PEDIATRIC PREDICAMENTS
Educational Objectives
| The goal of this program is to improve management of children who present with febrile and other seizures in the
emergency department (ED), and to improve diagnosis and treatment of bacterial meningitis in the ED. After hearing
and assimilating this program, the clinician will be better able to:
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 | 1. Assess and treat children in status epilepticus.
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| 2. Address febrile seizures and their underlying causes in children.
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| 3. Manage seizures occurring away from available intravenous access.
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| 4. Apply methods of differentiating bacterial from viral meningitis.
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| 5. Interpret results of a bloody lumbar puncture.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning
committee reported nothing to disclose.
Acknowledgements
Drs. Loiselle and Schunk were recorded at Pediatric Emergency Medicine 2008: Advances and Controversies for the
Clinician, held March 26-29, 2008, in Lake Buena Vista, FL, and sponsored by Nemours. The Audio-Digest Foundation
thanks the speakers and Nemours for their cooperation in the production of this program.
| SEIZURES: STAY CALM AND MANAGE EFFECTIVELY —John M. Loiselle, MD, Associate Professor of Pediatrics,
Jefferson Medical College, and Director, Emergency Medicine, Alfred I. duPont Hospital for Children, Philadelphia,
PA
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| Seizures: sudden abnormal or paroxysmal discharge of neurons within cerebral cortex that alters some function or behavior;
febrile seizures occur in 3% to 5% of normal children; single nonfebrile seizures occur in 2% of normal children;
epilepsy—recurrent nonfebrile seizures; occurs in 0.5% of children
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| Status epilepticus: continuous or repetitive seizures lasting >30 min, during which patient does not regain consciousness;
initiate anticonvulsant therapy for any seizure that lasts >5 min; studies reveal good outcomes for prevention of
death, and motor and cognitive disabilities in children after status epilepticus; morbidity and mortality low in aftermath
of treatment; most children experienced no sequelae; important to protect brain from risks other than seizures
themselves; conditions during seizures—hypoxia (oxygen demand increases and ventilation irregular); acidosis
(metabolic and respiratory); hyperpyrexia; hypoglycemia; effective and rapid treatments available
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| Priorities: support airway, breathing, and circulation (ABCs); stop seizures; prevent recurrences; only then diagnose
and treat any underlying life-threatening causes
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| Airway support: keep large suction available to address increased secretions and salivation; oral airway may prove difficult
to place during seizure because of trismus; alternatively, nasopharyngeal airway helpful; monitor breathing
(eg, pulse oximetry, cardiorespiratory monitor); always provide additional oxygen, regardless of pulse oximetry
reading; 100% rebreathing mask appropriate; prepare for additional ventilation and possible intubation; calculate
endotracheal tube size; have advanced airway kit available
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| Circulation: ideally, establish access concurrently with airway; intravenous (IV) or intraosseous (IO) access
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| Dextrose: hypoglycemia common cause of seizures in young children; easily tested and treated at bedside; rule of
50—multiply volume of fluid (in mL/kg) by concentration of dextrose in fluid; obtain result of 50 to raise blood
glucose by 50 mg/dL
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| Laboratory and other studies: glucose; electrolytes, especially sodium (hyponatremia common cause of status epilepticus
in very young children); complete blood cell count (CBC); no specific studies indicated beyond glucose; consider
additional studies to rule out conditions of concern; computed tomography (CT)—may have limited
usefulness in initial management
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| Stopping seizure: next priority after initial stabilization; building block model—multiple underlying factors can predispose
individual patients to seizures; administer antiepileptic drugs to raise seizure threshold and cause seizures to stop;
adequately monitor patient as interventions continue; ideally, provide IV access; cool febrile patient; consider possibility
of pyridoxine deficiency in neonate or young infant; address with 100 mg of pyridoxine (vitamin B6 )
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| Medications: usually start with benzodiazepine; 2 usual choices lorazepam (eg, Ativan) or diazepam (eg, Valium);
studies suggest better results with lorazepam in treating initial seizure; fewer recurrences within 24 hr; less need for
additional seizure medications, and lower incidence of respiratory depression; wait 5 min before second dose; risk
for respiratory depression increases with additional doses; wait additional 5 min after second dose; if no improvement,
move on to second-line medications
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| Second-line medications: fosphenytoin or phenytoin; less impact on mental status than other medications; less likely
to cause respiratory suppression in pediatric patients; wait 15 min after administration
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| Advantages of fosphenytoin: prodrug of phenytoin; administered more quickly, so less time to take effect; has better
safety profile; unlike phenytoin, may be given intramuscularly (IM)
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| Third-line medication: phenobarbital; significant respiratory depression likely; prepare to intubate; wait 15 to 20 min
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| Refractory status epilepticus: usually treated in intensive care unit (ICU); infusion of benzodiazepine, eg, midazolam;
others use pentobarbital or propofol infusion, depending on preference; infusion may interfere with clinical
findings of convulsive activity; institute continuous electroencephalography (EEG) during drug delivery
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| Valproate: single dose has proven helpful in studies of pediatric patients in refractory status epilepticus unresponsive
to standard benzodiazepines and phenytoin
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| Febrile patients in status epilepticus: consider bacterial meningitis; physical examination limited in revealing
bacterial meningitis; blood tests, eg, white blood cell (WBC) count limited in helpfulness; administer empiric antibiotics;
perform lumbar puncture (LP) when patient clinically stable
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| No available IV access: eg, in private office; options include rectal diazepam at somewhat higher dose, or IM midazolam;
note that IO administration of antiepileptic drugs requires same dose and equally effective; wait 10 min
for response; if no response, IM fosphenytoin available as second-line treatment; IM phenobarbital another option
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| Buccal midazolam: absorbed fairly readily from mucous membranes; mouth provides easily accessible route;
avoids treatment delay; emerging as possible treatment during initial emergency medical service (EMS) response;
multicenter study concluded buccal midazolam at least as effective as rectal diazepam for stopping seizures; no
increased risk for respiratory depression; use IV preparation, (5 mg/mL), dose 0.5 mg/kg; may begin to replace
rectal diazepam as treatment of choice outside hospital or when IV not available
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| Simple febrile seizure: patient between 6 mo and 6 yr of age (according to some sources, 5 mo and 5 yr of age); generalized
seizure associated with fever; no history of head trauma or ingestion; normal neurologic examination; obtain
thorough history and investigate fever sources
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| Meningitis: unlikely in otherwise healthy child with no clinical signs of meningitis; change in epidemiology—since
vaccine introduced, near eradication of Haemophilus influenzae meningitis and steep decline in pneumococcal meningitis
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| Consider LP: always perform when clinically indicated; observe patient closely over time; administering antipyretic
may help improve comfort level and decrease restlessness; decision to perform more difficult the younger the child;
consider overall behavior and health; determine whether child previously treated with antibiotics; detectable infection
source, eg, otitis media, does not preclude meningitis
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| Parental counseling: counsel anxious parents before releasing children from ED; in general, parental concerns focus
on 4 issues
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| Effects on intelligence: large study in United Kingdom followed 16,000 children, of whom 381 had febrile seizures;
measured academic progress, behavior, and intelligence; children who had experienced seizures differed from peers
in only 4 areas, possibly attributable to chance; parents sensed increased impulsiveness and anxiety; children felt
themselves “less gymnastically inclined” than their colleagues, but performed better on standarized reading tests
than other students; study in United States of 1700 children with febrile seizures revealed no deaths, no persisting
motor deficits; no IQ deficits, when compared with sibling pairs; reassure parents about future intelligence
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| Risk for recurrence: varies with age at initial seizure; if first seizure before 1 yr of age, risk 50%; if after 1 yr of age,
risk 30%; most recurrences within 1 yr of initial seizure; after second seizure, risk for recurrence again 50%; risk for
recurrence lower if fever higher at time of initial seizure
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| Handling recurrence: address myth of having to hold down child’s tongue; stress importance of avoiding this to prevent
bite to parent or injury to child
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| Preventing recurrence: effectiveness of phenobarbital offset by known significant adverse effects on behavior and
cognitive ability when used over time; phenytoin does not decrease risk, nor does carbamazepine; valproic acid effective
but carries risk for liver and kidney disorders; rectal diazepam given at time of febrile illness shown to decrease
risk for recurrence, but sedates child to point of making medical evaluation difficult; reserve rectal diazepam
for unusually frequent recurrences; antipyretic medication—while advisable to decrease uncomfortable fever,
does not decrease risk for recurrence
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| Complex febrile seizures: focal, prolonged (>15 min), or recurring within 24 hr; risk for epilepsy increased, but not
necessarily cause and effect relationship; possibly rather due to underlying predisposition for seizures; controversial
whether recurrence rate increased; no studies show increased risk for meningitis; neuroimaging—not routinely indicated;
yields results of limited helpfulness
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| DIAGNOSIS AND MANAGEMENT OF MENINGITIS —Jeff Schunk, MD, Professor of Pediatrics, Chief, Division of
Pediatric Emergency Medicine, University of Utah School of Medicine, and Primary Children’s Medical Center, Salt
Lake City, UT
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| Normal cerebrospinal fluid (CSF): number of WBCs normally found in CSF decreases with age; textbook
figures—ranges from 0/mm3 to 25/mm3 in preterm infants; 0/mm3 to 22/mm3 in term infants, with 8/mm3 considered
normal; 60% polymorphonuclear (PMN) leukocytes considered normal in infants; study data—infants 0 to 7 days of
age, 90th percentile for WBCs normally found in CSF 18/ mm3
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| Pleocytosis: debate about how many polymorphonuclear leukocytes (PMNs) constitutes normal; literature sometimes
states normal CSF has no PMNs; however, recent study of 424 LP results found 106 cases with PMNs in absence of
pleocytosis; most had <20% PMNs; none had meningitis; conclusion—having some PMNs in CSF common, having
large number uncommon
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| Absolute neutrophil count (ANC): important in examining significance of PMNs in CSF; calculate by applying percentage
of PMNs to number of WBCs found in CSF; thus WBC count of 10/mm3 in CSF with 20% PMNs would
result in ANC of 2; patients <6 wk of age may normally have ANC of 2, but in other patients, ANC of ≥2 may be
abnormal
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| Differentiating bacterial from viral meningitis: cases of bacterial meningitis declining in recent years; H influenzae
meningitis dramatically decreased; pneumococcal meningitis also decreased; higher proportion of patients in
ED present with viral meningitis; some may require hospitalization due to degree of illness or confusing clinical
picture
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| Gram stain: do not discount potential usefulness despite sometimes difficult application; studies reveal considerable
effectiveness in differentiating viral from bacterial meningitis; in one study, 90% of patients with bacterial meningitis
had positive Gram stain; no patient free of bacterial meningitis had positive Gram stain
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| Clinical studies on differentiation: found some classic signs of bacterial meningitis among confirmed cases of viral
meningitis
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| Cincinnati study: examined 103 cases of viral meningitis during summer enterovirus outbreak; some of these cases
showed classic symptoms of bacterial meningitis; 15% of cases had WBC >2000/µL in CSF; 20% of cases had
CSF with >60% PMNs; 48% of patients who had repeat LP showed increase rather than decrease in WBC
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| Utah study: examined 114 infants who had enterovirus-positive CSF; not all had pleocytosis; WBC count ranged up
to 1600/µL; over 5-yr period, researchers accumulated data from enteroviral seasons and all cases of bacterial
meningitis and compared them; discarded cases with antibiotic treatment in preceding 5 days; defined PMN predominance
at >50%; 57% of viral meningitis cases had PMN predominance; absence of PMNs does not differentiate
viral from bacterial infection
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| Multicenter study: retrospectively reviewed 3000 cases of pleocytosis; of these, 121 had bacterial meningitis, remainder
had viral; study authors devised bacterial meningitis score
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| Bacterial meningitis score: consists of 1) positive CSF Gram stain, 2) CSF ANC >1000, 3) CSF protein >80 mg/dL,
4) peripheral ANC >10,000/L, and 5) history of seizure before or at presentation; presence of any one of above
factors precluded designation as low risk; score failed to find 2 infants with bacterial meningitis, both <2 mo of
age; young age and pleocytosis alone would guarantee admission and treatment
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| Managing low-risk patients: if worried about patient, admit and treat, regardless of CSF findings; administer antibiotics
based on signs and symptoms; decide to admit based on severity of symptoms, eg, headache, nausea, and
vomiting; many low-risk patients may be managed as outpatients
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| Bloody CSF: occurs at teaching hospitals at rate of between 1 in 5 to 1 in 20 LPs; actual or observed contribution of
WBC from peripheral blood does not match expected or predicted contribution; ratio of observed to predicted WBC
(O/P ratio) much smaller (<1) in patients free of bacterial meningitis; O/P ratio larger (>10) in patients who have
bacterial meningitis; Mazor study—data on patients with culture-positive CSF (bacterial meningitis) accumulated
over 10-yr period; data on patients with culture-negative CSF accumulated over 1 yr; O/P ratio <0.01 in those with
culture-negative CSF; O/P ratio greater in those with bacterial meningitis; concluded that patients with O/P ratio
<0.01 do not have bacterial meningitis and can be discharged if clinical status permits; expected contribution from
peripheral blood—do not calculate; if calculated, ignore; base treatment decisions on WBC actually found in CSF;
conclusions—always base treatment decisions on combination of clinical and laboratory information; bear in mind
that not all bacterial meningitis cases exhibit pleocytosis; always treat suspected bacterial cases
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Suggested Reading
Abend NS, Dlugos DJ: Treatment of refractory status epilepticus: literature review and a proposed protocol. Pediatr
Neurol 38:377, 2008; Appleton R et al: Drug management for acute tonic-clonic convulsions including convulsive
status epilepticus in children. Cochrane Database Syst Rev July 16, 2008: CD001905; Bassan H et al: Neonatal seizures:
dilemmas in workup and management. Pediatr Neurol 38:415, 2008; Bonsu BK, Harper MB: Corrections
for leukocytes and percent of neutrophils do not match observations in blood-contaminated cerebrospinal fluid and have
no value over uncorrected cells for diagnosis. Pediatr Infect Dis J 25:8, 2006; Bonsu BK et al: A decision rule for
predicting bacterial meningitis in children with cerebrospinal fluid pleocytosis when gram stain is negative or unavailable.
Acad Emerg Med 15:437, 2008; Conicella E et al: The child with headache in a pediatric emergency department.
Headache 48:1005, 2008; Dubos F et al: Clinical decision rules to distinguish between bacterial and aseptic
meningitis. Arch Dis Child 91:647, 2006; Golnik A: Pneumococcal meningitis presenting with a simple febrile seizure
and negative blood-culture result. Pediatrics 120:e428-31; Mazumdar M: Febrile seizures and risk of death. Lancet
372:429, 2008; Meehan WP III, Bachur RG: Predictors of cerebrospinal fluid pleocytosis in febrile infants aged 1
to 90 days. Pediatr Emerg Care 24:287, 2008; Mpimbaza A et al: Comparison of buccal midazolam with rectal diazepam
in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial. Pediatrics 121:e58,
2008; Neuman MI et al: Test characteristics and interpretation of cerebrospinal fluid gram stain in children. Pediatr
Infect Dis J 27:309, 2008; Nigrovic LE et al: Children with bacterial meningitis presenting to the emergency department
during the pneumococcal conjugate vaccine era. Acad Emerg Med 15:522, 2008; Nigrovic LE et al: Clinical
prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis.
JAMA 297:52, 2007; Prasad K et al: Anticonvulsant therapy for status epilepticus. Br J Clin Pharmacol 63:640,
2007; Ryan G, Treston G: Do family members interfere in the delivery of care when present during invasive paediatric
procedures in the emergency department? Emerg Med Australas 19:234, 2007; Teng D et al: Risk of intracranial
pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics
117:304, 2006; Vestergaard M et al: Death in children with febrile seizures: a population-based cohort study.
Lancet 372:457, 2008.
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