Status epilepticus is divided into clinical stages: premonitory (prodromal); incipient (0–5 min); early stage (5–30 min); the transition stage, from the early to the late, or established, stage (30–60 min); refractory stage (greater than 60 min); and post-ictal stage [1, 20] (Table 27.3). The premonitory stage consists of confusion, myoclonus, or increasing seizure frequency. The early stage has continuous seizure activity whereas convulsive SE (CSE) evolves into NCSE in the refractory stage. If a premonitory stage is identified, treatment should be initiated (see pre-hospital treatment). Specific circumstances may require immediate seizure control in the incipient stage (0–5 min). We have called these the special circumstances of the early stage (Table 27.4) [1, 4]. The t1 and t2 time points of the new system are analogous to the transition stage, which may vary under different circumstances. ARS should be considered a ‘premonitory’ stage of SE and may be SE if there is no return to baseline mental status in between seizures.

Treiman reported that the EEG stage of SE correlates with the clinical stage and may occur in a predictable sequence: (1) discrete seizures with interictal slowing; (2) waxing and waning of ictal discharges; (3) continuous ictal discharges;(4) continuous ictal discharges punctuated by flat periods; and 5) periodic epileptiform discharges (PED), on a flat background [21] (Table 27.5). Early anti-seizure drug (ASD) treatment controls seizure activity better than when administered in a later stage [21]. One case reported an adult who went through all of these EEG stages during continuous EEG (C-EEG) monitoring [22], but not every episode of SE passes through each stage [23]. The PED stage may also consist of either bilateral (BPED) or lateralized (PLED) patterns [24]. These same stages have been documented in the developing brain in experimental animals [25]. The new classification includes the EEG correlates of SE; these include the location, name of pattern, morphology, time-related features, modulation, and effect of intervention with medication (see Table 27.1).

SE treatment had been divided into first-line through fifth-line, with recommendations for certain medications to be administered in sequence based on times from seizure onset. The Neurocritical Care Society SE guideline recommends that treatment terminology be changed from that of first through fifth-line therapy to ‘emergent’ initial therapy, urgent control therapy, and refractory therapy [3]. Hopefully, this change will shift treatment mentality from that of focusing on timelines from seizure onset to that of achieving seizure control. Therefore, SE is now defined by the time from seizure onset (t1) and the response to ASD treatment: SE, established SE (failure to respond to emergent therapy), and refractory SE, defined as SE not responding to the initial benzodiazepine and the second-line ASD [8, 26].

Status epilepticus is common in childhood-onset epilepsy. In a population-based study from Connecticut, 56 of 613 children (9.1%) had one or more episodes of SE [27]; from a Finnish cohort of children with epilepsy, 41 of 159 (27%) had SE. SE was more likely within the first 2 years after the onset of epilepsy; risk factors for SE included remote symptomatic cause, onset at age 6 years or younger, and partial seizures [28]. In a study of 394 children with SE from Richmond and the Bronx, SE was common in younger children, with over 40% of episodes occurring in those aged 2 years or less, and of these, over 80% had a febrile or acute symptomatic etiology; cryptogenic or remote symptomatic etiologies were most common in older children, as was a prior history of epilepsy [29]. In a prospective study, SE recurred in 16 of 95 cases (17%). Neurologic abnormalities (including severe cognitive or motor developmental delay or both, progressive encephalopathy, mental retardation, cerebral palsy, genetic syndromes, or multiple congenital anomalies) were found in 34% of all patients, but in 88% of those with two episodes of SE, and in all five patients with three or more episodes of SE [30]. The risk of recurrence varied by etiology: 4% in the idiopathic group, 44% in the remote symptomatic group, 3% in the febrile group, 11% in the acute symptomatic group, and 67% in those with progressive neurologic disorders.

Five population-based studies of SE include children [31–35]. The incidence varies from 41 cases per 100,000 people in Richmond [32], to 18/100,000 in Rochester [33], 10/100,000 in Switzerland [34], and 6.2/1,000,000 in California [35]. All studies show a higher incidence of SE in the youngest children and the elderly. The Richmond study stratified the incidence by age: 156/100,000 in infants, 38/100,000 in children, 27/100,000 in adults, and 86/100,000 in the elderly [32]. In the North London SE in Childhood Surveillance Study (NLSTEPSS), the age-adjusted incidence for acute symptomatic SE was 17/100,000 in children less than one year of age, 2.5/100,000 in those of age 1–4 years, and 0.9/100,000 in those 5–15 years of age. The incidence of an episode of acute on remote symptomatic SE (remote symptomatic with an acute precipitant) was 6, 5.3, and 0.7%, respectively, in the above age groups. A prolonged febrile seizure occurred in 4.1 cases per 100,000 population; acute symptomatic causes in 2.2/100,000; remote symptomatic in 2.3/100,000; acute on remote in 2.1/100,000; idiopathic in 1.4/100,000; cryptogenic in 0.2/100,000; and unclassified in 1/100,000 in children of all ages [16].

The prognosis of SE depends on etiology, age, duration, and treatment adequacy. The specific cause must be determined and treated, if possible, in order to prevent ongoing neuronal injury and facilitate seizure control. Etiology is a very important determinant of morbidity and mortality. In the classic paper on pediatric SE by Aicardi and Chevrie, including 239 children, 113 cases were symptomatic and 126 were cryptogenic [36]. In those with symptomatic SE, 63 of 113, or 26% overall, had acute CNS insults (including treatable disorders such as bacterial meningitis, encephalitis, dehydration or electrolyte disorders, toxic ingestions, or subdural hematoma), and 50, or 21% overall, had a remote symptomatic cause, also referred to as a chronic encephalopathy (e.g., anoxia, progressive encephalopathy, non-progressive encephalopathy, brain malformation, cerebral palsy, and Sturge–Weber syndrome). In those with cryptogenic SE, 67 of 126 (or 28% overall) were associated with fever (a prolonged, or complex, febrile seizure). In another classic study, Maytal et al. [37] reported similar data for etiology: 45 of 193 patients (23%) had acute symptomatic and 45/193 (23%) remote symptomatic causes. In the NLSTEPSS prolonged febrile seizures occurred in 32% of all SE cases, acute symptomatic SE in 17% of all cases, remote symptomatic SE in 16% of all cases, and acute on chronic SE in 16% of all cases [16].

The incidence of SE of different etiologies differs in children and adults. The Richmond Study included all ages; the most common cause of SE in adults was cerebrovascular disease (25.2%) whereas fever or infection (35.7%) was the most common cause in children [38]. Recent medication changes occurred in 20% of children and 19% in adults (Table 27.6). Symptomatic SE has a greatest frequency in the very young and has a higher morbidity and mortality. It occurs less frequently after one year of age. Idiopathic SE (in children without an underlying neurologic abnormality) is rare during the first several months but becomes more common after 6 months [39].

The SE mortality in children ranges from 3 to 11% and also varies by etiology and age [36, 37, 40–46]. In the Maytal study, the overall mortality was 4%, with deaths occurring only in those with an acute symptomatic or progressive symptomatic etiology [37]. The lowest mortality, 3%, was from Saudi Arabia [46]. The Richmond study had an overall mortality of 6% [39]; when age-stratified, the first-year mortality was 17.8%, but in the first 6 months, mortality was 24% compared to 9% in those aged 6–12 months. This difference results from a higher incidence of symptomatic SE in the youngest children [39]. Regarding morbidity, a Canadian study showed that 34% of 40 children with a seizure duration of 30–720 min had subsequent developmental deterioration [47]. Some of the morbidity and mortality of SE may be a direct consequence of the SE itself and some attributed to the illnesses underlying the SE [48]. An increased morbidity and mortality also occurs with NCSE, especially with a duration greater than 36 h [49]. This increased morbidity with NCSE is controversial [50, 51].

Fever is a common precipitant of seizures in children. In the absence of an underlying infection, neurologic abnormality, or epilepsy, these are referred to as benign febrile seizures. Benign febrile seizures are typically short, <15 min, non-focal, and not associated with a prolonged post-ictal state [52]. Febrile SE (FSE) is a subgroup of febrile seizures. In the Richmond series, over 50% of SE in children occurred due to infection, versus only about 5% in adults [38]. The NLSTEPSS data are similar, with prolonged febrile seizures occurring in 32% of children with convulsive SE [15]. A symptomatic cause, especially meningitis or encephalitis, must be excluded. There is also controversy regarding the prognosis of FSE. An Italian study reported a high incidence of neurologic sequelae, especially seizures, with an early age of onset, but did not exclude symptomatic cases [53]. Another study reported speech delay [54]. Maytal and Shinnar [55] reported a better prognosis of FSE in the neurologically normal child. The British National Cohort Study also found that the prognosis for lengthy febrile seizures and SE was determined more by the cause [56].

In a cohort of 381 Japanese children with febrile SE, 81.6% had prolonged febrile seizures, 6.6% had encephalopathy or encephalitis or both, 0.8% had meningitis, and 7.6% had previously diagnosed epilepsy. The seizures were longer in the encephalopathy/encephalitis cases than in the prolonged febrile seizures [57], but an earlier British Study found four cases of bacterial meningitis in 49 cases of febrile SE [58].

A prospective study to determine the consequences of FSE is in progress, the Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT) study. Patients are included for analysis if they have a seizure or series of seizures without full recovery lasting >30 min, fever >38.4 °C, with ages 1 month through 5 years, with no acute CNS insult or infection and no prior afebrile seizures [59]. So far, the data have been analyzed for cerebral spinal fluid (CSF), EEG, and neuroimaging. An LP (done in 154 of 200 cases) was non-traumatic in 136; 116 of 136 had <3 WBCs; the largest number was 12 in one child [60]. Acute EEG findings were analyzed in 199 children; 90 of 199 (45.2%) were abnormal, with non-epileptiform abnormalities in 85 (42.7%) and epileptiform abnormalities in 13 (6.5%) [61]. MRI findings showed hippocampal enlargement and increased signal in 11.5% and a malrotation of the hippocampus in 10.5% [62]. The long-term goal of FEBSTAT is to identify risk factors for mesial temporal (hippocampal) sclerosis, which may result from prolonged febrile seizures.

The treatment of a seizure, ARS, or SE starts with following the A, B, Cs (Table 27.7) and performing appropriate diagnostic studies (Table 27.8). Convulsive SE is relatively easy to recognize, but NCSE and nonconvulsive seizures require EEG identification. Appropriate diagnostic studies are determined by the history and examination. If the seizure occurs in the setting of an acute illness, especially with vomiting and diarrhea, hypoglycemia, electrolyte disturbances, and dehydration must be considered [1, 2, 4]. Even with a nonspecific upper respiratory tract infection, there may be an underlying disorder, with symptoms precipitated by the metabolic stress such as with a metabolic or mitochondrial disorder. Preceding psychiatric symptoms, movement disorders, or a family history of autoimmune disorders may be suggestive of an acute autoimmune disorder (e.g., NMDA receptor encephalitis). The patient must be stabilized before further testing, such as lumbar puncture or transport to neuroimaging.

Serum glucose should be checked rapidly by point-of-care testing to exclude hypoglycemia. A CBC may be helpful for suggesting infection, but leukocytosis may occur from the SE itself. Electrolytes, calcium, phosphorus, and magnesium values may be helpful in children with vomiting and diarrhea [63]. Low ASD levels may be associated with SE [64]. Serum studies may be needed if there is suspicion for a specific toxin [5].

The American Academy of Neurology (AAN) and the Child Neurology Society practice parameter on diagnostic abnormalities in SE found the following, when tested [5]: abnormal electrolytes (6%), positive blood cultures (2.5%), CNS infection (2.8%), low ASD levels (32%) ingestion of some toxic substance (3.6%), inborn errors of metabolism (4.2%), epileptiform abnormalities on EEG (43%), and neuroimaging abnormalities (8%). In a prospective study of new onset SE with an acute symptomatic etiology, febrile SE occurred in 32%, CNS infection in 9%, vascular causes in 3.4%, and electrolyte abnormalities, toxins, and trauma in 1.4% each [65]. With a remote symptomatic etiology, cerebral dysgenesis and inborn errors occurred in 5.6% each, 2.8% had a remote vascular cause, and a remote infection, chromosomal abnormality, or mesial temporal sclerosis occurred in 1.4% each.

In a review, Freilich et al. [66] recommended that electrolytes, EEG, and CT or MRI scans should always be done for new onset SE, and if the clinical suspicion exists, urine toxicology, genetic or metabolic testing, and lumbar puncture should also be considered. For refractory SE or with persistent encephalopathy, C-EEG monitoring is recommended. For SE in a known patient with epilepsy, ASD levels are always recommended, and electrolytes, EEG, and CT or MRI scan, and (if febrile) a lumbar puncture (LP), should be considered. With refractory or persistent encephalopathy, C-EEG monitoring [66] is recommended.

Meningitis can be a frequent cause of SE in children with fever, occurring in 4 of 24 cases in a prospective study [58]. Therefore, LP to exclude meningitis must be considered in every febrile child with a seizure or SE. The child may be assessed clinically if old enough, but the signs of meningitis may be absent in infants or after CSE [58]. If there is concern for increased intracranial pressure or a structural lesion, LP is deferred until neuroimaging is performed. In this situation, antibiotic treatment should be initiated prior to the LP, ultimately relying on the cell count and bacterial cultures to exclude an infection. CSF pleocytosis may occur without infection [67], due to either a CNS inflammatory process or breakdown in the blood–brain barrier from the seizure activity. The FEBSTAT, however, showed that CSF pleocytosis is unlikely in FSE, occurring in only 20 of 136 cases (15%) [60].

The AAN practice parameter for neuroimaging in seizures recommended an ‘emergent’ scan (immediately) for new onset SE or SE in a child with known epilepsy not responding to treatment [68, 69]. A greater incidence of life-threatening lesions (e.g., hemorrhage, brain swelling, mass effect) occurs with a first-time seizure or in a child with epilepsy and new focal deficits, persistent altered mental status, with or without intoxication, fever, recent trauma, persistent headache, cancer, or on anticoagulation [68–70]. MRI is more sensitive than CT scan but is rarely available for emergency studies; CT scans will identify life-threatening conditions adequately. In a study of new onset seizures presenting with SE, a diagnosis was made by neuroimaging (CT or MRI) in 30%, with management changed in 28 of 143 cases (24%), and 20% of cranial CT scans were abnormal, with 14 (10%) showing acute abnormalities, and 14 (10%) showing chronic abnormalities [65]. In a study of 71 cranial CT scans in children with new onset seizures admitted to the PICU, abnormal findings occurred in 16 of 71 patients (22%); clinically significant findings occurred in 14 of these; and findings resulted in a change in management in 5 of 14 patients, representing 7% of the original group. The findings that led to change in management included subdural hematoma, mass with midline shift and hydrocephalus, and arteriovenous malformation with intracranial hemorrhage (in one child each) and communicating hydrocephalus in two children. Risk factors for a positive scan included lack of fever, multiple seizures, and age less than 24 months [71]. It is imperative to stabilize the child before transport to the neuroimaging suite.

An immediate EEG is not usually done during the initial treatment of CSE, unless there is a strong suspicion for non-epileptic events. If convulsive movements stop after the initial therapy, without an improvement in consciousness, however, an EEG is needed to exclude NCSE. In adults, NCSE occurred in 14% of patients treated for CGSE [72]. In children, NCSE occurred in 5 of 19 cases following control of CSE; in 2 of these, NCSE occurred after treatment of CSE and in 3, NCSE occurred after treatment of RSE [73]. After the control of outward seizures in 98 children with CSE, electrographic seizures were seen in 32 of 98 cases (33%), and NCSE was present in 15 of 98 (15%) [74]. In comatose patients of all ages without obvious seizure activity, NCSE was detected in 8% [75], and in a study of children only, NCSE was detected in 2 of 19 patient following an hypoxic-ischemic insult [73].

The other indications for emergency EEG include unexplained altered awareness (to exclude NCSE); neuromuscular paralysis for SE, which eliminates the convulsive movements by neuromuscular blockade but does not stop the electrographic seizure activity; or when continuous intravenous (IV) therapy is needed for refractory SE (RSE) [76]. The EEG is useful whenever the diagnosis is in doubt, especially for non-epileptic events [77]. In one report, 6 of 29 children admitted with CSE had non-epileptic events [17].

As mentioned, treatment protocols have generally been time-based, with specific ASDs recommended after various times from seizure onset. At seizure onset, supportive measures must maintain the airway, breathing, and circulation (the A, B, Cs). The initial management of a seizure is detailed in Table 27.7. Vital signs are taken, oxygen is administered, IV access is secured, and initial blood studies sent. Many seizures will stop spontaneously while the above are in progress. If the seizure continues for 5 min, a first-line ASD is given. If the initial medication fails, then second-line treatment, followed by third-, fourth-, and fifth-line agents are used. These ASDs should be given in an IV formulation. Lorazepam has replaced diazepam (DZP) as first-line therapy [2]; these two agents have equal efficacy for controlling the seizure initially, but there is a shorter anticonvulsant duration with DZP, and repeat doses may be required [78, 79]. Midazolam is also used as a first-line agent. If lorazepam does not work within 5 min, many protocols repeat the dose and then administer the second ASD.

The initial benzodiazepine dose is given rapidly by an IV push. Subsequent IV ASDs are given by an IV loading dose. These have a fixed infusion time in order to prevent adverse effects, notably hypotension or cardiac arrhythmias. If the second agent does not work, the third agent is given, also with a specific infusion time. As it takes time to give a therapeutic dose, these infusion times can delay seizure control. Waiting for the infusion to be completed may increase the chance of brain injury, especially when the brain’s compensatory mechanisms are compromised. If there is no IV access, midazolam, 0.2 mg, or fosphenytoin, 20 mg/kg, may be given IM. Alternatively, rectal diazepam may be administered.

Historically, phenobarbital, phenytoin, and the benzodiazepines, diazepam and lorazepam, have been the first-line agents. The Veterans Affairs Cooperative Study assessed drug efficacy in adults with SE, comparing lorazepam (0.1 mg/kg), phenobarbital (15 mg/kg), diazepam (0.15 mg/kg) plus phenytoin (18 mg/kg), and phenytoin alone (18 mg/kg). Successful treatment was defined as SE control within 20 min. Efficacy was similar with lorazepam (65%), phenobarbital (58%), and diazepam plus phenytoin (56%), whereas phenytoin alone had a lower rate (44%). This lower rate was likely related to the infusion time needed: 4.7 min with lorazepam versus 33 min with phenytoin alone [80]. IV preparations of valproate, levetiracetam, and lacosamide are now available.

In children, many use the following sequence after lorazepam: fosphenytoin, followed by phenobarbital, then midazolam—which is followed by pentobarbital if seizure activity continues, considered RSE [81]. The American Epilepsy Society evidence-based guideline for the administration of ASDs in SE is shown in Table 27.9 [26]. In the NLSTEPSS treatment study, seizures stopped after a first-line agent in 65% and after a second-line agent in only 50% of the remainder (41/82); when the initial benzodiazepine dose was repeated, it worked in only 1 of 16 cases [82]. From Izmir, only 2 of 27 cases were controlled by first-line therapy (diazepam), whereas midazolam controlled 22 of 23 cases when used at various stages, including 3 treated in the early stage [83]. A study from Athens used a repeat midazolam bolus of 0.1 mg/kg every 5 min in children with chronic epilepsy, with a maximum of 5 doses; this protocol controlled 53% after one dose, another 26.3% after a second dose, and another 10.5% after the third dose, with a total of 90.7% control after five doses [84]. In the NLSTEPSS, it was common for lower doses to be used [82]. Pediatric treatment protocols need to be updated, to stop the SE more aggressively when it is considered refractory SE (e.g., after failure of the initial BZP followed by the second-line agent) and to emphasize using the recommended ASD doses.

As part of its development of SE Guidelines, the Neurocritical Care Society conducted an international survey of SE experts because of a lack of evidence-based research in SE [85]. Lorazepam was considered the drug of choice for initial therapy in all age groups.

The following ASDs are available in IV preparations and have been used as second and third-line therapy.

IV valproic acid is given in an initial loading dose of 20–40 mg/kg [86–89]. An additional 10 mg/kg is given 10 min after the loading dose if the seizure continues [90]. The infusion rate is from 3 to 6 mg/kg/min [91]. Adverse effects include hypotension, and hepatopathy (hyperammonemia) and pancreatopathy (elevated amylase and lipase), which may be seen acutely. Thrombocytopenia occurs, but usually with chronic administration. A randomized clinical trial of phenobarbital versus sodium valproate for the initial treatment for SE in children demonstrated seizure termination in 90% with sodium valproate versus 77% with phenobarbital, with significant adverse effects seen in 74% with phenobarbital versus only 24% with valproate [92].

Levetiracetam: the recommended loading dose ranges from 20 to 60 mg/kg. A typical dose for responders is 30 mg/kg, with infusion rates of 2–5 mg/kg/min [93, 94]. Loading doses of 50 mg/kg [95] and 60 mg/kg [96] have been used without significant side effects. In one study, the loading dose was given over 5–6 min [96]. Minor reactions include lethargy, fatigue, restlessness, and pain at the infusion site. Very high doses (240 mg/kg/day) have been used with good efficacy and limited adverse effects, with one child having an increase in seizures [97]. Adverse effects include agitation and behavior problems. Levetiracetam dosing must be adjusted for renal failure and is adjusted based on the glomerular filtration rate (GFR).

In a study of 88 children with ARS or SE, a comparison of IV phenobarbital, at a median loading dose of 20 mg/kg, versus IV levetiracetam, at a median loading dose of 30 mg/kg, led to seizure termination in 58% with levetiracetam versus 74% with phenobarbital [98]. A 30 mg/kg loading dose of levetiracetam is now considered low [99, 100].

Lacosamide is now available in IV formulation. In adults, a 200–400 mg IV loading dose has been used most often, although 50, 100, 150, and 300 mg doses have been used. One study in adults used an infusion rate of 40–80 mg/min, and 15 min is now suggested for the infusion time [101–103]. In a pediatric case report, 25 mg BID controlled refractory SE after 24 h [104]. Adverse effects include first-degree heart block and hypertension, so lacosamide should be used with caution in patients with known cardiac conduction problems [105]. In a study using lacosamide for refractory SE in 9 children, the mean loading dose was 8.7 mg/kg, with a range of 3.3–10 mg/kg; the average dose in the first 24 h was 13.8 mg/kg. For the loading dose, 7 of 9 patients received 10 mg/kg [106].

The patient’s condition, the type of SE, and the underlying epileptic syndrome must be taken into consideration when deciding how aggressive management should be. For example, the child with an acute brain insult and SE is more prone to brain injury than the child with absence SE in the setting of childhood absence epilepsy. The sequence of ASDs used for juvenile myoclonic epilepsy may differ from that used for symptomatic generalized SE. For patients with recurrent seizures or nonconvulsive seizures in the setting of chronic epilepsy with stable vital signs, less aggressive treatment should be considered. The risk of ongoing brain injury is less likely in the setting of chronic epilepsy, unless there is an acute precipitant (i.e., acute on chronic or remote symptomatic with an acute precipitant).

The Neurocritical Care Society Survey indicated that after failure of the first two agents, midazolam, pentobarbital, and propofol are used earlier in adults than in children [85]. This follows the previously recommended protocols. Research in pediatric SE has been increasing, in part based on the need for evidence-based treatment and management. Treatment studies now include children. In the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), a phase 3 non-inferiority study, intravenous lorazepam was compared to intramuscular midazolam (MDZ); IM MDZ was at least as safe and effective as IV lorazepam [107]. A current study, the Established Status Epilepticus Treatment Trial (ESETT), plans to determine the second-line agent to use after failure of the initial benzodiazepine, comparing IV fosphenytoin at 20 mg/kg, IV levetiracetam at 60 mg/kg, or IV valproic acid at 40 mg/kg, in patients older than 2 years of age [26, 108, 109].

High-quality data are needed to develop evidence-based treatment strategies for pediatric SE to improve management and prognosis. The Pediatric SE Research Group (pSERG) was established for the purpose of collecting data prospectively from multiple centers [110]. Although in general, randomized clinical trials are preferred, prospective observational study protocols using a comparative effectiveness approach may be more feasible.

The pSERG has evaluated time-based treatment, evaluating the elapsed time from the onset of pediatric CSE to the administration of ASD [111]. The first, second, and third ASD doses were administered at a median time of 28 min (range: 6–67 min), 40 (20–85), and 59 (30–120) min after SE onset. Even in the inpatient setting, the first and second ASDs were given at 8 (5–15) min and 16 (10–40) min after SE onset. This study is quite revealing, demonstrating that despite the many guidelines recommending that the initial ASD should be administered quickly, this has not yet happened.

There are rare genetic disorders of pyridoxine (vitamin B6) metabolism (pyridoxine responsive and pyridoxine resistant) that may result in SE. Therefore, IV pyridoxine administration is recommended for refractory SE in the infant and younger child, less than 3 years of age [112]. The dose is 30 mg/kg.

The premonitory or incipient stage of SE can now be treated in a pre-hospital setting with rectal, buccal, or nasal ASDs, and IV ASDs are now given in the field. A prospective pre-hospital treatment study in adults randomized IV treatment to 5 mg of diazepam, 2 mg of lorazepam, or placebo, and showed that lorazepam was more effective than diazepam in terminating SE [59% response to lorazepam versus 43% response with diazepam, versus a 21% response to placebo (P = 0.001)] [113]. A retrospective study of CSE in children (n = 38) showed that pre-hospital treatment with (0.6 mg rectal) diazepam resulted in a shorter duration of SE than occurred in children who received no pre-hospital treatment (32 min vs. 60 min) and less seizure recurrence in the emergency department (58% vs. 85%), and there was no difference in intubation rates [114]. Rectal diazepam gel is now established care at home for SE or serial seizures. The maximum dose is 10 mg in children, determined by age and weight. Although not FDA-approved for SE, we use it for SE in the home, but we do not consider it appropriate for inpatient use except under certain conditions, such as lack of IV access, or in the epilepsy monitoring unit when no IV has been placed in advance.