VERSION: 1.1
CREATED: January 30, 2026
REVISED: January 30, 2026
STATUS: Draft - Pending Review
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)
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.
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 β₯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
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
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.
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
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
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
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
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 β€9 days/month
CAD, prior stroke/TIA, uncontrolled HTN (>140/90), hemiplegic or basilar migraine, pregnancy, concurrent ergot/DHE within 24h
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)
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)
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Pain controlled to tolerable level (NRS β€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 β€3/10 for β₯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
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
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