A seizure is a paroxysmal central nervous system disorder resulting from excessive hypersynchronous discharge of cortical neurons.
Status epilepticus is a common pediatric neurologic emergency that requires rapid recognition and intervention.
An operational definition of status epilepticus recommends administration of an antiseizure medication (ASM) after 5 minutes of seizure activity; a predetermined pathway/guideline can expedite management.
Management goals include general supportive care, termination of status epilepticus, prevention of recurrence, correction of precipitating causes, and prevention and treatment of potential complications.
Common errors include underdosing the initial ASM and delay in advancing to a second-line ASM. A single drug should be maximized to a high therapeutic or supratherapeutic level before adding a second or third drug.
The longer seizures continue, the more difficult they are to stop with medications. Early diagnosis and aggressive intervention for both convulsive and nonconvulsive seizures are essential for successful treatment.
Prolonged seizures may cause selective neuronal loss in the hippocampus, cortex, and thalamus, areas rich in glutamate receptors.
A seizure is a paroxysmal disorder of the central nervous system (CNS) gray matter characterized by an abnormal neuronal discharge associated with a change in function of the patient. It results from the excessive hypersynchronous discharge of cortical neurons in the gray matter.
Factors that occur commonly in the pediatric intensive care unit (PICU) and are known to provoke seizures include fever, hyponatremia, hypoglycemia, hypocalcemia, meningitis, head trauma (accidental or nonaccidental), toxin exposure, ethanol, and many other drugs (both legal and illicit). Seizures are a common pediatric entity and occur in 5% to 8% of children, with the highest risk occurring during infancy and early childhood. A seizure must be differentiated from other paroxysmal events, which may include syncope, breath-holding spells, movement disorders, or hyperventilation syndrome.
Definition of status epilepticus
Status epilepticus (SE) is a common pediatric neurologic emergency estimated to affect between 25,000 to 50,000 children annually; 40% of all instances of SE will occur in children younger than 2 years. The incidence of convulsive SE (CSE) in children is approximately 10 to 27 per 100,000 per year. The definition of SE has undergone revisions—it was previously defined as a seizure lasting for greater than 30 minutes or recurrent seizures lasting for more than 30 minutes without the patient regaining consciousness between seizures. Recent definitions of SE—such as the one from the International League Against Epilepsy (ILAE)—include a shorter duration of seizure activity based on two ideas: (1) the time at which a seizure should be considered abnormally prolonged (t 1 ) and (2) the time beyond which there is risk of long-term consequences (t 2 ). In this approach, t 1 determines the time at which treatment should be considered and t 2 determines how aggressively treatment should be implemented to prevent long-term consequences.
The ILAE committee’s proposal is that t 1 = 5 minutes (based on the mean normal seizure duration + 5 standard deviations) and t 2 of 30 minutes or longer (based on historical experimental studies and literature). Hence, by definition, this new definition takes account of the fact that the majority of tonic-clonic generalized seizures will resolve within 5 minutes without any medication. Thus, it is appropriate that in adults and older children (>5 years old) SE refers to 5 minutes or more of either continuous seizure or two or more discrete seizures between which there is incomplete recovery of consciousness. , Of note, however, this new approach to defining SE lacks supportive pediatric data that would help to make recommendations in children younger than 5 years. That said, there is general agreement that seizures continuing for more than 5 minutes should be treated, but there is a concern that overaggressive treatment may lead to avoidable morbidity, such as respiratory depression and transient need for supportive mechanical ventilation. For example, the study by DeLorenzo et al. (which included 91 children) compared the outcome of patients with seizures lasting 10 to 29 minutes with that of traditionally defined SE (>30 minutes). Almost 50% of the seizures in the 10- to 29-minute group stopped spontaneously (without therapy), and this group had no deaths. In comparison, the other 50% of patients in the 10- to 29-minute group, who required therapy to stop the seizures, had a mortality rate of 4.4%. The traditional group (seizures lasting >30 minutes) had a mortality rate of 19%.
Refractory SE (RSE) is defined as continued SE despite the administration of multiple first- and second-line antiseizure medications (ASM) with different mechanisms of action, including benzodiazepines, fosphenytoin or phenytoin, and phenobarbital. Often, these patients have had continuous (clinical or electroencephalographic) seizure activity for hours. The care of these patients should be a collaborative effort between intensive care specialists and neurologists and requires standard invasive intensive care monitoring as well as the 24-hour availability of electroencephalography (EEG). Treatment of RSE requires continuous EEG (cEEG) monitoring because pharmacologic therapy is titrated to EEG seizure suppression or burst suppression.
Super-refractory SE (SRSE) is defined as SE that continues 24 hours or more after the onset of anesthetic therapy for SE, including those cases in which SE recurs during reduction or withdrawal of anesthesia.
Nonconvulsive status epilepticus (NCSE) is defined as clinically subtle or nonconvulsive seizures (NCSs), which may be common among patients in the PICU, particularly following prolonged CSE. Postictal stupor or coma due to the sedative effects of medications is often difficult to distinguish from continued NCSs without the aid of cEEG monitoring. Electrographic seizure activity has been reported to occur in up to 15% of patients whose overt clinical seizures are pharmacologically controlled.
Outcome of status epilepticus
Children with SE have an overall mortality of approximately 0% to 3%. Apart from mortality, survivors of SE have increased risk of subsequent epilepsy, reported to be between 13% and 74%, and recurrent episodes of SE in 20% within 4 years of initial presentation. Such seizures and SE recurrence are influenced by the underlying etiology, with structural or metabolic lesions associated with the highest risk.
Recently, Pujar and Scott reviewed the long-term follow-up of their prospective pediatric CSE studies in North London (United Kingdom). They found that long-term outcome in relation to mortality, development of epilepsy, motor and cognitive disability, behavioral impairments, educational difficulties, and quality of life (QoL) questioned prior understanding of seizure duration causing brain injury. For example, the hypothesis that prolonged febrile seizures (PFSs) lead to mesial temporal sclerosis (MTS) and temporal lobe epilepsy (TLE) is not what clinicians have taught or thought. Yes, there is substantial morbidity after childhood CSE, but this pathology (MTS/TLE) is seen primarily in children with symptomatic causes and preexisting neurologic abnormalities. The additional effect of seizure duration seems to be less than previously believed. They concluded that in children who have suffered an episode of CSE “early identification of cognitive and behavioral difficulties and appropriate interventions are likely to have a major positive impact on QoL.” Hence, most clinicians consider prolonged seizures as needing prompt and aggressive treatment with the aim of stopping seizures as soon as possible. Thereafter, follow-up is important for early recognition of morbidities.
Status epilepticus classification
SE may be classified with respect to cause. Symptomatic implies a known cause for SE (structural or metabolic) and can be further divided into acute and remote symptomatic . Acute symptomatic seizures are those occurring in close temporal association (<7 days) to a systemic metabolic or toxic insult or in association with an acute CNS insult. Remote symptomatic refers to seizures related to CNS injury beyond 1 week prior, such as infection, trauma, cerebrovascular disease, or cortical dysgenesis, which are presumed to result in a static lesion. Remote symptomatic SE is most often associated with a long-standing history of epilepsy or CNS insult. The term idiopathic SE is used when there is no known or suspected cause for the seizures. Children who had SE before a diagnosis of epilepsy were most likely to have remote symptomatic epilepsy. Younger age of epilepsy onset and symptomatic epilepsy increased the risk of SE.
Seizure types and classification
Seizures are classified based on the clinical presentation and electroencephalographic patterns and are divided into partial or generalized seizures. Partial seizures (also referred to as simple , local , or focal ) arise in specific areas of the brain. Their presentation depends on the primary function of the affected area (motor, sensory, visual, auditory, gustatory, or affective). Simple partial seizures may remain focal or can become complex (implying loss of consciousness) and further evolve into a generalized tonic-clonic seizure.
Generalized seizures arise from diffuse cortical areas at one time. Generalized seizures involve both cerebral hemispheres and are believed to originate within, and rapidly engage, bilaterally distributed neuronal networks. Consciousness is usually impaired. Generalized seizures include seizures with motor movements as well as absence seizures during which no convulsive signs may be present. EEG indicates seizure activity involving both cerebral hemispheres.
Febrile seizures and febrile status epilepticus
Febrile seizures (FSs) are the most common type of pediatric seizure, occurring in patients between 6 months and 5 years of age. They are associated with fever but without intracranial infection or defined cause. They occur at a peak incidence of about 18 months, are generalized tonic-clonic, and last less than 10 minutes followed by a brief postictal period. Factors associated with the risk of having an FS include a family history of FS, peak temperature, and the nature of the underlying illness. The mean temperature associated with FS is 39°C or higher. It appears that it is the peak temperature, not the rising phase of the fever, that is relevant. FSs are considered simple when they are generalized, do not recur within a defined illness, and last less than 10 to 15 minutes. Complex FSs are defined as those that are focal, last longer than 10 to 15 minutes, or occur multiple times within the same febrile illness.
Approximately 5% of children who present with an FS will have an episode of febrile status epilepticus (FSE), accounting for almost 25% of cases of pediatric SE. FSE rarely stops spontaneously, is fairly resistant to ASMs, and even with proper treatment may persist for a significant period of time. The consequences of prolonged FSs in childhood was reported in the FEBSTAT study, in which 199 subjects with FSE had a mean seizure duration of 81 minutes in subjects receiving medications before arriving at the emergency department (ED). The median time from the first dose of an ASM to the end of the seizure was 38 minutes; the initial dose of lorazepam or diazepam was suboptimal in 19% of patients (34 of 166). ,
Seizures in the pediatric intensive care unit
Chemically induced seizures
It is difficult at times to determine the immediate precipitant of a seizure/SE in critically ill patients. Multiple factors can lower the seizure threshold, including the underlying medical or surgical process, medications, renal or hepatic dysfunction or failure, fever, hypoxia, metabolic abnormalities, or alkalosis ( Box 64.1 ). Medications commonly associated with a decreased seizure threshold include antidepressants, antibiotics, analgesics, antiarrhythmics, baclofen, chemotherapeutic agents, drug withdrawal (barbiturates, alcohol, opiates), immunomodulators (cyclosporine, tacrolimus, interferons), lithium, neuroleptics, radiographic contrast agents, and theophylline. Drugs of abuse associated with seizures/SE include cocaine, amphetamines, phencyclidine, and γ-hydroxybutyric acid. Less common causes include carbon monoxide, lead, envenomations, camphor, iron, and organophosphates.
Antiepileptic agent withdrawal or change
Drug toxicity and withdrawal
Fever and febrile seizures
Genetic central nervous system disorders
Hypoxia and ischemia
↑↓ Serum osmol
Traumatic brain injury
Dialysis disequilibrium syndrome
Dialysis disequilibrium syndrome is characterized by neurologic symptoms (headache, nausea, disorientation, restlessness, blurred vision, asterixis, confusion, seizures, coma, and even death) seen during or immediately after hemodialysis. The pathophysiology is thought to involve the movement of water into the brain, causing cerebral edema following the rapid removal of urea, which lowers the plasma osmolality, causing a transient osmotic gradient that favors movement of water into the brain.
Postulated hepatic mechanisms of seizures in liver failure include hyperammonemia, abnormal glutamine metabolism, cerebral ischemia, accumulation of toxins, or associated electrolyte abnormalities, such as hyponatremia, hypomagnesemia, or elevated blood urea nitrogen or creatinine. The management of these seizures and possible SE is the same as in other conditions except that one must be cautious with the selection of an antiepileptic medication that is cleared by the liver. The degree of hepatic failure may influence the metabolism of an ASM—in the later stages of hepatic failure with necrosis and loss of hepatic cellular function, the ASM may not be cleared, leading to elevated and potentially toxic ASM levels. Hypoalbuminemia may also contribute to antiepileptic drug (AED) toxicity, particularly in highly protein-bound drugs such as phenytoin and valproic acid.
Patients with hypertensive encephalopathy have exceeded the upper limit of cerebral autoregulation and may develop what has been termed posterior reversible encephalopathy syndrome (PRES). Presenting signs and symptoms include headache, visual complaints, vomiting, and seizures. Cerebral autoregulation is the process by which cerebral blood flow (CBF) remains constant across a wide range of cerebral perfusion pressures (CPPs). As the mean arterial pressure (MAP) exceeds 150 to 160 mm Hg, arteriolar vasoconstriction is exhausted, and hydrostatic pressure increases continuously, resulting in a breakdown of the blood-brain barrier and cerebral edema. The increased incidence of vasogenic edema in the parietal and occipital lobes is thought to be due to poor sympathetic innervation of the posterior circulation of the brain.
Posttraumatic seizures occur in up to 30% of pediatric victims of moderate or severe traumatic brain injury (TBI) and are associated with adverse outcome (see Chapter 118 ). The occurrence of posttraumatic seizures or epilepsy increases with injury severity, younger age, and longer follow-up. Seizures seen in patients with severe TBI are frequently refractory to medical therapy. Posttraumatic epileptogenesis is a multifactorial process that may involve changes in excitatory and inhibitory networks, altered calcium-mediated second messenger activity, changes in ionotropic receptor function and composition, altered endogenous neuroprotectant activity, or TBI-induced cortical dysplasia.
Acute renal failure is associated with uremic encephalopathy and seizures that may result from metabolic abnormalities, including hyponatremia, calcium disorders, uremia, and hypertensive encephalopathy or disequilibrium syndrome seen with hemodialysis. Treatment of seizures in these patients can be difficult as a result of ASM pharmacokinetics in uremia, decreased albumin, and dialysis effects. ASMs that are tightly protein bound (phenytoin, valproic acid) are not significantly dialyzed and usually do not need to be replaced. Clinicians should be cautious, however, as the unbound portion of drug may be higher and dosing adjustments may be necessary.
Solid-organ transplantation can be complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures, or SE. These seizures can result from hyponatremia, hyper/hypoglycemia, immunosuppressive agents, high-dose antibiotics, infections, cerebral edema, infarction, or postanoxic encephalopathy following hypotension or sepsis. Most seizures occur in the postoperative period on days 4 to 6. The immunosuppressive agents most frequently implicated are the calcineurin inhibitors cyclosporine and tacrolimus. Medication interactions have been described, as phenytoin decreases absorption of cyclosporine, and enzyme inducers (phenytoin, phenobarbital) may increase the clearance of cyclosporine and methylprednisolone.
Pediatric hematopoietic stem cell transplantation (HSCT) is associated with a large spectrum of complications. The most frequent complications are CNS infections, cerebrovascular or metabolic events, and neurotoxicity of immunosuppressive agents manifesting as PRES. Seizures are reported in 7% to 12% of HSCT patients and in 53% to 75% of patients with neurologic complications. There is currently no specific evidence to guide the selection, administration, or duration of ASM treatment in HSCT patients.
Autoimmune status epilepticus
Autoimmune SE is an increasingly recognized condition by neurologists and PICU physicians. SE may be considered autoimmune if it is refractory to ASMs and there is no other known cause, and/or with detection of circulating anti-CNS antibodies; this may then lead to empiric immunomodulatory therapy. Major factors that raise the index of suspicion are recent cognitive or behavioral alterations, a history of malignancy or tumor, or the presence of other neurologic features. Treatment includes immunotherapy, such as corticosteroids, intravenous immunoglobulin (IVIG), plasmapheresis (plasma exchange [PLEX]), chimeric antibodies, and other immunosuppressive agents while attempting to optimize ASM therapy.
Neurophysiology and pathology
The physiology of a normal neuron and pathophysiology associated with seizures is detailed in an article by Stafstrom. The ineffective recruitment of inhibitory γ-aminobutyric acid (GABA) neurons coupled with excessive excitatory N -methyl- D -aspartate (NMDA) neuronal stimulation is key in the initiation and propagation of the electrical disturbance occurring in SE. Prolonged seizures have been associated with deficits in GABA-mediated neuronal inhibition because of the rapid internalization of synaptic GABA A receptors. Clinically, this phenomenon may be demonstrated by the poor response of prolonged seizures to the GABA agonists benzodiazepines and barbiturates, a phenomenon known as time-dependent pharmacoresistance .
Prolonged seizures may cause selective neuronal loss in the hippocampus, cortex, and thalamus, areas rich in glutamate (NMDA and non-NMDA) receptors. This calcium-mediated neuronal cell death is referred to as excitotoxicity and is similar to that proposed to occur in CNS ischemia. Although prolonged seizures may be sufficient to cause neuronal damage, the superimposition of hypoxia, hypotension, acidosis, and hyperpyrexia exacerbate the degree of damage.
Historically, SE is divided into two stages, with the first 30 minutes characterized by increased autonomic activity, including hypertension, tachycardia, hyperglycemia, diaphoresis, and hyperpyrexia. This is followed by a transition period after 30 minutes when patients enter a second phase, which is characterized by multiorgan involvement and includes respiratory failure, decreased CBF, increased intracranial pressure (ICP), and hypotension. Severe acidosis ensues; the patients may develop rhabdomyolysis with a leukocytosis, hyperkalemia, and elevated creatine kinase.
Cardiorespiratory failure in status epilepticus
Respiratory failure associated with SE is multifactorial in origin. There is an increase in carbon dioxide production from the hypermetabolic state, a decrease in respiratory drive, and an increased mechanical load on the respiratory muscles. The decrease in drive (hypoventilation) may be due to muscle fatigue or secondary to medications used to suppress the seizure. There may also be an increase in dead-space ventilation from aspiration or neurogenic pulmonary edema. ,
The cardiovascular changes and initial hyperadrenergic state are due to the release of endogenous catecholamines. Patients will have an initial increase in heart rate and systemic vascular resistance that will decrease over time. Of note, there is an entity called ictal bradycardia , which is a rare and probably underestimated manifestation of epileptic seizures whose pathophysiology is still being debated. Autonomic modifications may result from either a sympathetic inhibition or a parasympathetic activation probably due to the ictal discharge arising from or spreading to the structures of the central autonomic network.
Other organ systems
As SE progresses, it is imperative to prevent hyperpyrexia, as it will contribute to neuronal cell death. Studies in adult patients have shown that there may be a CSF pleocytosis. However, any elevation in the CSF cell count in a pediatric patient should suggest a possible infectious etiology. Prolonged muscle activity may produce an elevation in creatine kinase as well as myoglobinuria and acute kidney injury (AKI). Thus, attention to hydration, electrolyte status, and renal function is essential. Acidemia may be worsened by impaired ventilation, hypoxemia, and anaerobic metabolism.
Evaluation and electroencephalography in status epilepticus
The clinical presentation of SE is variable depending on seizure type and baseline developmental and medical status of the child. Diagnosis depends on the identification of continuous or repetitive seizures, typically straightforward with convulsive seizures. However, after prolonged convulsive seizures, the motor manifestations often diminish, and the seizures may become subtle or even nonconvulsive. Differentiating between such NCSs and a postictal state can be challenging. Patients with NCSE, including absence SE, may be difficult to identify by history and physical examination alone. These patients can have intermittent altered awareness and continuous lethargy or unresponsiveness with or without subtle myoclonic jerks of the face or limbs. In such cases, cEEG monitoring is critical for diagnosis. EEG monitoring also can be used to identify nonepileptic (psychogenic) pseudoseizures. Although uncommon, delays in EEG-based diagnosis of pseudoseizures can lead to unnecessary medical intervention.
Common clinical indications for cEEG monitoring in the PICU include (1) titration of ASMs; (2) screening for subclinical seizures among patients at high risk with conditions such as encephalitis, hypoxic ischemic encephalopathy (postarrest, drowning), TBI, and stroke; (3) screening for seizures among patients receiving neuromuscular blockade and at risk for seizures (extracorporeal membrane oxygenation); and (4) characterization of paroxysmal events suspected to represent electrographic seizures. Only half of critically ill children undergoing cEEG monitoring experience their first electrographic seizure during the initial hour of monitoring. Therefore, a routine 20- to 30-minute EEG recording will fail to identify the majority of children who go on to develop seizures, justifying the need for cEEG monitoring to accurately diagnose seizures and quantify seizure burden. The majority of electrographic seizures in the PICU are either subclinical or are accompanied by only subtle clinical signs and would likely go undetected without cEEG monitoring.
EEG interpretation requires the assistance of a trained neurologist or neurophysiologist. Abnormal waveforms on EEG can be divided into two categories: epileptiform and nonepileptiform. Epileptiform abnormalities are discharges associated with an increased risk of seizures, including sharp waves, spikes, polyspikes, and spike and slow-wave discharges. When present between seizures, these waveforms are termed interictal abnormalities . Seizures are defined electrographically by the presence of ictal EEG abnormalities, whose hallmark is rhythmicity and evolution in frequency or distribution over the course of a seizure. Generalized seizures are characterized by widespread bilateral rhythmic epileptiform discharges ( Fig. 64.1 A). Focal seizures are characterized by rhythmic epileptiform discharges that are confined to one brain region ( Fig. 64.1 B). Focal seizures may spread to involve both cerebral hemispheres, a process termed secondary generalization .
Nonepileptiform abnormalities are not necessarily associated with a risk of seizure but suggest CNS dysfunction. Slow waves are a nonspecific finding, suggesting a structural or functional abnormality, and often are seen after a seizure or SE. The location of slow waves after a seizure may aid in the differentiation between generalized and focal seizures. Generalized slow waves are associated with a diffuse encephalopathy such as a metabolic disturbance, hypoxia-ischemia, or a postictal state.
Two further EEG patterns are of particular relevance to the treatment of prolonged seizures. Burst suppression is characterized by brief bursts containing a mixture of spikes, sharp waves, and slow waves alternating with periods of very low voltage ( Fig. 64.1 C). An isoelectric EEG pattern refers to a continuous low-voltage record without any discernable cortical activity. Both burst-suppression and isoelectric EEG patterns can be seen in persons in a coma and may carry a poor prognosis in certain clinical situations. However, in the context of refractory SE, these patterns are often the desired end point for treatment with high-dose barbiturates or benzodiazepines.
Management of status epilepticus
The therapeutic goals for SE include (1) general supportive care, (2) termination of SE, (3) prevention of seizure recurrence, (4) correction of precipitating causes, and (5) prevention and treatment of potential complications. Immediate attention to the airway, breathing, and circulation (ABC) is essential. SE is a situation in which simultaneous evaluation and management should be undertaken.
Although most seizures (≈75%) are self-limited and stop within 5 minutes, it is reasonable to assume that most children who arrive at the ED or PICU have been seizing for over 5 minutes. This may include time seizing before discovery, time waiting for emergency personnel, time spent en route to the hospital, and time before administration of the first ASM. Many patients may have already received potentially sedating medications from family members or emergency medical personnel that may contribute to respiratory depression on arrival.
General supportive care
Immediate assessment of the airway, administration of supplemental oxygen, and airway management—including tracheal intubation, if necessary—apply to patients with SE and are discussed in Chapters 44 and 127 in more detail. It is essential to realize that some patients may require the administration of a neuromuscular blocking agent (NMBA) and, if so, it should be one with a short half-life. The NMBA will stop the motor component of the seizure but will not stop the underlying electrographic seizure activity in the brain. Patients with seizures who are going to receive continuous infusion of an NMBA require cEEG monitoring.
Tachycardia, cool extremities, delayed capillary refill, diminished pulses, and poor urine output suggest reduced cardiac output. Providers should follow established Pediatric Advanced Life Support guidelines to obtain vascular access (see Chapter 14 ). Once established, the patient may require isotonic fluid boluses (20 mL/kg). Consideration for the administration of antipyretics should occur early in the management of the patient in SE.
Diagnostic testing in children and adolescents with SE varies among centers and likely reflects the limited evidence supporting most diagnostic approaches in SE. Specific studies should be tailored to match the patient history; however, serum glucose should be checked immediately in all pediatric patients, particularly young infants. Other blood work may include serum electrolytes (sodium, calcium, and magnesium), liver function tests, arterial blood gas, urine toxicology, and AED levels if the patient is a known epileptic on medication.
In the event of respiratory, cardiovascular, or neurologic concerns or other contraindications to lumbar puncture (such as a coagulopathy or elevated ICP), antibiotics and antivirals (if indicated) should be administered. Although blood cultures and a lumbar puncture have a high yield in children with SE and a clinical suspicion of infection, there is insufficient evidence to either support or refute whether these studies should be routinely performed in children in whom there is no clinical suspicion of infection. Currently, evidence to support the performance of most diagnostic tests relies on limited data collected in heterogeneous settings with different study objectives.
Monitoring and termination of status epilepticus
Clinicians need to consider NCSE in patients who do not quickly return to their baseline. A study by Allen et al. demonstrated that most children regain consciousness within 30 to 40 minutes, although some took many hours to recover without a sinister cause. The two variables determining recovery were seizure etiology and the administration of medications to terminate the seizure. Children recover most quickly from FSs and most slowly from acute symptomatic seizures. The authors stated that, “it was surprising that seizure duration did not significantly affect recovery time; clinical dogma is that it does.”
Electrographic seizure activity has been reported to occur in up to 15% of patients whose overt clinical seizures are pharmacologically controlled. NCSE presents with altered mentation and absent or subtle motor findings (e.g., finger twitch) and is therefore defined by EEG criteria. The ictal episodes must be continuous or recurrent for at least 30 minutes without improvement in the patient’s clinical state. The incidence of NCSE in pediatrics is currently unknown; adult studies have shown a mortality rate between 30% and 50%. Adult studies have also shown that approximately 8% of patients in coma are in NCSE. Adult etiologies included hypoxia and cerebrovascular accident as the most common causes followed by infection, metabolic conditions, TBI, tumor, and a low ASM level.
First- and second-line pharmacotherapy
A prospective observational study of 182 children with CSE found that for every minute delay between SE onset and ED arrival there was a 5% cumulative increase in the risk of having SE last more than 60 minutes. The new operational SE definition (using t 1 and t 2 timepoints of 5 and 30 minutes, respectively) suggests the administration of ASM at 5 minutes. The goal of administering an ASM is to terminate the event rapidly and safely and to prevent recurrence. First-line medications commonly administered include the benzodiazepines (diazepam, lorazepam, and midazolam); second-line agents include phenytoin, fosphenytoin, and phenobarbital. These agents are summarized in Table 64.1 . Common errors in the management of SE include insufficient drug dosages, delay in advancing to a second-line drug, and inadequate supportive care. Third-line medications are indicated to treat RSE and are reviewed later in this chapter. There are few randomized controlled trials of ASMs in SE.
|Drug||Initial Dose||Maximum Single Dose||IV Administration||Onset of Action||Half-Life||Principal Adverse Effects in Short-Term Use|
|Lorazepam||0.05–0.1 mg/kg IV||4 mg||0.5 mg/min bolus||1–3 min||Sedation, hypotension, bradycardia, respiratory depression, paradoxical hyperactivity|
|Diazepam||0.05–0.3 mg/kg IV||0.1 mg/kg/min bolus||1–3 min||Sedation, hypotension, bradycardia, respiratory depression, paradoxical hyperactivity, thrombophlebitis|
|Phenobarbital||15–20 mg/kg IV||1 g||1 mg/kg/min bolus to max 60 mg/min||5 min||Hypotension, sedation, respiratory depression, paradoxical hyperactivity, immunosuppression|
|Phenytoin||15–20 mg/kg IV||1 g||1 mg/kg/min bolus, to max 50 mg/min||7–42 h (first-order kinetics do not apply)||Dysarthria, ataxia, sedation, hypotension, cardiac arrhythmia, thrombophlebitis, extravasation causes purple glove syndrome|
|Fosphenytoin||15–20 mg PE/kg IV||1 g PE||3 mg PE/kg/min bolus to max 150 mg PE/min||12–29 h (first-order kinetics do not apply)||Dysarthria, ataxia, sedation, hypotension, bradycardia, tachycardia|
|Valproic acid||10–30 mg/kg IV||30 mg/kg||5 mg/kg/min bolus||Hypotension, cardiac arrhythmia, hepatitis, pancreatitis|