Dr. Lori Billinghurst, MD MSc FRCPC Division of Neurology ... · 3 large studies have evaluated the causes of pediatric headache in the ED Burton et al (1997): retrospective, 288

Dr. Lori Billinghurst, MD MSc FRCPC Division of Neurology December 7 2011

1. Outline a rational approach to the child with headache in the emergency department

2. Review options for acute ED management of migraine and recent evidence supporting their use

3. Offer an expert opinion on therapy for migraine in the ED

Headaches are frequent presenting complaint to ED Vast majority of headaches are benign and self-limited

and can be diagnosed and treated effectively based upon careful clinical history and exam

However, headache may also be the presenting symptom of more serious and ominous illnesses, such as meningitis, intracranial hemorrhage, brain tumor, or hydrocephalus

Therefore, important to have an organized and rational approach to the evaluation and treatment of pediatric headache

HISTORY:

Onset and temporal pattern of the headache Headache duration, frequency, location Quality and severity of pain, any change Exacerbating and alleviating factors Medications, response to treatments Associated symptoms Nausea, emesis, photophobia, phonophobia,

allodynia Presence of an aura Visual, sensory, or motor symptoms

HISTORY:

Family history of headache Toxin exposure Recent or remote trauma Lifestyle and psychosocial factors: sleep, diet,

hydration, activity, obesity, stressors, psychiatric co-morbidities

Other chronic health conditions (asthma, allergy, inflammatory conditions)

PHYSICAL EXAMINATION

General examination Blood pressure, temperature, weight, head circumference Skin examination for stigmata of neurocutaneous disorder, rash Palpation of head and neck, TMJ Heart murmur, carotid bruit

Neurological examination Fundoscopic examination Motor examination and coordination Tendon reflexes, plantar response Examination of gait, tandem gait

The majority of children who present to the ED with headache and a normal neurologic exam need no further ancillary testing

Indications for further diagnostic studies must be directed by the Hx and PE:

Suspected infection: CBC, Blood Cx, LP Fever or altered LOC with VP shunt: CT, shunt series, tap shunt Altered mental status: CT prior to LP (increased ICP) Suspected mass lesion: CT/MRI Suspected SAH: non-contrast head CT identifies most but not all

bleeds (if CT is blood neg LP, coagulation studies, and platelets) Hypertension: electrolytes, ECG, and urinalysis Toxic exposure: labs as indicated (eg, carboxyhemoglobin level, lead

levels, tox screening)

Limit to: Trauma

Presence of intracranial shunt

Red flags on history: new onset, chronic progressive pattern, “worst headache of life”, thunderclap, early AM or nocturnal HA, AM emesis

Abnormal neurologic exam ▪ Altered LOC

▪ Papilledema, abnormal eye movements

▪ Nuchal rigidity

▪ Ataxia, hemiparesis

3 large studies have evaluated the causes of pediatric headache in the ED

Burton et al (1997): retrospective, 288 pts, 2-18 years1

Kan et al (2000): retrospective, 130 pts2

Lewis et al (2000): prospective case series, 150 pts3

Of the patients with serious neurologic diagnoses, all but one had abnormal examinations or histories suggestive of the diagnosis

1Pediatr Emerg Care 1997, 13:1–4 2Headache 2000, 4:25–29 3Headache 2000, 40:200–203

Cause Proportion of Disease Contribution to Causes of Acute Headache (%)

Viral Illness 39-57

Migraine 16-18

Sinusitis 9-16

Post-traumatic 6.6

Viral meningitis 5.2-9

Streptococcal pharyngitis 4.9-9

Tension Headache 4.5

Brain Tumour 2.6

VP Shunt malfunction 2

Post-ictal headache 1.3

Intracranial Hemorrhage 1.3

Post-concussive 1.3

Other 7.7

Once secondary causes are excluded, the diagnosis of a primary headache can be made and therapy is targeted to headache subtype (migraine, tension-type)

Primary headache in children:

Migraine

Tension-Type

Trigeminal autonomic cephalagia (paroxysmal hemicrania, cluster headache)

International Headache Society (IHS)

Developed criteria in 1988, revision in 2004 as the International Classification of Headache Disorders (ICHD-II)

Gold standard for diagnosis of headaches in children

Incorporate many developmentally appropriate changes which provide broader applicability to children and adolescents

Sensitivity ranges from 53-84% in various studies

ICDH-II Migraine Classification Migraine without aura (common)

Migraine with aura (classic)

Familial hemiplegic migraine

Basilar migraine

Childhood periodic syndromes ▪ Cyclical vomiting

▪ Abdominal migraine

▪ Benign paroxysmal vertigo, torticollis

▪ “Alice in Wonderland”

▪ Confusional migraine

At least five attacks fulfilling criteria A through C, not attributed to another disorder: A. Headache attacks lasting 1 to 72 hours B. Headache has at least two of the following characteristics:

▪ Unilateral location, which may be bilateral or frontotemporal (not occipital)

▪ Pulsing quality ▪ Moderate or severe pain intensity ▪ Aggravation by or causing avoidance of routine physical activity (eg,

walking, climbing stairs)

C. During the headache, at least one of the following: ▪ Nausea or vomiting ▪ Photophobia and phonophobia, which may be inferred from a child’s

behaviour

At least two attacks fulfilling criteria A through C, not attributed to another disorder: A. Aura consisting of at least one of the following, but no motor

weakness ▪ Fully reversible visual symptoms including positive features (eg. flickering

lights, spots or lines) and/or negative features (eg. loss of vision) ▪ Fully reversible sensory symptoms including positive features (eg. pins and

needles) and/or negative features (eg. numbness) ▪ Fully reversible dysphasic speech disturbance

B. At least two of the following: ▪ Homonymous visual symptoms and/or unilateral sensory symptoms ▪ At least one aura symptom develops gradually over ≥ 5 min and/or different

aura symptoms occur in succession over ≥ 5 min ▪ Each symptom lasts ≥ 5 min and ≤ 60 min

C. Headache begins during the aura or follows aura within 60 min

Headache pain transmitted by CN V from blood vessels of the pia and dura mater: “neurogenic inflammation”

Stimulation of trigeminovascular axons Release of neurogenic peptides stored in afferent C fibers innervating

cephalic blood vessels Stimulation of endothelial cells, mast cells, and platelets leading to inflammatory cascade

Vasodilatation with enhanced

permeability of plasma proteins

follows with a perivascular

inflammatory reaction

Serotonin (5-HT) receptors are known to modulate neurogenic peptide release and vasoconstrict dilated dural vessels Most important receptors in the final common pathway of headache

The goal of therapy is to prevent or abort the neurogenic inflammation that occurs as a result of neuropeptide release

“Triptans” are specific agonists at the 5-HT1 receptor,

whereas other medications, such as DHE, and dopamine antagonists (prochlorperazine, metoclopramide) act at a variety of 5-HT and other aminergic receptors

Objective: To study evidence-based practice variation in management of pediatric

migraine in ED setting First national and largest migraine study in pediatric ED, retrospective

chart review

Inclusion Criteria: 10 Canadian tertiary pediatric ED centers (PERC sites) July 1, 2004-June 30 2005 Children 5-17 years of age Discharge diagnosis of migraine/subtypes or headache (ICD-9/10)

Exclusion Criteria: Left before MD assessment An ED visit <7 days after initial presentation Possibility that another disorder (eg, intracranial shunt, mass,

hemorrhage, or infection) might explain the headache

Richer et al J Pediatrics 126(1) e150-155, 2010

Study-defined evidenced-based abortive therapies: Acetaminophen, ibuprofen and other NSAIDS

Serotonin 1b/1d receptor agonists (triptans)

Dihydroergotamine (DHE)

Dopamine receptor antagonists (metoclopramide, prochlorperazine, chlorpromazine)

Did not investigate: Oxygen

Diphenhydramine, dimenhydrinate

Opioids (codeine, meperidine, morphine, and oxycodone)

Steroids (prednisone, dexamethasone, and methylprednisolone)

Benzodiazepines, muscle relaxants, and ondansetron


Sample and demographics:

2515 charts screened 1694 included (67.4%) ▪ Mean age 12.1 years (95% CI: 11.4-12.9)

▪ Female 57.4% (95% CI: 51.8-62.9%)

Presentation 2.19 days after HA onset (95% CI: 1.62–2.75 days)

Aura present in 27.2% (95% CI: 19.9%–35.9%) Migraine > 15 days per month in 14.5% (95% CI:12.1%–

17.2%) Average length of stay was 4.4 hrs (95% CI: 3.7–5.1 hrs)


Medication use before presentation: 62.6% had already used ≥ 1 migraine-abortive medication (95% CI:

55.7%– 68.9%): ▪ Orally administered analgesics 52.6% (95% CI: 46.3%–58.9%), including

acetaminophen and ibuprofen

▪ Only 2.2% (95% CI: 1.5%–3.1%) used a triptan

▪ Overall, 4.7% (95% CI: 3.3%– 6.7%) used an opioid (eg, codeine, meperidine, morphine, or oxycodone)

6.1% used prophylactic medication (95% CI: 3.3%–11.3%) ▪ The most-common prophylactic treatments were tricyclic antidepressants (eg,

nortriptyline and amitryptiline): 38.9% (95% CI: 11.7%–75.3%) of cases.

In patients with migraine ≥ 15 days/mo ▪ 82.1% not receiving prophylactic treatment (95% CI: 58.5%–93.7%)


Investigations:

Head CT 16.3% (95% CI: 12.2%–21.3%) most common investigation 8.2% (95% CI: 5.1%–12.9%) demonstrated AbN findings

None of the abnormal findings altered management

Abnormalities included arachnoid cyst, previous infarction, and cerebral malformation

LP performed in 2.1% (95% CI: 1%–4.1%); none AbN The 10 EDs varied significantly in use of CT (P.001) and LP

(P=0.002)


Use of Evidence-Based Treatments


Practice Variation

Overall, significant variability between sites (P=.002) for all medication classes

No one type of medication used in >50% of cases

IV route used for 48.4% (95% CI: 34.6%– 62.4%) IV dopamine receptor antagonists (DRA) most frequently prescribed

▪ Metoclopramide 82.4% (95% CI: 60.4%–93.5%)

▪ Prochlorperazine 12.7% (95% CI: 2.8%– 42.0%)

▪ Chlorpromazine 4.9% (95% CI: 1.0%–20.0%)

Benadryl prescribed in 14% (95% CI: 3%–46%) of subjects who received a DRA


Practice Variation:

Oral analgesics (NSAIDs) often prescribed with a dopamine receptor antagonist 36.5% (95% CI: 21.3%–55.1%)

Opioid medications most frequently prescribed: Codeine 39.1% (95% CI: 20.4%– 61.6%)

Acetaminophen/ codeine combination 30.5% (95% CI: 15.5%–51.2%)

Morphine 27.6% (95% CI: 12.8%–49.7%)

Triptan medications used infrequently (0.5% cases): sumatriptan (n=6), eletriptan (n=1) and zolmitriptan (n=1)


Adverse Effects:

No serious adverse events were reported

Minor adverse events included vomiting (7 cases), dizziness (3 cases), nausea (2 cases), and 1 case each of dystonia, tachycardia, agitation, hypotension, and paresthesias

Dystonia, agitation, hypotension, and paresthesias were observed in association with a dopamine receptor antagonist


Post-ED Care:

Most-frequently prescribed, migraine-abortive medications at discharge: Ibuprofen 45.7% (95% CI: 34.2%–57.7%)

Acetaminophen 17.2% (95% CI: 12.1%–23.8%)

Other NSAIDs 10.8% (95% CI: 3.9%–26.6%)

Triptans prescribed in only 1% (95% CI: 0.5%–2.2%)

Prophylactic medications prescribed in 10.2% (95% CI: 2.7%–32%) Amitryptiline, topiramate, propranolol, cyproheptadine, flunarizine,

pizotifen, carbamazepine, and gabapentin (in order of frequency)


Post-ED Care:

Of those with migraine ≥15 days/mo: 47.7% (95% CI: 35.3%– 60.3%) referred to a neurologist or pediatrician

30% (95% CI: 13.3%– 44.6%) given prescriptions for prophylactic medications

Opioids prescribed in 5.4% (95% CI: 3.2%–9.1%)

Steroids prescribed in 2.4% (95% CI: 0.5%–11.6%)

Admission rate 2.2% (95% CI: 1.3%–3.6%)


Conclusions:

1. Practice variability in management of pediatric migraine in the ED due to lack of evidence for therapies

2. Children who present to ED with migraine represent a failure of outpatient therapy and display treatment resistance

1. Confidence in the diagnosis of migraine results in more evidence-based care: diagnostic tools for migraine for ED physicians may improve care


Conclusions:

4. ED physicians frequently employ combination therapy

4. Presentation to the ED provides unique opportunity for intervention: specific migraine management strategies after discharge may reduce disability and improve outcomes (?)

5. Prospective evaluation of discharge plans, in terms of reduced ED visits, improved quality of life, or reduced headache disability (?)


Legault et al recently studied the effect of ED migraine treatment on short term headache recurrence or “bounce-back” rate

Retrospective, single-center study (Montreal Children’s Hospital)

Recruitment from MCH ED database

All pts, age 8-17 years, Jan 1-Dec 31 2008, who received IV treatment for migraine and discharged directly home

Legault et al J Child Neuro 26(8) 949-955, 2011

Exclusions:

Surgical cases, hospitalization, pregnancy

Fever, intercurrent infection, CNS infection

Prophylaxis or IV treatment for migraine in ED 6 months prior to study visit

Methods:

Pts who returned to ED for headache within 1 mo of their initial visit (ie. bounce back) for status migrainosus compared pts who did not


Results:

300 cases 116 excluded 184 included

Median age 14.0 years (mean, 14.0 years; SD, 2.4 years; range, 8.3-17.9 years)

Median headache duration 72 hours (mean, 400 hours; SD, 2641 hours; range, 1 hour-4 yrs)

120 females (64.2% ) and 67 males (35.8% )

IV abortive therapy per MCH protocol: metoclopramide (187 pts) and chlorpromazine (5 pts)


Results:

64/187 (34.2%) received prophylaxis at DC

▪ 60 (32.1%) Vitamin B2

▪ 17 (9.1%) Prednisone

▪ 15 (8%) Vitamin B2 + prednisone

▪ 4 (2.1%) Other (amitryptiline, gabapentin, pizotifen)

21/187 (11.2%) returned for ED evaluation within 1 mo of initial presentation


Results:

21/187 (11.2%) returned for ED evaluation within 1 mo of initial presentation

Patient characteristics of both groups were not statistically different with exceptions: ▪ Recurrence more likely to result in CT scan at second visit, and

patients with “migraine equivalents” more likely to “bounce back”

Both the IV abortive therapy and treatment given upon DC were not statistically associated with the recurrence rate


Conclusions:

Majority of children evaluated and treated in ED for status migrainosus have a good prognosis for further immediate need of ED treatment

Acute abortive and discharge treatment given to children presenting to ED with status migrainosus does not seem to alter immediate recurrence rate


Goals of Acute Migraine Management:

1. Identify other causes of headache if clinically suspected (e.g. fever, trauma)

2. Rehydrate the patient as clinically indicated

3. Treat with effective medication to eliminate or significantly reduce head pain

4. Identify outpatient management goals (e.g. need for prophylaxis or improved abortive strategy for the next migraine attack)

Principles to guide ED practice and choice of abortive therapy:

1. Medications target excessive glutamatergic and dopaminergic

transmission, “neurogenic inflammation”

2. Insufficient evidence to support a definitive algorithmic approach

3. Lack of comparative efficacy trials precludes scientific standards that specify the use of one agent over the other

4. Migraine in children is well established (status migrainosus) and is relatively treatment-resistant

5. Combination approach of medications often used

6. Avoid the use of opioids

1. NS fluid bolus 20 cc/kg IV 2. Dopamine receptor antagonists

▪ Metoclopramide 0.1 mg/kg IV (max 10 mg)

▪ Prochlorperazine 0.1 mg/kg IV (max 10 mg)

▪ Metoclopramide: less sedating, less likely to produce akathisia, acute dystonic rxn; can pre-treat with Benadryl

3. IV Ketorolac ▪ 0.5-1 mg/kg IV (max dose 30 mg)

4. Vasoconstrictors: Dihydroergotamine (DHE) ▪ 1 mg IV slowly over 10 min

▪ Need pretreatment with metaclopramide (nausea)

5. Corticosteroids Dexamethasone 0.6 mg/kg IV (max 20 g) Methylprednisolone 2 mg/kg IV (max 125 mg)

6. 5 HT agonists/ triptan class Sumatriptan ( 5–20 mg intranasally at onset); can repeat every 2

hours (max 40 mg/d) Sumatriptan (6 mg SC injection at onset), repeat once at 1 hour Zolmitriptan (5-mg nasal spray)

7. Magnesium (glutamate antagonist) 250 mg-1 g in NS IV over 30 minutes (10-20 mg/kg); follow BP

8. Others: Ondansetron 0.15 mg/kg IV or 4-8 mg oral dis tab Gravol, oxygen, occipital nerve block

1. Normal saline 10 to 20 mL/kg IV bolus over 30 to 45 minutes (max 1 L)

1. Diphenhydramine (Benadryl) 1 mg/kg IV (max 50 mg)1

1. Ketorolac 1 mg/kg IV (max 30 mg)2

1. Prochlorperazine (Stemetil) 0.1 mg/kg (max 10 mg)3 IV (may repeat x 3)

OR Metoclopramide (Maxeran) 0.1 mg/kg (max 10 mg) IV (May repeat x 1)

3Ann Emerg Med, 2004. 43 (2): p. 256-62 1J Emerg Med, 2004. 26 (3): p. 265-70 2 Headache, 2005. 45 (7): p. 850-61

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Dr. Lori Billinghurst, MD MSc FRCPC Division of Neurology ... · 3 large studies have evaluated the causes of pediatric headache in the ED Burton et al (1997): retrospective, 288