Do you have a plan for your little patient when he just won’t stop seizing? What do you do when your typical treatment is not enough? Get up-to-date in the understanding and management of pediatric status epilepticus.
Definition of status epilepticus:
Continuous seizure activity of 5 minutes or greater
– OR –
Recurrent activity without recovery between intervals. (This definition includes clinically apparent seizures as well as those seen only on EEG.)
During a seizure, GABA receptors in the neuron’s membrane are internalized and destroyed. Seizure activity itself starts this self-defeating process – this is the first reason we need to act as quickly as possible and take advantage of the GABA receptors that are still recruitable.
Excitatory receptors – the NMDA receptors – are acutely upregulated and mobilize to the neuron’s surface. This is the second reason to act quickly and avoid this kindling effect.
In other words – time is brain.
Or… is it something else as well?
Pediatric status epilepticus is analogous to the multi-organ dysfunction syndrome in severe sepsis. Status epilepticus affects almost every organ system.
Cardiac – dysrhythmias, high output failure, and autonomic dysregulation resulting in hypotension or hypertension.
Respiratory – apnea and hypoxia, ARDS, and potentially aspiration pneumonia.
Renal – rhabdomyolysis, myoglobinuria, and acute renal failure.
Metabolic – lactic acidosis, hypercapnia, hyperglycemia, sometimes hypoglycemia, hyperkalemia, and leukocytosis.
Autonomic – hyperpyrexia and breakdown of cerebral circulation.
DeLorenzo et al.: Mortality correlated with time seizing. Once the seizure has met the 30 min mark, Delorenzo reported a jump from 4.4% mortality to 22%! If the seizure lasts greater than 2 hours, 45%. Time spent seizing is a vicious cycle: it’s harder to break the longer it goes on, and the longer it goes on, the higher the mortality.
Think about treatment of pediatric status epilepticus in terms of time: prehospital care, status epilepticus (greater than 5 min), initial refractory status epilepticus (greater than 10 min), later refractory status (at 20 min), and coma induction (at 25 minutes).
Case 1: Hyponatremic Status Epilepticus
Give 3 mL/kg of 3% saline over 30 min.
Stop the infusion as soon as the seizure stops.
Case 2: INH toxicity
Empiric treatment -- you are the test. If we know the amount of ingestion in adults or children, we give a gram-for-gram replacement, up to 5 grams.
If a child under 2 years of age arrives to you in stats epilepticus, give 100 mg of IV pyridoxime for potentially undiagnosed congenital deficiency.
Case 3: Headache and Arteriovenous Malformation
Unlike in adults, stroke in children is divided evenly between hemorrhagic and ischemic etiologies.
The differential is vast: cardiac, hematologic, infectious, vascaulr, syndromic, metabolic, oncologic, traumatic, toxic.
Treatment: stabilization, embolization by interventional radiology, elective extirpation when more stable. Other options for stable patients include an endovascular flow-directed microcatheter using cyanoacrylate. Radiosurgery is an options for others.
Non-convulsive Status Epilepticus
Risk factors include age < 18, especially age < 1, no prior history of seizures, and traumatic brain injury. This would prompt you to ask for continuous EEG monitoring for non-convulsive status epilepticus, especially when there is a change in mental status for no other reason. Also, a prolonged post-ictal state or prolonged altered mental status. Other considerations are those who had a seizure and cardiac arrest - ROSC without RONF, those with traumatic brain injury, and those needing ECMO – all within the context of seizures.
The longer the seizure lasts, the harder it is to break – act quickly
Have a plan for normal escalation of care, and Search for an underlying cause
Recognize when the routine treatment is not enough.
Before You Go
“Healing is a matter of time, but it is sometimes also a matter of opportunity.”
“Extreme remedies are very appropriate for extreme diseases.”
– Hippocrates of Kos
Abend NS et al. Nonconvulsive seizures are common in critically ill children. Neurology. 2011; 76(12):1071-7
Baren J. Pediatric Seizures and Strokes: Beyond Benzos and Brain Scans. ACEP Scientific Assembly. October 8th, 2009. Boston, MA.
Brophy et al. Guidelines for the Evaluation and Management of Status Epilepticus. Neurocrit Care. 2012; DOI 10.1007/s12028-012-9695-z
Capovilla G et al. Treatment of convulsive status epilepticus in childhood: Recommendations of the Italian League Against Epilepsy. Epilepsia. 2013; 54 Suppl 7:23-34
Chin RFM et al., for the NLSTEPSS Collaborative Group. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet. 2006; 368: 222–29.
Chen JW, Chamberlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006; 5:246-256.
DeLorenzo RJ. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia. 1999 Feb;40(2):164-9.
LaRoche SM, Helmers SL. The New Antiepileptic Drugs: Scientific Review. JAMA. 2004;291:605-614.
Minns AB, Ghafouri N, Clark RF. Isoniazid-induced status epilepticus in a pediatric patient after inadequate pyridoxine therapy. Pediatr Emerg Care. 2010; 26(5):380-1.
Ogilvy CS et al. Recommendations for the Management of Intracranial Arteriovenous Malformations: A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Stroke Council. Stroke. 2001; 32: 1458-1471
Rosati A et al. Efficacy and safety of ketamine in refractory status epilepticus in children. Neurology. 2012; 79:2355-2358.
Schwartz ID. Hyponatremic seizure in a child using desmopressin for nocturnal enuresis. Arch Pediatr Adolesc Med. 1998 Oct;152(10):1037-8
Trommer BL, Pasternak JF. NMDA receptor antagonists inhibit kindling epileptogenesis and seizure expression in developing rats. Brain Res Dev Brain Res. 1990 May 1;53(2):248-52.
Waterhouse EJ et al. Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond, Virginia. Epilepsia. 1999 Jun;40(6).
You have all of the skills you need to care for an acutely ill infant. Learn a few pearls to make this a smoother endeavor.
The Pediatric Assessment Triangle is a rapid, global assessment tool using only visual and auditory clues to make determinations on three key domains: appearance, work of breathing, and circulation to the skin.
The combination of abnormalities determines the category of pathophysiology: respiratory distress, respiratory failure, CNS or metabolic problem, shock, or cardiopulmonary failure.
Tone - the newborn should have a normal flexed tone; the 6 month old baby who sits up and controls her head; the toddler cruises around the room.
Interactiveness - Does the 2 month old have a social smile? Is the toddler interested in what is going on in the room?
Consolability - A child who cannot be consoled at some point by his mother is experiencing a medical emergency until proven otherwise.
Look/gaze - Does the child track or fix his gaze on you, or is there the "1000-yard stare"?
Speech/cry - A vigorously crying baby can be a good sign, when consolable - when the cry is high-pitched, blood-curling, or even a soft whimper, something is wrong.
If the child fails any of the TICLS, then his appearance is abnormal.
Work of Breathing
Children are respiratory creatures - they are hypermetabolic - we need to key in on any respiratory embarrassment.
Look for nasal flaring. Uncover the chest and abdomen and look for retractions. Listen - even without a stethoscope - for abnormal airway sounds like grunting or stridor. Grunting is the child's last-ditch effort to produce auto-PEEP. Stridor is a sign of critical upper airway narrowing.
Look for abnormal positioning, like tripodding, or head bobbing
Circulation to the skin
Infants and children are vasospastic - they can change their vascular tone quickly, depending on their volume status or environment. Without even having to touch the child, you can see signs of pallor, cyanosis, or mottling. If any of these is present, this is an abnormal circulation to the skin.
Pattern of Abnormal Arms = Category of Pathophysiology
Differential Diagnosis in a Sick Infant: "THE MISFITS"
Trauma - birth trauma, non-accidental - check for a cephalohematoma which does not cross suture lines and feels like a ballotable balloon, as well as for subgaleal hemorrhage, which is just an amorphous bogginess that represents a dangerous bleed. Do a total body check.
Heart disease or Hypovolemia - is there a history of congenital heart disease? Was there any prenatal care or ultrasound done? Does this child look volume depleted?
Endocrine Emergencies - Could this be congenital adrenal hyperplasia with low sodium, high potassium, and shock? Look for clitoromegaly in girls, or hyperpigmented scrotum in boys. Could this be congenital hypothyroidism with poor tone and poor feeding? Any history of maternal illness or medications? Congenital hyperthyroidism with high output failure?
Metabolic - What electrolyte abnormality could be causing this presentation? Perhaps diGeorge syndrome with hypocalcemia and seizures?
Inborn Errors of Metabolism - there are over 200 inborn errors of metabolism, but only four common metabolic pathways that cause a child to be critically ill. Searching for an inborn error of metabolism is like looking for A UFO - amino acids, uric acids, fatty acids, organic acids. If the child's ammonia, glucose, ketones, and lactate are all normal in the ED, then his presentation to the ED should not be explained by a decompensation of an inborn error of metabolism.
Seizures - Neonatal seizures can be notoriously subtle - look for little repetitive movements of the arms, called "boxing" or of the legs, called "bicycling"
Formula problems - Hard times sometimes prompt parents to dilute formula, causing a dangerous hyponatremia, altered mental status, and seizures. Conversely, concentrated formula can cause hypovolemia
Intestinal disasters - 10% of necrotizing enterocolitis occurs in full-term babies - look for pneumatosis intestinalis on abdominal XR; also think about aganglionic colon or Hirschprung disease; 80% of cases of volvulus occur within the 1st month of life
Toxins - was there some maternal medication or ingestion? Is there some home remedy or medication used on the baby? Check a glucose ad drug screen
Sepsis - Saved for last - You'll almost always treat the sick neonate empirically for sepsis - think of congenital and acquired etiologies.
The hyperoxia test is the single most important initial test in suspected congenital heart disease - we can test the child's circulation by his reaction to oxygen on an arterial blood gas. Place the child on a non-rebreather mask, and after several minutes, perform an ABG. (Ideally you obtain a preductal ABG in the right upper extremity, and compare that with one on the lower extremity, but this may not be practical.)
In a normal circulatory system, the pO2 should be high - in the hundreds - and certainly over 250 torr. This effectively excludes congenital heart disease as a factor. If the pO2 on supplemental oxygen is less than 100, then this is extremely predictive of hemodynamically significant congenital heart disease. Between 100 and 250, you have to make a judgement call, and I would side on worst first.
If you are giving this child 100% O2, and he doesn't improve 100% -- that is, his ABG is not at least 100 - then he has congenital heart disease until proven otherwise.
Give prostaglandin if the patient is less than 4 weeks old (typical presentation is within the first 1-2 weeks of life). Start at 0.05 mcg/kg/min. PGE keep the systemic circulation supplied with some mixed venous blood until either surgery or palliation is decided.
* When you see a sick infant, keep THE MISFITS around to keep you out of trouble.
* Before you decide on sepsis, ask yourself, could this be a cardiac problem?
* When in doubt, perform the hyperoxia test.
* All the rest, you have time to look up.
Before You Go: The Availability Heuristic
Brousseau T, Sharieff GQ. Newborn Emergencies: The First 30 Days of Life. Pediatr Clin N Am. 2006; 53:69-84.
Cloherty JP, Eichenwald EC, Stark AR: Manual of Neonatal Care, 5th edition. Philadelphia, PA, Lipincott Williams & Wilkins, 2004.
Horeczko T, Young K: Congenital Heart Disease, in Pediatric Emergency Medicine-A Comprehensive Study Guide, 4th Ed. ACEP/McGraw-Hill, 2013.
McGowan et al. Part 15: Neonatal Resuscitation: 2010 American Heart Association Guidelines. Circulation. 2010;122:S909-S919.
Okada PJ, Hicks B. Neonatal Surgical Emergencies. Clin Ped Emerg Med. 2002; 3:3-13.