Section 3: Neurology

INTRACRANIAL PRESSURE

• Normal 0 to 20 mmHg

CEREBRAL PERFUSION PRESSURE (CPP)

Formula: CPP = Mean Arterial Pressure (MAP) − Intracranial Pressure (ICP)

• Infants: 40 mmHg

• Adults: 65 mmHg

  • Changes throughout development: parallels changes in systemic blood pressure (BP); increases gradually throughout development to adult levels.

  • Consider patient's baseline BP: Baseline MAP should be considered when considering therapeutic target for CPP in setting of acute neurologic injury. A patient with baseline hypertension will need blood pressure supported to a level that approximates their baseline physiology.

  • In adults poor outcomes are associated with sustained CPP <40 mmHg.

CEREBRAL BLOOD FLOW (CBF)

• Infants: 40 mL/100 g/min

• Children (4 years): 100 mL/100 g/min

• Children (9 years): 50 to 70 mL/100 g/min

• Adults: 50 mL/100 g/min

CEREBRAL METABOLIC RATE FOR OXYGEN (CMRO₂)

• Normal: 3.0 to 3.8 mL O₂/100 g brain/min

CEREBROSPINAL FLUID (CSF)

Normal values:

• White blood cell count (WBC): 0 to 5

• Total protein: 22 to 38 mg/dL

• Glucose: 60% to 80% of serum glucose

GLASGOW COMA SCALE (GCS)

• See Table 38-1.

SUGGESTED READINGS

NEUROSURGICAL EMERGENCIES

MONRO KELLIE DOCTRINE

• Physiology: Most cases of neurosurgical emergencies are related to the volume-occupying relationship between the brain matter, cerebral blood volume, and cerebrospinal fluid volume sharing space in the fixed-volume compartment of the skull (See Figure 39-1)

  • Changes in the relative volume of one of these components require compensatory change in the volume occupied by one or more of the other components

  • In the event that a change in the volume of one component overwhelms compensatory mechanisms, brain matter may move along the path of least resistance as it is pushed by pathologically elevated pressure within the calvarium

    • Cerebellar herniation via the foramen magnum

    • Transtentorial herniation across the falx cerebri

    • Transcalvarial herniation via a surgical or traumatic defect in the skull

• Clinical presentation:

  • Cerebellar herniation (brainstem compression and hydrocephalus)

    • Somnolence/coma

    • Pupillary dilatation

      • Unilateral or bilateral

      • Nonreactive or sluggishly reactive

      • Due to compression of third cranial nerve

    • Respiratory pattern

      • Hyperventilation

      • Cheyne-Stokes

    • Decorticate or decerebrate posturing

  • Transtentorial herniation

• Cushing's triad: Clinical presentation of acute intracranial hypertension

  • Hypertension

  • Reflex bradycardia

  • Hypopnea

    • May not be apparent in setting of intubated and mechanically ventilated patient

    • May present as change in respiratory pattern

• Diagnostic approach: Aimed at determining underlying cause and developing definitive treatment plan

  • Computerized tomography (CT) brain

    • Advantages

      • Rapid study

      • Readily available at most institutions

      • Can identify:

        • Blood collection

          • Extraaxial

          • Intraparenchymal

          • Intraventricular

        • Hydrocephalus

        • Cerebral edema

        • Some masses

        • Skull defects

      • Contrast enhances ability to identify:

        • Vascular abnormalities (thromboses and anatomic variants)

        • Infectious processes (abscess)

      • CT angiography

    • Disadvantages

      • Limited ability to image posterior fossa for mass (though this is often overcome with sagittal reconstructions)

      • Large ionizing radiation exposure

  • Magnetic resonance imaging (MRI) brain

    • Advantages

      • Can reliably identify mass lesions in all parts of the central nervous system (CNS)

      • Can reliably identify acute ischemia, cerebral edema, and inflammatory parenchymal lesions

      • No ionizing radiation

    • Disadvantages

      • Not readily available in all centers

      • Long duration study (the use of the fast-brain MRI has improved this greatly)

      • Material restrictions for magnet exposure

DISORDERS RESULTING IN INCREASE IN PARENCHYMAL VOLUME OF INTRACRANIAL COMPARTMENT

• Cerebral edema: Wide variety of conditions

  • Trauma

  • Diabetic ketoacidosis

  • Hepatic encephalopathy

  • Ischemic brain injury

    • Stroke

    • Hypoxic ischemic encephalopathy

    • Encephalitis

  • Treatment

    • Hyperosmolar therapy

      • Hypertonic saline

        • 3 to 5 mEq/kg bolus

        • 1 mEq/kg can predictably increase serum sodium by 1

      • Mannitol

        • 0.25 to 1 g/kg

        • Results in diuresis, which can cause hypotension and should be treated immediately

    • Decompressive surgery

      • Lesion

      • Skull

• Brain mass: Tumors

  • Discussion of specific tumor types is beyond the scope of this chapter

  • Surgical decompression as necessary

  • Surrounding edema may be treated with dexamethasone acutely or subacutely

DISORDERS RESULTING IN DECREASED INTRACRANIAL VOLUME

• Craniofacial disorders

  • Craniosynostosis

  • Trauma

  • Iatrogenic

• Neurosurgical postoperative

  • Epilepsy

  • Craniofacial repair

DISORDERS RESULTING IN INCREASE IN BLOOD VOLUME WITHIN THE INTRACRANIAL COMPARTMENT

• Hemorrhagic conditions

  • Frequently occur after trauma

  • Initial diagnosis via CT scan

  • Treatment involves surgical evacuation of blood collection and surgical repair of bleeding vessel

  • May occur in setting of coagulopathy or thrombocytopenia

    • Therapeutic anticoagulation

    • Pathologic coagulopathy

    • Liver failure

    • Multiple system organ failure

    • Sepsis

  • Intraparenchymal hemorrhage

    • Traumatic

    • Arteriovenous malformation rupture

      • May be definitively diagnosed and treated with interventional radiological procedures

  • Subdural hemorrhage

    • Traumatic injury

      • Accidental

      • Nonaccidental trauma

  • Subarachnoid hemorrhage (SAH)

    • Most common cause is post-traumatic

    • Can be aneurysmal SAH as a consequence of rupture of an aneurysm associated with cerebral vasculature

    • May be definitively diagnosed and treated with interventional radiological procedures

    • Watch for clinical consequences of vasospasm

  • Epidural hemorrhage

    • Often after trauma

    • Associated with skull fractures

  • Tumor: hemorrhagic conversion

DISORDERS ASSOCIATED WITH INCREASE IN CEREBROSPINAL FLUID (CSF) COMPONENT OF INTRACRANIAL COMPARTMENT

• Hydrocephalus

  • May develop as a result of anatomic changes resulting from a prior insult

  • Ventriculoperitoneal shunt failure

  • Treatment includes surgical diversion of CSF from the intracranial compartment to external ventricular drain, ventricular shunt, or removal of obstruction

INFECTIOUS DISORDERS

• Empyema from intracranial infections behaves in the same manner as the disorders listed earlier and can result in herniation syndrome.

• Require neurosurgical drainage, but must find primary cause. Most common in children is sinovenous infection. Concurrent treatment of cause (sinusitis) and consequence (intracranial infection) important.

• Require antibiotic therapy.

• Diagnosed via CT with or without contrast, but MRI is more sensitive and can see associated brain inflammation.

• Most require antiseizure therapy.

OTHER THERAPIES

• Normoxia

  • Goal SaO₂ >95%

  • Hypoxemia results in cerebral vasodilation, which can exacerbate a herniation event (See Figure 39-2)

  • Hypoxemia exacerbates cellular injury in the injured tissue and is associated with increased mortality and worsened functional outcome after a variety of cerebral injuries¹

• Hyperventilation

  • Decrease in PaCO₂ results in cerebral vasoconstriction, which results in decrease in cerebral blood volume (See Figure 39-3)

  • This maneuver can be temporarily employed to prevent herniation while a definitive treatment plan is deployed

  • Prolonged hyperventilation cerebral vasoconstriction can result in ischemia—this maneuver should be considered a rescue maneuver

• Therapeutic temperature management

  • Normothermia (35.5–36.5°C) should be actively maintained

  • Hyperthermia results in cerebral vasodilation and may exacerbate a herniation event

  • No evidence to support therapeutic hypothermia to improve survival or improved functional outcome in setting of neurosurgical illness²

• Blood pressure: Should be maintained in the normal range for age³ (See Figure 39-4)

  • Hypertension can exacerbate cerebral hemorrhage.

  • Hypotension can result in tissue ischemia and worsen survival/outcome.

  • IMPORTANT: Hypertension associated with Cushing's triad should not be directly treated; rather, the underlying cause should be identified and definitively treated before initiating antihypertensive therapy. These decisions should be made in consultation with neurosurgical partners.

SPINAL CORD INJURY

• Presentation: Acute change in sensation and motor function detected below a particular spinal dermatome. Frequently bilateral, may be unilateral.

• Causes

  • Mass

  • Hemorrhage

  • Trauma and cord compression

• Diagnosis: MRI

• Requires urgent neurosurgical intervention to maximize neurologic recovery. Certain tumor syndromes respond to chemotherapy and will not need surgery.

• Postoperative care includes careful blood pressure management to ensure adequate cord perfusion.

  • Phenylephrine frequently used to support blood pressure in physiologic range

  • Spinal shock

NEUROLOGIC EMERGENCIES

HYPERTENSIVE ENCEPHALOPATHY

• Presentation: Headache, visual changes, somnolence/coma, seizure

• Pathophysiology: Unmitigated hypertension that exhausts the autoregulatory mechanism

  • This causes increase in cerebral blood flow and injury to brain–blood barrier

  • Causes tissue edema and injury to cerebral tissue

• Treatment:

  • Correct hypertension

  • Treat seizures (see Chapter 42)

SEIZURES – SEE CHAPTER 42

STROKE

• Presentation: Acute-onset focal neurologic deficit

  • Motor weakness

  • Sensory deficit

  • Cranial nerve finding

  • Alteration in consciousness

• Diagnosis: MRI with diffusion-weighted imaging and apparent diffusion coefficient sequences

• Conversion: Nascent strokes may undergo hemorrhagic conversion or develop diffuse edema, resulting in intracranial hypertension and herniation syndrome (Cushing's triad). Urgent neurosurgical evaluation along with therapeutic rescue maneuvers described earlier should be immediately employed.

• Please see Chapter 43 for a full discussion of stroke.

DEFINITION AND NORMAL INTRACRANIAL PRESSURE VALUES

Intracranial pressure (ICP) is the pressure of cerebrospinal fluid (CSF) within the cerebral ventricles. ICP is the product of the rate of cerebrospinal fluid (CSF) formation (I_formation), resistance to CSF drainage (R_out), and pressure in the dural venous sinuses (P_d), a formula proposed by Davson (ICP = R_out × I_formation + P_d).¹ Thus, ICP is regulated by venous pressure, cerebral blood flow, and CSF circulation.

• Normal values for CSF production, sagittal sinus pressure, and resistance to CSF outflow are 0.2 to 0.7 mL/min, 5 to 8 mmHg, and 6 to 10 mm Hg/mL/min, respectively.

• ICP increases with age.

  • In the newborn, the normal value for ICP is approximately 82 mm H₂O, or 6 mmHg.²

  • Normal CSF pressure in healthy children obtained during lumbar puncture is a mean of 19.6 cm H₂O (10th to 90th percentile, 11.5 to 28.0 cm H₂O).

    • Sedation may increase opening CSF pressure by up to 3.5 cm H₂O.

• Volume status, blood pressure, and end-tidal CO₂ may also affect ICP and must be considered when deciding on interventions to treat intracranial hypertension.

• An opening pressure above 28 H₂O may not be “abnormal” if signs of increased ICP (papilledema, abducens nerve palsy, hydrocephalus, subdural fluid, other intracranial pathology) are absent.³

PATHOPHYSIOLOGY

• Monro-Kellie doctrine

  • The skull is a rigid cavity containing brain (1200–1600 mL), arterial and venous blood (100–150 mL), and CSF or other extracellular fluid (100–150 mL)

  • Expansion of one compartment is offset by a decrease in volume of the others. The pressure–volume relationship is expressed by the formula C ∼ dV/dp, where C represents compliance and dV represents the change in volume that accompanies a change in pressure (dp) (Figure 40-1).

  • As ICP increases, compliance decreases. In cases of intracranial pathology, such as traumatic brain injury (TBI) or space-occupying lesions (tumors, arachnoid cysts, hemorrhage), compliance is decreased and small increases in the volume of one compartment result in large increases in ICP. Cranial causes of decreased compliance can include hyperostosis, craniosynostosis, and traumatic skull injury without brain injury such as a depressed skull fracture.

• Intracranial pressure, cerebral perfusion, and autoregulation

  • Under normal conditions, cerebral blood flow (CBF) is a constant of approximately 50 mL/100 gm brain/min.

  • CBF is determined by the vascular gradient across the cerebral beds and is a product of cerebral perfusion pressure (CPP) and cerebrovascular resistance (CVR), according to the formula CBF = CPP/CVR.⁴

  • The relationship between CPP and ICP is expressed by the formula CPP = MAP – ICP.

  • Autoregulation is the mechanism by which CBF is kept constant despite changes in CPP.

  • When autoregulation is intact, increases in blood pressure lead to a decrease in cerebral artery caliber to maintain a constant CBF by increasing CVR.

  • When CPP falls below the lower limit of autoregulation (40–50 mmHg in the mature brain), CBF is dependent on MAP.

    • This is a “pressure-passive” circulation in which decreases in MAP result in corresponding decreases in cerebral perfusion and risk for ischemic injury.

  • Cumulative data from pediatric traumatic brain injury studies suggest ICP >20 mmHg or CPP <40 mmHg are associated with poor outcome.

CLINICAL SIGNS OF INTRACRANIAL HYPERTENSION

Diagnosis of intracranial hypertension requires a high index of clinical suspicion and cannot be excluded based on a normal computerized tomography (CT) or magnetic resonance imaging (MRI) scan. Imaging signs of intracranial hypertension include decrease in size or loss of cisterns, uncal and other herniation, midline shift, and loss of grey-white differentiation. Clinical signs range from subtle changes in mental status to cranial neuropathies, focal weakness, posturing, stupor, and coma.

DIAGNOSIS

The diagnosis may be made, and therapy initiated, based on the clinical exam (Table 40-1) and imaging findings (edema, midline shift, loss of grey-white differentiation) in the appropriate clinical context of a patient at risk for increased ICP.

• Papilledema is a late finding.

  • Visual acuity is typically preserved with intracranial hypertension.

  • The absence of papilledema does not rule out intracranial hypertension.

• Lumbar puncture (LP) may increase the risk for herniation and is contraindicated if there is a focal finding on the neurologic exam, concern for obstruction (noncommunicating hydrocephalus), or an intracranial mass lesion.

  • Neuroimaging (MRI or CT) should first be performed to confirm the absence of a mass lesion.

  • Under some circumstances, after consultation with Neurosurgery, the LP may be used as a diagnostic or therapeutic intervention to measure opening pressure or to allow drainage of CSF.

INTRACRANIAL PRESSURE MONITORING

Severe traumatic brain injury is the best-established indication for ICP monitoring, although this is a level III recommendation.⁵ ICP-directed care in children with acute central nervous system (CNS) infections, acute liver failure, stroke, and diabetic ketoacidosis have been reported, but not linked to improved outcome.⁶

• ICP monitor types

  • ICP monitors are classified by mechanism (fluid or nonfluid coupled) and anatomy (extradural, subdural, ventricular, or parenchymal)

  • The gold standard for accurate ICP monitoring is the intraventricular drain, which both allows drainage of CSF and provides real-time measurement of ICP.⁷

  • Insertion may be difficult in certain clinical circumstances, including ventricular size and clinical status of the patient (location, coagulation/bleeding, other systemic abnormalities).

  • Noninvasive approaches to ICP monitoring include optic nerve sheath diameter measurement, tympanometry, and tonometry, none of which are in routine clinical use. MRI has been used to measure ICP, also without much adoption.

• Indications for ICP monitoring

  • Numerous pediatric studies report a relationship between intracranial hypertension (>20 mmHg) and poor outcome in severe TBI.⁸

    • Whether ICP monitoring improves outcome following severe TBI is controversial, with evidence for no benefit⁹ or some survival advantage.¹⁰

  • ICP monitoring without complications has been reported in children with other acute neurologic insults, including diabetic ketoacidosis, CNS infections, stroke, and acute liver failure, and may be considered at the treating physician's discretion.

MANAGEMENT

First establish a neurologic exam and identify the primary cause of intracranial hypertension. Notify Neurosurgery, and determine whether emergent operative intervention or CSF diversion is needed. Decompressive craniectomy with duraplasty or continuous ventricular CSF drainage with ICP monitoring may improve outcome in children with intracranial hypertension following severe TBI. Start medical management of intracranial hypertension (Figure 40-2).¹¹

• Key principles

  • Maintain ICP <20 to 25 mmHg; CPP > minimum of 40 mmHg

    • Use age-dependent goals for CPP thresholds

  • Limit interventions (suctioning, pain) that may cause increases in ICP

  • Prevent fever and use targeted temperature management if possible

  • Medical management may proceed without an ICP monitor

  • Be prepared to escalate the intensity of therapy based on serial neurologic examinations or imaging changes

  • If hypothermia is used to reduce ICP, rewarm slowly (0.5–1.0°C every 12–24 hours)

  • Ensure adequate access (arterial, venous, and central lines) if hyperosmolar and ICP-directed therapy are anticipated

MECHANISMS OF INJURY AND PATHOPHYSIOLOGY

INJURY PATTERNS

• Mechanism of Injury: It is important to know the cause of injury to determine severity of injury, triage the patient to the appropriate level of care, and anticipate possible complications.

• Primary Injury: Occurs on initial impact, either diffuse or focal. Often results in skull fractures. Focal injuries include contusions, lacerations, and hemorrhages. Diffuse brain injuries include concussions and diffuse axonal injury.

  • Concussion: Diffuse brain injury without associated head computerized tomography (CT) findings. Symptoms may include headache, disorientation, emesis, or brief loss of consciousness.¹

  • Diffuse axonal injury: Shearing injury caused by acceleration and deceleration resulting in trauma between the gray and white matter.¹

  • Epidural hematoma: Rapidly progressing arterial bleed occurring between the skull and dura.² Often secondary to middle meningeal artery and occasionally caused by a venous bleed.¹ Patients may have loss of consciousness followed by a lucid period prior to neurologic deterioration. Elliptical shape on head CT due to limitations of fluid spread by dural attachment at suture lines. See Figure 41-1.

  • Subdural hematoma: Venous bleed occurring between the dura and arachnoid. Caused by rupture of the bridging veins during rapid movement of the brain within the skull. Acute subdural hematomas progress rapidly and are associated with high morbidity and mortality.² Concave shape on neuroimaging, extending throughout the subdural space. See Figure 41-2.

  • Intracerebral hematomas: Tearing of small vessels in any area of the brain. Symptoms vary depending on location of bleed, but often occur in the frontal and temporal lobes.²

• Secondary Injury: Occurs due to decreased perfusion of surviving tissue that causes reduction in oxygen delivery, metabolite delivery, and metabolic waste and toxin clearance. Additional injury results from cerebral herniation syndromes, which can cause focal ischemic injury and brainstem compression.³

  • Vasogenic edema: Swelling of interstitial space. Capillary leak from cerebral vasculature into interstitial space due to disruption of blood–brain barrier, occurring primarily in the white matter. Secondary to ischemia, hemorrhage, brain injury, infection, and tumors.²

  • Cytotoxic edema: Swelling of brain cells. Secondary to altered osmotic state caused by ischemia with associated extracellular acidosis secondary to anaerobic metabolism and cell membrane rupture.²

SEVERITY OF TRAUMATIC BRAIN INJURY

• Severity of traumatic brain injury (TBI) is determined by the Glasgow Coma Scale (GCS). See Tables 41-1 and 41-2.

MANAGEMENT OF SEVERE TRAUMATIC BRAIN INJURY

GUIDELINES FOR MANAGEMENT OF SEVERE TRAUMATIC BRAIN INJURY

• The second edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents was published in 2012.³ The extensive literature review is broken down into recommendations with supporting strength of evidence and does not include recommendations made by expert opinion. These guidelines are endorsed by many important medical bodies, including the Society of Critical Care Medicine, Neurocritical Care Society, Pediatric Neurocritical Care Research Group, World Federation of Pediatric Intensive and Critical Care Societies, and American Academy of Pediatrics Section on Neurological Surgery.³

• Although the 2012 guidelines³ include 40 years of TBI literature, due to a lack of high-quality pediatric TBI evidence, specific treatment plans cannot be made for infants and children with severe TBI.⁴

PREVENTION OF SECONDARY INJURY

• Goals of TBI Management:

  

• Intracranial hypertension (ICH) and systemic hypotension are associated with poor outcomes in severe TBI³

• Neuroprotective Measures:

  • Positioning: Improve cerebral venous drainage by midline head positioning with head of bed elevated to 30 degrees.⁵

  • Electrolyte monitoring: Avoid hypoglycemia and hyperglycemia. Avoid rapid fluctuations in sodium and glucose levels. Hyponatremia can cause intracerebral swelling and seizures.⁵

  • Temperature: Avoid hypothermia and maintain normothermia⁵ using antipyretics and hypothermia or hyperthermia blankets as necessary.

  • Sedation: Provide adequate sedation and analgesia, which can help lower intracranial pressure (ICP).^3,5

    • Other benefits include preventing shivering, long-term psychological trauma, pain, stress, frequent coughing, and ventilator dyssynchrony.^3,5

    • Pain and stress increase cerebral metabolic demand, cerebral blood volume, and ICP.³

  • Normalize oxygenation and ventilation:

    • Maintain SpO₂ above 94% and use caution, as increased intrathoracic pressure (due to increased positive end-expiratory pressure [PEEP]) can decrease cerebral venous return and thus cause ICH.⁵

    • Goal pH is 7.35 to 7.45 with PaCO₂ 35 to 45mmHg because hyperventilation lowers cerebral perfusion pressure (CPP) by vasoconstricting cerebral blood flow and should generally be avoided to prevent further ischemia.^3,5

    • In severe, life-threatening periods of ICH, hyperventilation may be used briefly to a PaCO₂ of 20 mmHg while awaiting further treatment or surgical interventions.⁵

  • Fluid management: Avoid hypotonic fluids to avoid exacerbating cerebral edema; consider normal saline as fluid of choice

• Intracranial Pressure Monitoring: Placement of an ICP monitoring device is recommended in patients with severe TBI and may be considered in children with mild or moderate TBI with limited ability to undergo serial neurologic exams (i.e., sedation, anesthesia, or neuromuscular blockade).³

• Treatment Thresholds for Intracranial Hypertension: Sustained intracranial hypertension above 20 mmHg for longer than 5 minutes should be treated.³

  $IntracranialHypertension(ICH)=ICP>20mmHgfor>5​minutes$

  • Mortality and poor outcomes are associated with sustained increases in ICP.

  • ICP treatment thresholds should most likely be age dependent; however, the current literature does not provide enough evidence to determine ranges.³

• Cerebral Perfusion Pressure Thresholds: CPP is the pressure gradient providing cerebral blood flow and is calculated as the difference between the mean arterial pressure (MAP) and ICP.³ Survivors of severe TBI have higher CPP values than nonsurvivors.⁶

  

  • CPP should be maintained above a minimum level of 40 to 50 mmHg to prevent cerebral ischemia, with infants on the lower end and adolescents on the upper end.³

  • In severe TBI, patients should have continuous MAP (arterial line) and ICP monitoring to provide accurate CPP monitoring.³

    • Ideally, these pressure monitoring devices should be zeroed at the same level for accurate CPP monitoring.^3,5

• Hyperosmolar Therapy: Used for medical management of ICH. Target euvolemic hyperosmolar state (may trend central venous pressure).³

  • Hypertonic Saline: Dose: 6.5 to 10 mL/kg for acute ICH³ (dosing may range 2–10 mL/kg/dose⁶)

    Continuous infusion: 0.1 to 1 mL/kg/hr³ titrated for minimum effective dose.

    Maintain serum osmolarity less than 360 mOsm/L³

    • Side effects of hypertonic saline: May include rebound ICP, central pontine myelinolysis (with rapid shifts in sodium levels), renal impairment, subarachnoid hemorrhage, dehydration, and hyperchloremic metabolic acidosis, masking symptoms of diabetes inspidius.³

  • Foley catheter: Should be used in patients on hyperosmolar therapy to monitor urine output and prevent bladder rupture.³

  • Mannitol: Dose: 0.25 to 1 gm/kg intermittent dosing for acute ICH.

    Maintain serum osmolarity less than 320 mOsm/L^3,5

    • Initial effects (<75 minutes) reduces blood viscosity, thereby increasing laminar flow.

    • Osmotic effect (15–30 minutes) triggers diuresis of water from brain parenchyma into the systemic circulation, lasting about 6 hours.³

    • Long-term effects of mannitol:

      • Accumulation in injured brain tissue may reverse osmotic shift, drawing water into parenchyma and increasing ICP.

      • Acute tubular necrosis, possibly due to renal excretion of mannitol, hyperosmolar state, or dehydration.³

  Note: Although used frequently in practice, there is no evidence to support or refute the efficacy of mannitol within the most recent guidelines.³

• Antiepileptic Prophylaxis:

  • Post-traumatic seizures: Occur early (within 7 days) or late (more than 8 days after injury) with increased risk depending on location and severity of injury, depressed skull fracture, and neurologic deficits.³

  • Electroencephalogram (EEG): In patients on sedation, barbiturates, or neuromuscular blockade, continuous EEG should be placed to monitor for subclinical seizure activity.

  • There is limited data to suggest the appropriate agent for use for antiepileptic prophylaxis in pediatric severe TBI. Current guidelines suggest phenytoin for consideration for prophylaxis of early post-traumatic seizure activity.³ Antiepileptic medications may have sedating side effects, cause hypotension, or inhibit ability for recovery; thus, clinician assessment with neurology or neurocritical care–experienced physicians is useful.⁵

• Cerebrospinal Fluid Drainage: Cerebrospinal fluid (CSF) drainage may be considered in patients with ICH. Removal of CSF reduces the intracranial fluid volume and thus lowers ICP.³

  • External ventricular drain (EVD): Clinicians should consider intermittent vs. continuous fluid drainage.³

  • Lumbar drain: In patients with refractory ICH, open basal cisterns, EVD, and no mass lesions or shift on radiologic imaging.³

• Barbiturate Therapy: Barbiturates lower ICP by suppressing cerebral metabolic demand and altering vascular tone. High-dose barbiturates can be considered in refractory ICH after first-tier medical and surgical interventions, but are not supported for prophylactic use.³

  • Pentobarbital: Initial bolus dose range: 5 to 10 mg/kg; continuous infusion range: 1 to 4 mg/kg/hr^3,7

  • EEG monitoring: To achieve burst suppression, titrate barbiturate infusion to effect.

  • Side effects: Hypoxia and lower CPP due to decreased cardiac output, hypotension, and increased intrapulmonary shunt. Patients should have close hemodynamic and respiratory monitoring with available vasoactive medications.³

NEUROIMAGING AND NEUROSURGICAL INTERVENTIONS

• Neuroimaging: Initial head CT should be used to determine severity of TBI.

  • Repeat imaging: May be necessary in patients with unchanged neurologic exam, persistent ICH, or inability to assess neurologic status.

  • Risks of neuroimaging: Medically unstable patients may not tolerate CT imaging. Radiation exposure increases risks of fatal cancer.

  • Routine use of follow-up imaging in the absence of neurologic deterioration is not recommended; risks and benefits should be weighed.³

• Decompressive Craniectomy (DC): Performed with unilateral or bilateral removal of skull bone flap to allow for cerebral edema. Location depends on underlying injury.³

  • Primary DC: For treatment of cerebral herniation or early refractory ICH.³

    • Consider in patients with early herniation or neurologic deterioration or refractory ICH resistant to early medical management.

    • Primary DC can decrease ICP; however, whether it improves functional and neurologic outcomes is unknown.³

  • Secondary DC: For removal of mass lesion or hematoma to treat associated cerebral edema.³

DEFINITION

Status epilepticus (SE) is defined as 5 minutes or more of (1) continuous clinical and/or electrographic seizure activity or (2) recurrent seizure activity without recovery (returning to baseline) between seizures.¹

• May be convulsive (with motor features) or nonconvulsive (electrographic seizures only)

• SE progresses in phases

  • Early SE (5–30 minutes), established SE (>30 minutes), and refractory SE

  • Refractory status epilepticus

    • Clinical or electrographic seizures that persist after an adequate dose of an initial benzodiazepine and a second appropriate antiseizure medication

    • Associated with poor outcome, with mortality up to 30%, related to young age, etiology, and multifocal or generalized EEG abnormalities

BACKGROUND AND EPIDEMIOLOGY

• Epidemiology and morbidity of SE

  • Incidence of first-time SE is approximately 18 to 23 per 100,000 children per year²

  • Fifty percent of children with new-onset convulsive SE are neurologically healthy

  • One-year recurrence risk is 16% with 3% mortality, which is lower than adults

  • Risk for mortality and long-term morbidity related to primary cause of the seizure

• Factors associated with increased morbidity in SE

  • Time to the first dose of benzodiazepine in children with SE is often delayed or the drug not given until arrival at a hospital³

  • Delay in administration of the first anticonvulsant is associated with longer SE duration⁴

CAUSES OF SE

Prolonged febrile seizures and seizure due to remote neurologic injury account for 50% of SE cases in children.

• Other common causes in order of frequency include

  • Acute new neurologic injury

    • Central nervous system (CNS) infection; cardiac arrest, stroke; traumatic brain injury; drug or toxin

  • Acute exacerbation of underlying epilepsy

    • Missed anticonvulsant or subtherapeutic levels

    • Intercurrent illness

  • Progressive neurologic disorder

KEY PRINCIPLES OF SE MANAGEMENT

• After 5 to 10 minutes, most seizures will not stop unless treated with an anticonvulsant

• Early, sequential administration of adequate doses of anticonvulsants is essential⁵

• Treatment should be given in the field prior to arrival in the ICU

• Identify and treat precipitating cause

• Manage systemic complications

• All units should have a management pathway and agreed on time frame for treatment⁶

TREATMENT

Incipient SE 0 to 5 minutes of seizure onset

• Stabilize airway, breathing, and circulation

• Obtain fingerstick glucose in first-line labs

• Obtain IV access and administer IV benzodiazepine if seizure lasts 5 minutes

  • If IV access is not possible, administer benzodiazepine via intramuscular, intranasal, rectal, or buccal route (see Table 42-1)

  • Do not delay treatment in order to obtain IV access

Early (5–30 min) and established (>30 min) SE (Figure 42-1)

Refractory SE

• Continued seizures despite treatment with adequate doses of two to three anticonvulsants

• Load with midazolam 0.2 mg per kg

  • Continue with infusion at 0.05 to 0.2 mg per kg per hour with EEG monitoring to suppress clinical or electrographic seizures

  • No maximum rate established, but typical range is up to 1.0 to 1.5 mg per kg per hour

• If pharmacologic coma is required or insufficient response to midazolam, add pentobarbital 5 mg per kg bolus followed by infusion at 0.5 mg per kg per hour

• Optimal duration of treatment is not established, but guidelines suggest 24 to 48 hours of electrographic seizure control¹

• For add-on drugs or other therapies, see Abend et al.⁵

DIAGNOSTIC STUDIES

Zero to five minutes of seizure onset

• Goal is to identify rapidly reversible causes of SE within 5 minutes of seizure onset¹

  • Fingerstick glucose

  • Electrolytes including magnesium and calcium

  • Anticonvulsant drug levels

  • Blood gas

  • Complete blood count

Five to sixty minutes and beyond (Table 42-2)

• Diagnostic tests guided by history and risk factors for each patient

Neuroimaging

• No consensus on timing of imaging. The American Academy of Neurology Practice Parameter recommends imaging after SE is controlled and the child is stable⁷

• Where the cause of SE is clear, CNS imaging may be obtained at the physician's discretion⁸

INDICATIONS FOR EEG MONITORING

Nonconvulsive seizures occur in up to 30% of critically ill children, require continuous (c) EEG monitoring for detection, and are associated with worse outcomes.⁹

• Among children who present with convulsive SE, one-third have only electrographic seizures¹⁰

  • Consensus criteria for the use of cEEG in children have been established and include^1,11:

    • Persistent altered mental status following resolution of convulsive SE

    • Acute brain injury including moderate-severe traumatic brain injury, stroke, CNS infection, brain tumors, cardiorespiratory arrest, intracerebral hemorrhage

    • Sepsis with altered mental status

    • During extracorporeal membrane oxygenation¹²

    • Induction of pharmacologic coma for seizure management

• cEEG should be continued for 24 to 48 hours^1,11

BACKGROUND AND EPIDEMIOLOGY

DIFFERENCES FROM STROKE IN ADULTS

• Immature neuraxis

  • Causes subtle exam findings, leading to delay in diagnosis

    • Stroke must be considered in any patient with acute neurologic deficit

• Risk factors for stroke are different compared to adults

  • Atherosclerosis is not common cause of stroke in children

  • There are no randomized, controlled therapeutic trials in children

• Type of stroke: Arterial ischemic stroke (AIS), hemorrhagic stroke (HS), cerebral venous sinus thrombosis (CVST)

• Prompt recognition: Allows for optimization of cerebral perfusion and can minimize secondary injury

EPIDEMIOLOGY

• Pediatric stroke (age 30 days–18 years): annual average incidence of 1.6 to 13/100,000^1,2

• Arterial ischemic stroke (including CVST):

  • 50% to 70% of pediatric strokes

  • Comprises 15% of all ischemic strokes that occur in young adults and adolescents

  • Mortality after AIS ranges from 10% to 15% with 50% of survivors left with a neurologic deficit

  • Risk for recurrence ranges from 1% to 20%³

• Hemorrhagic stroke:

  • 41% to 49% of pediatric strokes

  • Two to three times the incidence of adults

  • Median age is 5 to 10 years

  • Males are at slightly higher risk (55% to 60%)

  • Mortality is lower in children than adults. While survival is greater, morbidity among survivors is high

RISK FACTORS (TABLE 43-1)

CONSIDERATIONS

• Many patients have multiple risk factors, whereas 10% to 38% have no risk factor identified^2,4

• Recurrent stroke increased if multiple risk factors identified⁵

• Chromosomal mutations (trisomy 21), genetic syndromes (Sturge Weber), and single-gene disorders (sickle cell) may predispose to stroke

AIS

• Arteriopathies: Identified in 31% to 60% of patients⁶

  • Nontraumatic dissections, vasculitis, moyamoya, postvaricella arteriopathy, primary vascular disorder, sickle cell disease, transient arteriopathies (recent viral infections)

  • Vasculopathy: Increases risk of stroke recurrence, especially in the first 6 months after stroke presentation⁷

• Congenital heart disease⁸

  • Highest stroke risk after cardiac catheterization or surgery

  • Most likely cardioembolic rather than vascular

• Hypercoagulable states

  • Methylene tetrahydrofolate reductase (MTHFR), factor V Leiden, protein C/S deficiency, homocystinuria, malignancy, iron-deficiency anemia, oral contraceptive use, autoimmune disease

• Trauma

  • Arterial dissection: Most commonly involving the internal carotid artery (usually intracranial) or vertebral artery (usually extracranial)⁹

  • Mechanism may seem minor (i.e., wrestling with friends or jumping off a bed)

HS

• Intracranial vascular abnormalities (aneursyms, arterial venous malformations, cavernous malformations), brain tumors, hematologic disorder

CVST

• Systemic or central nervous system (CNS) infection, chronic otitis media and orbital cellulitis, prothrombotic state, hematologic or metabolic disorder

• Dehydration and anemia

PRESENTATION

PHYSICAL EXAM

• AIS: Focal neurologic deficits 60% to 80%^2,4,5

  • Acute hemiplegia 50% to 70%; cranial nerve palsies, visual and speech impairments in 29% to 47%; seizures in 25% to 33%; altered consciousness in 32% to 52%; headache with posterior circulation strokes or larger lesions

  • Acute systemic conditions associated with more diffuse symptoms, whereas arteriopathies have more focal findings⁸

• HS: Similar presentation to AIS

  • Headache, vomiting, alteration in mentation, and vertigo more common in HS than AIS⁵

  • Focal weakness only in 35% to 38%, compared to 50% to 70% in AIS⁵

• CVST: Stiff neck and loss of consciousness or ataxia most common presenting signs

DELAY IN DIAGNOSIS

• Remains a significant challenge in pediatric stroke^4,5

• Immature neuraxis: Limited expression of focal neurologic deficits clinically coupled with inability for many patients to report symptoms

• Challenging to examine an uncooperative child

• Stroke mimics: 11% to 21% of suspected strokes are due to other causes¹⁰ (Table 43-2)

  • Cannot reliably differentiate mimics from stroke on basis of neurologic examination alone

  • Focal symptoms: Focal weakness with episode of demyelination, transient paresis following seizure, hemiplegic migraine

• Hospital delay⁴:

  • Median time from presentation to diagnosis is almost 24 hours, with in-hospital delays accounting for largest proportion of time

  • Failure of clinicians to recognize subtle neurologic deficits in children or to consider stroke in the differential diagnosis

  • Nonspecific symptoms like seizures, headache, ataxia

• Education of the general public: Remind that children have strokes too, incorporating into current campaigns (“FASTR – Face drooping-Arm weakness-Speech difficulty-Time to call 911-and ‘Remember children have stroke too’”)¹¹

USE OF NEUROIMAGING

• Imaging required due to frequency of stroke mimics in children

• Study of choice: Magnetic resonance imaging (MRI)

  • Noncontrast computerized tomography (CT) if MRI not immediately available

    • May miss early ischemia or posterior circulation involvement

  • “Fast” MRI: Diffusion-weighted imaging (DWI), axial T2 fluid-attenuated inversion recovery (FLAIR), susceptibility-weighted imaging (SWI) or gradient echo (GRE) with time-of-flight (TOF) magnetic resonance angiogram (MRA) of head and neck¹¹

    • 20 to 25 minutes to complete in most centers

  • MRA (magnetic resonance angiography): Perform concurrently with MRI, given the increased incidence of underlying arteriopathies

    • Good screening tool, but less sensitive than CT angiography in diagnosis of vertebral or internal carotid artery dissection¹²

    • Conventional cerebral angiography; gold standard for suspected arteriopathies

TREATMENT (FIGURE 43-1)

ACUTE TREATMENT AND SUPPORTIVE CARE

• Goal is to minimize injury and prevent early complications such as extension of penumbra and recurrent stroke

• Neuroprotection: Head flat to optimize cerebral perfusion (unless HS or CVST is of concern); maintain adequate oxygenation, isotonic fluids with dextrose, blood pressure 50% to 95% for height and age with permissive hypertension up to 20% above 95%, nothing by mouth for possible sedation and to avoid choking, avoid electrolyte abnormalities/hypoxemia/hyperthermia/hypo- or hyperglycemia (goal 80–180 mg/dL), as all are deleterious to preischemic brain tissue⁷

• Other considerations: Airway monitoring, as alteration in mentation may require intubation; exchange transfusions for sickle cell patients; anticonvulsant medication for any patients with seizures, as further seizures may compromise the vulnerable ischemic penumbra

• Aspirin: 3 to 5 mg/kg once hemorrhage is ruled out by imaging or history¹

• Laboratory evaluation (see Table 43-3)

• Neurology consult

• Consider electroencephalogram (EEG) monitoring: Clinical and subclinical seizures common in children with acute neurologic injuries

CONFIRMED STROKE

• Treatment with aspirin (ASA) or anticoagulation (low-molecular-weight heparin or unfractionated heparin) for up to 1 week after ischemic stroke¹; newer anticoagulants (dabigatran, rivaroxaban, apixaban) not yet studied in pediatric stroke

  • Cardioembolic source or acute extracranial dissection: Anticoagulation rather than antiplatelet therapy^1,9

  • Large territory MCA strokes (>30%–50% of MCA territory): Anticoagulation contraindicated due to risk for hemorrhagic conversion

    • Consider ASA for 2 to 3 days followed by anticoagulation if exam not improving

• Aspirin 3 to 5 mg/kg/day: Start if antithrombotic or thrombolytic medication not used and there is no contraindication such as intracranial hemorrhage¹

  • Decrease dose to 1 to 3 mg/kg/day if excessive bleeding or bruising

  • Treatment duration of 3 to 5 years, may extend indefinitely in high-risk patients

  • For extracranial dissection, mean treatment duration of 12 months

• Intravenous tissue plasminogen (IV tPA)¹¹

  • Mechanism of action: Facilitates degradation of fibrin in thrombus and can lead to early recanalization of an artery occluded by a thrombus

  • Currently no standards in pediatric stroke

  • May be considered in consulation with a stroke neurologist within 4.5 hours of symptom onset

• Intra-arterial thrombolysis⁷: Case reports in children with middle cerebral artery and basilar artery occlusion, but several potential complications (iatrogenic arterial dissection, intracranial hemorrhage, recurrent stroke distal to site of thrombosis)

• Decompressive hemicraniectomy: May be considered for large MCA territory stroke with declining mental status and cerebral edema

• Neurosurgery consult: If confirmation of hemorrhagic stroke

• Transthoracic echocardiogram (TTE): Indicated in all children with stroke due to congenital and acquired heart disease as a common cause of pediatric stroke

KEY PRINCIPLES FOR MANAGEMENT OF ACUTE STROKE

• High index of suspicion for stroke as etiology of neurologic deficit

• Needs immediate access to MRI for confirmation of ischemia

• Multidisciplinary management between Critical Care, Neurology, and Neurosurgery

• Optimize flow

  • Head of bed (HOB) flat and give fluids (AIS)

  • Reduce intracranial pressure (ICP) (HS)

  • Decompressive hemicraniectomy

• Limit excess metabolic demand (fever, seizures)

• Limit clot formation or restore patency of occluded vessel in AIS

  • Anticoagulation or antiplatelet therapy

  • Use of thrombolysis or thrombectomy on case-by-case basis

DEFINITIONS

Meningitis: Inflammation of the meninges, the membranes covering the brain and spinal cord

Encephalitis: Inflammation of the brain parenchyma

ETIOLOGY

NEONATES <2 MONTHS

• Bacteria:

  • Group B Streptococcus (52%)

  • Escherichia coli and other gram-negative bacilli (rods) (27%)

  • Listeria monocytogenes (6%)

  • Anaerobes (3%)

  • Other gram-positive organisms (7%): enterococci, Streptococcus pneumoniae, staphylococci

  • Other gram-negative organisms (5%): Haemophilus influenzae, Neisseria meningitides, Pseudomonas

• Viruses: Herpes simplex virus (HSV), human herpesvirus 6 (HHV-6), enteroviruses, arboviruses, human immunodeficiency virus (HIV), adenovirus, varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, mumps, rubella, influenza, parainfluenza, parvovirus B19, rotavirus, others

INFANTS >2 MONTHS AND CHILDREN

• Bacteria:

  • S. pneumoniae and N. meningitidis (90%–95%)

  • Other organisms: H. influenzae, Salmonella species, group B Streptococcus, L. monocytogenes, anaerobes

• Viruses: Enteroviruses, arboviruses, HSV, HHV-6, HIV, adenovirus, VZV, EBV, CMV, measles, mumps, rubella, influenza, parainfluenza, parvovirus B19, rotavirus, zoonotic diseases, arthropod-borne diseases, others

SPECIAL POPULATIONS

• Mycoplasma tuberculosis: Consider based on history of exposure

• Fungi: Immunocompromised patients

• Parasites and protozoa: Consider based on history of exposure

• Rabies: Consider based on history of exposure

Enteroviruses account for 85% to 95% of viral meningoencephalitis in which an etiologic agent is identified.

CLINICAL MANIFESTATIONS

NEONATES/INFANTS

• Fever of unknown origin

• Vomiting, poor feeding, failure to thrive (FTT)

• Apnea or respiratory distress

• Altered mental status: irritability or lethargy

• Signs of increased intracranial pressure (ICP): bulging fontanelle

• Focal neurologic deficits

• Seizures

• Petechiae/purpura or rash

• Shock

OLDER CHILDREN

• Fever: almost always present

• Nausea/vomiting

• Headache, photophobia

• Back pain

• Altered mental status

• Focal neurologic deficits

• Seizures

• Signs of increased ICP: papilledema (if present, look for brain abscess, venous sinus thrombosis, and subdural fluid collection/empyema)

• Signs of meningeal irritation: positive Kernig's and Brudinski's signs

• Petechiae/purpura or rash

• Shock

DIAGNOSIS

LABORATORY EVALUATION

• Serum tests: abnormal white blood cell (WBC) count (leukocytosis or leukopenia), prominence of atypical lymphocytes (EBV), viral studies

• Cerebrospinal fluid (CSF) studies: cell count, WBC differential, glucose, protein, Gram stain, culture, viral studies (enterovirus polymerase chain reaction [PCR], HSV PCR, etc.), acid-fast bacillus AFB stain, tuberculosis culture – See Table 44-1

• Blood culture: positive in 80% to 90% of patients with suspected bacterial meningitis who were not pretreated with antibiotics

• Nasopharyngeal swab: For viral studies

IMAGING

• Head computerized tomography (CT) or magnetic resonance imaging (MRI): may be useful in identifying complications (hemorrhage, mass, cerebral edema, hydrocephalus, abscess, subdural fluid collection/empyema, etc.)

• MR venogram: cerebral sinus venous thrombosis

• HSV: temporal involvement

EEG

• HSV: PLED (periodic lateralized epileptiform discharges) over the temporal region

• Rule out subclinical seizures

TREATMENT

See Surviving Sepsis Guidelines to reverse shock.

Additional medical management

• Frequent neurologic checks

• Monitor head circumference daily in neonates/infants

• Aggressively treat seizures and increased ICP

• Avoid overhydration because it may worsen cerebral edema

• Monitor and treat sodium dysregulation and disseminated intravascular coagulopathy (DIC)

ANTIMICROBIAL THERAPY

• Empiric IV antimicrobials:

  • Neonates <1 month: ampicillin + cefotaxime or ampicillin + gentamicin

  • Neonates 1 to 3 months: vancomycin + cefotaxime or ceftriaxone; consider ampicillin for Listeria coverage

  • Infants >3 months and children: third-generation cephalosporin + vancomycin

  • Consider acyclovir for anyone in which HSV is suspected

  • Special populations: additional antimicrobial coverage based on etiologic suspicion

• Switch to enteral antimicrobial: afebrile and able to tolerate enteral medications

• Narrow antimicrobial therapy: based on culture results

  • For meningococcus: use penicillin, cefotaxime, or ceftriaxone for a minimum of 7 days

• Pediatric ID consultation is recommended

• Duration: minimum of 10 to 14 days, sometimes up to 21 days

• May need to repeat lumbar puncture to see if CSF is being adequately treated

ANTI-INFLAMMATORY THERAPY

• Dexamethasone: give shortly before or at the time of first IV antibiotic administration

  • Reduces the frequency of hearing loss and neurologic sequelae in patients with H. influenzae type B meningitis

  • Reduces overall unfavorable outcomes and mortality in adults with pneumococcal meningitis

  • Benefits not conclusive in pneumococcal or meningococcal meningitis in children

  • No data for use in children <6 weeks old

SURGICAL INTERVENTION

• Drainage of abscess or subdural fluid collection/empyema

• Insertion of external ventricular drain (EVD) for hydrocephalus

OTHER

• Chemoprophylaxis for household and other close contacts of meningococcal disease

COMPLICATIONS

ACUTE

• Brain abscess

• Cerebral sinus venous thrombosis resulting in stroke or ischemia

• Hydrocephalus +/− increased ICP

• Subdural fluid collection/empyema

• Sodium dysregulation (syndrome of inappropriate antidiuretic hormone [SIADH] most common)

LONG-TERM NEUROLOGIC SEQUELAE (UP TO 50% OF PATIENTS)

• Hearing loss

• Seizures

• Motor abnormalities, including paralysis

• Language disorders or delay

• Cognitive impairment

• Cerebral palsy

• <1% relapse rate of infection after antibiotic therapy

OUTCOMES

• Mortality rates for bacterial meningitis is 1% to 5% in all pediatric patients, but is 15% to 20% for neonates.

SUGGESTED READINGS

INTRODUCTION

Weakness presenting to the ICU is either due to an acute/acquired cause or is a complication of chronic weakness, such as acute on chronic respiratory failure. This chapter will focus on the physical exam of a patient with new-onset weakness and summarize chronic neuromuscular diseases that could lead to ICU presentation.

LOCALIZATION OF WEAKNESS

Weakness can arise from pathology at any point along the neuroaxis from brain to muscle. It can be a single discrete lesion causing a focal deficit or a generalized process causing more disseminated signs. Physical exam is one of the key tools for localizing the lesion and narrowing the differential diagnosis. Table 45-1 describes the typical exam findings based on a lesion at each level of the neuroaxis and examples of associated disease states. Table 45-2 lists neurologic signs that are characteristic of specific lesions or disease processes.

ACUTE WEAKNESS

Acute weakness can be caused by ischemia/hypoperfusion, inflammation, toxin, or metabolic derangements affecting the neuroaxis. The following are summaries of pathologic conditions, starting at the spinal cord and moving distally, that could lead to ICU presentations of acute weakness. Other chapters in this handbook address brain pathology, including stroke.

SPINAL CORD

• Transverse myelitis (TM)^1,2: TM is classically thought to be an immune-mediated demyelinating disorder of the spinal cord. It can be idiopathic or the initial presentation of an underlying demyelinating disorder such as multiple sclerosis, neuromyelitis optica, or a manifestation of another systemic disease such as systemic lupus erythematosus (SLE).

  • Clinical features: TM affects children less frequently than adults in a bimodal distribution (<5 yr and >10 yr). Two-thirds have a history of infection in the previous month. It can present initially with back pain, followed by symmetric or patchy sensory changes such as paresthesias or numbness, flaccid motor deficits, and bowel/bladder dysfunction such as urinary retention requiring catheterization.

  • Diagnosis: Refer to Table 45-3

  • Evaluation: Magnetic resonance imaging (MRI) with and without contrast of entire spine and brain. Obtain cerebrospinal fluid (CSF) for cell count, protein, glucose, IgG index, oligoclonal bands, bacterial/viral culture, and polymerase chain reaction (PCR).

  • Treatment: Corticosteroids 30 mg/kg/day for 3 to 5 days (max 1000 mg/day). Consider plasma exchange for five to seven sessions. Consider IVIg 2 gm/kg divided over 2 to 5 days.

  • Prognosis: 50% have full recovery by 2 years, 25% are nonambulatory or require walking aids, 10% to 20% never regain mobility or normal bladder function. High cervical cord lesions and respiratory failure are associated with increased risk for mortality.

• Anterior spinal artery infarction^3,4: The anterior spinal artery supplies the anterior two-thirds of the spinal cord, which contains the corticospinal (motor) and spinothalamic (pain and temperature sense) tracts. The dorsal columns (proprioception and vibration) are supplied by the posterior spinal arteries. Anterior spinal artery infarction is a rare neurologic emergency in children and can be difficult to differentiate from transverse myelitis. Risk factors/causes include aortic surgery, trauma, umbilical artery catheter, thrombophilia, fibrocartilaginous embolism, cerebellar herniation, CNS vasculitis secondary to infection, lupus, arteriovenous malformation (AVM), and hypotension/cardiac arrest.

  • Clinical Features: Patients may have preceding back pain at the site of infarction followed by an abrupt onset of bilateral weakness. Classically there is also a loss of pain and temperature sensation while maintaining vibratory and proprioception sensation; however, case series have shown varying degrees of sensory dysfunction, including complete sensory loss. Bowel and bladder function is often affected. Cord infarction due to fibrocartilaginous embolism may differ in time course, causing a more slowly progressive neurologic deterioration over hours to 1 to 2 days.

  • Diagnosis: MRI of the spinal cord with diffusion-weighted and T2-weighted imaging in axial and sagittal planes.

  • Treatment: Treat the underlying mechanism for injury. Optimize oxygen and blood supply to the cord with supportive care. Consider anticoagulation and/or aspirin.

  • Prognosis: The majority of patients will have some degree of motor and bowel/bladder recovery, including a minority with complete recovery.

ANTERIOR HORN CELL

• Acute flaccid paralysis^5–7: Enteroviruses, of which poliomyelitis is the most notorious, can infect the anterior horn motor neurons leading to cell death and subsequent weakness. In some patients, infection is not restricted to the anterior horn and can involve the brainstem causing cranial neuropathies and bulbar weakness. Nonpolio enteroviruses generally have a milder clinical course; however, an entity called acute flaccid myelitis (AFM), first described in 2012–2014, is a syndrome of acute flaccid paralysis with anterior myelitis, which can cause a prolonged polio-like weakness, and was associated with an outbreak of enterovirus D68 infections, although the etiology is still unclear. Arboviruses such as West Nile virus can also cause an asymmetric flaccid paralysis.

  • Clinical Features: Patients may have a few days of prodromal symptoms such as fever, sore throat, headache, nausea, constipation, and malaise. After resolution of these symptoms, patients can develop a rapidly progressive, flaccid, asymmetric weakness involving the limbs. It is classically proximal, with the legs usually involved in polio and arms with AFM. Cranial nerves and muscles of respiration can also be involved, leading to respiratory failure. Sensation is usually preserved, and patients may experience myalgias and/or arthralgias. Autonomic dysfunction, especially bowel and bladder dysfunction, may be present.

  • Diagnosis: CSF may show pleocytosis with lymphocytic predominance (PMNs may predominate early on), normal to slightly elevated protein, and normal glucose. Polio can be confirmed by stool or throat culture. Suspected cases of polio should be reported to the state health department. For AFM, MRI of brain and spinal cord shows T2, nonenhancing, confluent, and longitudinally involved lesions of the gray matter of the cord +/− brainstem.

  • Treatment: Provide supportive care. For AFM, IVIg, plasmapheresis, and corticosteroids have been used. There are no current guidelines for immunomodulatory therapies.

  • Prognosis: For polio, 50% of patients with paralysis will have some residual deficits. For AFM, most patients will show improvement in strength; but only a minority will have full recovery. Some have ventilator dependence at time of hospital discharge.

PERIPHERAL NERVE

• Guillain-Barre syndrome (GBS)^8,9: GBS is an acute inflammatory demyelinating polyneuropathy or an acute axonal motor (+/− sensory) neuropathy. Preceding infection, classically Campylobacter jejuni, or immune stimulation, such as vaccines, leads to an autoimmune response by molecular mimicry in a susceptible host.

  • Clinical Features: Patients may have a respiratory or gastrointestinal illness in the month prior to symptom onset. Ascending, progressive, and generally symmetric flaccid weakness with areflexia then follows. Mild sensory symptoms and pain may be present. Autonomic dysfunction such as cardiac arrhythmias, blood pressure lability, ileus, and urinary retention should be monitored. Weakness can progress to respiratory failure. The Miller-Fisher variant has the triad of ophthalmoplegia, ataxia, and areflexia.

  • Diagnosis: GBS is a clinical diagnosis. Physical exam should show a progressive, relatively symmetric weakness in upper and lower extremities with areflexia. Nerve conduction studies can be helpful in supporting the diagnosis early in the course as evidenced by prolongation or loss of F-wave responses. It can also help in differentiating between demyelinating and axonal subtypes. MRI of spine may show enhancement of nerve roots. CSF analysis often reveals an albuminocytologic dissociation.

  • Treatment: IVIg 2 g/kg over 2 to 5 days or plasmapheresis for five cycles over 2 weeks. Provide supportive care, with close monitoring of respiratory function, including negative inspiratory force (NIF) and vital capacity (VC). Consider intubation if NIF > −30 or VC <20 cc/kg. Should also monitor for autonomic dysfunction leading to cardiac rhythm disturbances.

  • Prognosis: Recovery can take months to years.

NEUROMUSCULAR JUNCTION (NMJ)

• Myasthenia gravis (MG)^10–12: MG is an autoantibody-mediated disorder against acetylcholine receptor (AChR-Ab) and/or muscle-specific tyrosine kinase (anti-MuSK Ab) in most patients. These antibodies lead to direct blocking of acetylcholine at the receptor, receptor degradation, and NMJ membrane damage.

  • Clinical Features: The characteristic findings are fatigability, ptosis, ophthalmoplegia, and bulbar dysfunction. Weakness of the limbs is proximal and usually does not occur without ocular findings. Some patients may have isolated ocular findings. Myasthenic crisis is a rapid and life-threatening worsening of MG leading to airway compromise from ventilatory or bulbar dysfunction. Exacerbations can be triggered by heat, illness, stress, or medications (e.g. aminoglycosides, fluoroquinolones, neuromuscular blockade, magnesium sulfate, etc.)

  • Diagnosis: Diagnosis is made by a combination of history, physical exam, decrement on repetitive nerve stimulation, abnormal jitter on single-fiber electromyography, and positive AChR-Ab or anti-MuSK Ab. Absence of autoantibodies does not exclude the diagnosis.

  • Treatment for myasthenic crisis: Provide respiratory support if needed: noninvasive positive pressure ventilation (NIPPV) vs. endotracheal intubation. Administer IVIg 1 g/kg/day × 2 days OR plasma exchange × five cycles. Consider prednisone/methylprednisolone (1 mg/kg/day, max 100 mg/day), although its use can cause a transient exacerbation of weakness.

  • Chronic treatment: Titrate pyridostigmine (mestinon) to effect while monitoring for cholinergic side effects. Chronic immunomodulation should be managed by an expert (corticosteroids, azathioprine, cyclosporine, mycophenolate, tacrolimus, rituximab, chronic IVIg, or PLEX)

  • Prognosis: Variable.

• Botulism¹³: Botulism is caused by a neurotoxin released by Clostridium botulinum that disrupts presynaptic acetylcholine release. In infants, ingested spores from raw honey or environmental dust/soil develop into toxin-secreting bacteria, which leads to disease. Adults require ingestion of preformed toxin from improperly canned foods to cause disease.

  • Clinical Features: In infants, constipation is followed by symmetric descending weakness with cranial neuropathies such as dilated unreactive pupils and facial weakness. About half will require respiratory support during hospitalization. Adults present similarly with cranial neuropathies and descending symmetric weakness. Either age group may have bradycardia.

  • Diagnosis: Positive stool botulinum toxin. Repetitive nerve conduction studies can be helpful while waiting for stool studies to result.

  • Treatment: For infant botulism: BabyBIG (intravenous botulism immunoglobulin). For botulism in patients >1yo: equine serum botulism antitoxin. Provide supportive care, including possible need for mechanical ventilation.

  • Prognosis: Excellent prognosis for full recovery although it may take weeks to months. The mortality rate for infant botulism is <1% in the United States.

• Organophosphate and carbamate intoxication¹⁴: Organophosphates and carbamates are acetylcholinesterase inhibitors and are generally used as pesticides. Exposure to these compounds leads to excessive cholinergic stimulation at muscarinic and nicotinic receptors.

  • Clinical Features: Muscarinic stimulation leads to diarrhea, urination, miosis, bronchorrhea/bronchospasm/bradycardia, emesis, lacrimation, salivation (“DUMBELS”). Nicotinic stimulation leads to fasciculations, muscle weakness, and paralysis, which can cause respiratory arrest. Nicotinic stimulation of sympathetic ganglia can lead to tachycardia and hypertension, making the diagnosis of cholinergic poisoning challenging. CNS effects can lead to anxiety, ataxia, seizures, and coma.

  • Diagnosis: Diagnosis is made by clinical signs and symptoms.

  • Treatment: Decontaminate the patient by removing clothing and washing with soap and water. For muscarinic toxicity, atropine 2 to 5 mg IV for adults, 0.05 mg/kg IV for children. The dose should be doubled every 5 minutes until respiratory secretions and bronchoconstriction are alleviated and hemodynamics are acceptable. An atropine continuous infusion then should be initiated at 10% to 20% of the total given dose. For nicotinic toxicity, pralidoxime 1 to 2 G IV for adults, 20 to 50 mg/kg IV for children (max 2 G). Repeat dose at 1 hour, then every 10 to 12 hours until weakness resolves. For seizures, use benzodiazepines.

  • Prognosis: Variable depending on severity of poisoning.

• Tick paralysis¹⁵: Female gravid ticks secrete a salivary neurotoxin that can induce paralysis of the host during blood feeding. In North America, Dermacentor andersoni (most common), Dermacentor variabilis, Amblyomma americanum, Amblyomma maculatum, and Ixodes scapularis are the causal ticks.

  • Clinical Features: After the initial tick bite, which may go unnoticed by the patient, the patient can develop ataxia followed by rapid ascending symmetric weakness with areflexia, progressing to cranial nerve involvement and ultimately respiratory muscle failure.

  • Diagnosis: Careful inspection to locate the tick on the patient.

  • Treatment: Remove tick. Provide supportive care.

  • Prognosis: Improvement in weakness can be observed within hours and full recovery within 1 to 2 days.

MUSCLE

• Rhabdomyolysis/myositis¹⁶: Muscle injury, ischemia, and/or inflammation leads to necrosis, which results in release of intracellular contents of myocytes into the systemic circulation. It can be triggered by a preceding viral infection, trauma, strenuous exercise, heat stroke, metabolic myopathy, and medications such as statins.

  • Clinical Features: Myalgias, weakness, and dark urine are classic findings. Complications of rhabdomyolysis are acute kidney injury, electrolyte disturbances, and rarely compartment syndrome.

  • Diagnosis: Elevated creatine kinase, typically at least five times the upper limit of normal. Urinalysis with positive blood and absence of red blood cells (RBCs), consistent with myoglobinuria.

  • Treatment: Treat the underlying cause of muscle injury. Supportive care with aggressive intravenous hydration and close monitoring of electrolytes and kidney function. Consider urine alkalinization with a goal urine pH >6.5 for the theoretical benefit of preventing acute kidney injury (AKI) from myoglobin toxicity. Renal replacement therapy may be necessary to treat hyperkalemia, acidosis, fluid overload, and anuria.

METABOLIC

• Electrolyte derangements such as hypokalemia/hyperkalemia, hypercalcemia, hypoglycemia, hypermagnesemia, and hypophosphatemia can precipitate weakness. Generally, correction of the derangement will lead to a rapid resolution of weakness.

CHRONIC WEAKNESS

Chronic weakness in pediatrics can be caused by congenital/genetic changes leading to disruption of neuromuscular function. Presentation to the ICU is generally a consequence of acute or chronic respiratory failure, cardiomyopathy, or postsurgical management.

ANTERIOR HORN CELL DISORDER

• Spinal muscular atrophy (SMA)¹⁷: SMA is caused by a mutation/deletion of the SMN1 gene (survival motor neuron) and is traditionally inherited in an autosomal-recessive pattern. Loss of SMN1 gene function results in degeneration of alpha motor neurons in the spinal cord and motor nuclei in the brainstem causing a lower motor neuron pattern of weakness. SMA, in order of decreasing weakness/morbidity, is most commonly categorized into type 1 (cannot sit), 2 (sit but cannot walk), and 3 (walk but is weak). SMA0 kids are weak at birth and do not survive into infancy. Pulmonary complications cause significant morbidity and mortality for these patients.

  • Clinical Features: SMA is characterized by a progressive, symmetric flaccid weakness that is proximal > distal and involves the lower extremities > upper extremities, paradoxical breathing due to weak intercostal muscles with initially preserved diaphragmatic strength, and absence of deep tendon reflexes. Bulbar dysfunction increases the risk for aspiration. Respiratory insufficiency is most pronounced for type 0 to 2 SMA and causes impaired cough and secretion clearance, nocturnal hypoventilation that progresses to continuous hypoventilation, chest wall and lung underdevelopment, and recurrent infections that exacerbate muscle weakness.

  • Treatment: For respiratory insufficiency: cough assistance, chronic noninvasive positive pressure ventilation, and consideration for tracheostomy, depending on family's goals for care. Involving primary care and palliative care teams early on in the process of respiratory failure helps support the family. For malnutrition/aspiration, consider early gastrostomy placement (no consensus guideline). When placing a G-tube, Nissen fundoplication should be strongly considered. Orthopedic care includes management of scoliosis, hip subluxation, and joint contractures. Nusinersen, an antisense oligonucleotide delivered by intrathecal injection that increases production of full-length SMN protein by the SMN2 gene, was approved by the Food and Drug Administration (FDA) in December 2016 and is available at some institutions.

  • ICU Considerations: For acute-on-chronic respiratory failure, management should include cough assistance and airway clearance therapies, escalation of NIPPV, and possible intubation, if family goals for care align. Factors to consider for extubation readiness include low secretion burden, lack of atelectasis on chest x-ray, minimal ventilator support, and ability to extubate to NIPPV.

MUSCULAR DYSTROPHY

• Duchenne muscular dystrophy (DMD)^18,19: DMD is the most common and most severe muscular dystrophy. It is caused by an X-linked recessive mutation in the dystrophin gene. The resultant lack of functional dystrophin protein causes degeneration of striated muscle, elevated creatine kinase levels, progressive weakness, and cardiomyopathy. It overwhelmingly affects males; however, female carriers may also develop weakness and cardiomyopathy.

  • Clinical Features: Weakness onset is in early childhood with eventual progression to being nonambulatory. It initially involves proximal > distal and lower extremities > upper extremities. Neuromuscular scoliosis often results. Other classic findings are Gower's sign and calf pseudohypertrophy. Respiratory insufficiency is progressive and may begin with sleep-disordered breathing. Symptoms of dilated cardiomyopathy and cardiac conduction defects usually begin in early adolescence. Varying degrees of intellectual disability are present.

  • Treatment: Chronic corticosteroids have been shown to improve strength and pulmonary function and delay cardiomyopathy.²⁰ Chronic NIPPV can ameliorate sleep-disordered breathing and hypoventilation. Heart failure can be managed with angiotensin-converting enzyme (ACE) medications and/or beta blockers. Arrhythmia management may require antiarrhythmics and possible implantable cardioverter defibrillator (ICD) placement.²¹ Orthopedics can address scoliosis, contractures, and fractures.

  • ICU Considerations: Heart failure and respiratory failure are the leading causes of death. DMD-associated dilated cardiomyopathy is a cardiomyopathy out of proportion to weakness and respiratory dysfunction. It increases the risk for ventricular arrhythmias causing sudden death. For treatment of acute on chronic respiratory failure, consider escalation of airway clearance therapies, NIPPV, and possible endotracheal intubation if in line with the patient's goals of care. The following precautions should be observed with anesthesia²²: depolarizing muscle relaxants are contraindicated due to risk for rhabdomyolysis, hyperkalemia, and cardiac arrest; and inhalational anesthetics are associated with a risk for malignant hyperthermia.

CONGENITAL MYOPATHIES

Congenital myopathies are a clinically heterogeneous group of disorders that cause generalized weakness that result from mutations in multiple genes that code for and support the contractile apparatus of the muscle. These can include actin, tropomyosin, and ryanodine receptors, to name a few. A characteristic phenotype can help with focused genetic testing, or sometimes a muscle biopsy may be done prior to genetic testing to help narrow the differential. Genetic testing can elucidate the specific gene mutation; however, mutations in the same gene can lead to different types of congenital myopathies, and different myopathies can be caused by mutations in overlapping genes. Weakness generally does not progress after the neonatal/infantile period, and some patients may even gain strength and mobility. Patients with severe respiratory failure in the neonatal/infantile period are also at the highest risk for mortality. Multidisciplinary subspecialty care is recommended to manage the pulmonary, nutritional, orthopedic, and neurologic complications of these diseases. Following is a summary of clinical complications of interest to an intensivist that may arise in congenital myopathies.²³

• Respiratory failure: All patients with congenital myopathy are at risk for respiratory insufficiency. Respiratory failure presenting in the neonatal period is common in X-linked tubular myopathy and severe cases of nemaline myopathy with ACTA1 mutations. Respiratory weakness out of proportion to overall muscle weakness can be seen in multiminicore disease with SEPN1 mutations, nemaline myopathy with NEB or ACTA1 mutations, and selected patients with TPM3 mutation. Patients who did not have respiratory failure during infancy who then develop progressive respiratory failure during adolescence and adulthood generally carry the following mutations: SEPN1, TPM3, ACTA1, NEB, DNM2, MTM1.

• The most common phenotype of respiratory insufficiency is sleep disordered breathing. Respiratory failure can also develop from progressive hypoventilation and progressive atelectasis that is not initially clinically apparent, or restrictive lung disease from scoliosis. Decompensations during intercurrent illness may require escalation of cough assistance, airway clearance, and noninvasive positive pressure ventilation, and if unsuccessful, endotracheal intubation if within the patient's goals of care.

• Cardiomyopathy: Primary cardiomyopathies are unusual in congenital myopathies. There have been observed cases with actin α1 (ACTA1), dynamin 2 (DNM2), and tropomyosin 2 (TPM2) mutations. Secondary right ventricular dysfunction may be present in patients with significant pulmonary disease.

• Orthopedic: Scoliosis can develop in all congenital myopathies, especially when axial weakness is a prominent feature. Scoliosis correction with risk for postoperative respiratory failure may necessitate ICU admission and monitoring.

• Anesthesia Risk: As a general rule, inhalational anesthetics and depolarizing muscle relaxants should be avoided in patients with congenital myopathies and are contradindicated in patients with RYR1 mutation due to the risk for malignant hyperthermia.

• Bulbar Dysfunction: Bulbar dysfunction is commonly present in nemaline myopathy and can also be seen with recessive mutations in RYR1 causing multiminicore disease and subgroups of centronuclear myopathy. Gastric or jejunal feeding may be required due to poor handling of oral contents and the risk for aspiration. Anticholinergic agents may be trialed to treat sialorrhea while monitoring for the side effects of constipation and creation of thick tenacious secretions.

• Cognitive Impairment: Cognitive impairment is unusual in congenital myopathies, unless respiratory failure led to hypoxic-ischemic brain injury. Alternative or additional diagnoses should be explored if this is a prominent feature.

CONCLUSION

Weakness is a relatively common clinical entity requiring admission to the intensive care unit. Acute weakness should start with localization of the lesion in order to focus the differential diagnosis and diagnostic evaluation. Patients with chronic weakness are often cared for by intensivists in the setting of respiratory complications of their disease, but may have multiorgan involvement, including cardiac, gastrointestinal, and orthopedic.

DEFINITION AND SUBTYPES

• Delirium: A form of acute and fluctuating global cerebral dysfunction caused by the direct physiologic consequences of a general medication condition and characterized by disturbances in attentiveness and awareness and cognitive impairment affecting memory, cerebral orientation, language, perception, and/or visual or auditory hallucinations. Four current subtypes exist:

  • Hyperactive: The “classic” form of delirium and intensive care unit psychosis featuring episodic or progressive agitation, restlessness, hallucinations, delusions, and/or emotional lability. Most easily recognized subtype by providers and family members.

  • Hypoactive: Can also be referred to as “encephalopathy of critical illness” with decreased responsiveness, blunted levels of consciousness, quiet confusion, and apathy. Oftentimes can be confused with depressive symptoms or acute stress disorders.

  • Mixed: Waxing and waning occurrences of both hyperactive and hypoactive delirium throughout its fluctuating course.

  • Subacute: Usually related to an indolent, progressive medical condition over time with occasional occurrences of either hyperactive delirium or hypoactive delirium or both that is not defined by an additional psychiatric diagnosis.

ETIOLOGY

• Often is multifactorial. Care should be made to evaluate for all of the following etiologies as a possible cause:

  • Underlying disease processes – most often associated with compensated or uncompensated shock; systemic or localized infection; acute or chronic hypoxia/hypoxemia; neoplasms; seizures; and/or electrolyte, renal, or endocrine derangements

  • Environmental exposures – prolonged states of immobilization or paralysis, day and night lighting disturbances, and sleep deprivation

  • Iatrogenic – suspected to be related to certain acute or prolonged drug exposures (i.e., sedative medicines like benzodiazepines, barbiturates, or opioids or anticholinergic medications) or withdrawal from previously utilized medications

IMPACT AND RECOGNITION

• Delirium is widely accepted as a negative predictor for clinical outcomes in adult patients, particularly those on mechanical ventilation and prolonged sedative infusions.

• Although pediatric data remains limited, emerging literature suggests similar risk factors for developing delirium and an impact on short- and long-term outcomes for children.

• Diagnosing and recognizing delirium in pediatric patients is difficult and is complicated by variations in pediatric development and age.

• Once diagnosed, delirium has been shown to predispose adult patients to:

  • Increased in-hospital mortality

  • Longer lengths of stay, both in the ICU and general hospital

  • Higher medical costs

  • Long-term cognitive impairments

  • Developing post-intensive care syndrome (PICS)

SCREENING TOOLS

• Utilization of quick, reliable, feasible, and observational screening tools for pediatric patients aids physicians in diagnosing all four delirium subtypes.

• Three tools are currently in use:

  • Preschool Confusion Assessment Method for the ICU (psCAM-ICU)

  • Pediatric Confusion Assessment Method for the ICU (pCAM-ICU)

  • Cornell Assessment of Pediatric Delirium (CAPD) - See Figure 46-1

• The psCAM-ICU and pCAM-ICU cannot be fully utilized on developmentally delayed children, which is a recognized limitation of these tools. The CAPD scale can be applied to all children regardless of delay.

PROCEDURAL APPROACH TO DIAGNOSIS

• When referencing one of these screening tools, physicians and nurses should apply the CAPD questionnaire at the end of each shift to every ICU patient who exhibits a Richmond Agitation-Sedation Scale (RASS) of ≥ −3 (or for simplification purposes has spontaneous eye opening) See Figure 46-2.

• Each question is scored according to physician and/or nursing observation over the course of the shift.

• A score ≥9 is usually diagnostic of delirium in developmentally appropriate children.

• Children with developmental delay must be viewed on a spectrum to establish a change from their baseline, making diagnosis possible in these children but more difficult.

TREATMENT

• A three-tiered approach to the treatment of delirium should be applied for every patient:

  • Address the underlying disease process

    • Assess for infection, hypoxemia, and medication withdrawal

    • Achieve adequate pain control

  • Optimize the clinical environment

    • Clear and direct communication with the patient

    • Creation of a quiet, well-lit, controlled space

    • Frequent reorientation of the patient to their surroundings

  • Minimize iatrogenia

    • Reduce sedative exposure when possible

    • Avoid anticholinergics

    • Avoid physical restraints

    • Facilitate sleep through bundled nursing care and assessments

• Pharmacologic agents:

  • There currently are no studies on pharmacologic prevention of delirium in pediatrics, and treatment response is, at best, anecdotal.

  • Treatment for hyperactive delirium may include the use of typical (e.g., haloperidol) or atypical antipsychotics (risperidone, olanzapine) but should only be utilized in consultation alongside a clinical pharmacist and after discussion of the risks and benefits of these medications.

  • There are no current pharmacologic recommendations for the treatment of hypoactive delirium.

SUGGESTED READINGS

BRAIN DEATH DETERMINATION AND GUIDELINES

Brain death in infants and children according to current guidelines¹:

• Brain death guidelines: Defining brain death originates from the President's Commission of the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. For pediatric patients, the most recent brain death guidelines were published in 2011 by a multidisciplinary taskforce and are endorsed by the Society of Critical Care Medicine, the American Academy of Pediatrics, American Association of Critical Care Nurses, Child Neurology Society, and Society of Pediatric Neuroradiology. This definition of death is affirmed by the American Bar Association. Despite wide acceptance, no federal brain death law exists, so providers must review their state and institutional statutes and policies that may restrict this definition.

• Brain death: Cessation of all neurologic functions of the brain due to a known, irreversible cause.

  • Clinical Diagnosis: This is a clinical diagnosis and must be made by a physician who has taken the history and completed the exam. Coma and apnea must coexist.

  • Clinical examination: Includes evaluation of coma, loss of brainstem functioning, and apnea.

• Prerequisites for initiating brain death evaluation:

  • Irreversible coma with known cause: Although not considered ancillary studies, magnetic resonance imaging (MRI) or computerized tomography (CT) findings should show evidence of acute injury consistent with significant neurologic damage.

  • Hemodynamic and metabolic stability: Shock, hypotension, hypothermia, and severe metabolic disturbances that could affect neurologic function (i.e., glucose and electrolytes) must be corrected before initiating the exam.

  • Pharmacologic agents: Neuromuscular blockades, sedatives, barbiturates, opioids, and antiepileptics must be discontinued prior to the examination. For recently administered medications, adequate clearance should be allowed (based on half-life, organ dysfunction, and patient age).

  • Cardiopulmonary resuscitation: It may be necessary to wait 24 to 48 hours after cardiopulmonary arrest or severe acute brain injury due to patient instability or inconsistencies in neurologic examinations, as assessed by clinical judgment.

• Number of examinations: Two examinations should be performed, separated by an observation period.

  • Neonates: For patients 37 weeks up to 30 days of age, the observation period between two exams should be 24 hours. Due to open sutures and fontanelles, neonates are less likely to have as significant intracranial hypertension, leading to cerebral ischemia and herniation, as older children.

    • Current guidelines do not include information for preterm infants.

  • Infants and children: For infants older than 30 days of age and children up to 18 years of age, the observation period between two exams should be 12 hours.

  • Special considerations: Should there be a desire to decrease the period of observation, an ancillary test may be considered.

• Examiners: The clinical examinations should be performed by two different attending physicians, each with expertise in neurocritical care. Because the apnea exam is an objective exam, it may be performed by the same attending physician.

• Neurologic examination: To assess loss of all brainstem reflexes. The following are consistent with cessation of brainstem function:

  • Absence of pupillary response: Midposition or fully dilated pupils that are nonreactive to bright light.

  • Absence of bulbar musculature: Deep pressure on the condyles at the level of the temporomandibular joints and at the supraorbital ridge produce no movement of the facial and oropharyngeal muscles.

  • Absence of gag, cough, sucking, and rooting reflexes: Using a tongue blade or suction device for posterior pharynx and endotracheal suctioning at the level of the carina does not illicit a cough.

  • Absence of corneal reflexes: A soft tissue, cotton, or water to the cornea does not illicit eyelid movement.

  • Absence of oculovestibular reflexes: Cold caloric testing (irrigating each ear with 10–50 mL of ice water) into patent auditory canals does not produce movement of the eyes within 1 minute.

• Apnea test: The patient must have absence of respiratory effort coinciding with PaCO₂ ≥60 mmHg and ≥20 mmHg above baseline.

  • Prerequisites for testing: Normalized pH, PaCO_2, blood pressure, and temperature; preoxygenation with FiO₂ of 1.0 for 5 to 10 minutes prior to beginning the exam.

  • Apnea test: Patient should be removed from mechanical ventilation to T-piece or self-inflating bag with oxygen. Closely monitor for spontaneous respiratory effort and hemodynamic instability. If SpO₂ falls below 85% or patient has hemodynamic instability, the test should be stopped and patient should be placed back on mechanical ventilation.

  • Special consideration: If a patient has chronic lung disease and may only respond to supranormal PaCO₂, may start at baseline PaCO₂ and observe for rise ≥20 mmHg above baseline.

• Challenges to diagnosis of brain death

  • Spontaneous and reflex movements: May be noted in patients meeting criteria for brain death. These can either be spontaneous or triggered by a stimulus. These movements are known as spinal reflexes.² See Table 47-1.

    Table Graphic Jump Location

    TABLE 47-1

    Reflexes in Brain Death^1,2

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    TABLE 47-1

    Reflexes in Brain Death^1,2

    - Occur in response to a trigger and are often reproducible - Nonpurposeful - Often seen within the first 24 hours, but can be present longer - May mimic clinical patterns not consistent with brain death	Examples include:
    	Small finger movements Deep tendon reflexes Triple flexion Respiration-like movements Superficial abdominal reflexes Babinski's sign Head turning Lazarus’ sign Facial myokymia

• Ancillary studies: Used when components of the neurologic examination or apnea test are unable to be performed, results are not definitive, medications are present, or to reduce observation period. Otherwise, not required for a patient to meet brain death criteria. In pediatrics should be performed and interpreted by trained and qualified individuals.

  • Four-vessel cerebral angiography: Demonstrates absence of cerebral blood flow; gold standard but may be difficult to perform in a child due to need for transport, thereby affecting hemodynamic stability.

  • Radionuclide cerebral blood flow: Demonstrates absence of cerebral blood flow.

  • Electroencephalography (EEG): Documents electrocerebral silence (ECS).

  • If cerebral blood flow is present or EEG shows electrical activity, the patient cannot be pronounced brain dead and should be observed before clinical examination can confirm cessation of neurologic function. Waiting period of 24 hours is recommended prior to repeat testing.

• Declaration of brain death: Occurs after the second neurologic exam and apnea test are consistent with cessation of neurologic function. See Figure 47-1.

  FIGURE 47-1

  Algorithm to Diagnose Brain Death in Infants and Children¹

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• Supporting the family: Communication with families must be supportive, clear, and concise.

  • Parental presence during testing may be helpful in understanding that the child has died.

  • Families must understand that once a child meets criteria for brain death, the patient meets legal criteria for death.

  • Clinicians should avoid discussions of “withdrawal of support” after declaration of brain death, as this is confusing to families. Rather, discontinuation of medical equipment must occur unless there is a consideration of organ donation.