Neurology

Extra dry or up with a twist? A take on the ‘migraine cocktail’

You’re seeing a patient in the community emergency department with a primary headache disorder. Based on your history & physical examination skills, you have considered and ruled out all dangerous secondary headache causes such as intracranial hemorrhage, sentinel bleed, meningoencephalitis, abscess, tumor, temporal arteritis, hypertensive encephalopathy, acute angle closure glaucoma, etc. With many classes of treatments available, providers have typically used some form of a ‘migraine cocktail’ including IV prochlorperazine, IV ketorolac, IV diphenhydramine, IV dexamethasone, and/or IV normal saline.[1]

There are several considerations with the above typical ‘headache cocktail’ that I would like to discuss. Ideally, the treatment regimen implemented in the ED will be efficacious in providing modest headache relief, while also being safe (few side effects) and fast. Depending on other considerations for the department at that time, the nurse may be limited with time and unable to obtain IV access and initiate the typical multimodal intravenous components of the ‘migraine cocktail’. Furthermore, most headache patients will not need labs drawn. While not advocating for a one-size fits all approach, my goal is to discuss the evidence on the utility of commonly used therapeutics as well as providing you with additional time-efficient modalities to add to your armamentarium in effectively treating patients with primary headache disorder.

Antidopaminergics:

Any of the typical medications, whatever available readily, will work, including: metoclopramide 10 mg IM, prochlorperazine 10 mg IM, or promethazine 25 mg IM. The onset of action of all three medications via the IM route is between 10-20 minutes.[2-4]

Diphenhydramine:

Routine co-administration with metoclopramide has not been shown to improve migraine outcomes or prevent metoclopramide-induced akathasia.[5,6] Additionally, the sedative side effects will potentially keep the patient in the ED for a lengthier time frame.

IV Fluids:

In a post hoc analysis of 4 ED-based migraine clinical trials utilizing IV metoclopramide as well as IV fluids at the discretion of the treating physician, the patients receiving IV fluids had a lower improvement in pain scale after one hour and their use was not associated with sustained headache freedom.[7] Universal addition of this modality to patients with primary headache disorder similarly will likely add to a lengthier ED visit as the fluids trickle in.

NSAIDs:

Typical treatment is with ketorolac 60 mg IM, and has been proven to be effective for migraine treatment in comparison to many antidopaminergics.[8] It may also be fruitful to maximize the patient’s appropriate use of acetaminophen and ibuprofen/naproxen upon discharge.

Steroids:

Dexamethasone 10-25 mg IM can be administered to help prevent headache recurrence.[9]

Sumatriptan:

Frequently forgotten are triptains and anecdotally do not seem to be the go-to for many ED providers, but 6 mg subcutaneous has shown benefit in treating patient with primary headache disorder.[10]

For patients with primary headache disorder, it is vitally important to do several things:

  • Rule out dangerous secondary causes, as above, first and foremost

  • Set expectations with the patient, that their headache may not be completely resolved, but we hope to be aggressive up front

  • Delineate return precautions to the ED and close Neurology followup or referral

Faculty Reviewer: Dr. Kristina McAteer

References:

  1. Long B, Koyfman A. Headache management in the ED. emDocs Cases. http://www.emdocs.net/emdocs-cases-headache-management-ed/. Accessed June 2019.

  2. Promethazine: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/promethazine-drug-information?search=promethazine&source=panel_search_result&selectedTitle=1~79&usage_type=panel&kp_tab=drug_general&display_rank=1#F214058. Accessed June 2019.

  3. Metoclopramide: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/metoclopramide-drug-information?search=metoclopramide&source=panel_search_result&selectedTitle=1~149&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed June 2019.

  4. Prochlorperazine: drug information. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/prochlorperazine-drug-information?search=prochlorperazine&source=panel_search_result&selectedTitle=1~72&usage_type=panel&kp_tab=drug_general&display_rank=1. Accessed June 2019.

  5. Friedman BW, Cabral L, Adewunmi V, et al. Diphenhydramine as adjuvant therapy for acute migraine: an emergency department-based randomized clinical trial. Ann Emerg Med. 2016 Jan:67(1):32-39.

  6. Erdur B, Tura P, Aydin B, et al. A trial of midazolam vs diphenhydramine in prophylaxis of metoclopramide-induced akathisia. Am J Emerg Med. 2012 Jan;30(1):84-91.

  7. Balbin JE, Nerenberg R, Baratloo A, et al. Intravenous fluids for migraine: a post hoc analysis of clinical trial data. Am J Emerg Med. 2016 Apr;34(4):713-6.

  8. Taggart E, Doran S, Kokotillo A, et al. Ketorolac in the treatment of acute migraine: a systematic review. Headache 2013;53:277.'

  9. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008 Dec;15(12):1223-33.

  10. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD009665.

The Obtunded Patient

The Case

52 y/o male with HTN, hyperlipidemia, chronic back pain, and recent depression came back from a walk and per family was ataxic, dysarthric and confused, so his family drove him to the ED. On the way, he began vomiting repeatedly and became increasing obtunded.  As he entered the ED went into apparent cardiovascular and respiratory collapse. Given 2mg of Naloxone without response and intubated by RSI for further evaluation.

Examination

Vitals on arrival in the ED:  Temp: 36, RR:-no spontaneous breaths noted after entering the ED O2: 88% on bag valve mask, HR: 68 BP: 88/64. Glucose 104.  GCS 3 (non verbal, no motor movement, pupils 2mm and fixed). No corneal or occulacephalic reflexes noted, no cough or gag elicited. All extremities were flaccid and areflexic. EKG show sinus rhythm, no obvious conduction abnormalities.

Medication hx: Simvastatin 40 mg daily, amlodipine 10 mg daily, Baclofen 20 mg TID, Vicodin 5-300 1 tablet q6 hrs

Labs: ETOH: 150. CBC, lactic acid, chemistry, venous blood gas (on ventilator), CPK, LFT’s, troponin asa, acetaminophen, UA, UDS all WNL

Imaging: CTA pan scan negative except for mild aspiration in the R lung base.

 

So what happened…..?

Baclofen Toxicity

What is it?

Baclofen is a synthetic derivative of the naturally occurring inhibitory neurotransmitter GABA.

Acts principally on the GABA-B receptor at the spinal level and reduce the post-synaptic potentials along motor neurons, thus relaxing the skeletal muscles.

Baclofen is primarily used for the treatment of spastic movement disorders and now more ubiquitously for the treatment of chronic back pain.

 

How is it given?

Oral: Until the past 10 years, the primary method of administration of Baclofen was oral.

  • Peak concentration in 2 hours and half life of 3.5hours
  • Dosage 40-80mg daily dosed q8 hrs
  • Centrally acting but crosses the blood brain barrier ineffectively, limiting its bioavailability
  • Very low toxic range with severe toxicity from oral baclofen, necessitating ICU level care occurring fairly consistently with baclofen overdoses of over 200mg (a 3 day supply for most people)
Figure 2: Baclofen pump concept

Figure 2: Baclofen pump concept

Intrathecal: Intrathecal baclofen is administered through the implantation of a pump subcutaneously with a catheter from the pump inserted directly into the CSF fluid.

  • Dosage: 90 mcg to 800 mcg daily
  • Intrathecal baclofen allows for 4x the amount of baclofen to be delivered to the spinal cord with just 1% of the oral dose.

Intrathecal Baclofen Pumps: The pump is surgically implanted under the skin in the abdomen and the catheter is tunneled under the skin and inserted into the intrathecal space usually between the 1st and 2nd lumbar vertebrae.

Currently SynchroMed is the only pump currently being used in the US for intrathecal baclofen, hydromorphone and morphine

  • The catheter holds 3-4ml
  • The reservoir holds 20-40ml
  • Pump battery lasts for 5-7 years
Figure 3: Synchromed Baclofen pump

Figure 3: Synchromed Baclofen pump

Toxicities 

Baclofen has the potential for both overdose and withdrawal, which can both present with a wide array of symptoms.

Overdose Symptoms

Most commonly include CNS depression, lethargy, somnolence, hallucinations, agitation, mydriasis/miosis, nausea and vomiting

Severe toxicity is associated with bradycardia, hypotension (more common) or hypertension, respiratory failure, hypothermia, seizures, coma and death.

Rarely, rhabdomyolysis and conduction disturbances may occur

Causes

Oral Baclofen overdoses:

  • Usually intentional overdoses-either for recreational or self harm

Intrathecal baclofen overdoses:

  • Wrong dose is manually programmed into the pump
  • Wrong concentration is placed in the pump
  • Wrong bolus is given when starting the pump
  • Wrong port is accessed or wrong port filled

Treatment

Patients are usually treated by supportive methods only.

In severe overdoses, this often means supporting blood pressure with fluids and pressors and often-mechanical ventilation for respiratory failure until drug toxicity subsides.

Generally overdose symptoms will resolve in approximately 24-48 hours

For Intrathecal baclofen overdoses:

Most are correctable by emptying the pump reservoir:

  • Turn off pump-programmer (need external device programmer to do this)
  • Empty reservoir: Use a 22 gauge needle to stick the middle of the pump and pull out all the drug
Figure 4: Emptying the reservoir

Figure 4: Emptying the reservoir

Remove the CSF- Use a 24-25 gauge needle to stick the side port and aspirate 30-100 ml of CSF

In severe cases performing a lumbar puncture to reduce circulating baclofen in the CSF while performing all normal supportive strategies (small case reports- this involves replacing entire circulating volume of CSF with saline and has been used successfully in a few cases of massive overdose)

Withdrawal Symptoms

Similar to withdrawal from alcohol or benzodiazepines, with the loss of gaba-mediated inhibition: hyper metabolic states, spasticity/rigidity, hallucinations/seizures, tachycardia, hyperthermia, and hypertension are more commonly observed.

Mild: pruritus, agitation, diaphoresis and increased tone

Moderate: fever, tachycardia, spontaneous clonus and painful muscle spasm

Severe: worsening of above along with seizures, delirium, hallucinations, rhabdomyolysis and death.

Remember the mnemonic, "ITCHY, TWITCHY, BITCHY."

Causes of Withdrawal

Oral Baclofen Withdrawal:

  • Oral Baclofen withdrawal can occur when a person is abruptly stops taking baclofen or weans off to fast.
  • Of note oral baclofen diffuses through the blood brain barrier deep into the brain whereas- intrathecal baclofen stays almost exclusively in the CSF with a penetration of only approximately 1-2 inches into the brain. Therefore, a person who is being switched to intrathecal baclofen must still be tapered off their oral baclofen or they will withdraw.

Intrathecal Baclofen Withdrawal:

  • Intrathecal Pump Malfunction
    • Intrinsic pump malfunction is exceedingly rare.
  • Pocket Refill
    • Rather than an overdose this results in acute withdrawal as intrathecal dosing is 1/100th of oral dosing/subcutaneous dosing.
  • Battery failure
    • Expected to die at 84 months.
    • Will alarm 3 months prior. 

Medication Changes or interactions:

  • SSRI’s especially known for decreasing effect

Catheter malfunctions: (kink, micro/macroleaks, scarring, migration)

  • Most common cause of pump failure
  • KUB and AP/lateral spine first step to look for catheter fracture or migration
Figure 6: KUB demonstrating Baclofen pump

Figure 6: KUB demonstrating Baclofen pump

Treatment

Oral Baclofen withdrawal is usually easily treatable by restarting baclofen and introducing a slow tapered wean if discontinuation is desired.

Intrathecal Baclofen Withdrawal presents more of a challenge in both recognition and treatment.  It can be tricky to recognize baclofen withdrawal as it often masquerades as sepsis (ex-tachycardia, hyperthermia, altered mental status). It is important to recognize that many of these patients have severe spasticity and may have limited verbalization skills. Often they come from long term care facilities without much information, along with the fact that many times the baclofen will not be listed on their daily facility medication list, making it extremely important to look for a pump every time.

Recognizing that a patient’s symptoms may be secondary to intrathecal baclofen and interrogating the pump and obtaining pump series imaging to evaluate for catheter related malfunctions is a key first step

Essentially intrathecal baclofen withdrawal requires intrathecal baclofen. The key is finding the reason for the withdrawal and fixing the primary cause. Everything else is a temporizing measure.

To help with symptoms while attempting to fix the primary cause of pump failure treatment can include:

  • High Dose Oral Baclofen
    • Treating intrathecal baclofen withdrawal with oral baclofen is often unsuccessful as the vast difference in bioavailability of oral doses and intrathecal doses.
  • Benzodiazepine treatment
  • Propofol low dose
  • Experimentation with Dexamedetomidine and cyproheptadine
  • CSF infusion of Baclofen

So what happened to our patient?

After approximately 18 hours intubated, our patient began waking up, became agitated and self-extubated himself. He admitted to taking approximately 900 mg of baclofen in a suicide attempt the day of admission. He was discharged to inpatient psychiatry without any further medical sequela on hospital day 3. 

Take Home Points

  • Overdose: variable presentation, CNS depression is often involved, good supportive care is key.
  • Withdrawal: variable presentation, Itchy/twitchy/bitchy. Will have increased muscle tone from baseline.
  • Always remember the pump is there.
  • Overdose: For intrathecal overdose-2 ports from which you can draw drug and CSF back out.
  • Withdrawal: Look for the cause and treat supportively with oral baclofen, benzos, and propofol.

Faculty Reviewer: Dr. Kristina McAteer

References

Image 1: “Spasticity2” by Bill Connelly- Own Work

https://commons.wikimedia.org/wiki/File:Spasticity2.svg

Image 2: http://www.gablofen.com/patients/intrathecal-baclofen-therapy

Image 3: http://www.ajnr.org/content/32/7/1158

Image 4: http://www.rch.org.au/kidsinfo/fact_sheets/Intrathecal_baclofen_3_the_ITB_pump/

Image 5: http://www.cliparthut.com/clip-arts/175/people-clip-art-175256.gif

Image 6: https://emcow.files.wordpress.com/2014/01/baclofen-3.jpg

 

 

 

 

 

Asynchrony EM: Code Stroke

New to Asynchrony EM? It's an asynchronous learning course in its third year at Brown EM, with digital content curated into topic modules following our curricular calendar. In the spirit of #FOAMed, we've started putting it out there for the EM professional community at large. Check out the theme song, the 'extras', and the discussion questions -- and leave us your thoughts in the comments section.

Click here for more about us and for other curated teaching modules!

Note: Brown EM residents must complete the modules (including discussion/quiz) in Canvas to obtain credit hours.

 

This week in Asynchrony, we discuss code stroke.   Recognition of stroke is something ED practitioners must become very good at, however it is hard --and sometimes making the call can be difficult! 

We have a LOT of great #FOAMed content listed -- take your time and enjoy. Stroke mimics, posterior strokes, tPA (both recent data and old controversies, main line and endovascular) -- we've got it all here for you!

But before we wade into the velvet sea of 'code strokes', take a listen to a musical selection that could be aptly described as self-induced stroke symptoms from the consumption of stimulants followed by...whatever:

From EM Docs: how to recognize stroke and develop your ddx highlighting stroke mimics 

From Life in the Fast Lane - a succinct review of must know data & review of literature

"Stroke and TIA: Pearls and Pitfalls", again from EM Docs. Excellent review that helps you organize the management steps of stroke and gives treatment options (along w literature references - BONUS!!) to help streamline your approach 

From REBEL EM - summary of avail  lit to date focusing on effects of TPA

Another option on the data and rational for TPA usage -  from Life in the Fast Lane

 

Endovascular TPA

a) Drastic changes came to the landscape in 2014, when one of the first major positive trials for endovascular therapy emerged – the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). This study ushered in the new era in endovascular intervention.

Endovascular Stroke Therapy: The New Standard? - studies showing support for intravascular TPA

b) While the data may have been promising, the truth is that a limited population will actually benefit from the therapy. The trials focused on patients with severe strokes, with large vessel occlusions and salvageable brain tissue -- however this is a small portion of the stroke patients arriving to our EDs. 

A Word of Caution, from PulmCrit

c) Time to get a little wild & crazy... you think risk factors for vascular disease in our pediatric population are unlikely but they can have strokes too --BEWARE!!  - Pediatric Stroke: EM Focused Highlights (EM Docs)

d) The ever challenging and elusive posterior stroke - an EM Crit Podcast

e) Featuring HINTS and more on posterior strokes - Posterior Stroke and HINTS exam, EM Docs

f) HINTS Demo if you need it however if test of skew is your thing, then feel free to jump ahead!

HINTS Demonstration

 

The EXTRAS!! 

a) New information, will our stroke management change soon?  Data on the approach via low dose TPA. From EM Crit: The Case of the Non Inferior Inferiority Continues.

b) A bit older information and data you probably know well.  The following links highlight the history of how TPA came to be an accepted treatment for stroke and the very evidence you use to justify your decision in administering this drug...

The Secret of NINDS, from the SGEM - excellent review of the NINDS study that started the whole TPA regime.

c) The fragility of the NINDS - from PulmCrit

d) From 2014, EM Crit  - an animated and entertaining review of NINDS trial and limitations of the trail that has served as the basis for TPA use.  (Discussion of consent.)

e) EM Cases: Information on the ABCD2 score (if you are using it:) and more!

That's it! See you next time in Asynchrony EM  -- happy #FOAMing!