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| Postoperative Complications | Respiratory Care| Cardiovascular Therapy| Fluid Management| Nutrition in Critical Patients |Traumatic Brain Injury-Stroke-Brain Death |


I. Impact of traumatic brain injury (TBI)

Each year in the United States, approximately 52,000 people die and 80,000 people suffer permanent disability as the result of TBI. The death and disability result from the impact itself (primary injury), and from subsequent changes in cerebral substrate delivery (secondary injury [Table-1]). In patients with severe head injury (Glasgow Coma Scale [GCS] score 8), the presence of hypotension (systolic blood pressure [SBP] <90 mm Hg) or hypoxia (partial pressure of arterial oxygen [Pao2], 60 mm Hg) at the time of admission is associated with increased mortality (75% when both hypotension and hypoxia were present) and poorer functional outcomes. Intracranial complications such as edema, hemorrhage, and vasospasm contribute to a reduction in cerebral blood flow (CBF) to almost 50% of the pretrauma level during the first day after TBI. Patients who have sustained either moderate or severe TBI are therefore treated in an intensive care unit (ICU) to prevent and treat secondary brain injury.
Brain Trauma Foundation (BTF) clinical practice guidelines. The BTF has developed evidence-based clinical practice guidelines that it revises periodically as new data become available. Recent studies suggest that the following ICU protocols based on BTF guidelines can decrease morbidity, mortality, and the cost of care.
Initial resuscitation. Patients who have TBI should be treated at a designated trauma center that has neurosurgical coverage or transferred to such a center after initial stabilization. The management of TBI begins with the treatment of associated injuries that may cause hypoxia, hypoventilation, and shock. This is best accomplished by using a systemic approach such as the Advanced Trauma Life Support (ATLS) Algorithm, which consists of primary and secondary surveys of the patient.
A. Primary survey
(1) To the extent possible, a brief history and examination are performed. The history is obtained according to the AMPLE mnemonic (allergies, medications, past medical history, last meal, event). Examination and immediate resuscitation are performed according to the
ABCDE mnemonic (airway, breathing, circulation, disability, exposure).

Table-1. Systemic complications contributing to secondary injury

Minutes to hours after initial impact:
Hypoxia
Hypercarbia
Hypotension
Anemia
Hyperglycemia
Hours to days after initial impact:
Seizures
Infection/sepsis
Hyperthermia
Electrolyte disturbances
Coagulation abnormalities

(2) In the setting of TBI, airway management is performed with particular attention to changes in mean arterial pressure (MAP), intracranial pressure (ICP), and partial pressures of arterial carbon dioxide (Paco2) and of oxygen (Pao2).
(a) Indications for intubation include inability to protect the airway, difficulty with either oxygenation or ventilation, shock, GCS score <9, or rapid neurologic deterioration.
(b) Manual in-line stabilization of the head and neck is maintained during intubation to minimize the risk of cervical spinal cord injury in all patients in whom cervical spine injury has not been ruled out. A series of collaborative studies by a team of neurosurgeons, anesthesiologists, and radiologists has questioned this practice. Studies using fluoroscopy in cadaver models of injury found that spinal stabilization maneuvers during laryngoscopy and intubation were not helpful and may have worsened subluxation at the injury site. These results have not yet been replicated in other models or by other investigators, and as a result, manual in-line stabilization remains standard of care.
(c) Rapid sequence induction and intubation are performed in patients who have full stomachs, using direct laryngoscopy when this is thought to be feasible.
(d) Using these special precautions, direct laryngoscopy is considered the fastest and safest way to intubate the trachea of most patients including those who have a possible fracture of the cervical spine.
(e) Flexible fiberoptic intubation may be useful in patients who have difficult airways and unstable cervical spine fractures. This technique may be limited, however, in patients who are unstable or agitated or have either blood or particulate matter in the airway or significant trauma to it.
(f) Laryngeal mask airways (LMAs), including the intubating LMA, are useful backup techniques for ventilation and intubation.
(g) Surgical airway techniques, such as cricothyroidotomy and tracheotomy, are also backup methods for intubation and, in rare cases, the first line of management.
(h) Lidocaine, 1.5 mg/kg, given intravenously (i.v.) 1.5 minutes before intubation has been shown to blunt the increase in ICP in response to airway manipulation.
(i) The induction drugs propofol and thiopental decrease ICP, CBF, and the cerebral metabolic rate for oxygen consumption (CMRo2) and have anticonvulsantt effects. However, the associated decrease in MAP may be deleterious in patients after TBI. Etomidate, 0.3 mg/kg, may be a better choice because it produces similar decreases in ICP, CBF, and CMRo2 without a significant decrease in MAP.
(j) Muscle relaxants facilitate tracheal intubation and decrease the risk of straining.
(i) The depolarizing muscle relaxant succinylcholine, 1.5 mg/kg, which has the fastest onset of action among the currently available muscle relaxants (30 to 45 seconds), has been shown in animal studies to increase ICP. However, results in human studies have been inconsistent, and a controlled study in patients with brain injury demonstrated that the effects of succinylcholine on ICP were not significantly different from those of normal saline. Succinylcholine is contraindicated, however, 24 hours after TBI associated with spinal cord, crush, or burn injury owing to the risk of hyperkalemia.
(ii) Nondepolarizing neuromuscular blocking drugs (NDNMB) including rocuronium, 1 mg/kg, and mivacurium, 0.2 mg/kg, do not increase ICP and are associated with fewer side effects than succinylcholine. However, they have a slower onset of action (60 to 90 seconds).
(iii) The risks and benefits of each muscle relaxant should be carefully considered for the specific patient and situation.
(k) Endotracheal intubation must be confirmed by a CO2 detection method such as colorimetric or continuous capnography in addition to physical examination.
(l) Chest radiographs are useful for confirming endotracheal tube (ET) position as well as associated chest pathology such as pneumothorax, lung contusion, and pulmonary edema.
(3) Breathing considerations include the following:
(a) Supplemental high-flow oxygen is provided to all patients to prevent hypoxia (Pao2 <90 mm Hg). In patients who are mechanically ventilated, the benefit of positive end-expiratory pressure (PEEP) in improving oxygenation must be weighed against its potential effects on ICP and CBF. In patients who are euvolemic, PEEP of 5 to 10 cm H2O is not likely to increase ICP. In patients who are hypovolemic,
PEEP >10 cm H2O may reduce CBF.
(b) Positive pressure ventilation is provided as needed to maintain adequate ventilation and oxygenation. Paco2 should be maintained at near normal levels of 35 to 40 mm Hg. Hyperventilation to a Paco2 of 25 to 30 mm Hg decreases ICP, but its routine use is not recommended because it can also reduce CBF to ischemic levels. Hyperventilation should be used only when rapid reduction in ICP is necessary to prevent either neurologic deterioration or impending herniation.
(c) Sedation and analgesia are provided to patients who are conscious and mechanically ventilated. The ideal sedative drug for treating TBI would have a rapid onset and offset, anticonvulsant properties, and favorable effects on cerebral perfusion pressure (CPP), the difference between MAP and ICP. Short-acting sedative drugs, such as propofol, 10 to 50 mcg/kg/minute, and dexmedetomidine, load 1 mcg/kg over 10 minutes and then 0.2 to 0.7 mcg/kg/hour for <24 hours, have rapid onset and offset, which allows prompt awakening for neurologic assessment. The associated decrease in MAP, however, may be detrimental to CPP. Furthermore, dexmedetomidine-induced sedation in volunteers has been found to decrease regional and global CBF in excess of the accompanying fall in CMRo2. Benzodiazepines such as lorazepam, 1 to 2 mg over 5 minutes repeated as necessary, are longer acting and may interfere with intermittent neurologic examination but cause less hypotension. Analgesia can be provided with opioids such as fentanyl, 0.5 to 1 mcg/kg, and morphine, 0.05 to 0.1 mg/kg, with particular attention to their respiratory and neurologic depressant effects. All the drugs may also be administered by continuous infusion.
(4) Circulation. Life-threatening hypovolemic or cardiogenic shock should be identified and controlled or definitively treated (e.g., by the release of tension pneumothorax). SBP should be maintained at or above 90 mm Hg through the use of intravenous fluids, vasoactive drugs, or both, to maintain CPP.

Table-2. Signs and symptoms of increased intracranial pressure

Headache
Nausea, vomiting
Papilledema
Unilateral pupillary dilatation
Oculomotor or abducens palsy
Depressed level of consciousness
Irregular breathing
Midline shift (0.5 cm) or encroachment of expanding brain on cerebral ventricles (CT scan or MRI)
CT, computed tomography; MRI magnetic resonance imaging.

(5) Disability. When not absolutely contraindicated by the need for immediate intubation, the initial neurologic disability assessment should be performed before the administration of sedative or neuromuscular blocking drugs. Neurologic status is assessed by using the GCS and looking for signs and symptoms of increased ICP (Table-2) and brain herniation. The GCS, a quantitative measure of neurologic status with good interevaluator agreement and an estimate of progress and prognosis, defines neurologic impairment in terms of eye opening and verbal and motor responses (Table-3). The total score is 15. The scores indicate the following:
Severe head injury, 8, persisting for 6 or more hours.
Moderate injury, 9 to 12.
Mild injury, 13 to 15.
In addition, pupillary response and the presence of lateralizing signs and spinal motor and sensory levels are carefully noted. Signs of transtentorial brain herniation include unilateral pupillary dilatation, sudden neurologic deterioration, contralateral hemiparesis, coma, hypertension, and bradycardia. Emergency therapy includes reassessment and treatment of extracranial insults such as hypoxia and shock, elevation of the head of the bed (HOB) (up to 30), infusion of mannitol, brief hyperventilation, and surgical decompression.

Table-3. Glasgow Coma Scale

Eye opening: Spontaneous 4
To verbal command 3
To pain 2
None 1
Best verbal response: Oriented, conversing 5
Disoriented, conversing 4
Inappropriate words 3
Incomprehensible sounds 2
None 1
Best motor response: Obeys verbal commands 6
Localizes pain 5
Flexion/withdrawal 4
Flexion/abnormal (decorticate) 3
Extension (decerebrate) 2
None 1
Total: 3-15

(6) Exposure. The patient is fully undressed and examined for any associated injuries, while precautions are taken to avoid hypothermia.
B. Secondary survey. The secondary survey includes a more complete history and physical examination as well as laboratory and ancillary testing to diagnose the extent of TBI and associated injuries.
(1) Indicated investigations include radiologic examination of the chest and pelvis, complete metabolic panel, complete blood count, prothrombin time (PT) and partial thromboplastin time (PTT), urinalysis, ethanol level, urine drug screen, and blood type and screen.
(2) Unless contraindicated by the need for emergency laparotomy or thoracotomy to prevent death from exsanguination, all patients who have sustained TBI should have a noncontrast computed tomographic (CT) scan of the head and cervical spine as soon as possible. In addition, CT scan of the abdomen is often necessary.
(3) If immediate laparotomy, thoracotomy, or interventional procedure is required, the concurrent placement of an intraventricular catheter to monitor ICP should be discussed with a neurosurgeon.
(4)Plans for initial operative or nonoperative management should be based on the results of the primary and secondary survey. Epidural and subdural hematomas that exert significant mass effect have better outcomes after prompt surgical intervention than do other injury-related lesions.
Critical care management after the initial resuscitation includes the following:
ICP monitoring and treatment
(1) Indications for insertion of an ICP monitor include an abnormal CT scan and a GCS score of 3 to 8 after adequate resuscitation of shock and hypoxia or a normal CT scan and a GCS of 3 to 8 accompanied by two or more of the following: age >40 years, posturing, or SBP of <90 mm Hg.
(2) ICP monitoring using an intraventricular catheter is preferred because it provides dependable readings and allows therapeutic drainage of cerebrospinal fluid (CSF).
(3) Treatment to decrease ICP is usually initiated at ICP levels of 20 to 25 mm Hg. The aim is to maintain CPP >70 mm Hg. The CPP should be correlated with the patient's neurologic examination, overall physiologic status, and state of CBF autoregulation. Loss of autoregulation causes the CBF to depend on the MAP, which increases the risk of cerebral ischemia when the MAP falls and of hyperemia when the MAP rises. The BTF suggests maintaining a CPP of >70 mm Hg in patients whose autoregulation may be impaired because this level has been associated with improved outcome. Results of a recent study suggest that patients who have defective autoregulation, as evidenced by an increase in ICP >2 mm Hg in response to a 15 mm Hg increase in MAP (ICP/MAP slope >0.13), benefit from lowering the ICP treatment threshold to 20 mm Hg and the target CPP to 50 to 60 mm Hg. Patients whose autoregulation is intact (ICP/MAP slope <0.13) benefit from ICP treatment thresholds of 25 to 30 mm Hg and CPP >70 mm Hg.
(4) If an ICP monitor is not in place, treatment to decrease ICP should be initiated when either neurologic deterioration occurs or signs of brain herniation are present.
(5) Treatment of intracranial hypertension includes elevation of the head 15 to 30, control of seizure activity, ventilation to a low-normal Paco2 of 35 mm Hg, maintenance of normal body temperature, release of any obstruction to jugular venous outflow (e.g., tape placed circumferentially to secure the endotracheal tube), assurance of optimal fluid resuscitation and overall physiologic homeostasis, and the provision of sedation and pharmacologic muscle relaxation as needed. If these measures fail to decrease ICP, additional therapies are provided in a first- and second-tier stepwise manner.
(a) First-tier therapy involves the following:
(i) Incremental CSF drainage via an intraventricular catheter.
(ii) Diuresis with mannitol, 0.25 to 1.5 mg/kg over 10 minutes; recent data support the upper end of that range. Mannitol lowers ICP by deceasing brain edema and improving CBF. However, mannitol-induced diuresis may cause hypotension, especially in the early resuscitative phase when invasive monitoring is not yet in place and the extent of associated injuries is unknown. Therefore, either euvolemia or mild hypervolemia is maintained during mannitol therapy and serum osmolarity is monitored and maintained below 320 mOsm/L.
(iii) Moderate hyperventilation to a Paco2 of 35 to 40 mm Hg also decreases ICP by reducing CBF. Hyperventilation should therefore be used briefly to treat either acute neurologic deterioration or increased ICP refractory to CSF drainage and mannitol administration.
(b) Second-tier therapy involves the following:
(i) Aggressive hyperventilation to a Paco2 <30 mm Hg may be required for increased ICP refractory to first-tier therapy. When aggressive hyperventilation is used, monitoring of either jugular venous oxygen saturation (Sjo2) or cerebral tissue oxygenation is recommended to assess the effect of decreased CBF on cerebral oxygen metabolism. The Sjo2 percentages indicate the following:
40% or less is consistent with ischemic levels of CBF.
40% to 60% is consistent with hypoperfusion.
60% to 75% is within normal range.
75% to 90% is consistent with hyperperfusion.
90% or more indicates cessation of flow and brain death.
Changes in Sjo2 in response to therapeutic interventions provide a useful guide to the adequacy and appropriateness of these interventions and the need for further or alternative treatment.
(ii) High-dose barbiturate therapy decreases ICP by decreasing CBF in parallel with cerebral metabolism. It is reserved for patients who are hemodynamically stable, salvageable, and have increased ICP refractory to first-tier therapy. Treatment is typically provided in the form of pentobarbital with a loading dose of 10 mg/kg over 30 minutes followed by boluses of 5 mg/kg/hour for 3 hours and then an infusion of 1 to 3 mg/kg/hour. The infusion rate is titrated to achieve electroencephalographic (EEG) burst suppression using bedside monitoring. Complications include myocardial depression and hypotension.
(iii) Decompressive craniectomy has been shown to decrease ICP and improve certain physiologic parameters but not overall patient outcome.
Blood pressure monitoring involves the following:
(1) The insertion of an arterial catheter allows direct, accurate, real-time measurements of MAP and regular arterial blood-gas sampling.
(2)Adequate MAP is achieved by infusing isotonic fluids to maintain either euvolemia or mild hypervolemia. If hypotension persists despite adequate volume resuscitation, vasoactive medications are added. The need for vasoactive drugs should prompt consideration of occult bleeding and other critical illnesses such as sepsis, cardiac dysfunction, neurogenic shock, and adrenal insufficiency.
Monitoring intravascular volume includes the following:
(1)Insertion of a central venous catheter that allows continuous measurement of central venous pressure (CVP), which is an indicator of intravascular volume.
(2)Insertion of an indwelling urinary catheter that facilitates measurement of urinary volume and content. The volume of urine is an additional indicator of volume status and, with urine and serum composition, facilitates the diagnosis of conditions of altered urinary output associated with TBI such as diabetes insipidus (DI), the syndrome of inappropriate antidiuretic hormone (SIADH) secretion, cerebral salt wasting syndrome, and the hyperosmolar state.
(3) Insertion of a pulmonary artery catheter that allows the measurement of pulmonary vascular pressure and calculation of cardiac output. Recent studies have questioned the benefit of pulmonary artery catheters in the management of critically ill patients.
Seizure prophylaxis is recommended during the first week after TBI, particularly in high-risk patients such as those who have GCS scores <10; cortical contusion; depressed skull fracture; subdural, epidural, or intracerebral hematoma; penetrating head trauma; or seizures occurring within the first 24 hours after injury. This prophylaxis reduces the risk of seizures in the first week after injury but has not been demonstrated to improve outcome. The drug of choice is phenytoin, loading dose 15 mg/kg i.v., over 20 minutes followed by 5 to 7 mg/kg/day, or fosphenytoin, loading dose phenytoin equivalent (PE) 15 to 20 mg/kg i.v., and then 4 to 6 PE mg/kg/day. Adverse effects of phenytoin include fever and rash.
Nutritional support is required to facilitate recovery and should be initiated as soon as possible. By 1 week after injury, 15% of total calories should come from protein. Enteral feeding is preferred, and jejunal placement of the feeding tube protects against aspiration and gastric intolerance. Stress-ulcer prophylaxis should be provided using H2 antagonists such as famotidine, 20 mg every 12 hours, or proton-pump inhibitors such as pantoprazole, 40 mg daily.
Hyperglycemia has been shown in animal studies to exacerbate neurologic outcome after brain injury. Prospective randomized trials in patients who are critically ill have demonstrated that patients who receive intensive insulin therapy to achieve glucose levels of 80 to 100 mg/dL had better outcomes than control patients who had glucose levels of 180 to 200 mg/dL. Retrospective data of patients with TBI suggest that early hyperglycemia is associated with poor outcomes and that nutritional support does not increase serum glucose concentration. Hyperglycemia (>200 mg/dL) must be avoided; euglycemia (80 to 110 mg/dL) may be optimal if it can be achieved without significant risk of hypoglycemic episodes.
Fever increases ICP and cerebral metabolism and may worsen outcome after TBI. Fever should be treated with cooling blankets, acetaminophen, and evaluation for infection or pharmacologic causes (e.g., phenytoin). Studies of the protective effects of hypothermia in TBI have been inconclusive. A major trial reported in 1997 demonstrated significant outcome improvements at 3 and 6 months from injury in patients admitted with GCS scores between 5 and 7. A similar trial published in 2001 was stopped after interim analysis concluded that the probability of demonstrating a significant benefit was <1%. Studies of therapeutic hypothermia in TBI are ongoing.
Steroids have not been shown to provide any benefit to patients with TBI. A recent randomized, controlled trial suggested that they might actually increase mortality.
Drugs designed to reduce oxidative damage, antagonize N-methyl D-aspartate (NMDA) receptors, or mitigate neurotoxicity through other mechanisms have had encouraging results in animal studies but have not been demonstrated in human trials. Drugs currently being developed or investigated in clinical trials include cannabinoids, novel NMDA and/or amino-hydroxy-methyl-isoxalone propionic acid (AMPA) antagonists, and immune modulators.
Prophylaxis against deep venous thrombosis (DVT) with pneumatic compression devices should be initiated as soon as possible after the patient's admission to the ICU.

II. Stroke

Ischemic stroke
Pathophysiology. Ischemic stroke may result from cardioembolic, large-vessel atherothrombotic, or small-vessel pathology (e.g., lacunar infarct). Lacunar infarcts often occur in the basal ganglia and brain stem; they may remain subclinical or may produce dementia through multiple repeated events.
Diagnosis. The clinical presentation of ischemic stroke consists mainly of focal neurologic deficits. Headache and decreased level of consciousness are more likely to accompany hemorrhagic stroke. A noncontrast CT scan of the head differentiates between the two. The differential diagnosis of stroke includes migraine, postictal deficit, hypoglycemia, metabolic derangements, infection, and, when accompanied by chest or back pain, aortic dissection.
Treatment
A. Intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rTPA) has been shown to benefit patients after ischemic stroke. The randomized, double-blinded, placebo-controlled trial conducted by the National Institute of Neurologic Disorders and Stroke (NINDS) found that rTPA administered within 3 hours of the onset of symptoms resulted in a 12% absolute and 32% relative improvement in outcome. Patients who receive rTPA are more likely to have either minimal or no disability 3 months after a stroke. Patients in the treatment group experienced a 10-fold increased incidence of symptomatic intracranial hemorrhage (ICH) (6.4% vs. 0.6%), but there was no significant difference in mortality. A Cochrane review of this and other thrombolysis trials for ischemic stroke found that thrombolytic therapy reduced the combined endpoint of death or dependence and that rTPA may have advantages over the other thrombolytic agents.
(1) Treatment criteria. To minimize the risk of ICH and other complications, patients who receive rTPA for stroke must meet the stringent criteria derived from the NINDS and subsequent trials. Absolute and relative contraindications to the administration of rTPA must be carefully considered. There is some disagreement as to the importance of the different relative contraindications, so the risks and benefits of rTPA must be weighed in all cases.
(a) Medical history criteria
(i) Patients must be >18 years of age.
(ii) Patients must receive therapy within 3 hours of the onset of symptoms. Patients who cannot precisely recall the onset of symptoms (e.g., those who fell asleep >3 hours before possible drug administration and awakened with symptoms) are ineligible.
(iii) Patients should not have symptoms that suggest aneurysmal subarachnoid hemorrhage (SAH).
(iv) Patients should not have had seizures at the onset of the event.
(v) Patients must not have had another stroke, serious head trauma, or intracranial or intraspinal surgery within the past 3 months.
(vi) Patients should not have a history of ICH or bleeding from either an SAH or arteriovenous malformation.
(vii) Patients should not be taking oral anticoagulants (e.g., warfarin), have received heparin within the last 48 hours, or have coagulation abnormalities.
(viii) Relative contraindications include a major operation or trauma within the last 2 weeks, gastrointestinal or genitourinary hemorrhage within the last 3 weeks, arterial puncture at a noncompressible site within the last week, lumbar puncture within the last 3 weeks, myocardial infarction (MI) within last 3 months, or post-MI pericarditis.
(b) Clinical examination criteria
(i) Patients who have minor or rapidly resolving deficits are ineligible.
(ii) Patients should have an SBP of <185 mm Hg and diastolic blood pressure (DBP) of <110 mm Hg. A trial of nitroglycerin, 1 to 2 inches of paste; labetalol, 10 to 20 mg i.v. push over 1 to 2 minutes repeated once in 10 minutes, or enalapril, 0.625 to 1.25 mg i.v. over 5 minutes may be administered to lower blood pressure. Patients should not receive thrombolysis if these measures do not keep blood pressure below 185/110 mm Hg.
(c) Laboratory criteria
(i) Platelets must be >100,000/ mm3.
(ii) PT must be <15 seconds (international normalized ratio <1.7) with a normal PTT.
(iii) Relative contraindication is serum glucose below 50 or above 400 mg/dL. Hypoglycemia as the etiology of the neurologic deficit must be strongly considered, especially if improvement ensues after the administration of glucose.
(d) Radiographic criteria
(i) Noncontrast CT scan should demonstrate no evidence of either ICH or mass lesion.
(ii) Review of NINDS patients who developed symptomatic ICH after thrombolysis demonstrated that the risk of developing ICH was doubled for patients who had evidence of baseline edema on their initial CT scan.
(e) Additional relative contraindications include:
(i) Pregnancy
(ii) Marked lethargy or coma
(iii) Clinical or CT-scan evidence of infarction involving >one-third of the middle cerebral artery territory, which is predictive of a significantly higher incidence of ICH.
(2) Mode of administration
(a) If all the above criteria are met and consent is obtained, rTPA, 0.9 mg/kg, is given intravenously with 10% as a bolus and 90% as an infusion administered over 1 hour.
(b) The drug should be administered in the emergency department if transfer to the ICU will delay therapy.
(c) During therapy, patients are monitored for evidence of ICH and neurologic deterioration.
(d) After therapy, patients are admitted to the ICU for monitoring of neurologic status and blood pressure over the next 24 to 48 hours.
(e) Blood pressure should be checked every 15 minutes for the first 2 hours and every 30 minutes thereafter.
(i) Patients with SBP of >180 mm Hg or DBP of >110 mm Hg should be treated with either labetalol, 10 mg i.v., repeated or doubled every 10 minutes to a total dose of 150 mg followed by an infusion of 1 to 8 mg/minute, if necessary, or enalapril, 0.625 to 1.25 mg i.v. over 5 minutes.
(ii) Patients with severe refractory hypertension (DBP of >140 mm Hg) are treated with nitroprusside, i.v. infusion of 0.5 to 3 mcg/kg/minute, to reduce the MAP by 10% to 20%.
(f) Anticoagulants and antiplatelet drugs are contraindicated for 24 hours after rTPA administration.
(g) Because the criteria for administration of rTPA are so strict, relatively few stroke patients are eligible to receive therapy. Means of increasing the application of this beneficial therapy include:
(i) Public health campaigns emphasizing the urgency of stroke treatment and comparing stroke to heart attack (i.e., "brain attack") to increase public awareness of the need for earlier presentation to hospitals.
(ii) Organization of stroke teams that integrate prehospital, emergency department, neurologic, critical care, laboratory, and radiology staff to facilitate rapid patient evaluation and prompt securing of crucial laboratory and radiographic data.
(3) Future developments. Current diagnostic and therapeutic techniques under investigation that seek to lengthen the therapeutic window for rTPA administration, increase the efficacy of rTPA, and improve salvage rates include:
(a) Use of magnetic resonance imaging to identify patients who have salvageable brain tissue and low risk of ICH so that rTPA may be administered beyond the 3-hour window.
(b) Direct intra-arterial administration of thrombolytic drugs.
(c) Intra-arterial mechanical disruption of thromboembolic occlusion.
(d) Ultrasonographic enhancement of thrombolytic therapy.
(e) Use of different thrombolytic agents or dosing regimens, or both.
Nonthrombolytic therapy. The principles of care for patients after ischemic stroke who are not candidates for rTPA emphasize the optimization of CBF, prevention of secondary brain injury, infarct extension, hemorrhagic conversion, and poststroke complications (e.g., pulmonary embolus and aspiration pneumonia), early mobilization and rehabilitation, and attention to psychiatric and social consequences of stroke, including depression and the need for assistance with daily activities.
(1) Airway management, hemodynamic monitoring, and treatment of increased ICP.
(2) Antihypertensive therapy is generally avoided because, after ischemic stroke, patients tend to have long-term changes in CBF autoregulation so that optimal CBF occurs at higher MAP ranges than for healthy (normotensive) individuals. As a result, aggressive antihypertensive therapy may exacerbate ischemia by decreasing CBF. A generally accepted cutoff for the administration of antihypertensive therapies is SBP >220 mm Hg, DBP >120 mm Hg, or MAP >130 mm Hg.
(3) In the absence of hemorrhage on a CT scan, antiplatelet therapy is initiated in the form of aspirin starting with 325 mg by mouth followed by 81 to 160 mg daily.
(4) Multiple studies have failed to show a benefit to heparin administration, although anticoagulation is usually initiated when atrial fibrillation is present.
(5) Hyperglycemia worsens neurologic outcome. Therefore, euglycemia (80 to 110 mg/dL) is beneficial if it can be achieved without substantially increasing the risk of hypoglycemia.
(6) Seizures are treated with phenytoin, loading dose 15 mg/kg i.v. over 20 minutes followed by 5 to 7 mg/kg/day, or fosphenytoin, loading dose PE 15 to 20 mg/kg i.v., and then 4 to 6 PE mg/kg/day.
(7) DVT prophylaxis is provided using pneumatic compression or low-molecular-weight heparin such as enoxaparin, 0.5 mg/kg subcutaneously twice a day.
(8) After the evaluation of airway reflexes and adequacy of swallowing, nutrition is provided via a suitable route.
(9) Although elevation of the HOB to 30 is often prescribed to facilitate venous drainage and prevent aspiration, some evidence indicates that positioning the HOB at 15 for patients who have normal ICP improves CBF and neurologic function.
(10) Rehabilitation and psychiatric evaluation are essential. Depression often complicates cerebrovascular accidents. Treatment of depression and other psychiatric comorbidities facilitates rehabilitation and improves functional status.
Hemorrhagic stroke or intracranial hemorrhage (ICH)
Pathophysiology. Hemorrhagic stroke is caused primarily by hypertensive cerebrovascular disease, and occurs most commonly in the subcortical regions of the brain. Cortical ICH often results from amyloid angiopathy, which is increasing in incidence as the population ages. Hemorrhagic stroke is devastating; only 30% of patients are able to live independently 6 months after the event. Mass effect from the post-ICH hematoma has traditionally been thought to play a major role in the pathophysiology of ICH. Recent animal data indicate, however, that the most important pathophysiologic process may be the dissection of the hematoma along tissue planes followed by neurotoxicity and cerebral edema from blood proteins and their breakdown products. Early enlargement of the hematoma occurs in approximately 40% of ICH patients and significantly worsens prognosis.
Diagnosis. Hemorrhagic stroke typically presents with headache, nausea, and vomiting as well as seizures and focal neurologic deficits. Larger hemorrhagic strokes cause lethargy, stupor, and coma.
Treatment includes rapid assessment to detect treatable conditions that may mimic hemorrhagic stroke; support of airway, breathing, and circulation; seizure control; noncontrast CT scan of the head; reversal of iatrogenic and spontaneous coagulopathy; consideration of recombinant activated factor VII (rFVIIa) therapy; and general neurointensive care.
a. Treatable conditions that may mimic ICH include:
(1) Hypoglycemia and other metabolic abnormalities, including disorders of sodium and calcium homeostasis.
(2) Meningitis, encephalitis, sepsis, SAH, and shock.
(3) Toxins, including illicit drugs, ethanol, environmental and occupational agents, and prescription medications administered either by the patient or a physician.
(4) Many of these conditions can be detected by simple bedside tests and are easily treated. Hypoglycemic patients should receive glucose, 25 g i.v. Thiamine, 100 mg i.v., and naloxone, 1 mg i.v., may be initiated to patients who are suspected of either ethanol or opiate abuse.
b. Support of the airway, breathing, and circulation (ABC) is provided accordingly.
c. Coagulopathy must be corrected as rapidly as possible. Fresh frozen plasma (FFP), 15 mL/kg i.v., rapidly reverses coagulopathy. Because this can require an infusion of a liter or more of FFP, volume status must be carefully monitored. Long-term correction of coagulopathy can be achieved by administering vitamin K, 5 mg intramuscular (i.m.) or i.v. daily for 3 days. Intravenous administration effects more rapid correction but may cause anaphylaxis. Patients who have ICH related to rTPA administration may also be treated with FFP, although there are no data on efficacy to support any specific therapy.
d. Seizures are treated with lorazepam, 2 mg i.v.; phenytoin, loading dose 15 mg/kg i.v. over 20 minutes followed by 5 to 7 mg/kg/day, or fosphenytoin, loading dose PE 15 to 20 mg/kg i.v., and then 4 to 6 PE mg/kg/day. The American Heart Association (AHA) recommends that seizure prophylaxis with phenytoin be given for 1 month to all patients after ICH.
e. Euvolemia is maintained with an intravenous infusion of isotonic solution. Hypotonic fluids may exacerbate cerebral edema, and glucose-containing solutions are not used unless patients are hypoglycemic.
f. Treatment of elevated blood pressure has not been shown to benefit patients who suffered ICH. Concerns about exacerbating hemorrhage must be weighed against the possibility that antihypertensive drugs may reduce CBF and worsen ischemia. As with patients after ischemic stroke, many patients who have had an hemorrhagic stroke have altered autoregulation of CBF and require a higher MAP to maintain adequate CBF. In general, an MAP of 130 mm Hg is considered to be a trigger for treating hypertension. Either labetalol or enalapril may be used to reduce MAP by approximately 10% to 15%.
g. A recent randomized, placebo-controlled trial indicated that the administration of rFVIIa, 80 to 160 mcg/kg i.v., within 4 hours of the onset of symptoms of hemorrhagic stroke limits expansion of the hematoma and decreases the incidence of death and severe disability at 3 months. Contraindications include thrombotic and vaso-occlusive disease. Research to refine the doses and indications for this therapy is in progress.
h. Normothermia is maintained.
i. Indications for placement of an intraventricular catheter for ICP monitoring and therapeutic CSF drainage include intraventricular hemorrhage and hydrocephalus. ICP monitoring may also be instituted in patients who are either deteriorating or comatose but are thought to be salvageable. Prophylactic antibiotics, microbiologic monitoring, and weekly dressing changes have been recommended to decrease the risk of catheter infection.
j. Multiple trials in patients above 45 years of age have failed to demonstrate benefit from craniotomy and evacuation of an intracerebral hematoma. Indications for operation that have traditionally been accepted or may be inferred from recent trials include cerebellar hematomas >3 cm2 or accompanied by neurologic deterioration, large accessible cortical hematomas (<1 cm from cortical surface), and neurologic deterioration. Younger patients are more likely to benefit from surgery than older patients.
k. Trials of minimally invasive techniques using endoscopic evacuation of hematomas have been inconclusive, although it is possible that refinements in equipment and technique will result in improved outcome.
l. Pneumatic compressive devices are recommended for DVT prophylaxis.
m. Nutritional support and stress-ulcer prophylaxis are provided using H2 antagonists such as famotidine, 20 mg i.v., every 12 hours, or proton-pump inhibitors such as pantoprazole, 40 mg i.v. daily.
n. Steroids are contraindicated for patients with ICH.
o. Critical care issues such as the maintenance of CPP, treatment of elevated ICP, role of barbiturate therapy, and medical complications of ICH were discussed in the preceding text.

III. Brain death and organ donation

The importance of brain death and organ donation. Brain death is accepted as a legal definition of death in the United States and most other countries. Diagnosing brain death allows the discontinuation of artificial support of vital functions that maintain certain biologic functions in a brain-dead person. This diagnosis decreases the ambiguity and emotional suffering for family members, decreases the waste of medical resources, and allows for organ donation. Appropriate counseling of family members is essential in helping them understand and accept the reality of death despite the apparent maintenance of certain aspects of life through artificial means. Coordinators of organ procurement organizations (OPOs) assist in this process by counseling family members, clarifying legal issues, helping in the consent process, providing advice about care for the brain-dead organ donor, and arranging organ harvest. This process shifts the focus of care from resuscitation to organ preservation for harvesting and transplantation.
Physiology of brain death. Brain death entails the cessation of CBF with resultant loss of brain function. The final common pathway for brain death is the loss of cerebral perfusion with the cessation of brain stem activity. The process proceeds in a rostral to caudal direction. Loss of blood flow to the medulla is often accompanied by a catecholamine surge that results in increased MAP, followed by hemodynamic instability and even frank hypotension. This process is followed by metabolic derangements from ischemia or infarction of the pituitary gland. The most important consequence of pituitary dysfunction is central DI, requiring the replacement of antidiuretic hormone for the maintenance of sodium and fluid balance.
Diagnosis of brain death
Brain death is clinically marked by complete unresponsiveness, apnea, and loss of brain stem reflexes. Cessation of cortical function often precedes brain stem death but is not sufficient for diagnosis because patients may retain brain stem function indefinitely. Brain death can be diagnosed only when the cause of the coma has been identified (e.g., TBI, ICH, SAH) and conditions that mimic brain death have been ruled out clinically. These conditions include the locked-in syndrome, severe hypothermia, severe intoxication (including anesthetic and neuromuscular blocking drugs), and Guillain-Barre syndrome with peripheral and cranial nerve involvement. Brain death is diagnosed clinically; the need for confirmation with ancillary tests is based on patient status and age. Spinal reflexes are often maintained and do not contradict the diagnosis of brain death. Demonstration of the absence of brain stem reflexes and confirmation of apnea are central to the diagnosis (Table 22-4).
The apnea test is performed as follows:
1. The patient is preoxygenated with 100% oxygen.
2. Apneic oxygenation is provided at 15 L/minute through a catheter placed in the ET tube to the level of the carina.
3. The patient is disconnected from the ventilator and observed for spontaneous ventilation.
Paco2 typically rises at 3 mm Hg/minute of apnea. In the United States, apnea in the presence of a rise of Paco2 to 60 mm Hg or an increase of 20 mm Hg from baseline is considered confirmatory. The United Kingdom Code of Practice recommends a 10-minute apnea test.

Table-4. Clinical criteria for brain death in adults and children

Coma
Absence of motor responses
Absence of pupillary responses to light and pupils at midposition with respect to dilatation (4-6 mm)
Absence of corneal reflexes
Absence of caloric responses
Absence of gag reflex
Absence of coughing in response to tracheal suctioning
Absence of sucking and rooting reflexes
Absence of respiratory drive at a PacO2 of 60 mm Hg or 20 mm Hg above normal base-line valuesa
Interval between two evaluations, according to patient's age
Term to 2 mo old, 48 hr
>2 mo to 1 y old, 24 hr
>1 y to <18 y old, 12 hr
>18 y old, interval optional
Confirmatory test
Term to 2 mo old, 2 confirmatory tests
>2 mo to 1 y old, 1 confirmatory test
>1 y to <18 y old, optional
>18 y old, optional
aPaco2 denotes the partial pressure of arterial carbon dioxide tension.

Confirmatory testing for brain death includes:
1. Isoelectric EEG
2. Absence of cerebral perfusion
as demonstrated by cerebral angiography, technetium 99 scanning, or transcranial Doppler ultrasonography
Care of the brain-dead organ donor. This should be done in coordination with the local OPO coordinator.
Exclusion criteria for organ donation may vary by organ and by geographic region. This should be discussed with the OPO coordinator. In general, absolute contraindications include human immunodeficiency virus (HIV) disease, metastatic cancer, sepsis, and prion disease.
Screening tests for organ donors include:
1. HIV, hepatitis B, hepatitis C, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human T-cell lymphoma/leukemia virus-1 (HTLV-1) serology
2. ABO and human lymphocyte antigen (HLA) typing
3. Blood, sputum, and urine cultures
4. Complete blood count, metabolic panel, urinalysis, arterial blood gas
5. Organ-specific tests as requested by the OPO
Perioperative monitoring includes electrocardiogram, pulse oximetry, temperature, urine output, invasive arterial blood pressure, and central venous and/or pulmonary artery pressures. Because the process of organ harvest requires sequential vessel ligation, the arterial catheter should be inserted in the left arm, and the central venous or pulmonary artery catheterization should be performed on the right.
Optimal physiologic goals for organ donors include:
1. MAP 60 to 80 mm Hg; SBP >90 mm Hg
2. CVP 8 to 12 mm Hg; pulmonary artery wedge pressure 10 to 15 mm Hg
3. Heart rate 60 to 100 beats/minute
4. Cardiac index >2.1 L/minute/m2
5. Urine output 1 to 2 mL/kg/hour, with volume replacement generally 50 mL/hour more than urine output
6. Temperature maintained between 97 and 100 F using warming or cooling blankets
Therapeutic maneuvers include the following:
a. Antiarrhythmic drugs for the treatment of arrhythmia.
b. Isoproterenol or cardiac pacing for the treatment of severe bradycardia.
c. Isotonic intravenous fluids to maintain targeted blood pressure and CVP.
d. If hypotension persists after achieving CVP of 10 mm Hg, vasoactive drugs are used as follows:
(1) Dopamine, 5 to 15 mcg/kg/minutes, for hypotension with normal or elevated cardiac output.
(2) Dobutamine, 5 to 10 mcg/kg/minutes, is added for hypotension with decreased cardiac output. Dobutamine may cause hypotension through its beta-agonist effects and tachydysrhythmia, particularly when combined with dopamine.
(3) Phenylephrine, 100 mcg loading dose followed by an infusion of 50 to 150 mcg/minute, may be added to dobutamine to counteract its beta-agonist effects.
(4) Dobutamine, 5 to 10 mcg/kg/minute, is the drug of choice for patients who have decreased cardiac output and increased systemic vascular resistance.
e. DI involves increased urine output (>7 mL/kg/hour), decreased urine-specific gravity (<1.010), decreased urine osmolarity (less than serum osmolarity), hypernatremia (>150 mEq/L), and serum hyperosmolarity (>295 mOsm/L). Treatment includes the infusion of dextrose 5% in water (D5W) to replace free-water deficits and maintain serum Na at <155 mEq/L and the administration of vasopressin, 1 unit i.v., bolus followed by 0.5 to 4 units/hour, to maintain urine output between 1 and 2 mL/kg/hour.
f. Insulin infusion, 2 to 7 units/hour, may be needed to maintain serum glucose between 80 and 160 mg/dL. Replacement to maintain potassium (K) at >4 mEq/L may be needed with insulin infusions.
g. Triiodothyronine, 4 mcg i.v. bolus followed by 3 mcg/hour, is administered to maintain euthyroid status.
h. Mechanical ventilation should be performed with the aim of minimizing lung injury.
(1) Ventilation rate is set to maintain normocapnia. Triggered breaths may result from cardiac activity and may be confused with spontaneous ventilation.
(2) Tidal volume is set at 6 to 8 mL/kg. Pressure-controlled ventilation may be used as an alternative to minimize barotrauma.
(3) PEEP is kept as close to 5 mm Hg as possible.
(4) The fraction of inspired oxygen (Fio2) is reduced to the minimum value necessary to maintain Pao2 at >90 mm Hg. The target Fio2 is <40%.
i. Hypokalemia, hypophosphatemia, and hypocalcemia are common electrolyte abnormalities that must be monitored and corrected.
j. Packed red blood cells are transfused to maintain hemoglobin at 9 g/dL.
k. FFP and platelets are transfused to correct coagulopathy and bleeding disorders.
l. The OPO coordinator usually recommends methylprednisolone, 15 mg/kg i.v., as well as an antibiotic regimen.
Organ harvesting is typically performed by different teams that represent various potential recipients. The OPO coordinates the process which includes steps designed to minimize warm ischemia time for each organ. Muscle relaxants are often used to facilitate organ harvest and prevent reflex movements. After opening the thoracoabdominal cavity, the bowel is retracted, organ attachments are incised, and major vessels are cannulated for infusion of cold organ-preservation solution. The aorta is then cross-clamped, preservative solution is infused, and the organs are removed. Mechanical ventilation is terminated after the preservative solution is administered and cardioplegia occurs.
Non-heart beating donors (NHBDs). NHBDs are non-brain-dead patients who have irreversible disease processes from whom resuscitative care is withdrawn either because of advanced directives or upon request of the next of kin. Organ harvesting is initiated immediately after death. Success rates for renal transplants from NHBDs are similar to those for kidneys harvested from brain-dead donors. Livers and lungs may also be suitable. Corneas, bones, skin, and heart valves are all relatively durable and can be donated up to 24 hours after death. Physicians should consult with hospital ethicists, risk-management staff, and the local OPO when the withdrawal of resuscitative care from a potential NHBD is being considered.

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