Neurology

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!

Asynchrony EM: Dementia and Delirium in the ED

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

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

 You see them every shift. Could you be taking better care of them?

You see them every shift. Could you be taking better care of them?

This week, we start our Neurology block. There are lots of 'sexy' neuro topics we could be starting off with, but we're starting with care of elderly patients with dementia and delirium in the emergency department. We'll look at how to differentiate between the two diagnoses (which can co-exist), talk about best practices for caring for these patients in the ED, about the burden on caregivers, and some of the more 'humanistic' aspects of dementia. 

No theme song this week; a theme movie trailer instead.  Julianne Moore won the Oscar for her portrayal of 'Alice' in 'Still Alice' (the book is worth a read but I haven't seen the movie.)  

 

Now, before I forget, let's hit it. 

1)From EM Docs, Sept 2016. "Dementia in the Emergency Department: Can You Do Anything About It?" 

 

2)  In 2013, Geriatric ED Guidelines were jointly approved by ACEP, SAEM, the American Geriatric Society, and the Emergency Nurses Association.  But why would these guidelines not apply to the treatment of the elderly in any ED when possible?

Please read starting on page 26 the section entitled "Delirium and Dementia in the Geriatric Emergency Department". Also read the brief Palliative Care section immediately following.  (It's somewhat telling that the Palliative Care section is so short. See our discussion section.)

 

3) Did looking at all those screening tools make you crazy?  Think you can pick up delirium on your own without a screening tool? Well, maybe you can, Superdoc, but most of your colleagues can't: check out this Annals of EM 4 minute podcast about the May 2014 article, "Screening for Delirium in the Emergency Department." The podcast is assigned; reading the article is OPTIONAL.  The take-home point from both is that we stink at identifying delirium, and it's a dangerous thing to miss.

 

4) Now we're going to get a little more...humanistic.

It is difficult sometimes to imagine an elderly, frail, confused patient as the person they might have been once upon a time. We see these patients as a snapshot, without the benefit of knowing them "before,"and without the inherent compassion that comes with that knowing. When the snapshot is a screeching, drooling, vacant, shrunken being, it's easy to restrain or oversedate or ignore. But maybe, the next time (which will of course, be tomorrow) that you see this patient, imagine them as Pam (in this mini-documentary) or Alice, or someone you may have known in your own life that you have watched fall slowly into the abyss. You will find that it does wonders for your patience. 

Not a medical video, but worth watching. An eight minute, beautiful Op-Doc video called "A Marriage to Remember," from the New York Times. This very short film was made by a son documenting his mother's dementia and his father's efforts to care for her over a four year period.

"A Marriage to Remember"


 

5)  As the video above highlights, patients who are cared for at home create a heavy burden on families, even on families with means (as the family in the op-doc appears to have). Caregiver fatigue and burnout is increasingly recognized, and you will see and treat patients with depression and stress-related illness that stems directly from caregiver burnout.  And when caregivers burn out, where do the patients with dementia wind up?

With the silver tsunami gathering strength, it's time for us to learn to 'help the helpers', because they are the ones who will determine how much of an overall burden patients with dementia present to emergency departments.

True story: a few years ago, I treated a man with advanced dementia whose wife called 911 after she knowingly gave him an overdose of his pain medication. She then could not go through with her plan, which was to kill him, and then kill herself. (Both of them became my patients--she was admitted to psychiatry.)  The wife had no previous history of mental illness or depression; her symptoms stemmed entirely from caregiver burnout, and the stress of the promise she had made to her husband to 'never put him in a home.' 

This is an area that is only beginning to be addressed, and is ripe for research. In September 2016, the National Academies of Sciences, Engineering, and Medicine (NASEM, formerly known as the Institute of Medicine) released a very long report on "Families Caring for an Aging America." For our purposes, read this Geri Tech Blog Post. 

 

6) Because it's more prevalent among cognitively impaired patients: Elder Abuse, a quick reminder from LITFL.

 

7) Three quick news blurbs: lots of mainstream news attention on dementia and anti-psychotics/benzo use.  The immediate implications are for long term prescriptions, but you will find that (as in the Geriatric ED guidelines) there is counsel to avoid them even in the ED if non-pharmacologic methods can curb behaviors instead. You should also consider this when sending dementia patients back from whence they came after they are sedated for behaviors in the ED. 

a) From a March 5th, 2015 NPR post:  'Behavioral Therapy Helps More than Drugs' in dementia

b) From the March 1, 2015 NY Times: "Investigators are recommending that Medicare officials take immediate action to reduce unnecessary prescriptions to older Americans with dementia."  This is mostly about anti-psychotic drugs.

c) Couple those with the February 2015 JAMA Psychiatry article "Benzodiazepine Use in the US" (abstract/scroll through is enough) -- and you will find there is a lot of pressure to de-prescribe the elderly, maybe with good reason. 

 

The OPTIONAL (but really worth the time) blurbs:

a) Nursing homes that eschew the use of antipsychotics: from NPR.

b) A recent series from NPR, "Inside Alzheimer's" -- perspective from caregivers and afflicted. 

c) Speaking of non-pharmacologic methods, do you have a working iPod you don't use?  Music and Memory NEEDS IT. Check them out: awesome stuff.

d) If you didn't see the documentary Alive Inside (featuring the work Music and Memory does: won the Audience award at the 2014 Sundance film festival), this stuff is pure genius, and so, so simple.  (I'd love to see a trial of using music to calm and comfort  patients with dementia.)

 

 e) Finally, because the Music and Memory videos above feature the wonderful Dr. Oliver Sacks, who died in 2015, I'm throwing this in: very much worth the short time it takes to read. Not dementia related, but we're in the Neuro block, and he was the world's sweetheart neurologist/writer. If I haven't gotten you teared up yet, keep reading.  "My Own Life: Oliver Sacks on Learning He Has Terminal Cancer."  "Above allI have been a sentient being, a thinking animal, on this beautiful planet, and that in itself has been an enormous privilege and adventure."

That's all for this week. Share any thoughts or other #FOAMed resources you'd like us to know about in the comments.