Current concepts in neurocritical care

Anesthesiology Clin N Am 20 (2002) 441 – 462

Current concepts in neurocritical care Brenda G. Fahy, MD*, Vadivelu Sivaraman, MD Department of Anesthesiology, University of Maryland Medical System, 22 S. Greene Street, Suite S11C00, Baltimore, MD 21201, USA

Stroke Stroke is the third leading cause of death and the leading cause of adult disability in the United States. The National Institute of Neurological Disorders and Stroke defines stroke as sudden loss of brain function resulting from an interference with brain blood supply. This includes both ischemic and hemorrhagic insults with ischemic stroke predominant (85%). Subarachnoid hemorrhage (SAH), with its specialized management, will be covered in the next section. Once only supportive, therapy for acute ischemic stroke now includes therapeutic options with tissue plasminogen activator (tPA). Acute vascular occlusion, although rarely complete, limits oxygen and glucose delivery to that respective region of the brain. This results in a core area of tissue that infarcts almost immediately due to lack of blood and nutrient supply with a surrounding area of ischemic penumbra. The penumbra may not result in tissue infarction if ischemia can be reversed. Medical interventions target the potentially salvageable brain tissue. Intracranial hemorrhage (ICH), although less frequent than ischemic stroke, has a high mortality rate due to the extent of cerebral damage. Thrombolytics and anticoagulation are contraindicated with recent ICH. The mainstays of therapy include blood pressure management (as hypertensive disease is common), intracranial pressure (ICP) control, and optimization of cerebral perfusion. A decision for emergent surgical evacuation should be made in consultation with neurosurgery. These patients may require intraventricular catheter (IVC) placement for ICP monitoring and cerebrospinal fluid (CSF) drainage. Because time is crucial to minimize tissue death, there must be rapid assessment of the stroke patient including neurologic and physical examination and general medical assessment. It is crucial to establish the timing of the onset of stroke symptoms for possible administration of tPA. A head CT should be performed to rule out ICH, but this stage rarely shows ischemic changes. Although * Corresponding author. E-mail address: [email protected] (B.G. Fahy). 0889-8537/02/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved. PII: S 0 8 8 9 - 8 5 3 7 ( 0 1 ) 0 0 0 11 - 6

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not a complete neurologic examination, the National Institute of Health Stroke Scale Score (NIH-SSS) [1] (Table 1) utilizes a standardized scale to indicate the severity of neurological dysfunction. Table 1 NIH-SSS [1] Level of consciousness (LOC)

LOC questions (month and age)

LOC commands (close eyes, make fist)

Best gaze

Visual

Facial palsy

Best motor (repeat for each arm and leg)

Limb ataxia

Sensory

Dysarthria

Best language

Change from previous exam

Change from baseline

Alert Drowsy Stuporous Coma Answers both correctly Answers one correctly Incorrect Obeys both correctly Obeys one correctly Incorrect Normal Partial gaze palsy Forced deviation No visual loss Partial hemianopia Complete hemianopia Bilateral hemianopia Normal Minor paresis Partial paresis Complete palsy No drift Drift Can’t resist gravity No effort against gravity Absent Present in upper or lower Present in both Normal Partial loss Dense loss Normal articulation Mild to moderate dysarthria Near unintelligible or worse Mute No aphasia Mild to moderate aphasia Severe aphasia Mute Same Better Worse Same Better Worse

Abbreviation: NIH-SSS, National Institute of Health Stroke Severity Score.

0 1 2 3 0 1 2 0 1 2 0 1 2 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 0 1 2 0 1 2 3 0 1 2 3 0 1 2 0 1 2

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Table 2 Therapy guidelines for thrombolytic candidates Blood pressure (mmHg)

Treatment

Pretreatment SBP > 185 or DBP >110

Nitroglycerin paste or 1 to 2 doses of intravenous labetalol, 10 to 20 mg each. If these do not reduce blood pressure to < 185/110 mm Hg over 1 h, the patient should not be treated with rtPA.

During and after

Thrombolytics

Monitor BP

Every 15 minutes x 2 hours, then 30 minutes for 6 hours, then hourly x 16 hours Labetalol, 10 mg IV over 1 – 2 min, repeat or double every 10 – 20 min; total maximum dose 150 mg Use labetalol, 10 mg IV over 1 – 2 min, repeat or double every 10 min, to a maximum of 150 mg Sodium nitroprusside with continuous blood pressure monitoring

SBP: 180 – 230 or DBP: 105 – 130 SBP >230 or DBP: 121 – 140 DBP >140

Abbreviations: BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure.

During patient evaluation measures should be instituted to optimize blood flow. Hypertension is common in acute stroke, and should be treated cautiously to prevent cerebral ischemia. Treatment exceptions include hypertension associated with ICH and during the period surrounding tPA administration in ischemic strokes. The American Heart Association has established blood pressure guidelines (Table 2). Blood pressure should not exceed 185/110 at the time of tPA Table 3 Inclusion and exclusion criteria for use of thrombolysis in acute ischemic stroke Inclusion criteria Ischemic stroke with a measurable defect on NIHSSS Clearly defined time of onset within 3 h of the start of treatment Age >18 y Exclusion criteria Contraindications include: Evidence of intracranial hemorrhage on pretreatment CT scan Suspicion of SAH, even if CT scan normal Known arteriovenous malformation, aneurysm, or intracranial neoplasm Prior intracranial hemorrhage Intracranial or spinal surgery, serious head injury, or prior stroke in previous 3 mos Active internal bleeding Known bleeding diathesis including but not limited to: a) platelet count < 100,000/mm3, (b) prothrombin time >15 seconds, (c) international normalized ratio >1.7, (d) current use of oral anticoagulants; (e) use of heparin within 48 h and prolonged partial thromboplastin time Uncontrolled blood pressure at time of treatment (refer to Table 2) Recent (in previous 3 months): intracranial surgery, serious head trauma, or previous stroke Major surgery (in past 14 days) Pregnancy Seizure at stroke onset Abbreviations: NIHSSS, National Institute of Health Stroke Severity Score; SAH, subarachnoid hemorrhage.

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treatment [2]. Hypotension, or relative hypotension in a hypertensive patient, should be treated aggressively and an etiology sought. Cerebral blood flow during stroke is blood pressure dependent. Hypotension must be reversed to prevent further ischemia with subsequent infarction. Intravenous tPA is the only Federal Drug Administration approved primary treatment for acute ischemic stroke, and must be started within 3 hours of stroke onset. Appropriate indications and contraindications are detailed in Table 3. The most serious tPA complication is ICH. The risk of ICH after tPA increases with higher NIH-SSS scores [1]. Chronic anticoagulation in patients with atrial fibrillation is clearly warranted [3]. A comprehensive review of all therapies following acute stroke management is beyond the scope of this paper, and has been reviewed elsewhere [4]. Other neurologic complications following stroke include seizure and uncontrolled ICP. Seizures occur in 5% of strokes, usually with large strokes or cortical involvement. No evidence exists for prophylactic anticonvulsants; however, seizures can be treated acutely with benzodiazepines followed by phenytoin. Uncontrolled ICP is the leading cause of death in the first week following stroke. ICP measurements may be helpful with acutely deteriorating patients and help guide therapy. If an IVC is placed for ICP monitoring, it can permit therapeutic CSF drainage. Other therapeutic measures include elevating the head of the bed and hyperosmolar therapy with mannitol. Hyperventilation should be instituted cautiously due to concerns of worsening cerebral ischemia by hypocapnia-induced cerebral vasoconstriction decreasing cerebral blood flow. High-dose barbiturates may be used with uncontrolled ICP refractory to other therapies. Appropriate intensive supportive care must assure maintenance of hemodynamic stability during highdose barbiturates. Decompressive craniectomy has been used with intracranial hypertension in hemispheric infarctions [5], but its value requires further clarification. Medical complications are common following stroke. Coronary artery disease is present in a majority of stroke patients. Monitoring for detection and treatment of myocardial ischemia and infarction, arrhythmias, and congestive heart failure is warranted. Pulmonary complications include pneumonia, which can occur with dysphagia when oropharyngeal contents are aspirated. Stroke patients have a high risk of deep venous thrombosis (DVT), and may develop a pulmonary embolism (PE). Current prophylaxis recommendations in ischemic stroke for DVT and PE include low-dose unfractionated heparin, low molecular weight heparin, or danaparoid [6]. If anticoagulation is contraindicated, elastic stockings (ES) and intermittent pneumatic calf compression (IPC) can be used. Hyperthermia in the poststroke period increases morbidity and mortality [7]. Fever increases brain metabolic demand, and should be avoided following stroke.

Subarachnoid hemorrhage Nontraumatic subarachnoid hemorrhage (SAH) occurs in an estimated 30,000 Americans each year. Despite recent diagnostic and treatment advances, 25% of

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SAH patients will die, and 50% of survivors will suffer significant morbidity [8]. These patients require intensive care unit admission for neurologic observation and cardiopulmonary monitoring. The majority of SAH patients will have a cerebral aneurysm. [9]. SAH therapy is aimed at prevention and early detection of neurologic complications, and treatment of medical complications. Neurologic complications include rebleeding, hydrocephalus, seizure, and cerebral vasospasm. The most immediate concern is the risk of rebleeding with a mortality rate of 70%. The risk of rebleeding is 4% during the first 24 hours and 1– 2% per day during the following 4 weeks [ 10]. Because rebleeding rates are increased with high systolic blood pressure, simple treatment measures include blood pressure management, adequate pain control, and stool softeners until the aneurysm is secured. Early securing of the aneurysm is important not only to prevent rebleeding but also to allow more therapeutic options for subsequent cerebral vasospasm [11]. Antifibrinolytic therapy is no longer recommended because it increased secondary ischemia risk [12] and failed to improve outcome [13]. Acute hydrocephalus occurs in approximately 25% of patients after initial SAH, and can impair consciousness. Treatment is CSF drainage via an IVC. Overdrainage of CSF should be avoided, as it increases the risk of rebleed and cerebral vasospasm [14]. Blood in the ventricular system can obstruct the CSF drainage and absorption. Some SAH patients will require permanent shunt procedures following IVC drainage. Seizures occur in approximately 10% to 20% of patients with SAH, typically in the first 24 hours. Seizures may increase cerebral blood flow, potentially causing a rebleed. Respiratory compromise may occur with resultant hypoxemia. To prevent these complications, prophylactic intravenous phenytoin therapy is administered. Cerebral vasospasm following SAH is the most significant cause of mortality and morbidity in survivors of the initial SAH [9]. Cerebral vasospasm is an ischemic neurologic deficit associated with focal narrowing of intracranial arteries. Although the amount of SAH initially visualized on the CT scan is related to vasospasm [15], the pathogenic mechanisms of cerebral vasospasm need to be better defined. This is due to the complex nature of the pathophysiology of vasospasm and difficulty with its reproduction in animal models [16]. Blood products, especially oxyhemoglobin, have long been accepted as contributors to cerebral vasospasm [17]. More recent studies have examined oxyhemoglobin as an initiator of arterial wall contraction during cerebral vasospasm [18]. Although not completely elucidated, it has been postulated that cerebral vasospasm may result from oxyhemoglobin through a variety of pathways including arterial muscle fibers effects, local release of vasoactive compounds from the arterial wall, superoxide free radical production, and increased activity of lipid peroxidases. Cerebral vasospasm usually begins 4 days following SAH, peaks at 7 –10 days, and may continue for several weeks [19]. Transcranial doppler studies with elevated velocities can identify potential vasospasm. Angiography, however, is the gold standard for confirming the diagnosis of cerebral vasospasm. Clinical signs of vasospasm may manifest as altered level of consciousness or focal neurologic deficits over the course of minutes to hours. Because the neurologic signs can be

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subtle (pronator drift or slight change in consciousness level), serial neurologic examinations are crucial. The specific neurologic signs manifested will depend on the location of vasospasm and whether collateral circulation exists. Any acute neurologic deterioration needs to be investigated to rule out other etiologies including ICH and hydrocephalus. Early recognition and treatment of the potentially reversible ischemic deficit of vasospasm is the key. Delaying therapy until the appearance of a significant neurologic deficit may result in cerebral infarction. Clinical signs of vasospasm occur in approximately 30% of SAH, while angiographic evidence may occur in up to 70% [20]. Currently, hypervolemia, hemodilution, and hypertension therapy (HHH) are the main therapies for cerebral ischemia secondary to cerebral vasospasm. During cerebral vasospasm, cerebral blood flow regulation is assumed to become pressure dependent [21]. Hypovolemia occurs after SAH [22], correlating with symptomatic vasospasm [23]. Hypervolemic therapy with volume expansion has reversed neurologic deficits and increased cerebral blood flow. The resultant hemodilution as a result of hypervolemia therapy theoretically decreases blood viscosity, improving circulation to the ischemic area. After securing of the aneurysm to prevent the risk of a rebleed, hypertensive therapy becomes an additional option to improve pressure-dependent cerebral blood flow. Despite its widespread use, there is only one prospective randomized study of hypervolemic therapy involving 30 hypertensive patients with SAH [24]. They were randomized to begin volume expansion and antihypertensive therapy with vasodilators and centrally acting drugs compared to controls that received diuretics. The incidence of vasospasm and mortality was significantly higher in the group treated with diuretics without volume expansion. Several reports from studies describe improvement in neurologic deficits with elevating blood pressure, augmenting cardiac output, volume replacement, and/or hemodilution [25 – 27] when compared with historic controls. There were no control groups for these studies. However, studies have yet to determine which component(s) of HHH are most critical. Potential complications include pulmonary edema, myocardial ischemia, hemorrhagic infarction, and worsening cerebral edema [28]. Calcium antagonists usage to prevent or treat cerebral ischemia was based on the assumption that these drugs counteracted calcium influx in the vascular smooth. A meta-analysis of all published randomized nimodipine confirmed the benefit of prophylactic nimodipine in reducing neurologic deficits, cerebral infarction, and mortality, and improving outcome secondary to vasospasm [29]. Nimodipine, 60 mg orally every 4 hours for 21 days, usually is well tolerated, and may cause a mild degree of hypotension. It is one of the corner stones of therapy for prophylaxis against vasospasm. Another calcium antagonist, nicardipine, failed to show prophylactic benefit, and had side effects including hypotension, pulmonary edema, and renal failure [30]. The calcium antagonist, fausidil hydrochloride, in a prospective randomized trial reduced angiographic and symptomatic vasospasm with improved outcomes [31].

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Endovascular treatment for vasospasm with balloon angioplasty or selective arterial injection of vasodilators such as papaverine may improve neurologic symptoms when other medical therapies have failed. Lysis of the intracisternal blood clot by injection of intracisternal recombinant tPA has been shown to decrease angiographic and symptomatic vasospasm but not outcome [32]. One study suggested a nonstatistical trend toward decreased occurrence of severe vasospasm with intracisternal recombinant tPA [33]. Tirilizad, a 21-aminosteroid, inhibits lipid peroxidation and prevented cerebral vasospasm in an SAH animal model [34]. A European-Australian multicenter study showed tirilizad mesylate at 6 mg/kg was associated with better neurologic outcomes and reduced mortality versus controls [35]. However, it was felt that anticonvulsant therapy may increase drug clearance, and women received less benefit due to increased metabolism. However, the beneficial effects could not be reproduced in the North American Study [36] or in two additional trials with a higher dose (15 mg/kg) [37,38]. Other drugs tested clinically include the hydroxyl radical scavenger, nicaraven. It decreased symptomatic vasospasm; but did not alter outcome at 3 months [39]. Ebselen, a seleno-organic compound that inhibits lipid peroxidation, improved 3-month outcome without effecting symptomatic vasospasm [40]. Decreased nitric oxide (NO) activity may play a role in the pathogenesis of vasospasm. Preliminary data with intrathecal administration of NO donors such as sodium nitroprusside to a small group of patients with clinical or radiographic evidence of Grade III SAH (Table 4) resulted in 12 of 15 having at least a good or better outcome. Intrathecal sodium nitroprusside was also prophylactically administered to 10 patients with Grade III SAH; none developed vasospasm [41]. Side effects included three hypotensive episodes and frequent nausea. Medical complications following SAH are common, and are responsible for 23% of deaths [42]. Sepsis and pneumonia occur in 14.8% of patients [43]. Due to an inability to protect the airway, this patient population is prone to aspiration and subsequent pneumonia. Aggressive pulmonary hygiene to prevent atelectasis and antibiotics for bacterial pneumonia may be necessary. Neurogenic pulmonary edema [44] and non-neurogenic pulmonary edema may occur following SAH. Therapy includes inotropic support, if indicated, and gentle diuresis due to concerns over maintaining adequate volume status with the risk of cerebral vasospasm.

Table 4 Hunt and Hess Scale for Subarachnoid Hemorrhage Grade

Neurological status

I II III IV V

Asymptomatic Severe headache or nuchal rigidity; no neurological deficit Drowsy; minimal neurological deficit Stuporous; moderate to severe hemiparesis Deep coma; decerebrate posturing

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Cardiac arrhythmias are frequent following SAH including sinus tachycardia or bradycardia, ventricular or atrial extrasystole, and atrial fibrillation. Life threatening arrhythmias (asystole, AV block) occur 5% of the time. EKG abnormalities and cardiac enzyme elevations [creatine kinase (CPK) or troponin] are frequent following SAH. In a small retrospective series of 72 patients, nine patients had echocardiographic wall motion abnormalities. All were Grade III – IV (Table 4); all had CPK mb >2% [45]. There is currently no large prospective study examining cardiac enzyme elevation and echocardiographic changes. Hyponatremia is common after SAH, typically developing several days after hemorrhage. In the general medical population the etiology is often the syndrome of inappropriate antidiuretic hormone secretion (SIADH), necessitating fluid restriction. However, in the SAH population, there is evidence that cerebral salt wasting causing hypovolemia, and sodium depletion can occur following SAH [22]. Due to concerns over hypovolemia aggravating cerebral vasospasm, appropriate therapy for cerebral salt wasting includes sodium and fluid replacement. DVT (incidence 1% to 5%) and PE (incidence 0.8%) can occur following SAH. During the acute phase these patients are not candidates for anticoagulation due to recent SAH and often recent cranial surgery. ES or IPC can be used. If diagnosed with DVT or PE, an inferior vena caval filter can be placed. New potential monitoring modalities for SAH patients may include intracerebral microdialysis. These microdialysis catheters inserted in the cortex at the end of aneurysm surgery can measure markers of cellular injury and ischemia as well as neurotransmitters. During bedside microdialysis monitoring in a small series of SAH patients, impending ischemia was signaled by changes in lactate and glutamate, while increases in glycerol were associated with ischemic deficits [46]. This early detection of impending ischemia may lead to earlier intervention and prevention of cerebral infarction.

Traumatic brain injury Each year in the United States, traumatic brain injury (TBI) causes 52,000 deaths and 80,000 permanent severe disability, and is the most common cause of death and disability in young people. If TBI causes coma, there is a significant risk of hypotension, hypoxia, and intracranial hypertension. Any of these sequelae can exacerbate the degree of neurologic injury or cause death. Although primary injury occurs at the moment of impact, secondary injury due to the physiologic and metabolic processes caused by the primary injury occurs later. Secondary injury processes at the cell level may include calcium toxicity, lipid peroxidation, free radical generation, and excitatory neurotransmitter release [47]. Secondary brain injury is the primary cause of hospital deaths after TBI. Within hours of injury, vasogenic fluid accumulates in the brain, causing cerebral edema. This causes an increase in ICP, allowing cerebral ischemia to occur at a lower blood pressure threshold. Numerous pharmacologic agents including free

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radical scavengers, antagonists of excitatory neurotransmitters, and calcium channel antagonists have been investigated to attempt to block the secondary injury resulting from TBI. Efficacy remains to be proven [47]. Secondary insults to the brain caused by hypoxemia and hypotension can worsen outcome [48]. To decrease theses risks, attention must be given to airway, breathing, and circulation. TBI patients may present with other traumatic injuries such as a pneumothorax, hemothorax, or flail chest that require treatment to prevent hypoxemia. Airway protective reflexes may be absent with impaired consciousness. Appropriate establishment of an airway if needed is of paramount importance. Patients with a Glasgow Coma scale (see Table 5) of 8 or less are unable to protect their airway, and should be endotracheally intubated to prevent hypoxemia. Endotracheal intubation of these patients decreases the mortality significantly [49]. An orotracheal tube placement is usually preferred until a basilar skull fracture can be excluded due to possible brain entry via the cribiform plate with nasal placement. TBI patients are prone to aspiration pneumonia, and should receive aggressive pulmonary toilet and appropriate antibiotics if bacterial pneumonia ensues. Hypotension needs to be prevented to decrease the risk of secondary brain insult. A single episode of 90 mmHg or less systolic blood pressure with TBI worsens outcome [48]. If hypotension cannot be prevented, diagnosis and treatment should be rapid.

Table 5 Glasgow Coma Scale (GCS) Criteria points awarded best eye opening Spontaneously 4 To speech 3 To pain 2 None 1 Best verbal response Oriented 5 Confused 4 Inappropriate 3 Incomprehensible 2 None 1 Best motor response Obeys commands 6 Localized pain 5 Withdraws 4 Flexion to pain 3 Extension to pain 2 None 1 The highest level of response in each command is recorded and the sum of the three categories provides the GCS.

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The most significant cause of morbidity and mortality in TBI who survive to hospitalization is uncontrolled intracranial hypertension [50]. As already addressed above, initial management should be directed to opening, protecting, and maintaining the airway to prevent hypoxia and the deleterious effects of hypercarbia. If the patient has a clear cervical spine, the head of the bed may be elevated to improve cerebral venous drainage. Although static, CT scanning rapidly shows pathology and allows immediate intervention. CT scan signs of elevated ICP include midline shift, compression or obliteration of mesencephalic cisterns and the presence of subarachnoid blood (Fig. 1) [51]. ICP monitoring to allow appropriate interventions is vital. Indications for ICP monitoring include

Fig. 1. CT scan illustrating hemorrhage with obliteration of mesencephalic cisterns and right to left midline shift. (From Prys-Roberts C, Brown Burnell R Jr. International Practice of Anesthesia; 2(4), 2/125/2 and 2/125/3; reprinted by permission of Butterworth Heinemann, a division of Reed Educational & Professional Publishing Ltd.)

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Glasgow Coma Score of 8 or less and lesions prone to cerebral edema. Several continuous ICP monitoring devices are illustrated in the following diagram (Fig. 2), with advantages and disadvantages listed in Table 6. The most reliable for CSF drainage and ICP measurement is the IVC. The intraparenchymal

Fig. 2. Intracranial pressure monitoring sites. (From Prys-Roberts C, Brown Burnell R Jr. International Practice of Anesthesia; 2(4), 2/125/2 and 2/125/3; reprinted by permission of Butterworth Heinemann, a division of Reed Educational & Professional Publishing Ltd.)

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Table 6 Intracranial pressure monitor comparison IVC Accuracy CSF drainage Infection potential Recalibration possible Brain tissue disruption

± ± ± ± ±

± ± ± ± ±

± ± ± ± ±

± ± ± ± ±

SAB

Fibreoptic

± ± ± ± ± ± ± ±

± ± ± ± ± ± ± ± ±

Abbreviations: CSF, cerebrospinal fluid; IVC, Intraventricular catheter; SAB, subarachnoid bolt,

fiberoptic ICP monitoring system (Fig. 3) measures brain tissue pressure that has been shown to correlate well with ventricular pressure [52]. After correction of hypoxia and hypercarbia and proper positioning, if possible, to improve central venous drainage, ICP therapy involves elevation of serum osmolality (300 mosmol/kg approximately) by the use of osmotic diuretics or loop diuretics. The administration of mannitol should ideally occur with consultation of the neurosurgical team in TBI. If intracranial bleeding is present, mannitol may allow an intracerebral hematoma to expand by shrinking healthy brain tissue. In the pediatric population, hyperemia often causes diffuse swelling, and mannitol may further elevate ICP by increasing cerebral blood volume. Because of concerns that large doses of mannitol may cause a reverse osmotic gradient by removing so much tissue water that water and mannitol are

Fig. 3. Fiberoptic Camino Intracranial Pressure Monitoring System. (From Prys-Roberts C, Brown Burnell R Jr. International Practice of Anesthesia; 2(4), 2/125/2 and 2/125/3; reprinted by permission of Butterworth Heinemann, a division of Reed Educational & Professional Publishing Ltd.)

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drawn in to the cell [53], smaller doses (0.25 mg/kg) have been effective especially when repetitive dosing is required in the intensive care unit [54]. The osmotic diuretics have a faster onset of action (15 minutes) than the loop diuretics (30 minutes). Loop diuretics such as furosemide can lower ICP and potentiate the ICP-lowering effects of mannitol. Hypertonic saline in an animal hemorrhagic shock model [55] and a small human TBI series showed improved ICP [56]. More controlled studies are required assessing other variables to fully assess this therapy. Diuretic therapy may produce dehydration, hypotension, and electrolyte disturbances including hypernatremia, hypokalemia, hypophosphatemia, and hypomagnesemia. These electrolyte disturbances can precipitate cardiac arrhythmias. Hyperventilation due to hypocapnia causes cerebral vasoconstriction, which decreases cerebral blood flow and thus decreases ICP. Due to concern that hyperventilation can decrease cerebral blood flow in areas after TBI to the point of ischemia hyperventilation, it is used cautiously [57]. Prophylactic hyperventilation has been shown to worsen outcome following TBI. With acute ICP elevations, seizure must be considered, particularly if the patient recently received paralytic drugs, preventing observation of tonic –clonic seizure activity. Seizures can rapidly increase cerebral blood flow, and thus ICP. The first priority in a nonventilated seizing patient is to establish a patent airway and ensure adequate oxygenation. Arresting the seizure is paramount, and an intravenous barbiturate may be required. Diazepam decreases cerebral blood flow, cerebral metabolic rate, and ICP while raising the seizure threshold. When treatment fails to reduce ICP, other etiologies must be sought such as intracranial bleeding, status epilepticus, or worsening cerebral edema. Due to the high incidence of posttraumatic seizures, anticonvulsant drugs are routinely administered prophylactically. Prophylactic phenytoin is indicated in the first week following TBI [58]. If a seizure occurs beyond the initial injury phase, longer administration of anticonvulsant therapy is indicated. Although some centers have advocated the use of paralysis for ICP control, the trend is to avoid paralytics due to adverse effects including the inability to monitor neurologic changes, higher incidence of pneumonia, and prolonged weakness [59]. Adequate pain control and sedation are important to prevent ICP elevations; however, serial neurologic examinations are important for frequent assessment, and should be obtained if possible. Shorter acting sedatives, which can be stopped intermittently to allow serial neurologic examinations, are often being utilized. Propofol has resulted in better control of ICP with improved outcome in TBI patients but required more vasopressors [60]. With refractory ICP elevations (>25 mmHg), high-dose barbiturates can be used if the patient is hemodynamically stable. Satisfactory ICP control may occur in approximately one-quarter of patients with barbiturate infusion [61]. Due to the potential complications associated with high-dose barbiturate infusion, its use is limited to critical care settings that can provide appropriate monitoring and support. Consideration should be given to monitoring for oligemic cerebral hypoxia during high-dose barbiturate therapy [62].

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Although effective in reducing cerebral edema with brain tumors, the routine use of steroids in TBI is not recommended [63]. A review of 13 steroid trials revealed no reduction in mortality [64]. The administration of steroids can result in hyperglycemia, which may worsen outcome with head injury. The generation of free radicals may worsen secondary injury. However, clinical trials involving two free radical scavengers, polyethylene glycol-superoxidedismutase and tirilizad, did not effect outcome [65]. Other potential therapies to decrease secondary injury include blockade with glutamate antagonists to prevent excitatory neurotransmission. Although still under investigation, glutamate antagonists have not shown significant improved [65] outcome, and may have behavioral side effects, limiting its use [66]. Hypothermia has been explored as a possible therapy to provide protection from cerebral ischemia following TBI. A multicenter US trial in TBI did not show improvement with hypothermia [67]. However, hyperthermia has been shown to worsen brain infarct during cerebral ischemia [68], and thus should be avoided. In controlling ICP, maintaining adequate cerebral perfusion pressure is important. Unless there is brainstem failure, hypotension with an isolated head injury should force one to search for other causes including hemorrhage or spinal cord injury. With traumatic brain injuries, a minimum CPP of 70 mmHg has been shown to result in improved morbidity, mortality, and outcome [69]. The absolute level of CPP required is still under investigation [70], and whether higher CPP levels will improve outcome have yet to be proven. Other bedside monitoring methods to detect cerebral ischemia and intervene to prevent secondary injury following TBI are being investigated. Jugular bulb hemoglobin saturation (SjvO2) measures the saturation of the brain effluent blood providing an estimating global cerebral oxygenation. It can provide information on effectiveness of therapeutic interventions [71]. Desaturations are strongly associated with poor outcome [72]. Limitations of SjvO2 include the inability to detect small ischemia regions. Still experimental, direct brain tissue partial pressure of oxygen (PO2) can be measured by probes placed in brain parenchyma that detect tissue oxygenation changes in small focal areas of the brain. Changes in brain tissue PO2 correlate with outcome [73] and elevations in lactate and glutamate [74]. Intracerebral microdialysis can also detect cerebral ischemia during TBI. Cerebral ischemia increased lactate, and was associated with a poor outcome [75]. Other imaging modalities are being developed that may permit monitoring of the metabolic state of the brain following TBI. Although static, the CT scan has the ability to identify pathology and allow immediate intervention. Portable CT scanners are currently under development and may avoid transportation for CT scans of the intensive care unit patients. Xenon CT may provide cerebral blood flow information following TBI [76]. Magnetic resonance imaging (MRI) use early after TBI is limited due to the lengthy scan time for images compared to CT. MRI compatibility limits monitoring, and may hamper supportive and resuscitative abilities while in the MRI scanner. However, newer MRI technologies under development may reveal early cerebral edema and allow functional imaging.

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Medical complications can further complicate the course during head injury. Abnormal coagulation tests are common after head injury, and the severity of coagulopathy worsens outcome [77]. Because of the high risk of hemorrhage in this patient population, correction of clotting abnormalities should be attempted. Pulmonary complications are frequent with head injury. Neurogenic pulmonary edema is more common with severe isolated TBI. The chest radiograph typically shows fluffy infiltrates, and requires positive pressure ventilation and supportive care to prevent hypoxemia. Pulmonary infections are the most common infection and a major source of morbidity. Aggressive pulmonary hygiene is the key, including postural drainage. However, Trendelenburg positioning to accomplish optimal postural drainage may be poorly tolerated due to ICP elevations. These patients often lose airway protective reflexes and aspirate. Those who require long-term ventilation or require suctioning for pulmonary hygiene will require tracheostomies. Due to the prolonged bed rest and additional injuries, the TBI patient is at risk for DVT and PE. With recent trauma and potential for ICH, TBI patients are often not candidates for anticoagulation. Devices such as IPC or ES are usually employed. If a patient with an ICH is diagnosed with a DVT or PE, an inferior vena caval filter can be placed. Blood pressure and heart rate elevation occurs following TBI probably due to a sympathetic response. This can result in hypertension, which may raise ICP and cause ICH. It may also precipitate myocardial ischemia. With TBI, diabetes insipidus and SIADH can occur. Diabetes insipidus is common following severe head injury, and can be permanent or transient with eventual resolution. Serum hyperosmolality, urine hyposmolality, and ultimately the response to exogenous antidiuretic hormone (ADH) administration (intravenous pitressin in the acute setting), confirm diagnosis. The diagnosis of SIADH is confirmed with serum hyposmolality, urinary hyperosmolality, and adequate blood volume. The mainstay of treatment is fluid restriction. Active correction of hyponatremia with hypertonic saline should be reserved for those patients with extreme hyponatremia (serum sodium < 120 mmol/L) or lifethreatening side effects. Serum sodium correction should be done judiciously due to the concern of central pontine myelinolysis from a rapid increase in the serum sodium concentration. TBI is a risk factor for stress-induced gastritis and erosions. Prophylactic therapy requires more solid data. Potential complications include gastrointestinal hemorrhage. Due to the hypermetabolic state during TBI, early enteral feeding is advocated. These patients often require placement of a chronic feeding tube because of swallowing difficulties.

Spinal cord injury There are approximately 10,000 new cases of spinal cord injury in the United States yearly, with the average age at time of injury in the early thirties. The most common cause of spinal cord injuries is motor vehicle accidents. Spinal

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cord injuries occur in 2.6% of major trauma victims. Cervical spine injuries are most common followed by thoracic and lumbar spine injuries. Of these spine injuries, a little less that half will suffer complete loss of sensory and motor functions [78]. All trauma victims with a suspicion of spinal trauma as well as those patients with a high index for a spinal cord injury (head injury, altered mental status, neck or back pain, drug or alcohol intoxication) should have spinal immobilization. The primary injury to the spinal cord happens at the time of impact, and is irreversible. The forces may cause spinal cord contusion, hemorrhage, or shear injury. Maximizing the medical management of the patient can minimize secondary injury. Prehospital spinal immobilization has become a standard of care in the United States. These measures include placement of a rigid cervical collar, log rolling only of the patient, and transportation on a rigid spine board. During the initial hospital assessment of the spinal cord-injured patient, evaluation of airway, breathing, and circulation are critical. One most ensure and maintain a patent airway, maintain adequate oxygenation, and restore and maintain an adequate blood pressure. Patients with high cervical lesions often present with apnea, requiring mechanical ventilation. If apnea or respiratory failure ensues, options for intubation include orotracheal intubation with in-line traction, fiberoptic intubation, or if these fail, cricothyroidotomy or tracheostomy. Failed intubation is more common with spinal cord because in-line immobilization prevents optimal positioning for intubation. Cervical injuries at the level of the phrenic nerve (C3 through C5) risk acute respiratory failure due to loss of diaphragmatic muscles of breathing. With spinal cord injuries above T6 sympathetic denervation leads to unopposed parasympathetic activity. Patients often experience bradycardia, caused by loss of vascular tone and hypotension. Aggressive intravenous fluid replacement should occur. Adequate blood pressure should be maintained to decrease the risk of spinal cord ischemia. Aggressive blood pressure maintenance with a mean arterial blood pressure of above 85 mmHg has improved neurologic outcome [79]. Complete neurologic examination should be performed on admission. This includes evaluation of motor strength, sensory assessment, deep tendon reflexes, and Babinski’s responses. Anal sphincter tone must also be examined. Further evaluation to assess for spinal trauma is directed by patient’s clinical condition. Spinal evaluation to clear the spine is controversial [80,81]. Trauma victims with suspected spinal cord injury should undergo radiographic examination of the cervical, thoracic, and lumbar spines. Any patient with persistent neck pain needs further studies to rule out a ligamentous injury with normal plain cervical radiographs. A patient with a fixed neurologic deficit presumed secondary to spinal cord with normal plain spine radiographs warrants further imaging to rule out soft tissue spinal cord compression. Initial assessment of the trauma patient with a spinal cord injury can be complicated by the lack of sensation. These patients are often multitrauma victims, and being insensate may lack physical signs of intra-abdominal or thoracic trauma. A high index of suspicion must be maintained, and the diagnosis must often be made radiographically.

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Primary injury occurs at the time of impact followed by secondary injury processes. These may include autoregulatory loss, edema, and ischemia. Postulated cellular mechanisms following secondary injury include calcium toxicity, lipid peroxidation, free radical generation, and excitatory neurotransmitter release [82 – 84]. Several clinical trials have attempted to limit these secondary injury processes. A multicenter trial conducted by the National Acute Spinal Cord Injury Study revealed a methylprednisolone bolus (30 mg/kg) followed by continuous infusion (5.4 mg/kg) for 24 hours improved neurologic outcome after spinal cord injury if administered within 8 hours of injury [85]. Postulated mechanisms included decreased edema, inflammation, and lipid peroxidation. A follow-up study revealed spinal cord injury patients treated with the above methylprednisolone regime 3 to 8 hours after injury had better neurologic outcome [85] but a higher infection rate if the methylprednisolone infusion continued for 48 compared to 24 hours [86]. An additional study group compared tirilazad administration (2.5 mg/kg) every 6 hours for 48 hours with the previous methylprednisolone regime. All patients received 30 mg/kg bolus of methylprednisolone due to ethical concerns [87]. At 24 hours tirilazad and methylprednisolone were equally effective; however, 48-hour outcomes were better for the methylprednisolone group. Infection rates were higher in the methylprednisolone group. Gangliosides are glycolipids located in cell membranes and enhanced neurite outgrowth and neuronal regeneration in animals [88]. In a prospective clinical trial comparing GM-1 ganglioside to placebo, the treated spinal cord patients had significant improvement in motor function [89], even allowing enrollment up to 72 hours after injury. Spinal cord injury patients are at risk for a multitude of medical problems. An upper or midcervical injury involving the phrenic nerve (C3– C5) will often cause acute respiratory failure. More cephalad injuries will require tracheostomy for permanent mechanical ventilation to prevent apnea. Intercostal nerve transfer with phrenic nerve pacemaker implant has shown promising results in six patients after high cervical spine injury [90]. Any patient who has a spinal cord injury C6 or higher must be closely monitored for respiratory insufficiency over the first several days of admission postinjury. Those who have initially have an adequate airway status may deteriorate due to spinal cord edema raising the cervical injury level. These patients require aggressive pulmonary hygiene, and frequently develop pneumonia, which may require antibiotic therapy. Due to prolonged immobilization, spinal cord-injured patients are at risk for pressure necrosis and decubitus ulcers. Frequent turning may not prevent long-term skin breakdown, and these patients may require specialty beds to minimize further skin breakdown and prevent decubiti ulcers. Acute spinal cord injury patients have the highest risk of DVT among hospital admission [91], with PE being the third most common cause of death [92]. The highest risk period for venous thromboembolism occurs in the acute injury phase. Although several small randomized trails of prophylaxis have been performed in the spinal cord patient [93 –95] large well-controlled studies of prophylaxis for

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DVT have yet to be done. Low-dose fractionated heparin, IPC, or ES probably do not provide adequate protection alone [96,97]. Duplex surveillance scanning for spinal cord injury patients may be beneficial. If a DVT or PE develop, these patients may not be candidates for systemic anticoagulation due to concomitant trauma injuries or spinal cord hematoma. An inferior vena caval filter may be placed. Prophylaxis recommendations include low molecular weight heparin in the absence of contraindications [6].

Conclusion The management of the neurologic critical care patient (stroke, SAH, TBI, spinal cord injury) requires rapid recognition and treatment to limit or ideally prevent further neurologic sequelae. Medical complications further increase the morbidity and mortality in this patient population. New therapies and interventions are currently under investigation. These may lead to further advances in the management of this specialized patient population.

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