1 Sudden Deterioration in Neurologic Status
Patients admitted to the intensive care unit (ICU) with critical illness or injury are at risk for neurologic complications.1–5 A sudden or unexpected change in the neurologic condition of a critically ill patient often heralds a complication that may cause direct injury to the central nervous system (CNS). Alternatively, such changes may simply be neurologic manifestations of the underlying critical illness or treatment that necessitated ICU admission (e.g., sepsis). These complications can occur in patients admitted to the ICU without neurologic disease and in those admitted for management of primary CNS problems (e.g., stroke). Neurologic complications also can occur as a result of invasive procedures and therapeutic interventions performed. Commonly, recognition of neurologic complications is delayed or missed entirely because ICU treatments (e.g., intubation, drugs) interfere with the physical examination or confound the clinical picture. In other cases, neurologic complications are not recognized because of a lack of sensitive methods to detect the problem (e.g., delirium). Morbidity and mortality are increased among patients who develop neurologic complications; therefore, the intensivist must be vigilant in evaluating all critically ill patients for changes in neurologic status.
Despite the importance of neurologic complications of critical illness, few studies have specifically assessed their incidence and impact on outcome among ICU patients. Available data are limited to medical ICU patients; data regarding neurologic complications in general surgical and other specialty ICU populations must be extracted from other sources. In studies of medical ICU patients, the incidence of neurologic complications is 12.3% to 33%.1,2 Patients who develop neurologic complications have increased morbidity, mortality, and ICU length of stay. Sepsis is the most common problem associated with development of neurologic complications (sepsis-associated encephalopathy). In addition to encephalopathy, other common neurologic complications associated with critical illness include seizures and stroke. As the complexity of ICU care has increased, so has the risk of neurologic complications. Neuromuscular disorders are now recognized as a major source of morbidity in severely ill patients.6 Recognized neurologic complications occurring in selected medical, surgical, and neurologic ICU populations are shown in Table 1-1.7–41
TABLE1-1 Neurologic Complications in Selected Specialty Populations
| Medical | |
| Bone marrow transplantation7,8 | CNS infection, stroke, subdural hematoma, brainstem ischemia, hyperammonemia, Wernicke encephalopathy |
| Cancer9 | Stroke, intracranial hemorrhage, CNS infection |
| Fulminant hepatic failure10 | Encephalopathy, coma, brain edema, increased ICP |
| HIV/AIDS11,12 | Opportunistic CNS infection, stroke, vasculitis, delirium, seizures, progressive multifocal leukoencephalopathy |
| Pregnancy13,14 | Seizures, ischemic stroke, cerebral vasospasm, intracranial hemorrhage, cerebral venous thrombosis, hypertensive encephalopathy, pituitary apoplexy |
| Surgical | |
| Cardiac surgery15–19 | Stroke, delirium, brachial plexus injury, phrenic nerve injury |
| Vascular surgery20,21: | |
| Carotid | Stroke, cranial nerve injuries (recurrent laryngeal, glossopharyngeal, hypoglossal, facial), seizures |
| Aortic | Stroke, paraplegia |
| Peripheral | Delirium |
| Transplantation10,22–25: | |
| Heart | Stroke |
| Liver | Encephalopathy, seizures, opportunistic CNS infection, intracranial hemorrhage, Guillain-Barré syndrome, central pontine myelinolysis |
| Renal | Stroke, opportunistic CNS infection, femoral neuropathy |
| Urologic surgery (TURP)26 | Seizures and coma (hyponatremia) |
| Otolaryngologic surgery27,28 | Recurrent laryngeal nerve injury, stroke, delirium |
| Orthopedic surgery29: | |
| Spine | Myelopathy, radiculopathy, epidural abscess, meningitis |
| Knee and hip replacement | Delirium (fat embolism) |
| Long-bone fracture/nailing | Delirium (fat embolism) |
| Neurologic | |
| Stroke30–34 | Stroke progression or extension, reocclusion after thrombolysis, bleeding, seizures, delirium, brain edema, herniation |
| Intracranial surgery35 | Bleeding, edema, seizures, CNS infection |
| Subarachnoid hemorrhage32,36–38 | Rebleeding, vasospasm, hydrocephalus, seizures |
| Traumatic brain injury32,39,40 | Intracranial hypertension, bleeding, seizures, stroke (cerebrovascular injury), CNS infection |
| Cervical spinal cord injury41 | Ascension of injury, stroke (vertebral artery injury) |
CNS, central nervous system; HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency syndrome; ICP, intracranial pressure; TURP, transurethral prostatic resection.
Impairment in Consciousness
Global changes in CNS function, best described in terms of impairment in consciousness, are generally referred to as encephalopathy or altered mental status. An acute change in the level of consciousness undoubtedly is the most common neurologic complication that occurs after ICU admission. Consciousness is defined as a state of awareness (arousal or wakefulness) and the ability to respond appropriately to changes in environment.42 For consciousness to be impaired, global hemispheric dysfunction or dysfunction of the brainstem reticular activating system must be present.43 Altered consciousness may result in a sleeplike state (coma) or a state characterized by confusion and agitation (delirium). States of acutely altered consciousness seen in the critically ill are listed in Table 1-2.
| State | Description |
|---|---|
| Coma | Closed eyes, sleeplike state with no response to external stimuli (pain) |
| Stupor | Responsive only to vigorous or painful stimuli |
| Lethargy | Drowsy, arouses easily and appropriately to stimuli |
| Delirium | Acute state of confusion with or without behavioral disturbance |
| Catatonia | Eyes open, unblinking, unresponsive |
When an acute change in consciousness is noted, the patient should be evaluated keeping in mind the patient’s age, presence or absence of coexisting organ system dysfunction, metabolic status and medication list, and presence or absence of infection. In patients with a primary CNS disorder, deterioration in the level of consciousness (e.g., from stupor to coma) frequently represents the development of brain edema, increasing intracranial pressure, new or worsening intracranial hemorrhage, hydrocephalus, CNS infection, or cerebral vasospasm. In patients without a primary CNS diagnosis, an acute change in consciousness is often due to the development of infectious complications (i.e., sepsis-associated encephalopathy), drug toxicities, or the development or exacerbation of organ system failure. Nonconvulsive status epilepticus is increasingly being recognized as a cause of impaired consciousness in critically ill patients (Box 1-1).44–53
Box 1-1
General Causes of Acutely Impaired Consciousness in the Critically Ill
CNS, central nervous system.
States of altered consciousness manifesting as impairment in wakefulness or arousal (i.e., coma and stupor) and their causes are well defined.42,43,54,55 Much confusion remains, however, regarding the diagnosis and management of delirium, perhaps the most common state of impaired CNS functioning in critically ill patients at large. When dedicated instruments are used, delirium can be diagnosed in more than 80% of critically ill patients, making this condition the most common neurologic complication of critical illness.56–58 Much of the difficulty in establishing the diagnosis of delirium stems from the belief that delirium is a state characterized mainly by confusion and agitation and that such states are expected consequences of the unique environmental factors and sleep deprivation that characterize the ICU experience. Terms previously used to describe delirium in critically ill patients include ICU psychosis, acute confusional state, encephalopathy, and postoperative psychosis. It is now recognized that ICU psychosis is a misnomer; delirium is a more accurate term.59
Currently accepted criteria for the diagnosis of delirium include abrupt onset of impaired consciousness, disturbed cognitive function, fluctuating course, and presence of a medical condition that could impair brain function.60 Subtypes of delirium include hyperactive (agitated) delirium and the more common hypoactive or quiet delirium.58 Impaired consciousness may be apparent as a reduction in awareness, psychomotor retardation, agitation, or impairment in attention (increased distractibility or vigilance). Cognitive impairment can include disorientation, impaired memory, and perceptual aberrations (hallucinations or illusions).61 Autonomic hyperactivity and sleep disturbances may be features of delirium in some patients (e.g., those with drug withdrawal syndromes, delirium tremens). Delirium in critically ill patients is associated with increased morbidity, mortality, and ICU length of stay.62–64 In general, sepsis and medications should be the primary etiologic considerations in critically ill patients who develop delirium.
As has been noted, nonconvulsive status epilepticus is increasingly recognized as an important cause of impaired consciousness in critically ill patients. Although the general term can encompasses other entities, such as absence and partial complex seizures, in critically ill patients, nonconvulsive status epilepticus is often referred to as status epilepticus of epileptic encephalopathy.53 It is characterized by alteration in consciousness or behavior associated with electroencephalographic evidence of continuous or periodic epileptiform activity without overt motor manifestations of seizures. In one study of comatose patients without overt seizure activity, nonconvulsive status epilepticus was evident in 8%.51 Nonconvulsive status epilepticus can precede or follow an episode of generalized convulsive status epilepticus; it can also occur in patients with traumatic brain injury, subarachnoid hemorrhage, global brain ischemia or anoxia, sepsis, and multiple organ failure. Despite the general consensus that nonconvulsive status epilepticus is a unique entity responsible for impaired consciousness in some critically ill patients, there is no general consensus on the electroencephalographic criteria for its diagnosis or the optimal approach to treatment.65
Stroke and Other Focal Neurologic Deficits
The new onset of a major neurologic deficit that manifests as a focal impairment in motor or sensory function (e.g., hemiparesis) or results in seizures usually indicates a primary problem referable to the cerebrovascular circulation. In a study evaluating the value of computed tomography (CT) in medical ICU patients, ischemic stroke and intracranial bleeding were the most common abnormalities associated with the new onset of a neurologic deficit or seizures.66 Overall, the frequency of new-onset stroke is between 1% and 4% in medical ICU patients.1,2 Among general surgical patients, the frequency of perioperative stroke ranges from 0.3% to 3.5%.67 Patients undergoing cardiac or vascular surgery and surgical patients with underlying cerebrovascular disease can be expected to have an increased risk of perioperative stroke.19
The frequency of new or worsening focal neurologic deficits in patients admitted with a primary neurologic or neurosurgical disorder varies. For example, as many as 30% of patients with aneurysmal subarachnoid hemorrhage develop delayed ischemic neurologic deficits.36 Patients admitted with stroke often develop worsening or new symptoms as a result of stroke progression, bleeding, or reocclusion of vessels previously opened with interventional therapy. In patients who have undergone elective intracranial surgery, postsurgical bleeding or infectious complications are the main causes of new focal deficits. In trauma patients, unrecognized injuries to the cerebrovascular circulation can cause new deficits. Patients who have sustained spinal cord injuries, and those who have undergone surgery of the spine or of the thoracic or abdominal aorta, can develop worsening or new symptoms of spinal cord injury. Early deterioration of CNS function after spinal cord injury usually occurs as a consequence of medical interventions to stabilize the spine, whereas late deterioration is usually due to hypotension and impaired cord perfusion. Occasionally, focal weakness or sensory symptoms in the extremities occur as a result of occult brachial plexus injury or compression neuropathy. New cranial nerve deficits in patients without primary neurologic problems can occur after neck surgery or carotid endarterectomy.
Seizures
The new onset of motor seizures occurs in 0.8% to 4% of critically ill medical ICU patients.1,2,68 The new onset of seizures in general medical-surgical ICU patients is typically caused by narcotic withdrawal, hyponatremia, drug toxicities, or previously unrecognized structural abnormalities.3,68 New stroke, intracranial bleeding, and CNS infection are other potential causes of seizures after ICU admission. The frequency of seizures is higher in patients admitted to the ICU with a primary neurologic problem such as traumatic brain injury, aneurysmal subarachnoid hemorrhage, stroke, or CNS infection.69 Because nonconvulsive status epilepticus may be more common than was previously appreciated, this problem should also be considered in the differential diagnosis of patients developing new, unexplained, or prolonged alterations in consciousness.
Generalized Weakness and Neuromuscular Disorders
Generalized muscle weakness often becomes apparent in ICU patients as previous impairments in arousal are resolving or sedative and neuromuscular blocking agents are being discontinued or tapered. Polyneuropathy and myopathy associated with critical illness are now well recognized as the principal causes of new-onset generalized weakness among ICU patients being treated for non-neuromuscular disorders.5,70–73 These disorders also may be responsible for prolonged ventilator dependency in some patients. Patients at increased risk for these complications include those with sepsis, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome, as well as those who require prolonged mechanical ventilation. Other risk factors include treatment with corticosteroids or neuromuscular blocking agents. In contrast to demyelinating neuropathies (e.g., Guillain-Barré syndrome), critical illness polyneuropathy is primarily an axonal condition. Critical illness polyneuropathy is diagnosed in a high percentage of patients undergoing careful evaluation for weakness acquired while in the ICU. Because primary myopathy coexists in a large number of patients with critical illness polyneuropathy, ICU-acquired paresis72 or critical illness neuromuscular abnormalities5 may be better terms to describe this problem. Although acute Guillain-Barré syndrome and myasthenia gravis are rare complications of critical illness, these diagnoses should also be considered in patients who develop generalized weakness in the ICU.
Neurologic Complications of Procedures and Treatments
Routine procedures performed in the ICU or in association with evaluation and treatment of critical illness can result in neurologic complications.4 The most obvious neurologic complications are those associated with intracranial bleeding secondary to the treatment of stroke and other disorders with thrombolytic agents or anticoagulants. Other notable complications are listed in Table 1-3.
TABLE1-3 Neurologic Complications Associated with ICU Procedures and Treatments
| Procedure | Complication |
|---|---|
| Angiography | Cerebral cholesterol emboli syndrome |
| Anticoagulants/antiplatelet agents | Intracranial bleeding |
| Arterial catheterization | Cerebral embolism |
| Bronchoscopy | Increased ICP |
| Central venous catheterization | Cerebral air embolism, carotid dissection, Horner’s syndrome, phrenic nerve injury, brachial plexus injury, cranial nerve injury |
| DC cardioversion | Embolic stroke, seizures |
| Dialysis | Seizures, increased ICP (dialysis disequilibrium syndrome) |
| Endovascular procedures (CNS) | Vessel rupture, thrombosis, reperfusion bleeding |
| Epidural catheter | Spinal epidural hematoma, epidural abscess |
| ICP monitoring | CNS infection (ventriculitis), hemorrhage |
| Intraaortic balloon pump | Lower-extremity paralysis |
| Intubation | Spinal cord injury |
| Left ventricular assist devices | Stroke, seizures |
| Lumbar puncture or drain | Meningitis, herniation |
| Mechanical ventilation | Cerebral air embolism, increased ICP (high PEEP and hypercapnia), seizures (hypocapnia) |
| Nasogastric intubation | Intracranial placement |
CNS, central nervous system; DC, direct current; ICP, intracranial pressure; ICU, intensive care unit; PEEP, positive end-expiratory pressure.
Evaluation of Sudden Neurologic Change
Essential elements of the neurologic examination include an assessment of the level and content of consciousness, pupillary size and reactivity, and motor function. Additional evaluation of the cranial nerves and peripheral reflexes and a sensory examination are conducted as indicated by the clinical circumstances. If the patient is comatose on initial evaluation, a more detailed coma examination should be performed to help differentiate structural from metabolic causes of coma.43,55 When the evaluation reveals only a change in arousal without evidence of a localizing lesion in the CNS, a search for infection, discontinuation or modification of drug therapy, and a general metabolic evaluation may be indicated. Lumbar puncture to aid the diagnosis of CNS infection may be warranted in selected neurosurgical patients and immunocompromised individuals. Lumbar puncture to rule out nosocomially acquired meningitis in other patients is generally not rewarding.74 Electroencephalography should be performed in patients with clear evidence of seizures, as well as when the diagnosis of nonconvulsive status epilepticus is being entertained. Continuous electroencephalography should be considered when the index of suspicion for nonconvulsive status epilepticus remains high and the initial electroencephalographic studies are unrevealing.
CT is indicated for non-neurologic patients with new focal deficits, seizures, or otherwise unexplained impairments in arousal.66 In patients with primary neurologic disorders, CT is indicated if worsening brain edema, herniation, bleeding, and hydrocephalus are considerations when new deficits or worsening neurologic status occurs. In some cases, when the basis for a change in neurologic condition remains elusive, magnetic resonance imaging (MRI) may be helpful. In particular, the diffusion-weighted MRI technique can reveal structural abnormalities such as hypoxic brain injury, fat embolism, vasculitis, cerebral venous thrombosis, or multiple infarcts following cardiopulmonary bypass that are not apparent by standard CT or conventional MRI.75–80 MRI may be the imaging modality of choice in patients with human immunodeficiency virus (HIV) and new CNS complications.75 For patients who develop signs and symptoms of spinal cord injury complicating critical illness, MRI or somatosensory evoked potentials can be used to further delineate the nature and severity of the injury. For patients who develop generalized muscle weakness or unexplained ventilator dependency, electromyography and nerve conduction studies can confirm the presence of critical illness polyneuropathy or myopathy.
Monitoring for Neurologic Changes
The common occurrence of neurologic changes in critically ill patients emphasizes the need for vigilant monitoring. A variety of clinical techniques such as the Glasgow Coma Scale, National Institutes of Health Stroke Scale, Ramsay Sedation Scale, Richmond Agitation-Sedation Scale, and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) can be used to monitor clinical neurologic status.57,58,81–86 Neurophysiologic methods such as the bispectral index may provide more objective neurologic monitoring in the future for patients admitted to the ICU with and without primary neurologic problems.87–89 For patients admitted to the ICU with a primary neurologic disorder, a variety of monitoring techniques including measurements of intracranial pressure, near-infrared spectroscopy, brain tissue PO2, transcranial Doppler, and electroencephalography are available.90
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