydrocephalus, syndrome of the trephined, CPP breakthrough, and cerebral infarction.
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Barbiturates benefit TBI patients by decreasing the cerebral metabolic rate of oxygen (CMRO2), decreasing formation of free radicals and intracellular calcium influx, and lowering ICP. Side effects such as immunosuppression and hypotension from reduced sympathetic tone and mild myocardial depression often limit their use. TBI patients in coma (GCS score ≤8) receiving barbiturate therapy demonstrate infectious and respiratory complication rates in excess of 50%,59 and significant systemic hypotension may occur in 25% of patients63 despite adequate intravascular volume and pressor therapy. Barbiturates clearly reduce ICP, but studies have shown both improved and worsened outcomes for TBI patients receiving barbiturate therapy.
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Patients with hemodynamic instability, sepsis, respiratory infection, or cardiac risk factors are excluded from barbiturate therapy. Those receiving barbiturates should be closely monitored for signs of cardiac compromise or infection, with cessation of therapy if systemic effects of the treatment become significant and unmanageable. A pretherapy echocardiogram and intratherapy use of a pulmonary artery catheter should be considered.
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There is no role for prophylactic barbiturate therapy in TBI patients because it increases hypotension without significantly improving outcome.64 It should be reserved for use in controlling ICP only after other treatments have failed.
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A typical pentobarbital regimen is a loading dose of 10 mg/kg over 30 minutes, followed by a 5 mg/kg/h infusion for 3 hours. A maintenance dose of 1 mg/kg/h should then be started.24 Serum barbiturate levels of 3–4 mg% should be maintained, although poor correlation exists between serum level, therapeutic benefit, and systemic complications. Titration to clinical effect is commonly done. Continuous electroencephalographic evaluation is preferred by some, with dosing to the point of burst suppression producing near-maximal reductions of CMRO2 and CBF.
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Induced therapeutic hypothermia in TBI patients may reduce cerebral metabolism, ICP, inflammation, lipid peroxidation, excitotoxicity, cell death, and seizures. Adverse effects of hypothermia include decreased cardiac function, thrombocytopenia, elevated creatinine clearance, pancreatitis, and shivering with associated elevations in ICP. Initial interest in induced hypothermia stemmed from a large body of preclinical evidence, anecdotal observations (such as children trapped under the ice in frozen lakes), single-center clinical trials, and several meta-analyses.65,66,67,68,69 Although its use in TBI patients has been adopted by some trauma centers, and level 1 evidence supports its use in patients with cardiac arrest from ventricular fibrillation or ventricular tachycardia, clinical trials to date have not shown significant improvements in outcome from induction of hypothermia in TBI patients.
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Meta-analyses of more recent data and subsequent guidelines24 note a nonsignificant trend toward mortality reduction (compared to normothermic controls) when target temperatures are maintained for greater than 48 hours. Hypothermia-treated patients have been reported to reach significantly better outcomes. Additionally, patients who were hypothermic on admission seem to have improved outcomes if hypothermia is maintained, as opposed to rapidly warming them to normothermia. Interpretation of these results is limited, however, by small sample sizes and potential confounding factors in each study.
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Hypothermia is an option (ie, supported by only weak evidence) for treatment of patients with severe TBI. Patients who are hypothermic on arrival should be maintained in a cooled state or rewarmed only very slowly. An initial target temperature of 33°C may be targeted and, if possible, maintained for greater than 48 hours. This temperature may be carefully titrated upward to 34°C or 35°C while ICP is monitored because some patients may still demonstrate the ICP-lowering benefit of hypothermia at these temperatures, with perhaps less risk of adverse events from lower temperatures. Monitoring for untoward effects of hypothermia should include attention to potential electrolyte abnormalities and cardiac rhythm disturbances. Rewarming of these patients should take place very slowly, not exceeding 1°C per 4–6 hours or even more slowly (or even returning to a lower temperature) if ICP begins to rise precipitously.
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Glucocorticoids are not recommended for treatment of TBI.24,70,71 Increased mortality has been reported in trials investigating the effect of steroids on outcome after TBI. Of course, this restriction does not apply in cases when patients require steroids for treatment of other medical problems.
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Progesterone is another steroid that has been investigated as a potential therapy for TBI. Despite supportive preclinical and early-phase clinical data, progesterone failed to confer benefit to TBI patients in two large multicenter trials.72,73