Status Migrainosus

VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Approved

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DIAGNOSIS: Status Migrainosus

ICD-10: G43.901 (Migraine, unspecified, not intractable, with status migrainosus), G43.911 (Migraine, unspecified, intractable, with status migrainosus), G43.919 (Migraine, unspecified, intractable, without status migrainosus)

CPT CODES: 85025 (CBC with differential), 80053 (CMP), 83735 (Magnesium), 84703 (Pregnancy test (hCG, women of childbearing age)), 84443 (TSH), 85652 (ESR), 82306 (Vitamin D), 82728 (Ferritin), 80076 (LFTs (AST, ALT, Alk Phos)), 82140 (Ammonia), 82803 (Blood gas (VBG)), 80307 (Urine drug screen), 87040 (Blood cultures), 86235 (Autoimmune panel (ANA), 83605 (Lactate), 83090 (Homocysteine), 70450 (CT head without contrast), 93000 (ECG), 70551 (MRI brain without contrast), 70553 (MRI brain with and without contrast), 70544 (MRA head), 62270 (LUMBAR PUNCTURE), 89051 (Cell count (tubes 1 and 4)), 84157 (Protein), 82945 (Glucose with serum glucose)

SYNONYMS: Status migrainosus, intractable migraine, refractory migraine, prolonged migraine, migraine lasting more than 72 hours, severe intractable migraine, persistent migraine, unrelenting migraine, migraine emergency, debilitating migraine, migraine requiring hospitalization, migraine headache emergency, protracted migraine, treatment-resistant migraine attack, migraine not responding to treatment

SCOPE: Evaluation and management of status migrainosus (debilitating migraine lasting >72 hours), including acute abortive therapy, rescue protocols, and prevention of recurrence. Excludes routine migraine management, chronic migraine prophylaxis initiation, cluster headache, and secondary headache disorders.

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DEFINITIONS: - Status Migrainosus: Debilitating migraine attack lasting continuously for more than 72 hours, with or without brief periods of relief (ICHD-3 criteria) - Refractory Status Migrainosus: Status migrainosus not responding to standard first-line parenteral treatments in the ED or hospital - Medication Overuse Headache (MOH): Headache occurring ≥15 days/month in a patient using acute medications regularly for >3 months; a common contributor to status migrainosus - Headache Cocktail: Combination of IV antiemetic (dopamine antagonist) + IV NSAID + IV diphenhydramine, the standard first-line parenteral regimen for acute migraine/status migrainosus in the ED

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PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

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═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
CBC with differential (CPT 85025)	Rule out infection, anemia contributing to headache	Normal	STAT	ROUTINE	ROUTINE	STAT
CMP (CPT 80053)	Electrolyte abnormalities from dehydration/vomiting; renal function for medication dosing	Normal	STAT	ROUTINE	ROUTINE	STAT
Magnesium (CPT 83735)	Hypomagnesemia lowers migraine threshold and is common in status migrainosus	>1.8 mg/dL	STAT	ROUTINE	ROUTINE	STAT
Pregnancy test (hCG, women of childbearing age) (CPT 84703)	Pregnancy status affects treatment selection (contraindication to triptans, DHE, valproate)	Document status	STAT	STAT	ROUTINE	STAT
TSH (CPT 84443)	Thyroid dysfunction as contributing factor to refractory headache	Normal	-	ROUTINE	ROUTINE	-

1B. Extended Workup (Second-line)

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
ESR (CPT 85652) / CRP (CPT 86140)	Rule out giant cell arteritis (age >50, new-onset) or inflammatory etiology	Normal	URGENT	ROUTINE	ROUTINE	URGENT
Vitamin D (CPT 82306)	Deficiency associated with increased migraine frequency and chronification	>30 ng/mL	-	ROUTINE	ROUTINE	-
Ferritin (CPT 82728)	Iron deficiency associated with migraine; may contribute to refractoriness	>50 ng/mL	-	ROUTINE	ROUTINE	-
LFTs (AST, ALT, Alk Phos) (CPT 80076)	Baseline before valproate or repeated NSAID use	Normal	URGENT	ROUTINE	ROUTINE	URGENT
Ammonia (CPT 82140)	Baseline before valproate; elevated levels worsen encephalopathy	<35 micromol/L	URGENT	ROUTINE	-	URGENT
Blood gas (VBG) (CPT 82803)	Assess for metabolic derangement in prolonged vomiting/dehydration	Normal pH, bicarbonate	URGENT	ROUTINE	-	STAT

1C. Rare/Specialized (Refractory or Atypical)

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Urine drug screen (CPT 80307)	Occult substance use contributing to headache; medication overuse	Negative for unexpected substances	URGENT	ROUTINE	EXT	URGENT
Blood cultures (CPT 87040)	If fever present or meningitis suspected	No growth	URGENT	URGENT	-	STAT
Autoimmune panel (ANA (CPT 86235), ESR, CRP)	Suspected vasculitis or autoimmune etiology in atypical presentation	Negative	-	EXT	EXT	EXT
Lactate (CPT 83605)	If sepsis or meningitis suspected	<2 mmol/L	URGENT	URGENT	-	STAT
Homocysteine (CPT 83090)	Elevated levels associated with migraine with aura; refractory cases	Normal	-	-	EXT	-

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
CT head without contrast (CPT 70450)	Immediate if thunderclap onset, new focal deficit, altered mental status, worst headache of life	Rule out hemorrhage, mass, hydrocephalus	None in emergency	STAT	URGENT	-	STAT
ECG (CPT 93000)	Before DHE, triptan, or antiemetic administration	Normal QTc (<470 ms women, <450 ms men), no ischemia	None	STAT	STAT	ROUTINE	STAT

2B. Extended

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRI brain without contrast (CPT 70551)	When stable; new headache pattern, refractory to treatment, atypical features	Normal; rule out structural lesion, pituitary apoplexy, Chiari malformation	Pacemaker, metal implants	-	ROUTINE	ROUTINE	-
MRI brain with and without contrast (CPT 70553)	If mass, infection, inflammation, or venous thrombosis suspected	Rule out enhancement, meningeal disease	Contrast allergy, severe renal disease	-	ROUTINE	ROUTINE	-
MRV or CT venogram (CPT 70547 or 70498)	If cerebral venous thrombosis suspected (postpartum, OCP use, papilledema)	Patent venous sinuses	Per modality	URGENT	URGENT	ROUTINE	URGENT
MRA head (CPT 70544)	If vasculopathy or aneurysm suspected	Normal vasculature	Per modality	-	ROUTINE	ROUTINE	-
Fundoscopic exam	All patients; assess for papilledema suggesting elevated ICP	Normal optic discs	None	STAT	STAT	ROUTINE	STAT

2C. Rare/Specialized

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
CTA head and neck (CPT 70496, 70498)	If cervical artery dissection suspected (neck pain, Horner syndrome)	No dissection	Contrast allergy, renal disease	URGENT	URGENT	-	URGENT
Temporal artery ultrasound	Age >50, elevated ESR, suspected GCA	No halo sign	None	-	ROUTINE	ROUTINE	-

LUMBAR PUNCTURE (CPT 62270)

Indication: Thunderclap headache, suspected SAH (CT negative), suspected IIH (papilledema), suspected meningitis, fever with headache, immunocompromised patient Timing: URGENT after CT excludes mass effect Volume Required: 10-15 mL standard diagnostic

Study	Rationale	Target Finding	ED	HOSP	OPD	ICU
Opening pressure	Rule out elevated ICP (IIH) or low-pressure headache	10-20 cm H2O	STAT	STAT	-	STAT
Cell count (tubes 1 and 4) (CPT 89051)	Infection, SAH	WBC <5; RBC 0 or clearing	STAT	STAT	-	STAT
Protein (CPT 84157)	Infection, inflammation	15-45 mg/dL	STAT	STAT	-	STAT
Glucose with serum glucose (CPT 82945)	Infection (low in bacterial/fungal)	>60% serum glucose	STAT	STAT	-	STAT
Xanthochromia	SAH if CT negative and >12 hours from onset	Negative	STAT	STAT	-	STAT
Gram stain and culture (CPT 87205, 87070)	Bacterial meningitis	No organisms	STAT	STAT	-	STAT

Special Handling: Xanthochromia requires light-protected transport. Cell count within 1 hour. Contraindications: Signs of herniation, coagulopathy (INR >1.5, platelets <50K), skin infection at LP site. CT before LP if any concern for mass effect.

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3. TREATMENT

CRITICAL: Status migrainosus requires stepwise escalation. Start with the "headache cocktail" and escalate as needed. Each medication must be on its own row with complete dosing.

3A. Acute/First-Line - IV Rehydration and "Headache Cocktail"

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Normal saline IV	IV	Rehydration; prolonged vomiting and poor oral intake common in status migrainosus	1000 mL bolus; 75-125 mL/hr :: IV :: once :: NS 1L bolus over 1-2h, then 75-125 mL/hr maintenance	Heart failure, volume overload	I/O, signs of fluid overload	STAT	STAT	-	STAT
Lactated Ringer's IV	IV	Alternative IV fluid for rehydration with electrolyte replacement	1000 mL bolus; 75-125 mL/hr :: IV :: once :: LR 1L bolus over 1-2h, then 75-125 mL/hr maintenance	Heart failure, hyperkalemia	I/O, electrolytes	STAT	STAT	-	STAT
Prochlorperazine IV	IV	First-line antiemetic and primary analgesic for acute migraine via dopamine antagonism	10 mg IV once :: IV :: once :: 10 mg IV slow push over 5-10 min; may repeat x1 in 30 min; max 20 mg	QT prolongation (QTc >500 ms), Parkinson disease, pheochromocytoma	QTc, akathisia, dystonic reaction, sedation	STAT	STAT	-	STAT
Metoclopramide IV	IV	First-line antiemetic and primary analgesic for acute migraine via dopamine antagonism; alternative to prochlorperazine	10 mg IV once; 20 mg IV once :: IV :: once :: 10-20 mg IV over 15-30 min; may repeat x1 in 30 min; max 40 mg	QT prolongation, Parkinson disease, seizure disorder, bowel obstruction	QTc, akathisia, dystonic reaction, sedation	STAT	STAT	-	STAT
Diphenhydramine IV	IV	Prevention of akathisia and dystonic reactions from dopamine antagonist antiemetics	25 mg IV once; 50 mg IV once :: IV :: once :: 25-50 mg IV push with each antiemetic dose	Narrow-angle glaucoma, urinary retention, severe drowsiness risk	Sedation level	STAT	STAT	-	STAT
Ketorolac IV	IV	Potent parenteral NSAID for acute pain relief; synergistic with antiemetics	30 mg IV once; 15 mg IV once :: IV :: once :: 30 mg IV push (15 mg if age >65, CrCl <50, or weight <50 kg); max 2 doses in 24h; max 5 days total	Active GI bleeding, renal insufficiency (CrCl <30), coagulopathy, concurrent anticoagulation, third trimester pregnancy	Renal function, GI symptoms, bleeding	STAT	STAT	-	STAT
Dexamethasone IV	IV	Prevention of headache recurrence within 72 hours; does not treat acute pain	10 mg IV once :: IV :: once :: 10 mg IV once; single dose (NNT 9 for recurrence prevention)	Active untreated infection, uncontrolled diabetes mellitus	Blood glucose (check at 4-6h), mood changes	URGENT	URGENT	-	URGENT
Magnesium sulfate IV	IV	Direct analgesic effect in migraine; low magnesium lowers cortical spreading depression threshold	2 g IV once :: IV :: once :: 2 g IV in 50 mL NS over 20-30 min	Renal failure (GFR <30), myasthenia gravis, heart block	Magnesium level, deep tendon reflexes, respiratory status, flushing	URGENT	URGENT	-	URGENT

3B. Second-Line Acute Treatments

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Sumatriptan SC	SC	Triptan-naive or triptan-responsive patients without vascular contraindications; most effective when given early	6 mg SC once :: SC :: once :: 6 mg SC once; may repeat x1 in 2h; max 12 mg/24h	CAD, prior stroke/TIA, uncontrolled hypertension (>140/90), hemiplegic or basilar migraine, pregnancy, use of ergotamine/DHE within 24h, concurrent MAOI	Chest tightness, blood pressure, coronary symptoms	STAT	STAT	-	STAT
Sumatriptan nasal	IN	Alternative triptan route when SC not tolerated or for moderate attacks	20 mg IN once :: IN :: once :: 20 mg intranasal; may repeat in 2h; max 40 mg/24h	CAD, prior stroke/TIA, uncontrolled hypertension (>140/90), hemiplegic or basilar migraine, pregnancy, use of ergotamine/DHE within 24h, concurrent MAOI	Chest tightness, blood pressure, coronary symptoms	URGENT	URGENT	ROUTINE	URGENT
Valproate sodium IV	IV	Acute migraine treatment for patients who cannot receive triptans/DHE or as adjunct; also anti-nausea properties	500 mg IV once; 1000 mg IV once :: IV :: once :: 500-1000 mg IV over 15-30 min; may repeat once in 8h	Pregnancy (teratogenic - neural tube defects), hepatic disease, mitochondrial disease (POLG mutation), urea cycle disorders, pancreatitis	Ammonia, LFTs, platelet count	URGENT	URGENT	-	URGENT
Chlorpromazine IV	IV	Alternative dopamine antagonist with potent analgesic and sedative effect for refractory migraine	12.5 mg IV once; 25 mg IV once :: IV :: once :: 12.5-25 mg IV over 20 min with 500 mL NS bolus; may repeat x2 q30min; max 75 mg	QT prolongation, severe hypotension, Parkinson disease	BP q15min (orthostatic hypotension common), QTc, sedation	URGENT	URGENT	-	URGENT
Droperidol IV	IV	Alternative dopamine antagonist with strong antiemetic and analgesic effect; FDA black box for QT prolongation requires ECG	2.5 mg IV once :: IV :: once :: 2.5 mg IV over 2-5 min; may repeat x1 in 30 min; max 5 mg	QT prolongation (QTc >440 ms), hypokalemia, hypomagnesemia, Parkinson disease	ECG before and after (FDA black box), QTc, BP, akathisia	URGENT	URGENT	-	URGENT
Ondansetron IV	IV	Antiemetic for nausea/vomiting when dopamine antagonists contraindicated (Parkinson disease)	4 mg IV once :: IV :: once :: 4 mg IV over 2-5 min; may repeat q6-8h; max 16 mg/24h (FDA max single IV dose 16 mg due to QT risk)	QT prolongation (dose-dependent), concurrent serotonergic drugs (caution)	QTc at higher doses	URGENT	ROUTINE	ROUTINE	URGENT
Greater occipital nerve block	Local	Acute pain relief and potential sustained benefit (3-4 weeks); safe in pregnancy	2-3 mL per side :: Local :: once :: Bupivacaine 0.5% 2-3 mL per side (bilateral) at greater occipital nerve; may add triamcinolone 20 mg per side	Local anesthetic allergy, infection at injection site, concurrent anticoagulation (relative)	Local reaction, vasovagal response	URGENT	ROUTINE	ROUTINE	URGENT
Supraorbital nerve block	Local	Additional peripheral nerve block targeting frontal headache distribution	1-2 mL per side :: Local :: once :: Bupivacaine 0.5% 1-2 mL per side at supraorbital notch	Local anesthetic allergy, infection at site	Local reaction	-	ROUTINE	ROUTINE	-

3C. Refractory/Third-Line - DHE Protocol and Rescue Therapies

DHE Prerequisites: Confirm normal ECG, BP <140/90, negative pregnancy test. Do NOT administer if triptan given within 24 hours or history of CAD/CVA/PAD. Premedicate with antiemetic.

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Dihydroergotamine (DHE) IV - test dose	IV	First dose to assess tolerability before initiating repetitive DHE protocol	0.5 mg IV once :: IV :: once :: Premedicate: metoclopramide 10 mg IV + diphenhydramine 25 mg IV 30 min prior; then DHE 0.5 mg IV over 3-5 min as test dose	Pregnancy, CAD, CVA, PVD, uncontrolled HTN (>180/110), triptan within 24h, ergot allergy, basilar/hemiplegic migraine, severe hepatic or renal disease, concurrent CYP3A4 inhibitors	BP q15min during infusion, chest pain, limb ischemia, nausea	URGENT	STAT	-	URGENT
Dihydroergotamine (DHE) IV - repetitive protocol	IV	Repetitive IV DHE for sustained break of status migrainosus (Raskin protocol)	0.5 mg IV q8h; 1 mg IV q8h :: IV :: q8h :: If test dose tolerated: 0.5-1 mg IV q8h for up to 3-5 days; premedicate each dose with antiemetic; may titrate to 1 mg if 0.5 mg tolerated	Pregnancy, CAD, CVA, PVD, uncontrolled HTN (>180/110), triptan within 24h, ergot allergy, basilar/hemiplegic migraine, severe hepatic or renal disease, concurrent CYP3A4 inhibitors	BP q15min during infusion, chest pain, limb ischemia, nausea; daily ECG during protocol	-	STAT	-	URGENT
DHE nasal spray	IN	Alternative to IV DHE for patients who decline IV protocol or as bridge to outpatient	0.5 mg per nostril once :: IN :: once :: 0.5 mg per nostril (1 mg total); may repeat once in 15 min; max 3 mg/24h; max 4 mg/week	Pregnancy, CAD, CVA, PVD, uncontrolled HTN (>180/110), triptan within 24h, ergot allergy, basilar/hemiplegic migraine, severe hepatic or renal disease, concurrent CYP3A4 inhibitors	Nausea, nasal congestion, BP, chest pain	-	ROUTINE	ROUTINE	-
Ketamine IV sub-anesthetic	IV	Refractory status migrainosus not responding to standard therapies; NMDA receptor antagonism disrupts central sensitization	0.1 mg/kg bolus; 0.1-0.5 mg/kg/hr :: IV :: continuous :: 0.1 mg/kg IV bolus, then 0.1-0.5 mg/kg/hr infusion; titrate by 0.1 mg/kg/hr q30min; max 1 mg/kg/hr; typical duration 24-48h	Uncontrolled hypertension, active psychosis, elevated ICP (relative), age <18	BP, HR (may increase), dissociative symptoms, nystagmus, sedation level, psychiatric effects	-	EXT	-	URGENT
Propofol sub-anesthetic bolus	IV	Brief burst-like suppression of migraine pain via GABA modulation; requires monitored setting	20-30 mg IV once :: IV :: once :: 20-30 mg IV bolus; may repeat q5min up to 100 mg total; must have respiratory monitoring	Egg/soy allergy, hemodynamic instability, respiratory compromise without airway support	O2 sat, BP, respiratory status; requires procedural sedation monitoring	-	EXT	-	URGENT
Lidocaine IV infusion	IV	Sodium channel blockade for refractory status migrainosus; typically inpatient protocol	1-2 mg/kg bolus; 1-2 mg/min :: IV :: continuous :: Load 1-2 mg/kg IV over 20 min, then 1-2 mg/min (60-120 mg/hr) infusion x 24-48h	Heart block, severe CHF, hepatic failure	Continuous cardiac monitoring, lidocaine level q12h (target <5 mcg/mL), neuro checks for toxicity (perioral numbness, tinnitus, seizures)	-	EXT	-	EXT

3D. Adjunctive Treatments and Recurrence Prevention

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Dexamethasone PO taper	PO	Prevention of headache recurrence after ED/hospital discharge; bridge to preventive therapy	4 mg BID x 4 days :: PO :: BID :: 4 mg PO BID x 4 days; may taper over 1 week	Active infection, uncontrolled DM, GI ulcer	Blood glucose, GI symptoms, mood	-	ROUTINE	ROUTINE	-
Naproxen sodium PO	PO	Transitional therapy for recurrence prevention after discharge; scheduled dosing more effective than PRN	500 mg BID :: PO :: BID :: 500 mg PO BID with food x 5-7 days as bridge	GI bleeding, renal disease, third trimester pregnancy	Renal function, GI symptoms	-	ROUTINE	ROUTINE	-
Acetaminophen IV	IV	Mild-moderate pain adjunct when NSAIDs contraindicated; pregnancy-safe option	1000 mg IV q6h :: IV :: q6h :: 1000 mg IV q6h; max 3000 mg/day (2000 mg/day if hepatic risk)	Severe hepatic disease (Child-Pugh C), chronic alcohol use (>3 drinks/day)	LFTs if repeated use >3 days	URGENT	ROUTINE	-	URGENT
Methylprednisolone IV	IV	Alternative to dexamethasone for acute anti-inflammatory effect in severe cases	125 mg IV once :: IV :: once :: 125 mg IV once	Active infection, uncontrolled DM	Blood glucose, mood	URGENT	URGENT	-	URGENT
Promethazine IV/IM	IV, IM	Antiemetic and sedative adjunct for nausea-predominant status migrainosus when other antiemetics inadequate	12.5 mg IV once; 25 mg IM once :: IV, IM :: once :: 12.5-25 mg IV slow push (over 10-15 min to reduce phlebitis) or 25 mg deep IM; may repeat q4-6h; max 75 mg/day	QT prolongation, respiratory depression (especially with opioids), tissue necrosis risk with IV extravasation	Sedation, respiratory status, IV site (severe vesicant)	URGENT	ROUTINE	-	URGENT
Sumatriptan PO (post-discharge rescue)	PO	Outpatient rescue for breakthrough migraine after discharge from status migrainosus treatment	100 mg PO once :: PO :: PRN :: 100 mg PO at onset; may repeat in 2h; max 200 mg/24h; limit to ≤9 days/month	CAD, prior stroke/TIA, uncontrolled HTN (>140/90), hemiplegic or basilar migraine, pregnancy, concurrent ergot/DHE within 24h	Chest tightness, blood pressure, coronary symptoms	-	ROUTINE	ROUTINE	-
Rizatriptan PO (post-discharge rescue)	PO	Outpatient rescue for breakthrough migraine; rapid-onset oral triptan option	10 mg PO once :: PO :: PRN :: 10 mg PO at onset (ODT available); may repeat in 2h; max 30 mg/24h; limit to ≤9 days/month; use 5 mg if on propranolol	CAD, prior stroke/TIA, uncontrolled HTN (>140/90), hemiplegic or basilar migraine, pregnancy, concurrent ergot/DHE within 24h, concurrent MAOI	Chest tightness, blood pressure, coronary symptoms	-	ROUTINE	ROUTINE	-
Eletriptan PO (post-discharge rescue)	PO	Outpatient rescue for breakthrough migraine; high efficacy oral triptan option	40 mg PO once :: PO :: PRN :: 40 mg PO at onset; may repeat in 2h; max 80 mg/24h; limit to ≤9 days/month	CAD, prior stroke/TIA, uncontrolled HTN (>140/90), hemiplegic or basilar migraine, pregnancy, concurrent ergot/DHE within 24h, severe hepatic impairment	Chest tightness, blood pressure, coronary symptoms	-	ROUTINE	ROUTINE	-

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4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	ED	HOSP	OPD	ICU
Neurology consult for diagnosis confirmation, treatment escalation guidance, and preventive strategy	URGENT	ROUTINE	-	URGENT
Headache specialist referral for chronic migraine management and refractory status migrainosus	-	ROUTINE	ROUTINE	-
Pain management consult for refractory cases not responding to standard protocols, nerve block consideration	-	ROUTINE	ROUTINE	URGENT
Ophthalmology consult if papilledema found on fundoscopic exam to rule out IIH	URGENT	URGENT	ROUTINE	URGENT
Psychiatry or behavioral health referral for comorbid anxiety, depression, or significant psychosocial stressors contributing to refractoriness	-	ROUTINE	ROUTINE	-
Social work consult for discharge planning, outpatient resource coordination, and insurance authorization for specialty medications	-	ROUTINE	ROUTINE	-
Physical therapy referral for cervicogenic component evaluation, trigger point therapy, and postural correction	-	-	ROUTINE	-
Infusion center referral for outpatient DHE or ketamine infusion protocol if refractory	-	ROUTINE	ROUTINE	-

4B. Patient/Family Instructions

Recommendation	ED	HOSP	OPD	ICU
Return immediately if thunderclap headache onset, fever, neck stiffness, new neurologic deficits, or altered mental status develop (may indicate secondary cause requiring emergency evaluation)	ROUTINE	ROUTINE	ROUTINE	-
Return to ED if headache recurs at severe intensity within 72 hours of discharge despite rescue medications (may require repeat parenteral therapy)	ROUTINE	ROUTINE	ROUTINE	-
Treat recurrent migraine within the first hour of onset for maximal medication efficacy (early treatment is more effective than delayed treatment)	ROUTINE	ROUTINE	ROUTINE	-
Avoid medication overuse: limit triptans to no more than 9 days per month and NSAIDs to no more than 14 days per month to prevent medication overuse headache	ROUTINE	ROUTINE	ROUTINE	-
Keep a detailed headache diary documenting frequency, severity (0-10), triggers, medications used, and response to treatment for follow-up appointments	-	ROUTINE	ROUTINE	-
Follow up with neurology or headache specialist within 2-4 weeks of discharge for preventive therapy initiation and treatment plan adjustment	ROUTINE	ROUTINE	ROUTINE	-
Do not drive until headache has fully resolved and no sedating medications are on board due to impaired reaction time and concentration	ROUTINE	ROUTINE	ROUTINE	-
Take all prescribed discharge medications as directed and do not abruptly discontinue steroids if prescribed a taper (may cause rebound headache or adrenal insufficiency)	ROUTINE	ROUTINE	ROUTINE	-

4C. Lifestyle & Prevention

Recommendation	ED	HOSP	OPD	ICU
Maintain a regular sleep schedule of 7-8 hours per night as both sleep deprivation and oversleeping are established migraine triggers	-	ROUTINE	ROUTINE	-
Regular aerobic exercise (30 minutes, 5 days per week) reduces migraine frequency through endorphin release and stress reduction	-	ROUTINE	ROUTINE	-
Stress management with biofeedback, progressive muscle relaxation, or cognitive behavioral therapy (Level A evidence for migraine prevention)	-	ROUTINE	ROUTINE	-
Stay well-hydrated with at least 64 ounces of water daily as dehydration is a common and modifiable migraine trigger	ROUTINE	ROUTINE	ROUTINE	-
Avoid known dietary triggers including alcohol (especially red wine), aged cheeses, MSG, processed meats, and skipped meals	-	ROUTINE	ROUTINE	-
Limit caffeine to consistent moderate intake (less than 200 mg per day) and avoid abrupt caffeine withdrawal which is a potent headache trigger	-	ROUTINE	ROUTINE	-
Discuss preventive medication initiation at follow-up if experiencing 4 or more migraine days per month, significant disability, or recurrent status migrainosus episodes	-	ROUTINE	ROUTINE	-
Identify and manage comorbid conditions that worsen migraine including depression, anxiety, insomnia, and obesity	-	ROUTINE	ROUTINE	-

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═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Subarachnoid hemorrhage	Thunderclap onset ("worst headache of life"), neck stiffness, rapid deterioration, no prior migraine history	CT head (sensitivity >95% within 6h); LP if CT negative (xanthochromia)
Cerebral venous thrombosis	Progressive headache, seizures, focal deficits, risk factors (OCP, pregnancy, prothrombotic state), papilledema	MRV or CT venogram; D-dimer (low sensitivity)
Idiopathic intracranial hypertension	Papilledema, visual obscurations, pulsatile tinnitus, bilateral pressure headache worse with Valsalva; often obese women	Fundoscopic exam, LP with elevated opening pressure (>25 cm H2O), MRI with empty sella/optic nerve sheath distension
Cervical artery dissection	Acute neck pain, Horner syndrome (miosis, ptosis), preceding trauma or neck manipulation, focal neurologic deficits	CTA head/neck or MRA with fat-suppressed sequences
Giant cell arteritis	Age >50, new-onset headache, jaw claudication, scalp tenderness, visual symptoms, constitutional symptoms	ESR/CRP markedly elevated; temporal artery biopsy; temporal artery ultrasound (halo sign)
Medication overuse headache	Chronic daily headache (≥15 days/month), frequent acute medication use (>10-15 days/month for >3 months), headache worsens with continued overuse	Detailed medication diary; headache improves within 2 months of medication withdrawal
Meningitis/encephalitis	Fever, neck stiffness, photophobia, altered mental status, rash (meningococcal); may present subacutely	LP (cell count, protein, glucose, culture, PCR); blood cultures
Brain tumor	Progressive headache worse in morning or with Valsalva, new focal deficits, papilledema, weight loss, seizures	MRI brain with contrast
Hypertensive emergency	BP >180/120 with headache, visual changes, encephalopathy, end-organ damage	BP measurement, fundoscopic exam, renal function, troponin
Pituitary apoplexy	Sudden severe headache, visual field deficits (bitemporal hemianopia), ophthalmoplegia, known or unknown pituitary adenoma	MRI brain with pituitary protocol; hormone levels (cortisol, TSH, prolactin)
Spontaneous intracranial hypotension	Orthostatic headache (better lying down, worse upright), may have neck stiffness, subdural fluid collections	MRI brain with contrast (diffuse pachymeningeal enhancement, brain sagging); LP with low opening pressure
Reversible cerebral vasoconstriction syndrome	Recurrent thunderclap headaches, may mimic SAH, associated with vasoactive substances or postpartum	CTA/MRA (segmental vasoconstriction); may require repeat imaging as vasoconstriction evolves

6. MONITORING PARAMETERS

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Pain scale (0-10 NRS)	q1h during treatment, q4h if stable	Trending toward 0-3/10	Escalate to next treatment tier	STAT	ROUTINE	Each visit	STAT
Vital signs (BP, HR, RR, O2 sat, Temp)	q15min during IV infusions, q4h when stable	BP <140/90, HR 60-100, Temp <38°C	Address abnormality; hypertension may drive headache	STAT	ROUTINE	Each visit	STAT
ECG/QTc	Before dopamine antagonist or DHE; repeat if QT-prolonging agents used	QTc <470 ms (women), <450 ms (men)	Avoid QT-prolonging medications; correct electrolytes	STAT	STAT	-	STAT
Nausea/vomiting severity	With each pain assessment	Resolution of nausea/vomiting	Add or change antiemetic	STAT	ROUTINE	Each visit	STAT
Oral intake tolerance	q4-8h	Tolerating PO fluids and medications	Continue IV hydration; delay discharge	URGENT	ROUTINE	-	ROUTINE
Blood glucose (if on steroids)	q6h while on dexamethasone/methylprednisolone	<200 mg/dL	Sliding scale insulin; adjust steroid dose	URGENT	ROUTINE	Each visit	STAT
Magnesium level (if supplemented)	After IV magnesium; daily if repletion ongoing	1.8-2.5 mg/dL	Replete if low; hold if >3.0 mg/dL	URGENT	ROUTINE	ROUTINE	ROUTINE
Neurologic exam	At each encounter; after treatment changes	No new focal deficits, improving cognition	Urgent imaging if new deficits; reassess diagnosis	STAT	ROUTINE	Each visit	STAT
Akathisia/EPS assessment	30 min after each antiemetic dose	No restlessness or dystonia	Diphenhydramine 25-50 mg IV; switch antiemetic class	STAT	ROUTINE	-	STAT
Headache diary (MIDAS or HIT-6)	Outpatient visits	Improving disability score	Adjust preventive therapy; consider specialist referral	-	-	Each visit	-

7. DISPOSITION CRITERIA

Disposition	Criteria
Discharge from ED	Pain controlled to tolerable level (NRS ≤4/10); tolerating oral fluids and medications; no red flag features; able to ambulate; rescue medication and follow-up plan provided; headache diary instructions given
Admit to hospital (observation or floor)	Status migrainosus unresponsive to ED headache cocktail (2 or more treatment rounds); inability to tolerate oral intake despite antiemetics; need for repetitive IV DHE protocol; severe dehydration requiring ongoing IV fluids; concern for secondary headache requiring further workup
Admit to ICU	Refractory status migrainosus requiring ketamine infusion or sub-anesthetic propofol; hemodynamic instability from treatments (severe hypotension from chlorpromazine); altered mental status not explained by medications; suspected secondary cause requiring ICU-level monitoring
Transfer to higher level of care	Need for services unavailable at current facility (headache specialist, DHE protocol capability, interventional procedures)
Discharge from hospital	Pain controlled on oral medications (NRS ≤3/10 for ≥12 hours); tolerating oral fluids and solid food; ambulatory without significant dizziness; discharge medications reviewed with patient; follow-up with neurology arranged within 2-4 weeks
Outpatient follow-up intervals	Post-discharge: 2-4 weeks for treatment assessment; Chronic migraine: q1-3 months; Stable on preventive: q3-6 months

8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
IV prochlorperazine and metoclopramide are effective acute treatments for migraine in the ED	Class I, Level A	Friedman et al. Ann Emerg Med 2008; Kelley & Tepper. Headache 2012
IV metoclopramide 10-20 mg superior to placebo for acute migraine	Class I, Level A	Friedman et al. Neurology 2014
Single-dose IV dexamethasone reduces headache recurrence within 72 hours (NNT 9)	Class I, Level A	Singh et al. Acad Emerg Med 2008; Colman et al. BMJ 2008
Ketorolac IV effective for acute migraine; comparable to opioids without sedation	Class I, Level B	Friedman et al. Headache 2008
IV magnesium sulfate effective for acute migraine, especially with aura	Class I, Level B	Bigal et al. Headache 2002; Chiu et al. Pain Physician 2016
Subcutaneous sumatriptan 6 mg effective for acute migraine	Class I, Level A	Ferrari et al. Lancet 2001
Repetitive IV DHE effective for breaking status migrainosus	Class II, Level B	Raskin. Neurology 1986; Nagy et al. Headache 1993
Greater occipital nerve block effective for acute migraine and status migrainosus	Class II, Level B	Afridi et al. Headache 2006; Inan et al. J Headache Pain 2015
Valproate IV effective for acute migraine in ED	Class I, Level B	Tanen et al. Ann Emerg Med 2003
Chlorpromazine IV effective for acute migraine in ED	Class I, Level B	Kelly et al. Ann Emerg Med 2017
Sub-anesthetic ketamine infusion for refractory migraine	Class III, Level C	Pomeroy et al. Headache 2017; Schwenk et al. Reg Anesth Pain Med 2018
IV lidocaine for refractory migraine and status migrainosus	Class III, Level C	Williams & Bhatt. Anesthesiology 2007; Rosen et al. Headache 2009
Diphenhydramine co-administration prevents akathisia from dopamine antagonists	Class II, Level B	Vinson. Ann Emerg Med 2004
ICHD-3 diagnostic criteria for status migrainosus	Consensus	ICHD-3. Cephalalgia 2018
AHS consensus statement on migraine treatment in the ED	Consensus/Guidelines	American Headache Society. Headache 2016
Lifestyle modifications (sleep, exercise, stress management) reduce migraine frequency	Class I, Level B	AAN/AHS Practice Guidelines, Silberstein et al. Neurology 2012

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NOTES

• Status migrainosus is defined by ICHD-3 as a debilitating migraine attack lasting >72 hours; severity warrants parenteral treatment
• The "headache cocktail" (IV dopamine antagonist + IV NSAID + IV diphenhydramine) is first-line and should be administered promptly upon arrival
• Dexamethasone (single 10 mg IV dose) reduces recurrence but does not treat acute pain; give alongside the headache cocktail
• IV magnesium is safe and effective, particularly in patients with migraine with aura or low magnesium levels
• Always check ECG before administering DHE, triptans, or QT-prolonging antiemetics
• DHE and triptans must NOT be given within 24 hours of each other due to risk of vasospasm
• Opioids should be AVOIDED in status migrainosus: they increase ED return visits, worsen long-term outcomes, and contribute to medication overuse headache
• Screen for medication overuse headache as a common contributing factor to status migrainosus
• Pregnancy: Acetaminophen, metoclopramide, ondansetron (caution 1st trimester), magnesium, and nerve blocks are safest; avoid triptans, DHE, valproate, and NSAIDs (3rd trimester)
• All patients discharged after status migrainosus should have neurology follow-up within 2-4 weeks and consideration of preventive therapy

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CHANGE LOG

v1.1 (January 30, 2026) - Removed all cross-references across treatment tables; each row now fully self-contained - Expanded "Same as sumatriptan SC" in sumatriptan nasal row (Section 3B) to full contraindications and monitoring per C1 - Expanded "Same as test dose" in DHE repetitive protocol row (Section 3C) to full contraindications and monitoring per C2 - Expanded "Same as IV DHE" in DHE nasal spray row (Section 3C) to full contraindications and added BP/chest pain monitoring per C3 - Added ICU venue column to Section 4B (Patient/Family Instructions) for structural consistency across all tables per S1 - Added ICU venue column to Section 4C (Lifestyle & Prevention) for structural consistency across all tables per S2 - Corrected ondansetron IV max dose from 32 mg/24h to 16 mg/24h per FDA safety guidance on QT prolongation risk per V1 - Expanded grouped "Triptans PO (post-discharge rescue)" row into individual entries for sumatriptan, rizatriptan, and eletriptan with complete standalone dosing per R4 - Updated version to 1.1

v1.0 (January 30, 2026) - Initial template creation - Comprehensive first-line "headache cocktail" protocol with IV rehydration - Second-line treatments including triptans, valproate IV, nerve blocks, and alternative antiemetics - Refractory/third-line treatments including DHE protocol (Raskin), sub-anesthetic ketamine, propofol, and IV lidocaine - Adjunctive treatments and recurrence prevention (steroids, transitional therapy) - Full differential diagnosis for prolonged headache (12 diagnoses) - Evidence-based references with PubMed links - Setting coverage across ED, HOSP, OPD, ICU - Structured dosing format for all medications