Complex Case: Headache

David E. Zimmerman, PharmD, BCCCP

Associate Professor of Pharmacy at Duquesne University
Emergency Medicine Pharmacist at UPMC‐Mercy
Pittsburgh, Pennsylvania

Relevant Financial Relationship Disclosure

No one in control of the content of this activity has a relevant
financial relationship (RFR) with an ineligible company.

As defined by the Standards of Integrity and Independence in Accredited Continuing Education definition of ineligible company. All
relevant financial relationships have been mitigated prior to the CPE activity.
 Learning Objectives
• Evaluate medication related problems based on presentations,
history (e.g., pre‐hospital providers), medication use, and
laboratory data.
• Develop therapeutic and monitoring plans based on medication‐
related problems, patient and disease‐specific information, and
laboratory data.
• Modify treatment plan based upon monitoring patient’s response
to initial therapy.
• Develop education, discharge and follow‐up care plans based upon
patient‐ and disease specific factors to improve adherence and
continuity of care.

Key Abbreviations
• Acetaminophen (APAP)
• American Academy of Neurology (AAN)
• American College of Emergency Physicians (ACEP)
• American Headache Society (AHS)
• Computed tomography angiography (CTA)
• Emergency department (ED)
• Great occipital nerve blockade (GOTB)
• Intravenous (IV)
• Intramuscular (IM)
• Lumbar puncture (LP)
• Non‐steroidal anti‐inflammatory drugs (NSAIDs)
• Subarachnoid hemorrhage (SAH)
 Patient Case #1
• BM is a 42‐year‐old female who presents to the emergency
department (ED) with acute onset of severe headache that
started 3 hours prior to arrival to the ED. The patient denies
trauma, and the headache first manifested while the patient
was watching TV. The patient took a dose of sumatriptan but
the headache did not resolve, so she presented to the ED. She
states her pain is a 10/10 at this time.

Patient Case #1 (con’t)

• PMH • Home medications
– Sumatriptan 50 mg orally as needed for
– Migraines (reports 4 episodes over headache
the last 6 months) – Acetaminophen 500 mg orally as needed
for headache
– Hypertension
– Amlodipine 5 mg orally daily

• SH • Vital signs
– Denies tobacco and illicit substances – HR 86 bpm
– Two 5‐oz glasses of wine per week – RR 14 breaths/min
– BP 144/74 mm Hg
– O2 Sat: 100% on room air
• Allergies
– None • Height: 5’2’’, 132 lb
 Headache Epidemiology
• Seventh most common chief complaint in the ED accounting
for ~3% of all ED visits in the United States
• More than 15% of Americans ≥18 years of age report having a
migraine or severe headache in the last 3 months

Raam R et al. Emerg Med Clin North Am. 2021;39:67‐85.

Acute Migraine. Centers for Disease Control and Prevention. https://www.cdc.gov/acute‐pain/migraine/index.html. Accessed Dec 21, 2021.

Types of Headache
• Primary • Secondary: headaches due to
– Migraine underlying disorder
– Tension‐type • Examples
– Cluster – Subarachnoid hemorrhage (SAH)
– Trigeminal autonomic cephalgia – Meningitis
– Encephalitis
– Dural vein thrombosis
– Medication‐induced
– Artery dissection
– Giant cell arteritis

Raam R et al. Emerg Med Clin N Am. 2021;39:67‐85.

 Diagnosis
• Physical Exam
– Differentiating fast vs. slow onset
– Pain severity
– Similar headaches in the past
– Past medical and family history
– Medications
– Other notable signs/symptoms

Levin M. Semin Neurol. 2015;35(6):667‐74.

Diagnosis: Imaging
• American College of Emergency Physicians (ACEP) clinical policy statement
on evaluation and management of adults presenting to the ED with acute
headache recommends utilizing the Ottawa Subarachnoid Hemorrhage
Rule (Level B Recommendation) in age  15 years old with severe, non‐
traumatic headache if one of the following is present:
– Symptoms of neck pain or stiffness
– Age  40 years old
– Witnessed loss of consciousness
– Onset during exertion
– Thunderclap headache
– Limited neck flexion on exam

Godwin SA et al. Ann Emerg Med. 2019;74(4):e41‐74.

 Diagnosis: Imaging (con’t)
• Ottawa Rule not to be used for patients with:
– New neurological deficits
– Previous central nervous system aneurysms
– Subarachnoid hemorrhage (SAH)
– Brain tumors
– History of similar headaches ( 3 episodes over  6 months)

Godwin SA et al. Ann Emerg Med. 2019;74(4):e41‐74.

Diagnosis of SAH: Lumbar Puncture

• Head CT has a high sensitivity within the first 6 hours after onset
• If still concerned, either a lumbar puncture (LP) and computed
tomography angiography (CTA) are viable options
• When evaluating LP results, there is no a universally agreed
upon cutoff for SAH diagnosis but a red blood cell count of 2,000
mm3/L AND xanthochromia has an acceptable sensitivity and
specificity

Godwin SA et al. Ann Emerg Med. 2019;74(4):e41‐74.

Perry JJ et al. BMJ. 2016;350:h568.
Question 1: Which of the following statements about the diagnostic
work up for BM is correct based on the ACEP clinical policy statement
on managing adults with acute headache in the ED and the Ottawa
Subarachnoid Hemorrhage Rule?

A. Head CT imaging is recommended as first line imaging

B. Head CT with angiography is recommended as first line imaging
C. The Ottawa Subarachnoid Hemorrhage Rule should not be used
D. A lumbar puncture should be done prior to Head CT imaging

First‐Line Treatment of Migraine Headaches

 First‐line Therapies
• There are multiple first‐line therapies to select from
– Whether giving multiple agents initially is superior to a single agent is
superior for relieving headache is unclear
• Selection of agents should be patient‐specific, taking into
consideration demographics, drug allergies, current
medications, and therapies that were effective for relieving
headache previously
• Patients should be asked about any recent medication use

First‐line Therapies (con’t)

• Parenteral therapies have been the mainstay of treatment and
use is supported by results of research studies
• Paucity of evidence and guidelines for oral therapies but there
may be selected scenarios when oral therapies are as effective
as parenteral ones. Examples include:
– Lack of IV access
– National shortage of parenteral drugs
– Prohibitively high cost of parenteral drugs
– Difficulty stocking parenteral drugs in the ED

Kazi F et al. Headache. 2021;61(10):1467‐74.

 Antidopaminergics
• Prochlorperazine, metoclopramide
– Prochlorperazine was shown to be more effective for relieving migraine
headache than metoclopramide when both are dosed at 10 mg IV (Coppola et al)
• 2016 American Headache Society (AHS) guideline for parenteral
therapies for migraine headache (Orr et al): both prochlorperazine and
metoclopramide “should be offered” (Level B recommendation)
• Adverse effects
– Akathisia, drowsiness, dizziness, generalized weakness
– Reducing the rate of infusion has been shown to reduce the incidence of
akathisia Coppola M et al. Ann Emerg Med. 1995;26(5):541‐6.
Jones J et al. Am J Emerg Med. 1996;14(3):262‐4.
Vinson Dr et al. J Emerg Med. 2001;20:113‐9.
Friedman BW. Ann Emerg Med. 2017;69(2):202‐7.
Orr SL, et al. Headache. 2016;56(6):911‐40.

Antidopaminergics (con’t)
• Addition of diphenhydramine
– Commonly added for prevention of akathisia from prochlorperazine
– Absolute risk reduction in akathisia of 22% was seen when
diphenhydramine 50 mg IV was given with prochlorperazine
– Benefit was not seen when used with metoclopramide 10 mg but it
was with 20‐mg metoclopramide dose
– Diphenhydramine should be administered to treat akathisia if not
already given as a prophylactic
Vinson DR et al. Ann Emerg Med. 2001; 37:125‐31.
Friedman BW et al. Ann Emerg Med. 2016;67(1):32‐39.
Friedman BW et al Ann Emerg Med. 2009;53(3):379‐85.
 NSAIDs
• Ketorolac 10‐15 mg IV/IM
– According to the 2016 AHS guideline, “may offer” (Level C
recommendation)
• Two studies have shown that 10‐ to 15‐ mg dose is as effective
as higher doses

Friedman BW. Ann Emerg Med. 2017;69(2):202‐7.

Orr SL, et al. Headache. 2016;56(6):911‐40.
Motov S et al. Ann Emerg Med. 2017;70(2):177‐84.
Eidinejad L et al. Acad Emerg Med. 2021;28(7):768‐75.

NSAIDs (con’t)
• Ketorolac IM is an option if no IV access
– In a recent study by Turner et al, 15 mg IM was non‐inferior to 60 mg
IM for relieving acute musculoskeletal pain
• Oral NSAIDs are also an option but oral route of administration
is less studied than parenteral route and theoretically may lead
to a delay in pain relief, discharge, or both
• Always important to ask the patient whether they took an
NSAID (or any other medication) prior to arrival at the ED

Turner NJ et al. Am J Emerg Med. 2021;50:142‐7.

 Triptans
• Used commonly in the outpatient setting as initial therapy
• Several studies demonstrated the efficacy of sumatriptan 6 mg
subcutaneously but it has not been shown to be more
efficacious than antidopaminergics
• Large percentage (~66%) of patients report recurrence of
headache within 24 hours after sumatriptan dose
• According to the 2016 AHS guideline, “should offer” (Level B
recommendation)
Friedman BW. Ann Emerg Med. 2017;69(2):202‐7.
Orr SL, et al. Headache. 2016;56(6):911‐40.

Triptans
• Adverse effects
– Chest tightness, flushing, and worsening of headaches
– In general, higher rate seen compared with other first‐line therapies
• Verify that patient did not use a triptan within 24 hours before
arrival at ED
• Less studied than and similar in efficacy for relieving headache
to NSAIDs, with oral route of administration as an option

Friedman BW. Ann Emerg Med. 2017;69(2):202‐7.

Orr SL, et al. Headache. 2016;56(6):911‐40.
 Summary of First‐Line Agents
Dose & Route of
Class Agent Adverse Effects Special Notes
Administration

Recommend addition
Akathisia,
of diphenhydramine
Prochlorperazine drowsiness,
10 mg IV 50 mg IV for
Antidopaminergic Metoclopramide dizziness,
10 mg IV prophylaxis of
generalized
akathisia from
weakness
prochlorperazine
NSAID Ketorolac 10‐15 mg IV/IM Well tolerated N/A
Chest tightness,
Verify lack of triptan
6 mg flushing,
Triptans Sumatriptan use within 24 hr prior
subcutaneously worsening of
to ED arrival
headache

Question 2: DM has been diagnosed with migraine headache.

Which of the following would be the most appropriate initial
treatment for BM’s headache?

A. Metoclopramide 10 mg IV + diphenhydramine 50mg IV

B. Prochlorperazine 10 mg IV + diphenhydramine 50mg IV
C. Sumatriptan 6 mg subcutaneously
D. Ketorolac 30 mg IV
Second‐Line Treatment of Migraine Headache

Second‐Line Therapies
• There is a paucity of evidence specifically evaluating second‐
line therapies
• Agents discussed have been shown to have similar or less
efficacy than first‐line agents in head‐to‐head studies
• Selection of agent should be based on the therapy used
initially and patient‐specific characteristics. such as age, sex,
drug allergies, current medications, therapies that were
effective for relieving headache previously, and concomitant
disease states

Kazi F et al. Headache. 2021;61(10):1467‐74.

 Acetaminophen (APAP)
• Available in various dosage forms for use by multiple routes of
administration
• Studies have predominantly evaluated IV APAP but based on
similarity in pharmacokinetics, oral administration may be an
option
• Efficacy of IV APAP for relieving headache has been shown to be
superior to placebo and similar to NSAIDs and triptans
• According to the 2016 AHS guidelines, “may offer” (Level C
recommendation)
• Need to assess APAP use prior to arrival at ED to prevent iatrogenic
APAP toxicity
Orr SL, et al. Headache. 2016;56(6):911‐40.

Butyrophenones: Droperidol
• Shown to be effective for alleviating headache at doses of 2.5
mg IM or IV
• Adverse effects
– Extrapyramidal symptoms
– Sedation
– QTc interval prolongation very rare with the low doses used in
treatment of headaches
• According to the 2016 AHS guideline, “may offer” (Level C
recommendation) Orr SL, et al. Headache. 2016;56(6):911‐40.
Thomas MC et al. Ann Pharmacother. 2015;49(2):233‐40.
Mattson A et al. Am J Health‐Syst Pharm. 2020;77:1838‐45.
 Butyrophenones: Haloperidol
• In a small, recent THE‐HA study (McCoy et al) haloperidol 2.5 mg IV
was superior to placebo for relieving severe benign headache pain
• In a small study (Gaffigan et al), there was no significant difference
between haloperidol 5 mg IV and metoclopramide 10 mg IV in
migraine pain reduction but significantly less rescue medication was
needed in the haloperidol group
• 43% of haloperidol‐treated patients and 10% of metoclopramide‐
treated patients reported restlessness on follow up
• According to the 2016 AHS guideline, “may offer” (Level C
recommendation) Orr SL, et al. Headache. 2016;56(6):911‐40.
McCoy J et al. J Emerg Med. 2020;59(1):12‐20.
Gaffigan ME et al. J Emerg Med. 2015;49(3):326‐34.

Chlorpromazine
• Typical dose: 25 mg IV
• Shown to be superior to placebo and similar efficacy in relief of
headache to metoclopramide and ketorolac but with higher
rate of adverse effects
• According to the 2016 AHS guideline, chlorpromazine “may
offer to adults” (Level C recommendation) but patients should
be warned about side effects of orthostatic hypotension,
drowsiness, and akathisia

Orr SL, et al. Headache. 2016;56(6):911‐40.

 Dexamethasone
• Dexamethasone has shown only modest efficacy with acute
migraine pain reduction; however, it has shown a role in
managing recurrent migraines (discussed later)

Orr SL, et al. Headache. 2016;56(6):911‐40.

Opioids
• Approximately 23% of adolescents/young adults who visited an ED in
the U.S. with a migraine received a prescription for an opioid
• Opioids have been shown to be non‐inferior or inferior to alternative
agents for relieving headache
• According to ACEP "preferentially use nonopioid medications in the
treatment of acute primary headaches” (Level A recommendation)
• Takeaway: opioids should be avoided for routine treatment of
headaches in the ED
Acute Migraine. Centers for Disease Control and Prevention. https://www.cdc.gov/acute‐pain/migraine/index.html .Accessed Dec 21, 2021.
Godwin SA et al. Ann Emerg Med. 2019;74(4):e41‐74.
Orr SL, et al. Headache. 2016;56(6):911‐40.
 Valproic Acid
• Generally reserved as third‐line option at doses of 500‐1000
mg IV
• According to the 2016 AHS guideline, “may offer” (Level C
recommendation)
• Imperative to screen women of childbearing potential for
pregnancy because of the teratogenicity of valproic acid

Orr SL, et al. Headache. 2016;56(6):911‐40.

Magnesium
• Potentially useful therapy with a mild adverse effect profile
(e.g., flushing)
• According to the 2016 AHS guideline, “no recommendation”
(Level U)
• In a small 2020 study (Kandil et al), similar efficacy for relieving
migraine pain was reported with IV magnesium,
prochloperazine, and metoclopramide but the study was
stopped early due to COVID‐19
• Takeaway: potential second‐ or third‐line therapy
Orr SL, et al. Headache. 2016;56(6):911‐40.
Kandil M et al. Am J Emerg Med. 2021;39:28‐33.
 Dihydroergotamine and Ergotamine
• Ergotamines are a class of drugs widely used to treat migraine
historically
• Shown to be superior to NSAIDs, sumatriptan, and aspirin for
relieving migraine symptoms
• Typically reserved as a last‐line therapy due to high cost, drug
interactions (including triptans), and adverse effects
• According to the 2016 AHS guideline, “no recommendation”
(Level U)

Orr SL, et al. Headache. 2016;56(6):911‐40.

Propofol
• A variety of IV regimens have been investigated ranging from weight‐based
doses of 1 mg/kg to one‐time non‐weight‐based doses of 30‐60 mg or
smaller doses administered every 5‐10 min
• A recent meta‐analysis of studies of acute migraine treatment (Piatka et al)
summarizes the available evidence of propofol efficacy, but the analysis is
of limited usefulness in determining its place in therapy due to lack of first‐
line treatments as comparators in the studies included in the analysis
• According to the 2016 AHS guideline, “no recommendation” (Level U)
• Additional practical considerations include local regulations and
institutional protocols that may limit use of the drug for treating migraine

Orr SL, et al. Headache. 2016;56(6):911‐40.

Piatka C et al. Acad Emerg Med. 2020;27(2):148‐60.
 Great Occipital Nerve Blockade (GOTB)
• Emerging option with use of local anesthetics, such as
bupivacaine
• Contradictory evidence on efficacy for treating migraine
headache compared with metoclopramide
• Place in therapy unclear partly due to practical limitations
because of complicated mode of administration and need for
specially trained personnel
Friedman BW et al. Headache. 2020;60(10):2380‐8.
Friedman BW et al. Headache. 2018;58(9):1427‐34.
Korucu O et al. Acta Neurol Scand. 2018;138(3):212‐8.

IV Fluids
• IV fluids have been considered a mainstay of treatment for
headaches, especially if concerned about dehydration
• In a small study (Jones et al), no analgesic benefit was provided
by giving normal saline 1 L over 1 hour instead of 10 mL/h to
ED patients with acute migraine all of whom received IV
prochlorperazine and diphenhydramine
• At this time, IV fluids should be given to patients with
headache only if there is a separate indication for use

Jones CW et al. Ann Emerg Med. 2019; 73(2):150‐6.

 IV Ketamine
• Ketamine is an N‐methyl‐D‐aspartate (NMDA) receptor antagonist
and a commonly used analgesic/sedative in the ED
• High doses (> 0.5 mg/kg IV) are used for rapid sequence intubation,
procedural sedation, or acute agitation
– Sub‐dissociative doses of 0.1‐0.3 mg/kg IV are an option for the treatment
of acute pain
• When studied as an IV treatment for headache, ketamine failed to
show superiority to placebo or prochlorperazine
• According to the 2016 AHS guideline, “no recommendation” (Level
U) Etchison AR et al. West J Emerg Med. 2018; 19(6):952‐60.
Zitek T et al. Ann Emerg Med. 2018;71(3):369‐77.
Orr SL, et al. Headache. 2016;56(6):911‐40.

Intranasal Ketamine
• Intranasal ketamine has also been investigated (Benish et al)
and found to provide a similar reduction in headache pain as IV
metoclopramide
• Smaller studies have shown mixed results though
• As with IV ketamine, intranasal ketamine should be considered
a last‐line therapy at this time

Benish T et al. J Emerg Med. 2019;56(3):248‐57.

Bilhimer MH et al. Adv Emerg Nurs J. 2020;42(2):96‐102.
 Nonpharmacologic Interventions
• A variety of nonpharmacologic techniques that can be used to
treat migraine, including placing the patient in a dark, quiet
room
• Transcutaneous electrical nerve stimulation was more effective
than a sham for treating acute migraine in one study (Hokenek
et al), but further studies are needed before this intervention is
implemented widely

Hokenek NM et al. Am J Emerg Med. 2021;39:80‐5.

Question 3: Unfortunately, the initial therapy given to BM was

not successful, and she is still complaining of pain with a severity
of 10/10. Which of the following therapies would be most
appropriate for BM at this time?

A. Valproic acid 500 mg IV

B. Hydromorphone 0.5 mg IV
C. Droperidol 2.5 mg IV
D. Ketamine 1 mg/kg IV
 Treatment of Refractory Headache
• Patients with headache that is refractory to several classes of
agents should be evaluated for other causes of headache (if
not already ruled out)
• Rarely, patients will require hospitalization for further
treatment, and a neurology consult should be considered

Disposition
• Headache recurrence within 24‐48 hours is unfortunately very
common, and recurrence rate can be as high as 75%
• A single parenteral dose of dexamethasone has been shown to
provide a 26% relative reduction in the incidence of recurrent
migraine headache (NNT = 9)
• According to the 2016 AHS guideline, parenteral dexamethasone
“should be offered” (Level B recommendation) to adults who
present to the ED with a migraine
• Other options that have shown some benefit upon discharge from
the ED include naproxen and sumatriptan subcutaneously
Friedman BW et al. Ann Emerg Med. 2010;56(1):7‐17.
Colman I et al. BMJ. 2008;336(7657):1359‐61.
Orr SL, et al. Headache. 2016;56(6):911‐40.
Question 4: Two hours later (and after receiving first‐ and second‐line
therapies), BM’s headache pain severity is reduced to 1/10 and she is
ready for discharge. Which of the following therapies is most
appropriate to prevent headache recurrence based on the AHS
recommendation as a “should offer”?

A. Acetaminophen
B. Dexamethasone
C. Naproxen
D. Sumatriptan

Pediatric Headaches
 Pediatric Headaches
• Diagnosis and management of headache in pediatric and adult
patients differ
• According to the American Academy of Neurology (AAN)/AHS
2019 guideline for the acute treatment of migraine in children
and adolescents, clinicians should:
– Diagnose the specific headache type (primary, secondary, or other
headache symptom) (Level B Recommendation)
– Ask about premonitory and aura symptoms, headache semiology,
symptoms, and pain‐related disability (Level B Recommendation)
Oskoui M et al. Neurology. 2019;93:487‐99.

Treatment
• Based on clinical studies, treatments consists primarily of
acetaminophen, NSAIDs, and triptans
• Prior to selecting an agent, a history of recent medication use,
past agents that were successful (if applicable), and an
accurate weight should be obtained

Oskoui M et al. Neurology. 2019;93:487‐99.

 Treatment (con’t)
• According to the AAN/AHS:
– Initial therapy: ibuprofen oral suspension 10 mg/kg (Level B)
– For adolescents, sumatriptan/naproxen tablets, zolmitriptan nasal
spray, sumatriptan nasal spray, rizatriptan oral disintegrating tablet
(ODT), or almotriptan tablets (Level B recommendation)
– It is important to note that some triptans are approved by FDA for
use in certain age groups: almotriptan (≥ 12 years), rizatriptan (6‐17
years), sumatriptan/naproxen (≥ 12 years), and zolmitriptan (≥ 12
years)

Oskoui M et al. Neurology. 2019;93:487‐99.

Treatment (con’t)
• Additionally, according to the AAN/AHS guidelines
– Antiemetics should also be offered if the patient experiences
prominent nausea or vomiting (Level B recommendation)
– Clinicians should offer an alternative triptan if a triptan fails to
provide pain relief (Level B recommendation)
– If the patient is discharged but headache recurs within 24 hours after
initial treatment, a second dose of acute migraine medication can be
used to treat the recurrent headache (Level B recommendation)

Oskoui M et al. Neurology. 2019;93:487‐99.

 Protocolized Approach
• Protocol implementation has been shown to reduce migraine
pain scores and time to treatment compared with pre‐
implementation period
– Protocol used by Kaar et al in children 5‐20 years old, involved IV
0.9% sodium chloride, ketorolac (0.5 mg/kg, max 30 mg),
diphenhydramine 2 mg/kg, max 50 mg), and either metoclopramide
0.2 mg/kg, max 20 mg) or prochlorperazine 0.1 mg/kg, max 10 mg)
– Protocol used by Skora et al involved IV fluids, NSAIDs, and
prochlorperazine
Kaar CRJ et al. Pediatr Emerg Care. 2016;32(7):435‐9.
Skora CE et al. J Child Neurol. 2020;35(3):235‐41.

Protocolized Approach (con’t)

• Prochlorperazine was part of protocols used by both Kaar et al
and Skora et al but absent from the AAN/AHA guideline
(Oskoui et al)
• Either metoclopramide or prochlorperazine can be considered
because prochlorperazine was shown to be superior to
ketorolac for providing migraine headache relief in in a study of
pediatric patients (Brousseau et al)
Brousseau DC et al. Ann Emerg Med. 2004;43(2):256‐62.
Kaar CRJ et al. Pediatr Emerg Care. 2016;32(7):435‐9.
Skora CE et al. J Child Neurol. 2020;35(3):235‐41.
Oskoui M et al. Neurology. 2019;93:487‐99.
 Patient Case #2
PL is a 11‐year‐old female presenting to the ED complaining of a
headache that started 2 hours ago. PL denies any traumatic
injury and reports the headache seems similar to one that she
had ~12 months ago.

Patient Case #2 (con’t)

• Past medical history: None • Allergies: none

• Social history: None • Vital signs:

– HR 94 bpm
• Home medications: None – RR 16 breaths/min
– BP 122/64 mm Hg
– O2 Sat: 100% on room air

• Height: 5’1’’, 110 lb

Question 5: According to the AAN/AHS guideline, which of the
following therapies would be the best initial treatment for PL’s
headache?

A. Ibuprofen 500 mg orally as an oral suspension

B. Ibuprofen 800 mg orally as an oral suspension
C. Sumatriptan 10 mg/naproxen 60 mg orally as a tablet
D. Zolmitriptan 2.5 mg intranasally in 1 nostril

Hypertensive Urgency
 Hypertensive Urgency
• Hypertensive crisis consists of hypertensive emergency and
hypertensive urgency.
– Please note that hypertensive emergency will be covered in a
separate module
• Hypertensive urgency is defined as BP of  180/120 mm Hg
without evidence of target organ injury
• Although still done in practice, there is no indication for
referral of patients to the ED or immediate reduction in blood
pressure in the ED for acute management

Whelton PK et al. J Am Coll Cardiol. 2018;71(19):e127‐248.

Diagnosis
• Screening according to an ACEP clinical policy statement on
evaluating and managing adults with asymptomatic elevated
blood pressure in the ED (Wolf et al):
– Routine screenings (ECG, serum creatinine, urinalysis) for acute target
organ injury in asymptomatic patients is not required (Level C
recommendation)
– In selected patients, for example those with poor follow up,
screening for an elevated serum creatinine may identify kidney injury
that could affect disposition from the ED (Level C recommendation)

Wolf SJ et al. Ann Emerg Med. 2013;62:59‐68.

 Management
• Patients should be assessed if there is a concern about
nonadherence with outpatient antihypertensive therapy to
determine the reason (e.g., cost, adverse effects)
• According to the ACEP clinical policy statement:
– Routine ED medical intervention is not required in patients with
asymptomatic elevated blood pressures (Level C recommendation)
– In selected patient populations, for example those with poor follow up,
clinicians may treat markedly elevated blood pressure in the ED and/or
initiate therapy for long‐term control (Level C‐consensus recommendation)
– Patients should be referred for outpatient follow up (Level C‐consensus
recommendation)
Wolf SJ et al. Ann Emerg Med. 2013;62:59‐68.

Management (con’t)
• According to 2017 guidelines from the American College of
Cardiology, American Heart Association, and other
organizations, “reinstitution or intensification of oral
antihypertensive drug therapy and arrange follow‐up” is
recommended for patients with hypertensive urgency

Whelton PK et al. J Am Coll Cardiol. 2018;71(19):e127‐248.

 Nonadherence & Educating Patient/Caregiver
• Patients and/or caregivers should be screened for potential
causes of hypertensive urgency to prevent recurrence
• In a prospective study conducted in the Netherlands, plasma
levels of prescribed antihypertensive agents were measured in
patients presenting to the ED with hypertensive urgency
– Eighteen (30.5%) of 59 patients were nonadherent to at least one
medication, and this was considered a contributing factor to the
hypertensive urgency

Overgaauw N et al. J Hypertens. 2019;37(5):1048‐57.

Nonadherence & Educating Patient/Caregiver

• In another prospective study that took place in Germany,
patients presenting to the ED with hypertensive urgency were
classified as adherent or nonadherent
• Compared with adherent patients, patients who were
nonadherent were more often male, received prescriptions for
a larger number of antihypertensive drugs, and were more
often treated with a calcium channel blocker and/or diuretic.
• Interestingly, there was no difference between the two groups
in health literacy

Lauder L et al. J Hypertens. 2021;39(8):1697‐1704.

Non‐Adherence & Educating Patient/Caregiver
• Not all patients discharged from the ED will have established
primary care
• A small pilot study at Yale New Haven Hospital found that
utilization of a coordinated referral from the ED to an
outpatient clinic led to decreases in mean blood pressure at
visit 1 (after an average of 7.8 days) and at 6 weeks, along with
a reduction in ED visits

Giaimo AA et al. Am J Hypertens. 2021;34(3):291‐5.

Question 6: Returning to Patient Case #1. BM's blood pressure was checked right
before her planned discharge, and it had increased to 180/120 mm Hg. Her
headache had completely resolved, and she was not in any distress. She admitted
to not taking her amlodipine for the past couple of days because her supply had run
out and she had not had time to pick up her refill from the outpatient pharmacy. In
addition to counseling BM on the importance of compliance with medications,
which of the following statements about managing BM’s hypertensive urgency is
correct?

A. ED medical intervention is not required

B. Parenteral antihypertensive therapy should be initiated
C. An ECG should be performed prior to discharge
D. A new prescription for amlodipine should be sent to her outpatient pharmacy
 Key Takeaways
• Key Takeaway #1
– A physical exam should be completed, and patients should be assessed to
determine whether their presentation is a primary or secondary type of
headache
• Key Takeaway #2
– The patient's age, sex, drug allergies, current medications, therapies that
were effective for relieving headache previously, and disease states should
be taken into consideration in choosing a treatment approach for
headache
• Key Takeaway #3
– Patients in the ED with hypertensive urgency should be counseled about
the importance of medication adherence to prevent recurrence

Complex Case: Headache

David E. Zimmerman, PharmD, BCCCP

Associate Professor of Pharmacy at Duquesne University
Emergency Medicine Pharmacist at UPMC‐Mercy
Pittsburgh, Pennsylvania