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888 SECTION 12: Pediatrics macroscopic hematuria, a more complete anatomic evaluation is needed, including CT, angiography, or retrograde urethrography depending on the history and clinical suspicion. TREATMENT The treatment of hematuria, like its evaluation, depends on the sus pected cause. Most children without signs of major or life-threatening etiologies can be managed as outpatients. Children with isolated microscopic hematuria do not require an extensive evaluation if the blood pressure and urine output are normal. Hematuria requires a more rigorous evaluation when the blood pressure is elevated or there is significant proteinuria, so consult with a nephrologist. Refer to a urologist if there is suspicion of a urogenital tract anatomic abnormality, obstructing calculi, tumor, or recurrent nonglomerular macroscopic hematuria. CHRONIC KIDNEY DISEASE Chronic kidney disease is defined as a glomerular filtration rate <60 mL/min/1.73 m2 for more than 3 months regardless of other mark ers of chronic kidney disease or >60 mL/min/1.73 m 2 with evidence of structural damage, functional abnormalities, or pathologic abnormalities.54 End-stage renal disease occurs when the glomerular filtration rate is <10% of normal for age. Mortality in end-stage renal disease usually results from cardiovascular causes (40% to 50%) and infection (20%). The only definitive treatment for end-stage renal disease is transplanta tion; however, the morbidity and mortality associated with chronic renal replacement therapy have decreased. Chronic kidney disease is classified into five separate stages based on glomerular filtration rate with the addition of categories of albumin uria and proteinuria ( Table 137-7). 54 The recommended method for determination of glomerular filtration rate is with spot urine and serum creatinine using either the Schwartz or Counahan calculation. Twentyfour–hour urine collections for creatinine are no longer recommended. ETIOLOGY AND DIFFERENTIAL DIAGNOSIS Congenital renal disease is the most common cause of chronic renal failure in young children, whereas glomerulonephritis and reflux nephropathy predominate in older children. Congenital structural lesions include dysplasias and cystic malformations (e.g., polycystic kidney disease). Obstructive uropathy leading to end-stage renal disease may be caused by posterior urethral valves in boys, severe vesicoureteral reflux with recurrent infection, and ureteropelvic junction obstruction. End-stage renal disease in children can be caused by hereditary nephritis or acquired nephropathies such as hemolytic-uremic syndrome, glomerulonephritis, and cortical necrosis (more common in children with sickle cell disease). CLINICAL FEATURES Take a complete history to obtain information about changes in urina tion, fatigue, swelling, anorexia, emesis, bone pain, muscle cramps, headache, and change in mental status. Ask about signs and symptoms related to potential complications from chronic kidney disease. Complications associated with chronic kidney disease include disorders of fluids, electrolytes, and mineral metabolism. Anemia, hyper tension, dyslipidemia, and endocrine abnormalities, including growth impairment, are present. End-stage renal disease is associated with car diovascular problems and cerebrovascular events from malignant hypertension. Skeletal, hematologic, and intestinal abnormalities accompany renal failure. Renal failure predisposes to non-Hodgkin’s lymphoma and skin cancer.
alities, including growth impairment, are present. End-stage renal disease is associated with car diovascular problems and cerebrovascular events from malignant hypertension. Skeletal, hematologic, and intestinal abnormalities accompany renal failure. Renal failure predisposes to non-Hodgkin’s lymphoma and skin cancer. Pertinent physical findings in patients with end-stage renal disease include short stature, CNS problems, peripheral neuropathies, and rickets. Fever should prompt an aggressive search for a source. Fluid overload is suggested by peripheral edema and pulmonary congestion. Pericarditis is less common in children with end-stage renal disease than in adults. Abdominal pain and tenderness in children receiving perito neal dialysis suggests peritonitis. TREATMENT The standard of treatment for most patients with end-stage renal disease is hemodialysis. Children <2 years of age are often treated with peri toneal dialysis because it is associated with fewer complications than hemodialysis in young children. Renal transplantation is the ultimate goal. In dialysis patients presenting to the ED with fever, an aggressive search for infection must ensue. Use of empiric antibiotics is directed by the source of the infection (e.g., S. aureus, S. epidermidis), after cultures are drawn. If a patient on peritoneal dialysis presents with abdominal pain, suspect bacterial peritonitis. In patients presenting with severe electrolyte abnormalities, fluid overload, severe hypertension, or uremic pericarditis, urgent dialysis is indicated. Dialysis patients presenting with syncope should be evaluated for electrolyte abnormalities, hypo volemia, and cardiac dysrhythmias. See Chapter 90, “End-Stage Renal Disease, ” in the adult section for detailed discussion. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 137-7 Staging of Pediatric Chronic Kidney Disease Glomerular Filtration Stage Albuminuria and Proteinuria Stage G1: Normal GFR (≥90 mL/min/1.73 m2) G2: GFR between 60 and 89 mL/min/1.73 m2 G3a: GFR between 45 and 59 mL/min/1.73 m2 G3b: GFR between 30 and 44 mL/min/1.73m2 G4: GFR between 15 and 29 mL/min/1.73 m2 G5: GFR of <15 mL/min/1.73 m2 (kidney failure) A1: Normal to mildly increased (<30 milligrams albumin/gram creatinine) A2: Moderately increased (30 to 300 milligrams albumin/gram creatinine) A3: Severely increased (>300 milligrams albumin/ gram creatinine) Abbreviation: GFR = glomerular filtration rate. Seizures in Infants and Children Maija Holsti INTRODUCTION AND EPIDEMIOLOGY Unusual movements and changes in behavior in children often lead to an ED visit. Most seizure activity stops before the child is seen in an ED; therefore, history is key to the correct diagnosis. Although seizures account for many of these events, as many as 30% or more of paroxysmal events may be misdiagnosed as seizures. 1,2 There are many different causes of pediatric seizures. The goal is to identify and treat the underlying cause. Some seizures require emer gency management and extensive evaluation (e.g., status epilepticus, neonatal seizures), whereas others are common, benign, and need little or no ED evaluation (e.g., febrile seizures, first-time seizure in an oth erwise well child). This chapter focuses on the diagnosis and manage ment of ongoing seizures first and then discusses the approach to febrile seizures, neonatal seizures, and seizures in special populations (e.g., children with epilepsy, neurologic shunts, and trauma) under “Special Considerations/Populations. ” The prevalence of pediatric seizures in the United States is approxi mately 1% of all children up to the age of 14 years and is highest in CHAPTER Tintinalli_Sec12_p0669-0996.indd 888 8/2/19 7:56 PM
al populations (e.g., children with epilepsy, neurologic shunts, and trauma) under “Special Considerations/Populations. ” The prevalence of pediatric seizures in the United States is approxi mately 1% of all children up to the age of 14 years and is highest in CHAPTER Tintinalli_Sec12_p0669-0996.indd 888 8/2/19 7:56 PM CHAPTER 138: Seizures in Infants and Children 889 children <1 year old (120 cases per 100,000) and in certain high-risk groups.2-4 Febrile seizures, the most common type of pediatric sei zure, affect 3% to 4% of all children between 6 months and 5 years of age. 5 Epilepsy is defined as recurrent unprovoked seizures. 4,5 Roughly 326,000 American children <15 years old have epilepsy, and the lifetime prevalence of epilepsy is roughly 1%. 3 The incidence of status epilepticus in developed countries is between 18 and 23 cases per 100,000 and is higher for younger children. PATHOPHYSIOLOGY Seizures represent abnormal, excessive, paroxysmal neuronal activity in the brain, primarily the cortex. Glutamate released from firing neurons activates N-methyl-D-aspartic acid receptors that subsequently initiate and propagate seizure activity. 7 Seizures are inhibited by γ-aminobutyric acid, and failure of this inhibition facilitates seizure spread.8 Incomplete myelination of the brain may limit secondary generalization of seizure activity in young infants, and a relative imbalance between glutamate and γ-aminobutyric acid with paradoxical excitation from γ-aminobutyric acid makes younger children more susceptible to seizures. 2,7 Seizures can be primary (unprovoked) or secondary (provoked). 9,10 Primary seizures are often idiopathic or may be caused by congeni tal developmental abnormalities, in utero CNS insult (e.g., infection, infarct), or genetic factors. Secondary seizures may result from trauma or injury, infection, metabolic abnormalities (e.g., hypoglycemia, electrolyte abnormalities, inborn errors of metabolism), toxins, or systemic illness. CLINICAL FEATURES TYPES OF SEIZURE The clinical manifestation of seizures depends on the area(s) of the brain that are affected and whether the seizure activity is localized (focal) or widespread (generalized). Generalized seizures involve both hemispheres of the brain and lead to loss of consciousness, usually fol lowed by a period of postictal drowsiness. In convulsive generalized seizures or grand mal seizures, rhythmic motor activity affects both sides of the body. 7 Nonconvulsive generalized seizures produce loss of consciousness without motor activity and can only be recognized on electroencephalogram. 7,11 In one study, nonconvulsive status epilepti cus appeared in 51 of 117 critically ill patients, with 75% of these patients showing no clinical evidence of seizure activity. 12 Other examples of generalized seizures in children include absence seizures (brief episode of staring without a postictal state), atonic seizures (sudden loss of muscle tone with a sudden “drop” to the floor), and myoclonic seizures. 2,7 Partial seizures represent focal neuronal activity, and clinical features correlate with the affected area. In simple partial seizures, the patient remains awake, whereas complex partial seizures are focal but produce alterations of consciousness. 2 Partial seizures may secondarily spread and become generalized. Y oung children with new-onset focal seizures are at increased risk for structural anatomic abnormalities, and neuro imaging is more likely to be abnormal in these children. Although status epilepticus was originally defined as a seizure lasting longer than 30 minutes, today any “prolonged” seizure or recurrent seizures lasting >5 minutes without return to full consciousness are considered status epilepticus.
abnormalities, and neuro imaging is more likely to be abnormal in these children. Although status epilepticus was originally defined as a seizure lasting longer than 30 minutes, today any “prolonged” seizure or recurrent seizures lasting >5 minutes without return to full consciousness are considered status epilepticus. 6,14 Status epilepticus is a medical emergency, and rapid termination is important to prevent irreversible neuronal damage. 6 Refractory status epilepticus is a prolonged seizure that cannot be controlled with two or more doses of standard treatment.6 Nonconvulsive status epilepticus may present as a prolonged postic tal state12 and must be considered in any patient with altered mental status; morbidity and mortality increase when nonconvulsive status epilepticus is untreated, although less so than with untreated convulsive status epilepticus. 7,11 HISTORY Obtain a detailed history of the event from a reliable observer. Table 138-1 lists historical clues that may help identify the etiology of a TABLE 138-1 History Relevant to the Child Presenting With Seizure • Age of child • Seizure duration and description of seizure activity prior to arrival • History of trauma • History of possible ingestion • History of fever • History of associated illness (vomiting or diarrhea) • Feeding problems (especially in an infant) • Changes in behavior • History of seizures and type of seizures • History of developmental delay • Other medical history • Medications • Anticonvulsants with milligrams per kilogram dose and recent changes or missed doses • Recent new medications (may alter metabolism of antiepileptic drugs) • Allergies • Developmental history • Family history of seizures seizure.15 Patient age alone is an important consideration in the poten tial cause of seizures ( Figure 138-1). Other important details include the events surrounding the seizure (e.g., emotional upset and crying that may indicate breath holding in a toddler), the nature of the seizure activity (e.g., tonic stiffening, clonic jerks, generalized or focal charac teristics), the duration of the event (often difficult for frightened parents to accurately report), and postictal observations and duration. Seizureprovoking events can include recent illness, possible trauma, ingestions, and medications (both over-the-counter and prescribed). In addition to the past medical history (especially epilepsy), recent changes or missed doses of medication can also provoke seizure activity. A developmental history is important, as children with underlying developmental delay are at increased risk for epilepsy. A family history of febrile seizures, epilepsy, or neurologic disease is also important for prognosis. PHYSICAL EXAMINATION Perform a complete head-to-toe examination with the patient undressed. The physical examination should be focused on whether the patient is actively seizing and identify potential causative factors (e.g., head trauma, rash indicative of infection, neurocutaneous lesions). Table 138-2 outlines a number of clinical signs and symptoms of seizures. Rhythmic repetitive movement, incontinence of bowel or bladder, postictal state after a seizure, and tongue biting are strong clues to a seizure. Lateral tongue biting was found to have a specificity of 100% and a sensitivity of 24% for the occurrence of a seizure. 2,16 DIAGNOSIS DIFFERENTIAL DIAGNOSIS AND CONDITIONS MASQUERADING AS SEIZURES A number of benign conditions may masquerade as seizures, leading to an ED visit; up to 30% of new-onset paroxysmal events may be mis diagnosed as epileptic. 1,2 Syncope is the most common condition that may be mistaken for seizures; however, there are many differentiating features.
CONDITIONS MASQUERADING AS SEIZURES A number of benign conditions may masquerade as seizures, leading to an ED visit; up to 30% of new-onset paroxysmal events may be mis diagnosed as epileptic. 1,2 Syncope is the most common condition that may be mistaken for seizures; however, there are many differentiating features. 1,2 Syncope is commonly preceded by dizziness, weakness, tunnel vision, pallor, and diaphoresis (presyncopal aura). It is also associated with a brief loss of consciousness and a quick recovery with no postictal state (see Chapter 130, “Syncope, Dysrhythmias, and ECG Interpreta tion in Children”). Seizures, on the other hand, may be preceded by an aura but usually do not have a provoking factor noted before the event. Seizures are associated with tongue biting, rhythmic motor activity, incontinence, and a slow recovery and postictal state. Table 138-3 lists nonepileptic causes of syncope and abnormal movements that can Tintinalli_Sec12_p0669-0996.indd 889 8/2/19 7:56 PM
usually do not have a provoking factor noted before the event. Seizures are associated with tongue biting, rhythmic motor activity, incontinence, and a slow recovery and postictal state. Table 138-3 lists nonepileptic causes of syncope and abnormal movements that can Tintinalli_Sec12_p0669-0996.indd 889 8/2/19 7:56 PM 890 SECTION 12: Pediatrics mimic seizures. In infants, myoclonic jerks, sleep myoclonus, shudder attacks, and Sandifer’s syndrome (gastroesophageal reflux) are common. 2 In toddlers, breath-holding spells become more prevalent. 2 Self-stimulation and night terrors should be considered in preschool and young school-age children, whereas tic disorders typically begin in older children. 2 Psychogenic nonepileptic seizures may present in ado lescents with and without epilepsy.2 LABORATORY TESTING Check bedside glucose on all seizing or postictal patients. Additional laboratory evaluation is directed by the history and is not routinely indicated for febrile seizures or first-time afebrile seizures that are non focal in a child with a normal examination (see “Special Considerations/ Populations” below). 15,17 If indicated by the history and examination, labs that may be helpful include electrolytes (including calcium), serum antiepileptic medication levels, toxicologic testing, and spinal fluid for evaluation of possible CNS infection in the appropriate setting. 15 Urine culture and analysis may be indicated in the evaluation of febrile seizures in the child with fever and no identifiable source. IMAGING Similar to laboratory testing, imaging should be directed by the history and examination. Routine neuroimaging is rarely indicated or help ful. When trauma is suspected, in infants less than a year old (inflicted injury), or in the setting of focal deficits, obtain a head CT. 13 Todd’s paralysis is a temporary condition characterized by a focal deficit of unknown etiology that can last up to 36 hours after a seizure. The paralysis is usually unilateral and lasts on average 15 hours; however, it can be bilateral and involve a patient’s speech or vision. It may be impossible to distin guish Todd’s paralysis from stroke or hemorrhage, and emergent imaging should be considered. Most first-time seizures in the well-appearing child with a normal examination can follow up with neurology to determine if further imaging is necessary. 13,18 If necessary, outpatient MRI avoids ionizing radiation and provides better anatomic detail.13,18 0–6 months 6–24 months >2 years – Fever + Fever Febrile Seizures (6 months to 5 years) Trauma Known Epilepsy Patients and/or VP Shunt Intracranial Brain Abnormalities: Brain Tumor, Stroke, Arterial Venous Malformation, Idiopathic Seizures Infection: Meningitis/Encephalitis, Other Infections (Shigella) Dysrhythmias, Prolonged QTc Neonatal Seizures Inborn Errors of Metabolism Hyponatremia, Hypocalcemia, Hypomagnesemia Hypoglycemia Drug Exposure/Ingestion Herpes Infections Drug Withdrawal Inflicted Head Injury Complex Febrile Seizures FIGURE 138-1. Age-based approach to the evaluation of pediatric seizures. VP = ventriculoperitoneal. TABLE 138-2 Signs and Symptoms Associated With Seizures • Head deviation • Eye deviation • Rhythmic or repetitive arm or leg movement • Posturing • Stiffening • Jerking • Change in breathing pattern • Increase in heart rate • Increase in blood pressure • Cyanosis or apnea • Eye dilatation • Vomiting • Lip smacking • Tongue biting • Incontinence of bowel or bladder • Postictal or sleepy period after a seizure • Mood or behavior changes before a seizure • Subjective aura before seizure (noted in older patients) Tintinalli_Sec12_p0669-0996.indd 890 8/2/19 7:56 PM
s or apnea • Eye dilatation • Vomiting • Lip smacking • Tongue biting • Incontinence of bowel or bladder • Postictal or sleepy period after a seizure • Mood or behavior changes before a seizure • Subjective aura before seizure (noted in older patients) Tintinalli_Sec12_p0669-0996.indd 890 8/2/19 7:56 PM CHAPTER 138: Seizures in Infants and Children 891 ANCILLARY TESTS Consider obtaining an ECG for evaluation of syncope with seizure activity to rule out arrhythmia.15 Emergent electroencephalogram monitoring may be required for patients with refractory status epilepticus (especially those requiring rapid-sequence intubation with a paralytic) or concern for nonconvulsive status epilepticus 19-21; otherwise, outpatient electroencephalogram may help identify specific epilepsy syndromes and guide future treatment. SUMMARY OF APPROACH TO EVALUATION Figure 138-2 summarizes the approach to the evaluation of pediatric seizures. TREATMENT PREHOSPITAL Children may have been treated at home or by EMS personnel. Take this into consideration when treating refractory status epilepticus. 6,22 Benzodiazepines (Table 138-4) are the first-line treatment for pro longed seizures because of their rapid onset and effectiveness23; however, their effectiveness is inversely related to the duration of the seizure, and treatment should not be delayed. 6,10,15 Not all benzodiazepines or routes are available in the prehospital setting, and establishing IV access can be difficult in a child who is having a seizure. Benzodiazepines may be given by the intranasal, buccal, rectal, or intraosseous route when an IV is difficult to place. Although not significantly different in efficacy, lorazepam is recommended if an IV has been placed; midazolam is recommended if intramuscular, intranasal, or buccal administration is performed; and diazepam is recommended if given rectally. 2,6,7,10,15,23-28 Rectal diazepam is one “rescue” medication commonly used at home and by EMS personnel. The advantage is that no refrigeration or IV line is needed. The disadvantage is the need for rectal administration. Mid azolam, also an effective rescue medication, can be given via the intranasal route using a mucosal atomization device. 24,25 Midazolam can also be given buccally.6,10,15,27 Lorazepam is not generally used in the prehospital setting because of its need for refrigeration. Although IV lorazepam is generally preferred, there is evidence that intranasal lorazepam using a mucosal atomization device may be as effective as IV lorazepam in the treatment of status epilepticus. ED TREATMENT Most seizures stop within 5 minutes and do not require medical treat ment. Status epilepticus is a medical emergency, however, and is more responsive to medications when treated early, and treatment becomes less effective with time. 6,10,15 To expedite therapeutic decisions and avoid treatment delays, status epilepticus management guidelines are recommended; an overview of one treatment algorithm for status epilepticus is depicted in Figure 138-3. 6,29-31 Administer oxygen by facemask and institute continuous pulse oximetry and cardiac monitoring. Establish IV or IO access, but administer medication early via alternative routes (intranasal, IM, PR, buccal) if there is delay. 2,6,10,15,32 Providers should obtain bedside glucose testing for afebrile seizures because hypoglycemia represents an easily correctable cause of seizures. 2,6 Additional laboratory studies and imaging should be directed by the history and examination as the yield for routine testing is abysmally low. 2,6,7 Subtherapeutic antiepileptic drug levels are found in almost one third of children with epilepsy presenting in status epilepticus.
asily correctable cause of seizures. 2,6 Additional laboratory studies and imaging should be directed by the history and examination as the yield for routine testing is abysmally low. 2,6,7 Subtherapeutic antiepileptic drug levels are found in almost one third of children with epilepsy presenting in status epilepticus. 32 Meningitis and encephalitis should be considered in all children who present with fever and status epilepticus or multiple sei zures; however, research supports using clinical judgment when decid ing to do a lumbar puncture because the rate of bacterial meningitis is low (0.5% to 2.4%) in a fully immunized patient. 8,33 The decision to intubate is clinical. Intubate for apnea and persistent hypoxia. Blood gas concentrations are not needed to guide the decision to intubate because the seizure itself causes a metabolic and respiratory acidosis. 2,6,10 The use of a paralytic with intubation obscures the ability to assess ongoing seizure activity, so arrange continuous electroencephalogram monitoring for intubated patients with status epilepticus. 6,21 Administer a benzodiazepine (Table 138-4) as the initial treatment for status epilepticus.2,6,7,10,22 Benzodiazepines are effective in terminating seizure activity and act by binding to γ-aminobutyric acid receptors 7; they are preferred over other medications because of their rapid onset of action. 6,7,10,15,22,23 The decision of which benzodiazepine to give should be dictated by the route readily accessible. A particular benzodiazepine has not proven to be more or less effective in the cessation of seizure activity; however, delays in treatment make seizures increasingly harder to stop. 2,6,7,10,15,22,23 Generally, if two doses of benzodiazepines are administered without effect, additional doses are unlikely to be successful and increase the risk for respiratory depression. 2,6,7,10,15,22,23,31 Because there is no standard treatment for refractory status epilepticus, approaches to treatment and order of medication administration may vary. 2,6,10,17,31,32,34-36 Figure 138-3 represents one approach to refractory status epilepticus. If a seizure persists after two doses of a benzodiazepine have been given, fosphenytoin, levetiracetam, or valproic acid are preferred second-line treatment choices. 2,6,10,17,31,34-36 The National Institutes of Health–funded Established Status Epilepticus Treatment Trial will compare these three treatment choices for convulsive status epilepticus. A provider should generally choose two of the four medications for refractory status epilepticus and then move on to a fourth-line treatment option if a seizure persists. Table 138-5 summarizes the medications used for refractory status epilepticus. Second- And Third-Line Treatments Phenytoin and valproic acid, metabolized hepatically, and levetiracetam, metabolized renally, may affect second- and third-line choices in patients with hepatic and renal dysfunction.
if a seizure persists. Table 138-5 summarizes the medications used for refractory status epilepticus. Second- And Third-Line Treatments Phenytoin and valproic acid, metabolized hepatically, and levetiracetam, metabolized renally, may affect second- and third-line choices in patients with hepatic and renal dysfunction. 6,7,10,15 Phenytoin and its prodrug, fosphenytoin, inhibit neuronal firing by stabilizing sodium channels and reducing neuronal TABLE 138-3 Events Masquerading as Seizures Syncope Breath-holding spells • Cataplexy • Narcolepsy • Vasovagal event • Standing for long periods of time • Standing quickly from lying or sitting • Hair-grooming syncope • Earring-changing syncope • Micturition syncope • Emotional distress or pain • Hypoglycemia • Hypovolemia Sandifer’s syndrome (gastroesophageal reflux) • Acute life-threatening event • Acute dystonic reactions/drug reactions (i.e., promethazine [Phenergan® ]) • Movement disorders Tics Myoclonic jerks Chills or rigors • Shudder attacks • Mannerisms • Self-stimulation • Choreoathetosis Night terrors, sleep walking • Migraine variants • Benign paroxysmal vertigo Nonepileptic paroxysmal event (pseudoseizures) Note. Events in bold are more common. Tintinalli_Sec12_p0669-0996.indd 891 8/2/19 7:56 PM
nic jerks Chills or rigors • Shudder attacks • Mannerisms • Self-stimulation • Choreoathetosis Night terrors, sleep walking • Migraine variants • Benign paroxysmal vertigo Nonepileptic paroxysmal event (pseudoseizures) Note. Events in bold are more common. Tintinalli_Sec12_p0669-0996.indd 891 8/2/19 7:56 PM 892 SECTION 12: Pediatrics calcium uptake.6,7,10,15,34-36 Fosphenytoin is safe and effective; it can be administered more rapidly with fewer cardiac effects than phenytoin, which can precipitate in an IV line and cause significant tissue injury with extravasation. 6,7,10,15 Phenobarbital is not preferred as a second-line treatment, except in neonates, because both phenobarbital and benzodiazepines have the same mechanism of action and bind γ-aminobutyric acid receptors and can cause significant risk for respiratory failure. 6,7,10,15 Levetiracetam is also safe and effective for treatment of status epi lepticus, although it has not been prospectively compared with other anticonvulsants. 6,10,15,34,37-44 Levetiracetam is eliminated solely via renal excretion and has no hepatic metabolism, and it has few adverse effects and essentially no drug and food interactions. 34,37-44 Another advantage of levetiracetam over fosphenytoin (phenytoin) and phenobarbital is that it is commonly used for maintenance therapy for multiple seizure types. 34,37-44 Phenobarbital is most commonly used in neonates who are often maintained on daily phenobarbital for subsequent seizure control.45 Side effects include sedation and cardiorespiratory depression, which may be amplified by benzodiazepines. 6,10,15 Valproic acid is approved by the U.S. Food and Drug Administra tion for treatment of status epilepticus and is also effective for partial and generalized seizures. 46 Consider valproic acid for treatment of children already taking this medication who are suspected of having subtherapeutic levels. A dose of 20 to 40 milligrams/kg of IV valproic New-Onset Seizure • Noncompliance with seizure medications • Outgrown seizure medication dose • Accidental Head Trauma • Abusive Head Trauma Focal Neurologic Exam • Brain Tumor • AVM • Stroke • Abusive Head Trauma • Febrile Seizures (6 mo–5 y) • Complex Febrile Seizures • Meningitis • Encephalitis • Herpes Infections • Other Infections (Shigella) • Hypoglycemia • Hyponatremia • Hypocalcemia • Hypomagnesemia • Prolonged QTc • Other Arrhythmias • Drug Exposure • Drug Withdrawal (infant) Idiopathic Epilepsy Known Trauma? – + – – – – – – + + + + + + Fever? Electrolyte Abnormalities? Dysrhythmias? Possible Drug Exposure or Ingestion? Infant or Toddler? • Inborn Errors of Metabolism • Abusive Head Trauma • Idiopathic Epilepsy Known Seizure Disorder FIGURE 138-2. General approach to the evaluation of pediatric seizures. AVM = arteriovenous malformation. TABLE 138-4 Benzodiazepines for Initial Treatment of Prolonged Seizures Drug Route Dose* Maximum Onset of Action Duration of Action Lorazepam IV, IO, IN 0.1 milligram/kg 0.1 milligram/kg 4 milligrams 4 milligrams 1–5 min 15–30 min 12–24 h 12–24 h Diazepam IV, IO 0.1–0.3 milligram/kg 0.5 milligram/kg 10 milligrams 20 milligrams 1–5 min 3–5 min 15–60 min 15–60 min Midazolam IV, IO Buccal 0.1–0.2 milligram/kg 0.2 milligram/kg 0.2 milligram/kg 0.5 milligram/kg 4 milligrams 10 milligrams 10 milligrams 10 milligrams 1–5 min 5–15 min 1–5 min 3–5 min 1–6 h 1–6 h 1–6 h 1–6 h Abbreviation: IN = intranasal. *Initial and repeat doses are the same. Tintinalli_Sec12_p0669-0996.indd 892 8/2/19 7:56 PM
IV, IO Buccal 0.1–0.2 milligram/kg 0.2 milligram/kg 0.2 milligram/kg 0.5 milligram/kg 4 milligrams 10 milligrams 10 milligrams 10 milligrams 1–5 min 5–15 min 1–5 min 3–5 min 1–6 h 1–6 h 1–6 h 1–6 h Abbreviation: IN = intranasal. *Initial and repeat doses are the same. Tintinalli_Sec12_p0669-0996.indd 892 8/2/19 7:56 PM CHAPTER 138: Seizures in Infants and Children 893 acid effectively terminates seizure activity with few side effects or less sedation.2,6,7,10,15,46,47 Use with caution in children at risk for metabolic disease, because in rare cases it may cause hepatic failure and has rarely been associated with thrombocytopenia. 2,6,7,10,15,46,47 Fourth-Line Treatment Propofol is an IV anesthetic agent that acts on γ-aminobutyric acid receptors differently from benzodiazepines or barbiturates and has been shown to effectively treat refractory status epilepticus better than pentobarbital. 10,15,35,48 Propofol has a rapid onset 5 min 5 min 7 min Initial Treatment Refractory Status Epilepticus Time IV in place or easily placed 1. Propofol 0.5–2 milligrams/kg IV; infuse at 10 milligrams/min 2. Pentobarbital 5–10 milligrams/kg IV; infuse at 0.2–0.4 milligram/kg/min 3. Midazolam 0.1–0.2 milligram/kg slow IV push Third- Line Treatment Second- Line Treatment Fourth- Line Treatment Choose one of the following: 1. Fosphenytoin 20 milligrams PE/kg 2. Levetiracetam 20–40 milligrams/kg 3. Phenobarbital 20–30 milligrams/kg (max: 800 milligrams): consider in children <2 y/age 4. Valproic acid 20–40 milligrams/kg: consider only if patient is on valproic acid After infusion of second line of treatment After infusion of second line of treatment Successful IV placement Choose another different from previous treatment: 1. Fosphenytoin 20 milligrams PE/kg 2. Levetiracetam 20–40 milligrams/kg 3. Phenobarbital 20–30 milligrams/kg (max: 800 milligrams): consider in children <2 y old 4. Valproic acid 20–40 milligrams/kg: consider only if patient is on valproic acid Patient arrives to ED with seizures >5 min IV not easily placed All medications: given IV over 20 min All medications: given IV over 20 min IN/Buccal/IO Midazolam IN: 0.2 milligram/kg, max 10 milligrams Buccal: 0.5 milligram/kg, max 10 milligrams IO: 0.2 milligram/kg, max 4 milligrams IN/IO Lorazepam (0.1 milligram/kg) 2–4 milligrams max IV Lorazepam (0.1 milligram/kg) 2–4 milligrams max Maximum 2 doses total in past hour (including prehospital) FIGURE 138-3. Initial treatment of status epilepticus: an example of one approach. IN = intranasal; PE = phenytoin sodium equivalents. TABLE 138-5 Medications for Refractory Status Epilepticus Drug Route Loading Dose Repeat Dose Maximum IV Infusion Fosphenytoin IV, IM 20 milligrams/kg PE 5–10 milligrams/kg PE 30 milligrams/kg PE 3 milligrams/kg/min PE Phenobarbital IV 20–30 milligrams/kg 5–10 milligrams/kg 40 milligrams/kg 1–30 milligrams/min Valproic acid IV 20–40 milligrams/kg 15–20 milligrams/kg 40 milligrams/kg 5 milligrams/kg/h Levetiracetam IV 20–40 milligrams/kg — 3 grams — Pentobarbital IV 5–10 milligrams/kg 1–2 milligrams/kg 15 milligrams/kg 0.5–5.0 milligrams/kg/h Propofol IV 0.5–2.0 milligrams/kg 0.5–1.0 milligram/kg 5 milligrams/kg 1.5–4.0 milligrams/kg/h Midazolam IV 0.1–0.3 milligram/kg 0.1–0.2 milligram/kg 10 milligrams 0.05–0.4 milligram/kg/h Ketamine IV 0.5–2 milligrams/kg May repeat loading dose — 5–20 micrograms/kg/min Abbreviation: PE = phenytoin sodium equivalents. Tintinalli_Sec12_p0669-0996.indd 893 8/2/19 7:56 PM
am/kg 5 milligrams/kg 1.5–4.0 milligrams/kg/h Midazolam IV 0.1–0.3 milligram/kg 0.1–0.2 milligram/kg 10 milligrams 0.05–0.4 milligram/kg/h Ketamine IV 0.5–2 milligrams/kg May repeat loading dose — 5–20 micrograms/kg/min Abbreviation: PE = phenytoin sodium equivalents. Tintinalli_Sec12_p0669-0996.indd 893 8/2/19 7:56 PM 894 SECTION 12: Pediatrics of action, but it is quickly metabolized and should be followed by con tinuous infusion if seizure activity persists and must be infused slowly because of the potential for serious side effects, including bradycardia, apnea, and hypotension. 10,15,35,48 Prepare for intubation and provide continuous cardiopulmonary monitoring when administering propofol for seizures. 10,15,35,48 Patients receiving sustained propofol administration (>24 hours) should be monitored for development of “ propofol infusion syndrome” (metabolic acidosis, rhabdomyolysis, renal failure, and cardiac failure). Ketamine, a noncompetitive N-methyl-d-aspartate–type glutamate receptor antagonist, may be effective in later stages of refractory status epilepticus. 10 It is also commonly used for intubation. 15 Recently, literature does not support concerns that ketamine causes increased intracranial pressure.10,15,50 A “pentobarbital coma, ” or continuous infusion, has been used for refractory status epilepticus not responsive to multiple anticonvul sant treatments with reported efficacy between 74% and 100%. 34 Side effects include respiratory depression, hypotension, and decreased cardiac contractility, and most patients require intubation and inotropic support. 6,10,15,35,36 Midazolam infusion has a low rate of adverse effects; however, com pared with propofol and pentobarbital, midazolam has a higher rate of seizure recurrence. 6,7,10,15,35 Treatment of Glucose and Electrolyte Abnormalities Most laboratory results are not immediately available when treating status epilepticus; however, a glucose should be checked at a minimum (see Chapter 146, “Metabolic Emergencies in Infants and Children”). Abnormal glucose, sodium, calcium, and magnesium, especially low levels, can cause seizures, particularly in infants. 2 Seizures caused by abnormal electrolytes respond poorly to conventional medication but do respond to replacement electrolyte therapy (see Chapter 132, “Fluid and Electrolyte Therapy in Infants and Children”). 2,6,10,15 Hypoglycemia can be the cause or an effect of prolonged seizures, and bedside testing is essential in seizing patients. Treat hypoglycemia with a rapid infusion of 2 mL/kg of 25% dextrose in water or 4 to 5 mL/kg of 10% dextrose in water. Hyponatremia (serum sodium <135 mEq/L) is most commonly seen in infants <6 months of age and sometimes in athletes and can cause seizures, especially if the serum sodium is <120 mEq/L. 9 The goal of therapy is to correct the level to >120 mEq/L quickly and then correct to normal levels over the next 24 hours (see Chapter 132, “Fluid and Elec trolyte Therapy in Infants and Children”). Treat the seizing patient with hyponatremia with 3% NaCl 1 to 2 mL/kg over 20 minutes or begin an infusion of 20 mL/kg of 0.9% NaCl if 3% NaCl is not immediately available. The sodium level should be rechecked after the bolus to determine whether a second bolus is necessary. Hypocalcemia is more common in neonates and young infants and may be associated with congenital anomalies such as DiGeorge’s syn drome. Calcium gluconate, 100 milligrams/kg (rate <100 milligrams/ min), is preferred over calcium chloride when infusing through a small peripheral IV because calcium chloride can cause local irritation. Hypomagnesemia (serum magnesium <1.5 mEq/L) is treated with magnesium sulfate, 50 milligrams/kg IV infused over 30 minutes.
alcium gluconate, 100 milligrams/kg (rate <100 milligrams/ min), is preferred over calcium chloride when infusing through a small peripheral IV because calcium chloride can cause local irritation. Hypomagnesemia (serum magnesium <1.5 mEq/L) is treated with magnesium sulfate, 50 milligrams/kg IV infused over 30 minutes. DISPOSITION AND FOLLOW-UP Infants >6 months of age with febrile seizures (see later) and children with single seizures lasting <15 minutes who return to baseline mental status and have no focal neurologic deficits or secondary cause of seizure requiring ongoing treatment are candidates for discharge and outpatient follow-up with their primary care provider or a pediatric neurologist (in the case of new-onset seizures or breakthrough seizures in children with epilepsy). Parents of discharged children should be given guidance to prevent injury in association with subsequent seizures: children should not be in a position where they could drown, fall, or injure someone else during a seizure. Caregivers should never allow their children to bathe or swim alone. If they are old enough to take a shower, children should not lock the bathroom door. Those old enough to drive should not be allowed to do so until cleared by a neurologist. Information about recurrence risk should also be provided in the ED. Although the recurrence risk for a particular child cannot be predicted, population statistics pertaining to febrile seizures and first-time seizure recurrence can be shared with parents (see the following section “Special Considerations/Populations”). In many cases, children treated for seizures who return to their base line may go home with close follow-up. Some children may need to be monitored in the hospital for recurrence or side effects from medication, especially if they have not returned to baseline. Children with refractory status epilepticus usually require intensive care for continuous infusion of antiseizure treatment or induction of a “pentobarbital coma. ” SPECIAL CONSIDERATIONS/POPULATIONS FEBRILE SEIZURES Febrile seizures are common in the general pediatric population, with an incidence of 2% to 5%. Simple Febrile Seizures The definition of a simple febrile seizure is a generalized tonic-clonic seizure lasting <15 minutes with a fever 38°C (100.4°F) in a child 6 months to 6 years of age that occurs only once in a 24-hour period. 51 The American Academy of Pediatrics holds that no blood studies, neuroimaging, or electroencephalogram is neces sary for simple febrile seizures and the evaluation should focus on identifying the source of fever (e.g., urinalysis and culture). 5,17,33,51-54 The American Academy of Pediatrics does recommend that a lumbar puncture be strongly considered in these children when there are clinical signs or symptoms that suggest meningitis or intracranial infection (see Chapter 120, “Meningitis in Infants and Children”). 17,33,51-53 Although bacterial meningitis is rare even in children with fever and seizures, the American Academy of Pediatrics recommends consideration of lumbar puncture for infants 6 to 12 months of age who are unim munized for Haemophilus influenzae type B or Streptococcus pneumoniae and those taking antibiotics, which can mask the signs and symptoms of meningitis. 17,33,51-55 Parents of children experiencing a simple febrile seizure need edu cation regarding the natural history of febrile seizures. Only 50% of children <12 months old and 30% of children >12 months old will have another simple febrile seizure. 17,52,55 Having a febrile seizure does not mean that a child will develop epilepsy. Children who experience a simple febrile seizure have roughly the same 1% risk as the general population of developing epilepsy by the age of 7 years.
nths old and 30% of children >12 months old will have another simple febrile seizure. 17,52,55 Having a febrile seizure does not mean that a child will develop epilepsy. Children who experience a simple febrile seizure have roughly the same 1% risk as the general population of developing epilepsy by the age of 7 years. 17,52,55 Factors that increase that risk up to 7% include a family history of seizures, complex or multiple febrile seizures, and first febrile seizure before 12 months of age. 5,17,51,53,54 Other factors that increase the risk of recurrence include developmental delay, focal seizures, Todd’s paralysis, focal neurologic findings on examination, and abnormal findings on electroencephalo gram, CT, or MRI. 5,17,51,53,54 Complex Febrile Seizures Complex febrile seizures are defined as seizures with fever that last >15 minutes, recur within a 24-hour period, are focal, or occur in children <6 months or >6 years of age without any signs of serious infection. 5,17,51-55 Routine blood tests, lumbar puncture, and imaging are not indicated, even in the setting of complex febrile seizure, in the absence of other signs or symptoms. 17,33,52,54,55 One study noted that children with fever and seizures lasting >30 minutes had a significantly higher incidence of bacterial meningitis (15% to 18%) than children with simple febrile seizures (0.4% to 1.2%). 56 Other studies, however, found meningitis to be rare without clinical signs and symp toms of meningitis8,33; one study found only two patients with meningitis among 526 patients with complex febrile seizures, and both patients had clinical signs and symptoms of meningitis. Children with a prolonged seizure associated with a fever who appear ill should undergo evaluation to rule out serious bacterial infection in the blood and cerebrospinal fluid, 17 although parenteral antibiotics should not be delayed while sick children are being evaluated (see Chapter 119, “Fever and Serious Bacterial Illness in Infants and Children” and Chapter 120, “Meningitis in Infants and Children”). 17,52,55 Treatment of Febrile Seizure Anticonvulsant therapy is not recom mended for simple febrile seizures because side effects outweigh the Tintinalli_Sec12_p0669-0996.indd 894 8/2/19 7:56 PM
er 119, “Fever and Serious Bacterial Illness in Infants and Children” and Chapter 120, “Meningitis in Infants and Children”). 17,52,55 Treatment of Febrile Seizure Anticonvulsant therapy is not recom mended for simple febrile seizures because side effects outweigh the Tintinalli_Sec12_p0669-0996.indd 894 8/2/19 7:56 PM CHAPTER 138: Seizures in Infants and Children 895 minor risks of seizure recurrence.51,53 Although antipyretics are indicated in children with fever, there is no evidence that antipyretics can prevent subsequent febrile seizures.17,51,53,57 FIRST AFEBRILE SEIZURE Practice guidelines for the evaluation of a first unprovoked seizure in a child who returns to baseline following the seizure suggest that routine laboratory evaluations and emergent neuroimaging are not necessary. 2,18,58 If there is evidence that the child had vomiting or diar rhea, is dehydrated, or has failed to return to baseline, laboratory tests are recommended. A toxicology screen should also be included if there is concern for drug exposure or substance abuse or the cause of the seizure cannot be determined. Lumbar puncture is unnecessary unless there is a clinical concern for meningitis or encephalitis. 2 An electroencephalogram should be performed, although availability may be limited and the timing is unclear in a child who has returned to baseline and it is rarely indicated in the ED. 2,15 An electroencephalogram within 24 hours of the seizure is most likely to show abnormalities and can help identify patients suspected of being in continuous convulsive and nonconvulsive status epilepticus. 2,6,47,59 Indications for emergent head CT include children with a condition predisposing them to intracranial abnormalities, trauma, and children with focal seizures who are younger than 33 months of age. 2 Patients who do not meet the criteria for high risk and are well appearing may be discharged with outpatient follow-up. Outpatient MRI should be considered in any child with any of the following: significant cognitive or motor impairment, abnormal findings on neurologic examination, abnormal electroencephalogram findings, partial seizure, or infants <1 year of age. 2,58 The overall risk of recurrence after a single afebrile seizure is approximately 54%.2 Factors that increase this risk are a family history of sei zures, previous febrile seizures, developmental delay, abnormal CT or MRI findings, presence of focal deficits on neurologic examination, Todd’s paralysis, abnormal electroencephalogram findings, and seizure occurring during sleep. 2,58 Most neurologists do not recommend initiating daily anticonvulsant medications after a first seizure. 2,58 Noninitiation of treatment does not increase the risk of epilepsy, affect prognosis, or increase the risk of intractable epilepsy or death, but does allow the physician to better clarify the type and frequency of seizures and also avoids the side effects of unnecessary daily anticonvulsant medications in those not destined to experience recurrence. 2,58 NEONATAL SEIZURES Neonates do not have a fully developed neurologic system, and seizures in this age group (<1 month) can be subtle, are more likely to be focal, and often carry a poor prognosis. 2,45,60 Identifying seizure activity in the neonate and distinguishing it from normal newborn myoclonus and jitters can be challenging. Subtle focal movements or stereotyped activities (e.g., lip smacking, eye deviation, or bicycling) may represent 50% of seizure activity; neonates less often have generalized tonic-clonic seizures.
ifying seizure activity in the neonate and distinguishing it from normal newborn myoclonus and jitters can be challenging. Subtle focal movements or stereotyped activities (e.g., lip smacking, eye deviation, or bicycling) may represent 50% of seizure activity; neonates less often have generalized tonic-clonic seizures. 2,45,60 Apparent life-threatening events with pallor or cyanosis and a change in muscle tone may be a manifestation of seizure activity.11,19,49,61 A birth and maternal history may identify risks for congenital or neonatal infection (e.g., herpes simplex virus, cytomegalovirus, or group B streptococci) or potential withdrawal from maternal narcotics.45 Complications with labor and delivery may suggest birth asphyxia with subsequent seizures. Regardless of the history or presence of fever, neonates with witnessed seizures require extensive evaluation. Obtain cultures of blood, urine, and cerebrospinal fluid; test for herpes simplex virus; and begin empiric parenteral antibiotics and acyclovir. 2,45 Toxicologic evaluation may provide the physician with evidence of withdrawal or overdose of abused substances. Neonates with seizures are more likely to have electrolyte abnormalities than older children, and electrolytes including calcium and glucose should be measured. 2,45 Consider head CT for concerns of nonaccidental trauma, intracranial hemorrhage, infarction, or mass (even without external signs of injury). 2,45 Finally, if inborn errors of metabolism are suspected, obtain serum levels of lactate and ammonia, as well as serum amino acids and urine organic acids (see Chapter 146, “Metabolic Emergencies in Infants and Children”). 2,45 Neonates with witnessed seizure require admission to the hospital. Treat the actively seizing neonate with benzodiazepines as with older children; consider phenobarbital for second-line therapy because many will be sent home on phenobarbital. Identify and treat hypoglycemia and electrolyte abnormalities. SEIZURES IN CHILDREN WITH EPILEPSY Parents, old records, and pediatric neurologists can be very helpful in identifying past causes of seizures, successful (and unsuccessful) treat ments, and other issues that can help direct the care of patients with epilepsy presenting to the ED with seizure. Table 138-6 62 lists common anticonvulsants prescribed for children with epilepsy. Subtherapeutic drug levels may result when a child outgrows a previously prescribed dose, vomits medications due to an intercurrent illness, starts a new medication (due to changes in drug pharmacokinetics from drug interactions), or does not adhere to the original drug regimen. Sub therapeutic drug levels are a common cause of breakthrough seizures, and serum levels of home antiepileptic medications should be checked as part of the routine ED evaluation of these patients, although results may not be readily available for some newer agents. When low levels are identified, the cause should be determined so that proper adjustments in daily anticonvulsant dosing can be made with advice from the patient’s neurologist. Children with epilepsy may have a lower seizure threshold with febrile illness, even with therapeutic anticonvulsant levels, and the ED evalu ation in these situations may be limited to determining the source of fever. Lumbar puncture is unnecessary unless there are clinical signs or symptoms of meningitis. 2,8,33 SEIZURES IN CHILDREN WITH VENTRICULOPERITONEAL SHUNTS Many children with ventriculoperitoneal shunts also have a medical history of seizures. Considerations include underlying epilepsy, shunt malfunction, and CNS infection.
mbar puncture is unnecessary unless there are clinical signs or symptoms of meningitis. 2,8,33 SEIZURES IN CHILDREN WITH VENTRICULOPERITONEAL SHUNTS Many children with ventriculoperitoneal shunts also have a medical history of seizures. Considerations include underlying epilepsy, shunt malfunction, and CNS infection. The standard approach to the evalua tion for a shunt malfunction consists of a radiographic ventriculoperi toneal shunt series and a head CT or “quick brain MRI” to evaluate for increased ventricular size. If CNS infection is a concern, a pediatric neurosurgeon should be consulted and the shunt tapped for cerebro spinal fluid analysis and culture. Seizures in children with ventriculo peritoneal shunts are more likely to be related to shunt infection than to mechanical shunt malfunction, especially if associated with fever, 63,64 and the risk of infection increases in children with a history of a prior shunt infections. 63,64 In most cases, consulting past medical records, parents, and the neurosurgeon who placed the shunt is needed for prudent decision making (see Chapter 148, “The Child with Special Healthcare Needs”). SEIZURES IN TRAUMA “Impact seizures” (seizures that occur within minutes of head trauma) do not, by themselves, increase the risk of having an intracranial injury; seizures that occur in a more delayed fashion, however, are more indicative of severe injuries. 65 Guidelines for the TABLE 138-6 List of Anticonvulsants Commonly Used in Children Before 1993 1993–2005 2009–2011 Carbamazepine Felbamate Vigabatrin Clonazepam Gabapentin Rufinamide Diazepam Lamotrigine Lacosamide Ethosuccimide Levetiracetam Clobazam Lorazepam Oxcarbazepine Ezogabine Phenobarbital Pregabalin Phenytoin Tiagabine Primidone Topiramate Valproic acid Vagus nerve stimulation Tintinalli_Sec12_p0669-0996.indd 895 8/2/19 7:56 PM