Management of Children with Status Epilepticus

Jo M Wilmshurst

Dept of Paediatric Neurology, Red Cross War Memorial Children's Hospital & School of Child and Adolescent Health, University of Cape Town, South Africa 7700

[+] Corresponding author:
Associate Professor Jo M Wilmshurst
Head of Paediatric Neurology
Red Cross War Memorial Children's Hospital
School of Child and Adolescent Health
University of Cape Town
South Africa 7700
E-mail: Fax: 021 658 1289


Status epilepticus is defined as generalised convulsions lasting 30 minutes or longer that are continuous or where there is failure to regain consciousness between seizures. The longer the time taken to gain control of seizures, the worse the neurological outcomes for the child, and the harder it is to terminate the seizures. The outcome is further influenced by the underlying aetiology. Treatment of status epilepticus consists of four stages: pre-hospital treatment, emergency department, in-hospital treatment (ward or high care), and anaesthesia (ICU). There are numerous protocols available worldwide. Most are based on the available facilities and the anecdotal preferences of the units involved. Beyond the first level of intervention, there are no large, evidence- based guidelines with which to identify the optimal intervention. Newer agents are increasingly being used, but studies to assess the true efficacy of these are not available. Further, protocols differ between resource-poor countries compared to equipped countries where the capacity to provide intensive care support and expensive medical interventions is limited. There are two targets in the management of status epilepticus, namely the rapid identification of the underlying aetiology, as this affects treatment and prognosis, and the early initiation towards terminating status epilepticus, which decreases morbidity and mortality.

Keywords: Seizures, Status Epilepticus

© 2015 Wilmshurst JM; licensee JICNA


Status epilepticus is defined as generalised convulsions lasting 30 minutes or longer that are continuous or where there is failure to regain consciousness between seizures. This is based on the concept that brain damage through neuronal cell death occurs from this point [1]. Much of this assumption is based on animal experiments, and, in fact, damage can occur with shorter events typically associated with the underlying cause and specific genetic markers, rendering the child more vulnerable [2,3]. Established and refractory status refers to generalised convulsions that last up to and longer than one hour. These seizures are resistant to first, second, and third line interventions, and, as such, require paediatric intensive care intervention. The longer the time taken to gain control of seizures, the worse the neurological outcomes for the child, and the harder it is to terminate the seizures [4]. The outcome is further influenced by the underlying aetiology. For example, a child with encephalitis often suffers the worst neurodisability. There are multifactorial and interlinked issues beyond the seizure duration that affect outcomes. For example, a child under one year of age will suffer from a different infective disease spectrum than older children [5,6,7].


The underlying trigger factors for status epilepticus in children are reported to be most commonly due to fever (presumed infection) in 36% of cases, change in medication (20%), no clear cause (9%), metabolic derangement (8%), congenital malformations (7%), anoxic events (5%), and a diverse array of other factors (trauma, vascular, infection, tumour, drugs) [8,9]. These figures originate from studies of children residing in developed, resource equipped settings and may not be true reflections of the proportions in resource-limited settings, such as South Africa, where neuroinfections are so prevalent.

The mortality in adults is reported at 15-22% and between 3-32% in children. There is no data for South Africa. In a rural population from Kenya, mortality ranged between 15- 21%. This was considered an under estimation, with many children suspected to have died before arrival at the hospital [10,11,12,13].

Most children under 5 years of age will typically have generalized tonic clonic seizures (GTCS) that last less than 5 minutes. For younger children and infants, there is a paucity of data, and the suggested timeframe for a typical GTCS is less than 10-15 minutes. The mean age for status epilepticus in children is quoted as 3.4 years in 2 studies [3,9] and less than 1 year in another [14].


Optimal investigations for the child in status include blood glucose, anti-epileptic drug (AED) levels (if relevant), toxicology testing and blood cultures, as well as basic biochemistry. Lumbar puncture for cerebrospinal fluid analysis should be considered as clinically indicated and for all children less than 18 months of age [7]. With a reported yield of only 8%, there is insufficient evidence to recommend routine neuroimaging. Indications supporting neuroimaging would include an unexplained convulsive status, the patient remaining unconscious, or new focal neurological signs becoming apparent [15].


The optimal brain monitoring of the child with suspected sub-clinical seizures should be continuous, non-invasive, highly sensitive to a variety of brain insults, reasonably specific, user friendly, and not too expensive [16]. One such device would be cEEG (continuous EEG – full head montage). This is the optimal tool, but it is not viable in most resource- limited settings. It is effective for identifying non-convulsive seizures and ischaemia. A simpler device is aEEG (amplitude-integrated EEG). This is effective for assessing if burst suppression is attained and for non-convulsive seizures. However, the recording can be affected by potential artefact.

Basic external monitoring (blood pressure, saturation, and heart rate) often underestimates true cerebral function. Cerebral Near-Infrared Spectroscopy (cNIRS) is a non-invasive tool that can be used to assess regional brain saturations (RSO2). Comparison studies with serological markers (S100beta and cNIRS) showed that the latter performed well, better in fact than the S100beta screens [17].


Treatment of status epilepticus consists of four stages: pre-hospital treatment, emergency department, in-hospital treatment (ward or high care), and anaesthesia (ICU).

There are numerous protocols available worldwide. Most are based on the available facilities and the anecdotal preferences of the units involved. Evidence-based data to support these guidelines does not exist. Figure 1 illustrates the protocol followed at the authors centre, Red Cross War Memorial Children's Hospital. This recommendation is also not evidence based but is the most effective regimen to follow for the facilities available to manage these children where intensive care beds are lacking.

First line intervention refers to the care given on arrival at the hospital, regardless of any pre-hospital intervention. Benzodiazepines in the form of diazepam (per rectal, intravenous, or interosseous), midazolam (intranasal, sublingual, intravenous, or interosseous), or lorazepam (per rectal, intravenous, or interosseous) are recommended and can be repeated if necessary. There is acceptance for intervention at this stage with a benzodiazepine and good study data to support it as an intervention [18,19,20]. Comparing diazepam and lorazepam, both are equally effective at aborting status epilepticus. Rectal lorazepam might be more effective than rectal diazepam. Lorazepam has a substantially longer duration of anti-seizure activity; it is lipid-soluble, and, as such, less seizure recurrence is seen and fewer repeat doses are required [21]. Intranasal midazolam is as effective as intravenous diazepam. Buccal midazolam is as effective as rectal diazepam. Intravenous formulations of midazolam (given via buccal or intranasal routes) are relatively inexpensive. Caregivers often prefer to give intranasal midazolam compared to administering rectal diazepam [21].

Paraldehyde is no longer readily available but remains part of some management guidelines [22]. In fact, treatment with intravenous phenytoin as a second-line therapy was found to be nine times more effective at seizure termination than was treatment with paraldehyde [4].

Second line intervention consists of intravenous phenytoin or phenobarbitone (via intravenous or intramuscular route). Both agents are fairly accepted, but studies are more limited, consisting of small numbers and fewer children [23]. Phenobarbitone can be given as a rapid push and flushed through while monitoring for respiratory depression and hypotension. Phenytoin is administered over 30 minutes through a large vein, but not a central line, using a syringe driver and requires cardiac monitoring for potential cardiac toxicity. It can only be given by intravenous route (in a solution not mixed with dextrose), cannot be repeated, and is not as effective as phenobarbitone [24]. Fosphenytoin would be a more favourable agent. Since it does not contain propylene glycol and has a pH of 8.6-9, it can be administered in dextrose-containing intravenous solutions at a more rapid rate and is equally effective. However, it is three times more expensive than an equivalent dose of phenytoin. Consequently, this agent is not readily available in South Africa and requires Section 21 Medicine Control Council clearance. Experimental rescue therapy with nasogastic phenobarbitone has been used in South Africa. It is given at a dosage of 20mg/kg during second line intervention to patients with good airway protection and the capacity for gastric absorption. This practice was reviewed in a study at Red Cross War Memorial Children's Hospital. Therapeutic levels were attained between 1 to 4 hours after dosage [25]. This practice was found to be safe, there was no need to repeat the dosage to attain therapeutic levels, and for control of seizures, it could be safely repeated. It was considered an effective, viable addition to the protocol, especially where parenteral access or supply of parenteral phenobarbitone was lacking [26,27].

Third line intervention is needed when the child is approaching refractory status. This is a disastrous situation. The child has resistant seizures that are probably exacerbated by the underlying cause, is suffering the secondary complications from the drugs already given, and is developing hypotension and respiratory depression. All these factors adversely affect brain perfusion [5,6,28].

There are no prospective randomised trials comparing the effects of anesthetics in the treatment of refractory status epilepticus. Safety data is lacking. Existing therapeutic options include barbiturate anesthetics (Pentobarbital (US) or Thiopental (Europe and Australia), propofol, or midazolam infusions. As regards evidence-based practice, there are no recommendations that can be made on the data available. Even in a large survey of neurologists in United States of America, there was little consensus for third line intervention [29].

Intravenous midazolam infusion requires a syringe driver and carries greater risk of airway suppression, especially following previous benzodiazepine boluses. It takes a long time to gain seizure control, with ranges of 15 minutes to 4.5 hours reported [30,31]. There is the potential for children to be left with prolonged seizures and irreversible neuronal cell death in centres without high care facilities. This intervention is not part of the internationally accepted Advanced Paediatric Life Support (APLS) guidelines [22]. Clonazepam infusions are used in some centres, but there is no evidence to support its use.

Thiopentone is a poor anticonvulsant with marked haemodynamic effects. It has prolonged drug effects if the infusion is used, and it challenges local ICU capacity where there is limited staffing, monitoring capacity, and anaesthetic experience.

Figure 1

Dose of Phenobarbitone for neonates < 28days. (Note: AVOID BENZODIAZEPINES – High risk of apnoea!)

Weight of infant
2 kg or less
3 kg
Initial dose of Phenobarbitone, 20 mg/kg, 200 mg/ml solution 0.2 ml 0.3 ml
If convulsions continue after 30 mins, give another dose at 10 mg/kg 0.1 ml 0.15 ml

Acknowledgement: This convulsion protocol is from the Emergency Treatment Assessment & Triage S Africa (ETAT-SA) manual 2011.

A very high dose of phenobarbitone is reported as a viable option. Both barbiturates and benzodiazepines exert a primary effect on the GABA receptor complex. There is no antiepileptic ceiling effect and no maximum dose. Complications are sedative and have respiratory-depressant properties that are more likely to occur when used in combination with benzodiazepines. Hypotension is unusual, related to the highest phenobarbitone levels, and easily controllable. Such complications are usually related to the underlying aetiology [32].

Intravenous sodium valproate received FDA approval in1996 for its role in the management of status, but it is not part of the APLS guidelines. There are no reports of respiratory depression or hypotension. It should be used with caution in children with underlying liver disease or suspected mitochondrial disorders, and there is the potential for hepatic encephalopathy to be induced [33]. Valproate performed well in both comparative studies of intravenous sodium valproate versus diazepam infusion and another study of intravenous sodium valproate versus phenytoin. However, there are no large studies measuring efficacy and larger, paediatric focused studies are needed. The agent still requires a syringe driver, and it is expensive. It would be the drug of choice for absence status [34,35].

Intravenous levetiracetam received FDA approval for adults over 16 years in 2006. There is limited data for children (most are retrospective case reviews consisting of n=10 and n=32 children). These children were loaded with 25- 50mg/kg as part of third line intervention. The results were effective and safe, but larger comparison studies are needed. The cost of this product currently precludes its availability in many settings [36,37].

Most centres in South Africa follow a policy of repeated parenteral phenobarbitone boluses; this has resulted (anecdotally) in a dramatic reduction in admissions to PICU and the complications of status epilepticus. Parenteral phenobarbitone is listed in the WHO / IMCI guidelines as first line for neonates and second line for infants and children in the management of status epilepticus [40,41]. This agent is highly effective at controlling status, safe, and inexpensive. If control is not attained within one hour, there should be time to arrange transfer to a tertiary unit; however, in this setting, the need for transfer is exceptional [32,38].


There are two targets in the management of status epilepticus

  1. Rapid identification of the underlying aetiology, as this affects treatment and prognosis.
  2. Early initiation towards terminating status epilepticus, which decreases morbidity and mortality.

It is possible to recommend benzodiazepines for first line intervention; phenytoin, phenobarbitone, or sodium valproate for second line intervention; and “other medications”, such as levetiracetam and pharmacologic coma induction for third line intervention [7]. Future treatments currently under investigation in the adult sector include parenteral lacosamide and oral topiramate loading [1,7]. More extreme interventions include a ketogenic diet, epilepsy surgery, and immunomodulation [20,39]. Although aiming for complete cessation of seizure events is the ideal outcome, it is the underlying aetiology that remains the defining aspect of the outcome for the child.

Competing interests

The author has declared that no competing interest exists.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycredited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


1. Zawadzki L, Stafstrom CE (2010) Status epilepticus treatment and outcome in children: what might the future hold? Semin. Pediatr. Neurol. 17 (3):201-5. crossref pubmed

2. Meldrum BS, Vigouroux RA, Brierley JB (1973) Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons. Arch Neurol 29 (2):82-7. pubmed

3. Lowenstein DH, Bleck T, Macdonald RL (1999) It's time to revise the definition of status epilepticus. Epilepsia 40 (1):120-2. pubmed

4. Chin RF, Neville BG, Peckham C, Wade A, Bedford H, Scott RC (2008) Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 7 (8):696-703. crossref pubmed

5. Scott RC, Surtees RA, Neville BG (1998) Status epilepticus: pathophysiology, epidemiology, and outcomes. Arch Dis Child 79 (1):73-7. pubmed

6. Holtkamp M, Othman J, Buchheim K, Meierkord H (2005) Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry 76 (4):534-9. crossref pubmed

7. Schreiber JM, Gaillard WD (2011) Treatment of refractory status epilepticus in childhood. Curr Neurol Neurosci Rep 11 (2):195-204. crossref pubmed

8. Haafiz A, Kissoon N (1999) Status epilepticus: current concepts. Pediatr Emerg Care 15 (2):119-29. pubmed

9. Singh RK, Stephens S, Berl MM, Chang T, Brown K, Vezina LG et al. (2010) Prospective study of new-onset seizures presenting as status epilepticus in childhood. Neurology 74 (8):636-42. crossref pubmed

10. Fountain NB (2000) Status epilepticus: risk factors and complications. Epilepsia 41 Suppl 2 ():S23-30. pubmed

11. Lacroix J, Deal C, Gauthier M, Rousseau E, Farrell CA (1994) Admissions to a pediatric intensive care unit for status epilepticus: a 10-year experience. Crit Care Med 22 (5):827-32. pubmed

12. Newton CR (2009) Status epilepticus in resource-poor countries. Epilepsia 50 Suppl 12 ():54-5. crossref pubmed

13. Sahin M, Menache CC, Holmes GL, Riviello JJ (2001) Outcome of severe refractory status epilepticus in children. Epilepsia 42 (11):1461-7. pubmed

14. Chin RF, Neville BG, Peckham C, Bedford H, Wade A, Scott RC et al. (2006) Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet 368 (9531):222-9. crossref pubmed

15. Riviello JJ, Ashwal S, Hirtz D, Glauser T, Ballaban-Gil K, Kelley K et al. (2006) Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 67 (9):1542-50. crossref pubmed

16. Kurtz P, Hanafy KA, Claassen J (2009) Continuous EEG monitoring: is it ready for prime time? Curr Opin Crit Care 15 (2):99-109. crossref pubmed

17. Subbaswamy A, Hsu AA, Weinstein S, Bell MJ (2009) Correlation of cerebral Near-infrared spectroscopy (cNIRS) and neurological markers in critically ill children. Neurocrit Care 10 (1):129-35. crossref pubmed

18. Scott RC, Besag FM, Neville BG (1999) Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet 353 (9153):623-6. crossref pubmed

19. Jeannet PY, Roulet E, Maeder-Ingvar M, Gehri M, Jutzi A, Deonna T (1999) Home and hospital treatment of acute seizures in children with nasal midazolam. Eur J Paediatr Neurol 3 (2):73-7. crossref pubmed

20. Loddenkemper T, Goodkin HP (2011) Treatment of pediatric status epilepticus. Curr Treat Options Neurol 13 (6):560-73. crossref pubmed

21. Appleton R, Macleod S, Martland T (2008) Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev (3):CD001905. crossref pubmed

22. Appleton R, Macleod S, Martland T. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst. Rev. 2008 Jul 16;(3)(3):CD001905.

23. Prasad A, Williamson JM, Bertram EH (2002) Phenobarbital and MK-801, but not phenytoin, improve the long-term outcome of status epilepticus. Ann Neurol 51 (2):175-81. pubmed

24. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ et al. (1998) A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 339 (12):792-8. crossref pubmed

25. Wilmshurst JM, van der Walt JS, Ackermann S, Karlsson MO, Blockman M (2010) Rescue therapy with high-dose oral phenobarbitone loading for refractory status epilepticus. J Paediatr Child Health 46 (1-2):17-22. crossref pubmed

26. Syed GB, Sharma DB, Raina RK (1986) Pharmacokinetics of phenobarbitone in protein energy malnutrition. Dev Pharmacol Ther 9 (5):317-22. pubmed

27. Yska JP, Essink GW, Bosch FH, Lankhaar G, van Sorge AA (2000) Oral bioavailability of phenobarbital: a comparison of a solution in Myvacet 9-08, a suspension, and a tablet. Pharm World Sci 22 (2):67-71. pubmed

28. Sahin M, Menache CC, Holmes GL, Riviello JJ (2003) Prolonged treatment for acute symptomatic refractory status epilepticus: outcome in children. Neurology 61 (3):398-401. pubmed

29. Rosenow F, Arzimanoglou A, Baulac M (2002) Recent developments in treatment of status epilepticus: a review. Epileptic Disord 4 Suppl 2 ():S41-51. pubmed

30. Hayashi K, Osawa M, Aihara M, Izumi T, Ohtsuka Y, Haginoya K et al. (2007) Efficacy of intravenous midazolam for status epilepticus in childhood. Pediatr Neurol 36 (6):366-72. crossref pubmed

31. Lampin ME, Dorkenoo A, Lamblin MD, Botte A, Leclerc F, Auvin S (2010) [Use of midazolam for refractory status epilepticus in children]. Rev Neurol (Paris) 166 (6-7):648-52. crossref pubmed

32. Crawford TO, Mitchell WG, Fishman LS, Snodgrass SR (1988) Very-high-dose phenobarbital for refractory status epilepticus in children. Neurology 38 (7):1035-40. pubmed

33. DeWolfe JL, Knowlton RC, Beasley MT, Cofield S, Faught E, Limdi NA (2009) Hyperammonemia following intravenous valproate loading. Epilepsy Res 85 (1):65-71. crossref pubmed

34. Limdi NA, Knowlton RK, Cofield SS, Ver Hoef LW, Paige AL, Dutta S et al. (2007) Safety of rapid intravenous loading of valproate. Epilepsia 48 (3):478-83. crossref pubmed

35. Rossetti AO, Bromfield EB (2005) Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 65 (3):500-1; author reply 500-1. pubmed

36. Kirmani BF, Crisp ED, Kayani S, Rajab H (2009) Role of intravenous levetiracetam in acute seizure management of children. Pediatr Neurol 41 (1):37-9. crossref pubmed

37. Abend NS, Monk HM, Licht DJ, Dlugos DJ (2009) Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures. Pediatr Crit Care Med 10 (4):505-10. crossref pubmed

38. Wilmshurst JM, Newton CR (2005) Withdrawal of older anticonvulsants for management of status epilepticus: implications for resource-poor countries. Dev Med Child Neurol 47 (4):219. pubmed

39. Mastrangelo M, Celato A (2012) Diagnostic work-up and therapeutic options in management of pediatric status epilepticus. World J Pediatr 8 (2):109-15. crossref pubmed

40. World Health Organisation (2015, Feb 11). Antiepileptic drugs for acute convulsive seizures or status epilepticus in adults and children. Retrieved from

41. World Health Organisation. (2015, Feb 11). WHO Model Lists of Essential Medicines. Retrieved from

Cite this article as: Wilmshurst JM.: Management of Children with Status Epilepticus. JICNA 2015 15:104. DOI:

Back to top