Key Points for Issue

p. December 2018, Vol.24, No.6 doi: 10.1212/01.CON.0000550299.96348.b9
Key Points for Issue
BROWSE ARTICLES
KEY POINTS

The aim of multimodality monitoring is to understand the complexity of the changes that lead to secondary brain injury.

The most severe limitation to the application of cerebral microdialysis in bedside decision making is the unfinished work of defining markers of health and crisis in different clinical contexts.

Brain tissue oxygen tension monitors have shown low rates of complication.

Many factors affect brain tissue oxygen tension including cerebral perfusion pressure, hemoglobin concentration, oxygen saturation, metabolic rate (from fever, agitation, or shivering), and cerebral vasospasm.

Near-infrared spectroscopy devices have an excellent safety profile.

Near-infrared spectroscopy shows promise as a method of assessing cerebral autoregulation when used in concert with systemic blood pressure and intracranial pressure monitors.

Understanding global physiology is key to detecting significant changes that affect large areas in the brain after traumatic brain injury, aneurysmal subarachnoid hemorrhage, ischemic stroke, intracranial hemorrhage and status epilepticus, among other conditions.

Nonconvulsive seizures have been described in 5% to 15% of patients with acute intracranial injury (eg, traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, postneurosurgery), and nonconvulsive status epilepticus has been described in 5% to 20% of such patients.

EEG is recommended for patients during therapeutic hypothermia after cardiac arrest and within 24 hours of rewarming, not only to diagnose and treat seizures and myoclonic status epilepticus, but also because of its prognostic factors.

If brain oxygenation monitoring is desired, the preferred choice is brain tissue oxygen tension sensors.

Intracranial pressure monitoring is recommended as part of protocol-driven care for patients with acute brain injury who are at risk of elevated intracranial pressure based on clinical or imaging features.

The gold standard intracranial pressure monitor is the ventriculostomy.

Intracranial pressure monitors are recommended in patients with a Glasgow Coma Scale score of 8 or less and who have an abnormal head CT.

Noninvasive intracranial pressure monitors are still under development and are not yet recognized as providing an accurate intracranial pressure measurement.

Dynamic cerebral autoregulation monitoring has evolved to allow bedside calculation of optimal cerebral perfusion pressure and optimal mean arterial pressure with invasive and noninvasive methods.

The importance of cerebral autoregulation multimodal monitoring technology is that calculation of optimal mean arterial pressure and cerebral perfusion pressure would allow physicians to individualize cerebral perfusion pressure or mean arterial pressure goals and potentially improve a patient’s outcomes.

Cerebral perfusion pressure below the optimal level increases the incidence of fatal outcome, whereas excessively high cerebral perfusion pressure is associated with an increased proportion of severe disability.

Monitoring systems will find their greatest utility when appreciated in concert with each other and with other forms of clinical data including laboratory values, imaging results, and medical record documentation.

Lack of common formatting standards stands as a significant barrier to true data integration, which necessitates a patient data management system that translates monitor output from proprietary formats and merges them into a common stream.

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Neurocritical Care

Article 1: Cerebral Edema and Elevated Intracranial Pressure

Matthew A. Koenig, MD, FNCS. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1588–1602.

ABSTRACT

PURPOSE OF REVIEW

This article reviews the management of cerebral edema, elevated intracranial pressure (ICP), and cerebral herniation syndromes in neurocritical care.

RECENT FINDINGS

While corticosteroids may be effective in reducing vasogenic edema around brain tumors, they are contraindicated in traumatic cerebral edema. Mannitol and hypertonic saline use should be tailored to patient characteristics including intravascular volume status. In patients with traumatic brain injury who are comatose, elevated ICP should be managed with an algorithmic, multitiered treatment protocol to maintain an ICP of 22 mm Hg or less. Third-line ICP treatments include anesthetic agents, induced hypothermia, and decompressive craniectomy. Recent clinical trials have demonstrated that induced hypothermia and decompressive craniectomy are ineffective as early neuroprotective strategies and should be reserved for third-line management of refractory ICP elevation in severe traumatic brain injury. Monitoring for cerebral herniation should include bedside pupillometry in supratentorial space-occupying lesions and recognition of upward herniation in patients with posterior fossa lesions.

SUMMARY

Although elevated ICP, cerebral edema, and cerebral herniation are interrelated, treatments should be based on the distinct pathophysiologic process. Focal lesions resulting in brain compression are primarily managed with surgical decompression, whereas global or multifocal brain injury requires a treatment protocol that includes medical and surgical interventions.

KEY POINTS

  • Corticosteroids are ineffective for the treatment of cytotoxic edema and are contraindicated in the treatment of patients with severe traumatic brain injury.
  • Frequent administration of hypertonic saline may cause hyperchloremic metabolic acidosis, which is associated with higher mortality in neurocritical care. Buffering hypertonic solutions with acetate may lower the chance of developing hyperchloremic metabolic acidosis.
  • Serum osmolality should be monitored in patients treated with frequent doses of mannitol. Mannitol should be held when serum osmolality exceeds 320 mOsm/kg to 340 mOsm/kg or when the osmolar gap exceeds 20 mOsm/kg.
  • Osmotic agents can be used as a temporizing measure to treat mass effect from cytotoxic edema related to stroke and intracerebral hemorrhage, but evidence for efficacy is weak. These lesions may require surgical decompression.
  • In states of poor intracranial compliance due to global cerebral edema, small changes in intracranial volume related to flat head position, hyperemia, hypercarbia, fever, or pain may result in exaggerated increases in intracranial pressure.
  • Spontaneous oscillations in intracranial pressure called Lundberg A and B waves may cause self-limited increases in intracranial pressure that last several minutes. These oscillations are an indicator of poor intracranial compliance, but they typically resolve spontaneously without treatment.
  • Augmentation of cerebral perfusion pressure with systemic vasopressors may lower intracranial pressure by causing reflex cerebral vasoconstriction, thereby lowering the intracranial volume of blood. Excessive cerebral perfusion, however, may contribute to vasogenic edema in regions with a disrupted blood-brain barrier.
  • Current Brain Trauma Foundation guidelines recommend maintaining an intracranial pressure of 22 mm Hg or less and a cerebral perfusion pressure of at least 50 mm Hg to 60 mm Hg in patients with severe traumatic brain injury.
  • A recent clinical trial of an intracranial pressure–based treatment protocol for severe traumatic brain injury compared to a treatment protocol based on clinical examination and imaging without intracranial pressure monitoring showed no difference in outcomes between the two groups.
  • Pentobarbital infusion for intracranial pressure reduction can result in severe medication side effects such as propylene glycol toxicity, immunosuppression, impaired gastrointestinal motility, and distributive shock.
  • A recent clinical trial of early induced hypothermia as a neuroprotective strategy in severe traumatic brain injury showed reduction of intracranial pressure–directed interventions, but neurologic outcomes were worse in patients treated with hypothermia.
  • Induced hypothermia continues to be a useful third-line intervention for refractory intracranial pressure elevation, but an effective hypothermia protocol that includes multimodality treatment of shivering is required.
  • A recent clinical trial demonstrated that decompressive craniectomy for refractory intracranial pressure elevation in severe traumatic brain injury improves survival and reduces the chance of severe disability, but more patients survived in a vegetative state compared to medical management alone.
  • With transtentorial herniation, the pupil dilation is ipsilateral to the mass lesion, but hemiplegia may be contralateral because of direct corticospinal tract involvement or ipsilateral because of compression of the contralateral cerebral peduncle against the tentorial edge (Kernohan notch phenomenon).
  • Serial bedside quantitative pupillometry may detect reduction in the pupillary constriction velocity hours prior to frank clinical signs of transtentorial herniation, which may afford time for preemptive treatment.
  • Although patients can survive and recover from transtentorial herniation in some cases, the sequelae of herniation can include Duret brainstem hemorrhage, ipsilateral anterior cerebral artery stroke, and contralateral posterior cerebral artery stroke.
  • Posterior fossa mass lesions can cause cerebellar tonsillar herniation or upward herniation of the cerebellum through the tentorial incisura, which may not be accompanied by intracranial pressure elevation or pupillary changes.

Article 2: Intracerebral Hemorrhage

Wendy C. Ziai, MD, MPH, FAHA, FNCS, FESO; J. Ricardo Carhuapoma, MD, FAHA. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1603–1622.

ABSTRACT

PURPOSE OF REVIEW

This article describes the advances in the management of spontaneous intracerebral hemorrhage in adults.

RECENT FINDINGS

Therapeutic intervention in intracerebral hemorrhage has continued to focus on arresting hemorrhage expansion, with large randomized controlled trials addressing the effectiveness of rapidly lowering blood pressure, hemostatic therapy with platelet transfusion, and other clotting complexes and clot volume reduction both of intraventricular and parenchymal hematomas using minimally invasive techniques. Smaller studies targeting perihematomal edema and inflammation may also show promise.

SUMMARY

The management of spontaneous intracerebral hemorrhage, long relegated to the management and prevention of complications, is undergoing a recent evolution in large part owing to stereotactically guided clot evacuation techniques that have been shown to be safe and that may potentially improve outcomes.

KEY POINTS

  • Treatment for intracerebral hemorrhage revolves around acute management of blood pressure, intracranial pressure, and cerebral edema.
  • Although the majority of intracerebral hemorrhage is attributed to hypertensive small penetrating vessel arteriopathy, vascular imaging (CT angiography, magnetic resonance angiography, or catheter angiography) and MRI are essential to rule out other etiologies of intracerebral hemorrhage.
  • The Intracerebral Hemorrhage Score and the Functional Outcome in Patients With Primary Intracerebral Hemorrhage score allow rapid outcome stratification of patients with intracerebral hemorrhage. Nevertheless, they should not be used independently to guide goals of care discussions of patients with intracerebral hemorrhage.
  • A spot sign, defined by the presence of contrast within the hematoma visualized on CT angiography or contrast-enhanced CT, is associated with a high risk of early intracerebral hemorrhage expansion.
  • Although hematoma expansion is a complication that negatively modifies mortality and functional outcome after intracerebral hemorrhage, it lacks specific interventions aimed at ameliorating its impact.
  • Currently, no proven benefit has been shown from recombinant activated factor VII in spontaneous or anticoagulation-associated intracerebral hemorrhage.
  • In patients with intracerebral hemorrhage with disorders of primary or secondary hemostasis, rapid reversal of coagulopathy is indicated in an attempt to improve neurologic outcomes and survival.
  • In patients with intracerebral hemorrhage with a history of recent use of antiplatelet agents, routine use of platelet transfusions is not indicated. The only exception for this recommendation is if surgical interventions are anticipated in the emergency care of these patients.
  • Perihematomal edema, which contributes to early neurologic deterioration and poor outcome, develops rapidly following intracerebral hemorrhage, reaching maximal volume by 2 weeks. There is currently no proven clinical therapy that both reduces perihematomal edema and improves outcomes.
  • The routine use of antiepileptic drugs following intracerebral hemorrhage is currently not recommended. There should be, however, a high degree of suspicion of electrographic seizures or status epilepticus in patients with intracerebral hemorrhage with decreased level of consciousness.
  • Use of an external ventricular drain is recommended in cases of intracerebral hemorrhage with intraventricular extension and obstructive hydrocephalus. External ventricular drains can facilitate relief of obstructive hydrocephalus as well as reduce the neurotoxic effects of intraventricular blood.
  • Minimally invasive endoscopic surgery for intraventricular hemorrhage volume reduction is considered experimental at this time and awaits large-scale studies to evaluate safety and efficacy.
  • After several randomized clinical trials and contemporary meta-analyses, no clear recommendation for open craniotomy and surgical evacuation of supratentorial hypertensive hematomas can be made at this point.
  • Several new devices placed via stereotactic imaging enable enhanced drainage of parenchymal clots and await demonstration of whether successful volumetric clot reduction is matched with improvement in functional outcomes.

Article 3: Subarachnoid Hemorrhage

Susanne Muehlschlegel, MD, MPH, FNCS, FCCM. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1623–1657.

ABSTRACT

PURPOSE OF REVIEW

This article reviews the epidemiology, clinical presentation, diagnosis, and management of patients with aneurysmal subarachnoid hemorrhage (SAH). SAH is a type of hemorrhagic stroke and is a neurologic emergency with substantial morbidity and mortality. This article reviews the most common and potentially life-threatening neurologic and medical complications to promote their early recognition and prevent secondary brain injury.

RECENT FINDINGS

Over the past 30 years, the incidence of SAH has remained stable; yet, likely because of improved care in specialized neurocritical care units, discharge mortality has considerably decreased. Two consensus guidelines by the American Heart Association/American Stroke Association and the Neurocritical Care Society have outlined best practices for the management of patients with SAH. The most important recommendations include admission of patients to high-volume centers (defined as more than 35 SAH admissions per year) under the management of a multidisciplinary, specialized team; expeditious identification and treatment of the bleeding source with evaluation by a multidisciplinary team consisting of cerebrovascular neurosurgeons, neuroendovascular specialists, and neurointensivists; management of patients in a neurocritical care unit with enteral nimodipine, blood pressure control, euvolemia, and close monitoring for neurologic and medical complications; and treatment of symptomatic cerebral vasospasm/delayed cerebral ischemia with induced hypertension and endovascular therapies. This article also highlights new insights of SAH pathophysiology and provides updates in the management approach.

SUMMARY

SAH remains a neurologic emergency. Management of patients with SAH includes adherence to published guidelines, but some areas of SAH management remain understudied. Clinical trials are required to elucidate the role of these controversial management approaches in improving patient outcomes.

KEY POINTS

  • Despite a decline in the mortality, subarachnoid hemorrhage remains a highly morbid disease.
  • In patients with subarachnoid hemorrhage, aneurysm rupture occurs at an average age of 53 years. This young age at onset results in a high societal cost and number of years of productivity lost.
  • The most common cause for subarachnoid hemorrhage is a ruptured cerebral aneurysm (85%); however, 10% of subarachnoid hemorrhages may not reveal a bleeding source, while the minority of cases (5%) may be due to other vascular causes.
  • Subarachnoid hemorrhage is predominant in women, African Americans, and Hispanics. Hypertension, smoking, and excess alcohol intake are modifiable risk factors that individually double the risk of subarachnoid hemorrhage.
  • Current guidelines recommend screening for aneurysms if the patient has two or more first-degree relatives with aneurysms or subarachnoid hemorrhage.
  • Subarachnoid hemorrhage typically presents with a sudden and severe headache (“worst headache of life”), which is distinctly different from usual headaches.
  • Physical examination of a patient with subarachnoid hemorrhage should include determination of the level of consciousness and the patient’s score on the Glasgow Coma Scale, evaluation for meningeal signs, and the presence of focal neurologic deficits.
  • Transient elevation in the intracranial pressure is the cause of nausea, vomiting, and syncope and may be associated with additional cardiac and pulmonary complications after subarachnoid hemorrhage.
  • The most rapidly available and appropriate initial diagnostic test for patients with suspected subarachnoid hemorrhage is a noncontrast head CT.
  • In cases of negative or equivocal head CT findings in which a high suspicion still exists for subarachnoid hemorrhage, a lumbar puncture is the immediate next recommended step.
  • CSF should be spun down and evaluated for xanthochromia by visual inspection and, if available, spectrophotometry. Xanthochromia takes approximately 12 hours to develop and may not be present if a lumbar puncture is performed earlier after headache onset.
  • Head CT and MRI are considered equally sensitive in detecting subarachnoid hemorrhage in the first 2 days, except in the hyperacute first 6 hours after subarachnoid hemorrhage, during which head CT may miss a small proportion of subarachnoid hemorrhages and MRI may be slightly superior.
  • Hemosiderin-sensitive MRI sequences (gradient recalled echo and susceptibility-weighted imaging) or fluid-attenuated inversion recovery sequences have superior sensitivity to detect subacute or chronic subarachnoid hemorrhage compared to head CT.
  • The “gold standard” vessel imaging remains cerebral digital subtraction angiography.
  • Approximately 15% of patients with subarachnoid hemorrhage will have negative imaging studies for a source of bleeding, of which approximately 38% have nonaneurysmal perimesencephalic subarachnoid hemorrhage.
  • The focus in the first few minutes to hours after subarachnoid hemorrhage, until the patient can undergo treatment of the ruptured aneurysm, should be directed toward the prevention of rebleeding.
  • Risk factors for rebleeding include poor-grade subarachnoid hemorrhage, hypertension, a large aneurysm, and, potentially, the use of antiplatelet drugs.
  • The short-term use (up to a maximum of 72 hours until aneurysm securement) of antifibrinolytics (tranexamic acid or ε-aminocaproic acid) is recommended by guidelines, although there is institutional variation in their use.
  • The two most commonly used clinical scales, the World Federation of Neurological Surgeons Scale and the Hunt and Hess Scale, are strong predictors of outcome in patients with subarachnoid hemorrhage. The most reliable and validated radiologic scale is the modified Fisher Scale.
  • For the treatment of aneurysm, endovascular coiling is preferred over surgical clipping whenever possible, but the choice of treatment depends on the patient’s age as well as the aneurysm’s location, morphology, and relationship to adjacent vessels.
  • Patients with subarachnoid hemorrhage are at risk for several additional neurologic complications, including hydrocephalus, brain edema, delayed cerebral ischemia, rebleeding, seizures, and neuroendocrine disorders, the latter of which can lead to impaired regulation of sodium, volume, and glucose.
  • Acute symptomatic hydrocephalus occurs in 20% of patients with subarachnoid hemorrhage, usually within minutes to days after subarachnoid hemorrhage onset. In cases of hydrocephalus, insertion of an external ventricular drain can be lifesaving.
  • If seizures occur prior to aneurysm securement, they are usually a sign of early rebleeding.
  • The occurrence of nonconvulsive seizures (7% to 18%) and nonconvulsive status epilepticus (3% to 13%) is more common in patients with subarachnoid hemorrhage who are comatose and has been associated with delayed cerebral ischemia and worse outcomes.
  • Continuous EEG monitoring should be considered in patients with high-grade subarachnoid hemorrhage.
  • In the absence of randomized controlled trials of antiepileptic drug treatment in subarachnoid hemorrhage, but with known negative effects of anticonvulsants, particularly phenytoin, on neurocognitive recovery after subarachnoid hemorrhage, treatment with antiepileptic drugs should be limited to the preaneurysm treatment time frame only.
  • Delayed cerebral ischemia after subarachnoid hemorrhage is defined as any neurologic deterioration that persists for more than 1 hour and cannot be explained by any other neurologic or systemic condition.
  • Delayed cerebral ischemia occurs on average 3 to 14 days after subarachnoid hemorrhage. The risk for delayed cerebral ischemia increases with subarachnoid hemorrhage thickness and intraventricular hemorrhage, as demonstrated by the modified Fisher Scale.
  • Delayed cerebral ischemia should be suspected if patients with subarachnoid hemorrhage develop a focal or global neurologic deficit or have a decrease of 2 or more points on the Glasgow Coma Scale that lasts for at least 1 hour and cannot be explained by any other cause.
  • Patients with subarachnoid hemorrhage should undergo physiologic or imaging monitoring routinely during the risk period for delayed cerebral ischemia.
  • Transcranial Doppler has adequate sensitivity and specificity to detect increased cerebral blood flow velocities secondary to cerebral vasospasm in the middle cerebral and basilar arteries but is highly dependent on the operator and cranial bone window.
  • Digital subtraction angiography remains the gold standard for detection of large- and middle-sized artery vasospasm.
  • Only symptomatic vasospasm, occurring in 30% of patients with subarachnoid hemorrhage, has been associated with delayed cerebral ischemia and poor outcome after subarachnoid hemorrhage.
  • Hypervolemic, hypertensive, and hemodilutional (Triple H) therapy is no longer supported by guidelines because of the existing evidence of adverse associations with outcomes after the use of hemodilution. Standard treatment is now hypertensive and mild hypervolemic therapy (HHT).
  • In the management of patients with symptomatic vasospasm, hypertension is preferably induced using α1 receptor agonists by a continuous infusion (norepinephrine or phenylephrine).
  • Cardiopulmonary dysfunction is a well-known complication of subarachnoid hemorrhage and can range from minor ECG changes to severe stress cardiomyopathy and neurogenic pulmonary edema.
  • The severity of subarachnoid hemorrhage is an independent predictor of cardiopulmonary injury, suggesting that the cardiopulmonary injury is neurally mediated.
  • Takotsubo cardiomyopathy in subarachnoid hemorrhage is associated with higher mortality and worse long-term outcomes.
  • Fever is the most common medical complication after subarachnoid hemorrhage, occurring in up to 70% of patients.
  • Fever has been associated with delayed cerebral ischemia and worse clinical outcomes and is likely related to systemic inflammatory response syndrome and chemical meningitis, rather than an infectious process.
  • Deep vein thrombosis after subarachnoid hemorrhage is common, with rates between 2% and 20%.
  • Mechanical venous thromboembolism prophylaxis should be initiated immediately on admission with the use of pneumatic compression devices. At the author’s institution, chemoprophylaxis with subcutaneous fractionated or unfractionated heparin is usually initiated immediately after endovascular aneurysm repair and within 24 hours after craniotomy for clipping.
  • In the absence of clinical trials of glucose control in patients with subarachnoid hemorrhage, current recommendations are to maintain a blood glucose level between 80 mg/dL and 200 mg/dL.
  • Hyponatremia is the most common electrolyte disorder in patients with subarachnoid hemorrhage and can occur in up to 30% of patients.
  • The laboratory findings are similar in both cerebral salt wasting and syndrome of inappropriate secretion of antidiuretic hormone. The only differentiating finding is the patient’s intravascular volume status; cerebral salt wasting is a hypovolemic state, while patients with syndrome of inappropriate secretion of antidiuretic hormone are euvolemic or even hypervolemic. It is of utmost importance to correctly differentiate these two syndromes because treatment is opposite.
  • Cerebral salt wasting is treated with fluid administration and sometimes a continuous infusion of hypertonic saline and fludrocortisone if diuresis and natriuresis impede maintenance of adequate volume status. Patients with syndrome of inappropriate secretion of antidiuretic hormone are treated with fluid restriction and sometimes diuresis with loop diuretics.
  • Anemia and hemoglobin concentrations of less than 9 g/dL have been associated with delayed cerebral ischemia and poor clinical outcomes; however, optimal hemoglobin goal levels and transfusion thresholds are not known.

Article 4: Management of Stroke in the Neurocritical Care Unit

Chethan P. Venkatasubba Rao, MD, FNCS; Jose I. Suarez, MD, FNCS, FANA. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1658–1682.

ABSTRACT

PURPOSE OF REVIEW

This article provides updated information regarding the diagnosis and treatment (specifically critical care management) of acute ischemic stroke. This article also discusses the increased use of thrombolysis and thrombectomy in clinical practice.

RECENT FINDINGS

Stroke is the leading cause of disability in the United States. A significant proportion of patients with acute ischemic stroke require critical care management. Much has changed in the early evaluation and treatment of patients presenting with acute ischemic stroke. The introduction of embolectomy in large vessel occlusions for up to 24 hours post–symptom onset has resulted in one in every three eligible patients with acute ischemic stroke with the potential to lead an independent lifestyle. These patients increasingly require recognition of complications and initiation of appropriate interventions as well as earlier admission to dedicated neurocritical care units to ensure better outcomes.

SUMMARY

This article emphasizes issues related to the management of patients with acute ischemic stroke undergoing mechanical thrombectomy and thrombolysis and addresses the complex physiologic changes affecting neurologic and other organ systems.

KEY POINTS

  • One in every four patients with acute ischemic stroke will need critical care intervention.
  • Factors predicting critical care admission in patients with acute ischemic stroke include severity of stroke, age, elevated systolic blood pressure, and hyperglycemia.
  • Circulation, airway, and breathing stabilization followed by rapid neurologic assessment, neuroimaging, and point of care testing should be the initial response in the evaluation of patients presenting with acute ischemic stroke.
  • The main neurologic reasons for intensive care unit admission in patients with acute ischemic stroke include blood pressure management post-thrombolysis or post-thrombectomy, cerebral edema, symptomatic hemorrhagic transformation, and seizures.
  • The main cardiac and respiratory indications for admission of patients with acute ischemic stroke to the neurocritical care unit include myocardial infarction, cardiac arrhythmias, heart failure, inability to maintain the airway, and the need for mechanical ventilation.
  • Management of hemodynamics in patients with fluctuating neurologic symptoms should be targeted individually and adjusted for optimum symptom control.
  • Interpretation of the neurologic evaluation of patients with acute ischemic stroke with larger deficits can be obscured when only using the National Institutes of Health Stroke Scale and no other clinical parameters.
  • In patients with acute ischemic stroke, treatment of hemorrhagic transformation should be directed toward hemodynamic control and coagulopathy reversal.
  • Recombinant tissue plasminogen activator–related symptomatic intracranial hemorrhage should be treated initially with cryoprecipitate.
  • While interpreting the levels of fibrinogen, it is important to realize that it is one of the acute phase reactants and, hence, a lower level is more reliable, and a normal level should be considered with healthy skepticism.
  • Patients with acute ischemic stroke with a National Institutes of Health Stroke Scale score of greater than 15, altered sensorium, and infarction of more than 50% of the middle cerebral artery territory should be considered for prophylactic hemicraniectomy within 48 hours.
  • Patients with acute ischemic stroke who present with cerebellar strokes involving more than 25% to 33% of a hemisphere should be considered for suboccipital decompressive craniectomy.
  • Short-acting IV agents should be used to provide optimal hemodynamic management in patients with acute ischemic stroke.
  • Early mobilization in the intensive care unit should be encouraged in patients with acute ischemic stroke.
  • When possible, endotracheal intubation and general anesthesia administration should be avoided for patients undergoing mechanical thrombectomy.

Article 5: Status Epilepticus, Refractory Status Epilepticus, and Super-refractory Status Epilepticus

Sarah E. Nelson, MD; Panayiotis N. Varelas, MD, PhD, FNCS, FAAN. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1683–1707.

ABSTRACT

PURPOSE OF REVIEW

Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes.

RECENT FINDINGS

Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level. Management of patients with status epilepticus generally requires several studies, with EEG of utmost importance given the pathophysiologic changes that can occur during the course of status epilepticus. Status epilepticus is treated with benzodiazepines as first-line antiepileptic drugs, followed by phenytoin, valproic acid, or levetiracetam. If status epilepticus does not resolve, these are followed by an IV anesthetic and then alternative therapies based on limited data/evidence, such as repetitive transcranial magnetic stimulation, therapeutic hypothermia, immunomodulatory agents, and the ketogenic diet. Scores have been developed to help predict the outcome of status epilepticus. Neurologic injury and outcome seem to worsen as the duration of status epilepticus increases, with outcomes generally worse in super-refractory status epilepticus compared to status epilepticus and sometimes also to refractory status epilepticus.

SUMMARY

Status epilepticus can be a life-threatening condition associated with multiple complications, including death, and can progress to refractory status epilepticus and super-refractory status epilepticus. More studies are needed to delineate the best management of these three entities.

KEY POINTS

  • While in the past, tonic-clonic status epilepticus was defined as continuous seizure activity or two or more seizures without recovery of consciousness lasting longer than 30 minutes, tonic-clonic status epilepticus is now defined as seizure activity lasting 5 minutes or longer, with 30 minutes being the cutoff for development of long-term consequences.
  • No standard definition for nonconvulsive status epilepticus currently exists. A working definition differentiates diagnostic criteria based on whether epileptic encephalopathy is present.
  • Refractory status epilepticus is continuous seizure activity not controlled by first-line and second-line antiepileptic drugs; it occurs in 9% to 43% of all cases of status epilepticus.
  • Super-refractory status epilepticus is defined either as status epilepticus not controlled by third-line anesthetic agents or as status epilepticus continuing for 24 hours or longer after anesthesia is administered. The exact incidence and associated mortality of super-refractory status epilepticus are unknown.
  • The annual incidence of status epilepticus is approximately 12.6 per 100,000 person-years and is increasing over time. Seizures or status epilepticus may occur in up to 19% of patients hospitalized in the intensive care unit.
  • The etiology of status epilepticus may be divided into known or symptomatic causes and unknown or cryptogenic causes. In general, acute causes appear to be more common than chronic causes.
  • Encephalitis appears to be a common cause of both refractory status epilepticus and super-refractory status epilepticus.
  • New-onset refractory status epilepticus (NORSE) has recently emerged as a challenging disorder in which the etiology of refractory status epilepticus is not immediately apparent.
  • Multiple changes at the cellular and molecular level occur in status epilepticus as time passes.
  • With increasing duration of seizure activity, the frequency of systemic complications, neurologic injury, and mortality increase.
  • Continuous video-EEG is a valuable tool given its ability to detect nonconvulsive status epilepticus.
  • Imaging modalities, including CT, MRI, single-photon emission CT, and positron emission tomography, may help in the diagnosis and management of status epilepticus.
  • Status epilepticus requires urgent treatment because the response to treatments and the prognosis diminish with elapsed time. A staged approach to treatment has thus been advocated, with different medications used in early (stage I), established (stage II), refractory (stage III), and super-refractory status epilepticus (stage IV).
  • Treating status epilepticus generally begins with benzodiazepines and is followed by IV administration of fosphenytoin, valproic acid, or levetiracetam.
  • The extent of suppression needed to treat refractory status epilepticus (burst suppression versus merely suppressing seizures) is not known.
  • Continuous anesthetic agents are used to treat refractory status epilepticus and are typically maintained for 24 to 48 hours before being weaned.
  • Several alternative therapies can be used in patients with refractory status epilepticus and, especially, super-refractory status epilepticus, including surgical resection, repetitive transcranial magnetic stimulation, immunosuppression or immunomodulation, and the ketogenic diet.
  • In some cases, seizures and status epilepticus may be epiphenomena for severe brain injury rather than the primary offender. It is unknown whether treating these conditions will improve outcomes.
  • Up to 50% of patients with super-refractory status epilepticus die, and outcomes are worse in super-refractory status epilepticus compared to nonrefractory status epilepticus.

Article 6: Coma and Brain Death

Alejandro A. Rabinstein, MD, FAAN. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1708–1731.

ABSTRACT

PURPOSE OF REVIEW

This article discusses the diagnostic and therapeutic approach to patients who are comatose and reviews the current knowledge on prognosis from various causes of coma. This article also provides an overview of the principles for determination of brain death as well as advice on how to avoid common pitfalls.

RECENT FINDINGS

Technologic advances have refined our understanding of the physiology of consciousness and the spectrum of disorders of consciousness; they also promise to improve our prognostic accuracy. Yet the clinical principles for the evaluation and treatment of coma remain unaltered. The clinical standards for determination of death by neurologic criteria (ie, brain death) are also well established, although variabilities in local protocols and legal requirements remain a problem to be resolved.

SUMMARY

Effective evaluation of coma demands a systematic approach relying on clinical information to ensure rational use of laboratory and imaging tests. When the cause of coma is deemed irreversible in the setting of a catastrophic brain injury and no clinical evidence exists for brain and brainstem function, patients should be evaluated for the possibility of brain death by following the clinical criteria specified in the American Academy of Neurology guidelines.

KEY POINTS

  • Coma is a state of unresponsiveness in which the patient is not awake and cannot interact with the environment, even after vigorous stimulation.
  • Bilateral diffuse alterations in cortical function or severe diencephalic or brainstem dysfunction can produce coma.
  • Focused history and physical examination very often provide clues to the etiology of coma.
  • Coma scales are useful but should not replace a more complete neurologic examination.
  • The differential diagnosis and diagnostic testing should be guided by the history, physical examination, and location of the patient (out of hospital, in the emergency department, on a hospital floor, or in the intensive care unit).
  • CT is a reasonable and practical first imaging study when structural damage is suspected, but MRI may be more useful for various causes of coma.
  • The value of EEG for the evaluation of patients who are comatose without clinical seizures remains to be established.
  • When evaluating coma of unclear etiology, always think of treatable causes first.
  • Do not assume coma is irreversible when the cause remains indeterminate.
  • Treatable causes of coma most often represent a medical emergency.
  • The value of pharmacologic or nonpharmacologic neurostimulation for coma recovery is unproven.
  • The prognosis of coma depends mostly on its cause and duration.
  • Prolonged disorders of consciousness (longer than 28 days) are typically the result of widespread brain damage.
  • Prolonged disorders of consciousness constitute a spectrum that includes vegetative state (also referred to as unresponsive wakefulness syndrome) and minimally conscious state.
  • Although the problem is improving, practice variations in the determination of brain death continue to occur across different states and countries.
  • The diagnosis of brain death demands an established cause of irreversible coma, the absence of confounding factors, the complete absence of motor response and brainstem reflexes, and no breathing efforts on a formal apnea test.
  • Angiography, nuclear scans, EEG, and transcranial Doppler are ancillary tests that can be used to confirm brain death, but they all have limitations.
  • The most appropriate use of ancillary tests to confirm brain death is to complement the neurologic examination when certain aspects of the examination (such as the apnea test) cannot be performed.
  • Not recognizing confounding factors (especially the residual effects of central nervous system depressants) is a common pitfall in brain death evaluations.
  • The concept of brain death is accepted by all major religions, but small cultural and religious groups continue to challenge the validity of the concept.

Article 7: Management of Comatose Survivors of Cardiac Arrest

David B. Seder, MD, FCCP, FCCM, FNCS. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1732–1752.

ABSTRACT

PURPOSE OF REVIEW

Because the whole-body ischemia-reperfusion insult associated with cardiac arrest often results in brain injury, neurologists perform an important role in postresuscitation cardiac arrest care. This article provides guidance for the assessment and management of brain injury following cardiac arrest.

RECENT FINDINGS

Neurologists have many roles in postresuscitation cardiac arrest care: (1) early assessment of brain injury severity to help inform triage for invasive circulatory support or revascularization; (2) advocacy for the maintenance of a neuroprotective thermal, hemodynamic, biochemical, and metabolic milieu; (3) detection and management of seizures; (4) development of an accurate, multimodal, and conservative approach to prognostication; (5) application of shared decision-making paradigms around the likely outcomes of therapy and the goals of care; and (6) facilitation of the neurocognitive assessment of survivors. Therefore, optimal management requires early neurologist involvement in patient care, a detailed knowledge of postresuscitation syndrome and its complex interactions with prognosis, expertise in bringing difficult cases to their optimal conclusions, and a support system for survivors with cognitive deficits.

SUMMARY

Neurologists have a critical role in postresuscitation cardiac arrest care and are key participants in the treatment team from the time of first restoration of a perfusing heart rhythm through the establishment of rehabilitation services for survivors.

KEY POINTS

  • Top treatment priorities in the early hours after resuscitation include determining and reversing the cause of cardiac arrest to prevent circulatory collapse and rearrest as well as maintaining a neuroprotective hemodynamic and biochemical milieu.
  • Restoration and maintenance of a favorable thermal, hemodynamic, biochemical, and metabolic milieu after cardiac arrest is of great concern and should be a key element of urgent recommendations.
  • Because many patients who undergo targeted temperature management after cardiac arrest receive neuromuscular blockade to control shivering (and therefore never have convulsions) and because others experience primarily nonconvulsive seizures, it is ideal to monitor for seizures with continuous EEG.
  • Prognostication after cardiac arrest is problematic. Many of the frequently cited studies describing prognostic factors after cardiac arrest are flawed, and imprecise early prognostication can lead to unnecessary deaths.
  • Cognitive dysfunction is a significant source of morbidity among survivors of cardiac arrest.
  • Unlike traditional prognostication after a cardiac arrest, the goal of early neurologic evaluation is to classify patients into categories of high, medium, and low risk of a poor neurologic outcome in a time frame that allows for triage to individualized treatment pathways.
  • Rapid diagnostic testing modalities that allow for accurate early neurologic triage after cardiac arrest include assessment of the total ischemic time, the no-flow and low-flow intervals, neurologic examination, CT, EEG background, continuity and reactivity at different time points after resuscitation, and the bispectral index and suppression ratio.
  • Patients whose risk assessment suggests mild or moderate brain injury should be considered for initiation of aggressive strategies for circulatory support, as they are likely to benefit, up to and including extracorporeal membrane oxygenation or surgical revascularization, if necessary, and should undergo an accelerated diagnostic workup to identify the cause of the arrest with the intention of maintaining adequate cerebral blood flow and preventing rearrest.
  • All patients who are comatose after cardiac arrest should be treated in a maximally neuroprotective milieu.
  • Because the cerebral microcirculation depends on maintenance of an adequate perfusion pressure in the hours after resuscitation to prevent progression of vulnerable cortical and subcortical regions from ischemia to necrosis, the maintenance of adequate blood pressure and cardiac output is crucial.
  • Hypotension after resuscitation is associated with worse outcomes and must be avoided.
  • Body temperature should be controlled as soon as possible following resuscitation to a target temperature between 32°C (89.6°F) and 36°C (96.8°F) for 24 to 72 hours after resuscitation, with careful management of the complications of therapy.
  • Data suggest the superiority of a 35°C (95°F) to 36°C (96.8°F) target for patients with severe shock, and the higher target should also be considered in patients with active bleeding or life-threatening infections.
  • Rewarming after targeted temperature management should always be performed slowly to minimize adverse consequences of the inflammatory and vasodilatory effects of warming.
  • Because of the strong independent association of hyperglycemia and poor outcome after cardiac arrest, plasma glucose levels should be normalized by insulin administration.
  • Hypoxic-ischemic encephalopathy–related seizures are both a marker of brain injury severity and a cause of ongoing secondary injury.
  • Patients who are comatose after cardiac arrest should be monitored with continuous EEG, at least through the process of rewarming to normal body temperature and the resolution or waning of epileptiform activity.
  • Patients with hypoxic-ischemic encephalopathy–related seizures who do not have very high neuron-specific enolase levels and extensive brain injury on MRI may make a good recovery, and ongoing supportive therapy is appropriate unless circulatory collapse or multiple organ failure preclude ongoing aggressive care.
  • When performed too soon or without adequate diagnostic testing, prognostication after resuscitation from cardiac arrest can cost some patients their lives.
  • Multimodal prognostication is standard after cardiac arrest.
  • When the prognosis after cardiac arrest is uncertain, the principles of shared decision making are employed to help the family and treatment team determine a patient- and family-centered pathway of care that offers comfort, support, hope, and direction.
  • Many experts believe formal assessment of prognosis after cardiac arrest should be delayed for at least 72 hours after rewarming from targeted temperature management and potentially longer.
  • Neurologists should be familiar with factors associated with delayed awakening after cardiac arrest, including renal insufficiency, older age, and postresuscitation shock.
  • Shared decision making is considered the standard approach to conversations about end-of-life care. When prognostication has been performed, a multidisciplinary meeting that includes the patient’s surrogates and health care stakeholders should be held to exchange information, deliberate, and make a decision about the goals of care.
  • More than half of survivors of cardiac arrest have measurable neurocognitive dysfunction, and 20% to 50% have persistent deficits of memory, learning, or executive function even after 3 months.

Article 8: Critical Care of Neuromuscular Disorders

Diana Greene-Chandos, MD, FNCS; Michel Torbey, MD, MPH, FCCM, FAHA, FNCS, FAAN. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1753–1775.

ABSTRACT

PURPOSE OF REVIEW

Weakness is a common reason patients are seen in neurologic consultation. This article reviews the differential diagnosis of neuromuscular disorders in the intensive care unit (ICU), discusses the intensive care needs and evaluation of respiratory failure in patients with neuromuscular disorders, and provides a practical guide for management.

RECENT FINDINGS

Although primary neuromuscular disorders used to be the most common cause for weakness from peripheral nervous system disease in the ICU, a shift toward ICU-acquired weakness is observed in today’s clinical practice. Therefore, determining the cause of weakness is important and may have significant prognostic implications. Guillain-Barré syndrome and myasthenia gravis remain the most common primary neuromuscular disorders in the ICU. In patients with myasthenia gravis, it is important to be vigilant with the airway and institute noninvasive ventilation early in the course of the disease to attempt to avoid the need for intubation. On the other hand, patients with Guillain-Barré syndrome should be intubated without delay if the airway is at risk to avoid further complications. In patients with ICU-acquired weakness, failure to wean from the ventilator is usually the challenge. Early mobility, glucose control, minimizing sedation, and avoiding neuromuscular blocking agents remain the only therapeutic regimen available for ICU-acquired weakness.

SUMMARY

Critical care management of neuromuscular disorders requires a multidisciplinary approach engaging members of the ICU and consultative teams. Developing an airway management protocol could have implications on outcome and length of stay for patients with neuromuscular disorders in the ICU. Tending to the appropriate nuances of each patient who is critically ill with a neuromuscular disorder through evidence-based medicine can also have implications on length of stay and outcome.

KEY POINTS

  • Intensive care unit–acquired weakness is a clinical diagnosis.
  • Early clinical signs of respiratory failure include tachycardia, tachypnea, increased sweating, and use of accessory muscles.
  • Hypercapnia, as indicated on arterial blood gases, is often a late sign of intensive care unit–acquired weakness; therefore, arterial blood gases are not very useful in acute triage decisions.
  • Early mobilization and glucose control are key in the prevention of intensive care unit–acquired weakness.
  • Rhabdomyolysis occurs with a wide spectrum of signs and symptoms, ranging from severe muscle pain and varying degrees of generalized weakness. Markedly elevated plasma creatine kinase may lead to myoglobinuria and acute kidney injury.
  • Noninvasive ventilation should be considered early in a patient with myasthenia gravis.
  • A hallmark of Lambert-Eaton myasthenic syndrome is postexercise facilitation. Tendon reflexes and muscle strength improve immediately after a brief maximal contraction.
  • Lambert-Eaton myasthenic syndrome should be considered in patients with any unexplained weakness after pharmacologic neuromuscular blockade.
  • The potassium channel blocker 3,4-diaminopyridine is an effective symptomatic treatment for Lambert-Eaton myasthenic syndrome.
  • Plasma exchange and IV immunoglobulin are equally effective for the treatment of Guillain-Barré syndrome. The decision to use either should depend on the availability of these treatments at the specific treatment center.
  • No evidence exists to recommend any specific ventilatory mode in patients with Guillain-Barré syndrome.
  • Noninvasive ventilation has a limited role in patients with severe Guillain-Barré syndrome.
  • Appropriate psychological support is recommended for patients with Guillain-Barré syndrome in the intensive care unit.
  • The types of amyotrophic lateral sclerosis include limb-onset amyotrophic lateral sclerosis, which has both upper motor neuron and lower motor neuron signs; bulbar-onset amyotrophic lateral sclerosis, which features dysphagia and dysarthria and upper motor neuron and lower motor neuron signs that occur after the disease progresses; primary lateral sclerosis, which has upper motor neuron involvement only; and progressive muscular atrophy, which has lower motor neuron involvement only.
  • Respiratory complications are the main cause of death in patients with amyotrophic lateral scerlosis due to diaphragmatic weakness, aspiration, or pneumonia.
  • Patients with amyotrophic lateral sclerosis without severe bulbar dysfunction treated with noninvasive positive pressure ventilation had an improved quality of life and survived longer compared with those who underwent standard care.
  • Ventilation via tracheostomy should be offered as an alternative to patients who do not tolerate noninvasive positive pressure ventilation.
  • Organophosphates irreversibly inhibit acetylcholinesterases, resulting in excessive amounts of acetylcholine at the neuromuscular junction and prolonged endplate potential and desensitization of the postsynaptic membrane.

Article 9: Multimodality Monitoring in the Neurocritical Care Unit

Lucia Rivera Lara, MD, MPH; Hans Adrian Püttgen, MD. Continuum (Minneap Minn). December 2018; 24 (6 Neurocritical Care):1776–1788.

ABSTRACT

PURPOSE OF REVIEW

This article focuses on the multiple neuromonitoring devices that can be used to collect bedside data in the neurocritical care unit and the methodology to integrate them into a multimodality monitoring system. The article describes how to apply the collected data to appreciate the physiologic changes and develop therapeutic approaches to prevent secondary injury.

RECENT FINDINGS

The neurologic examination has served as the primary monitor for secondary brain injury in patients admitted to the neurocritical care unit. However, the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care concluded that frequent bedside examinations are not sufficient to detect and prevent secondary brain injury and that integration of multimodality monitoring with advanced informatics tools will most likely enhance our assessments compared to the clinical examinations alone. This article reviews the invasive and noninvasive technologies used to monitor focal and global neurophysiologic cerebral alterations.

SUMMARY

Multimodal monitoring is still in the early stages of development. Research is still needed to establish more advanced monitors with the bioinformatics to identify useful trends from data gathered to predict clinical outcome or prevent secondary brain injury.

KEY POINTS

  • The aim of multimodality monitoring is to understand the complexity of the changes that lead to secondary brain injury.
  • The most severe limitation to the application of cerebral microdialysis in bedside decision making is the unfinished work of defining markers of health and crisis in different clinical contexts.
  • Brain tissue oxygen tension monitors have shown low rates of complication.
  • Many factors affect brain tissue oxygen tension including cerebral perfusion pressure, hemoglobin concentration, oxygen saturation, metabolic rate (from fever, agitation, or shivering), and cerebral vasospasm.
  • Near-infrared spectroscopy devices have an excellent safety profile.
  • Near-infrared spectroscopy shows promise as a method of assessing cerebral autoregulation when used in concert with systemic blood pressure and intracranial pressure monitors.
  • Understanding global physiology is key to detecting significant changes that affect large areas in the brain after traumatic brain injury, aneurysmal subarachnoid hemorrhage, ischemic stroke, intracranial hemorrhage and status epilepticus, among other conditions.
  • Nonconvulsive seizures have been described in 5% to 15% of patients with acute intracranial injury (eg, traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, postneurosurgery), and nonconvulsive status epilepticus has been described in 5% to 20% of such patients.
  • EEG is recommended for patients during therapeutic hypothermia after cardiac arrest and within 24 hours of rewarming, not only to diagnose and treat seizures and myoclonic status epilepticus, but also because of its prognostic factors.
  • If brain oxygenation monitoring is desired, the preferred choice is brain tissue oxygen tension sensors.
  • Intracranial pressure monitoring is recommended as part of protocol-driven care for patients with acute brain injury who are at risk of elevated intracranial pressure based on clinical or imaging features.
  • The gold standard intracranial pressure monitor is the ventriculostomy.
  • Intracranial pressure monitors are recommended in patients with a Glasgow Coma Scale score of 8 or less and who have an abnormal head CT.
  • Noninvasive intracranial pressure monitors are still under development and are not yet recognized as providing an accurate intracranial pressure measurement.
  • Dynamic cerebral autoregulation monitoring has evolved to allow bedside calculation of optimal cerebral perfusion pressure and optimal mean arterial pressure with invasive and noninvasive methods.
  • The importance of cerebral autoregulation multimodal monitoring technology is that calculation of optimal mean arterial pressure and cerebral perfusion pressure would allow physicians to individualize cerebral perfusion pressure or mean arterial pressure goals and potentially improve a patient’s outcomes.
  • Cerebral perfusion pressure below the optimal level increases the incidence of fatal outcome, whereas excessively high cerebral perfusion pressure is associated with an increased proportion of severe disability.
  • Monitoring systems will find their greatest utility when appreciated in concert with each other and with other forms of clinical data including laboratory values, imaging results, and medical record documentation.
  • Lack of common formatting standards stands as a significant barrier to true data integration, which necessitates a patient data management system that translates monitor output from proprietary formats and merges them into a common stream.
© 2018 American Academy of Neurology