Podcast 98 – Cyclic (Tricyclic) Antidepressant Overdose

stormtrooper-pills

I had a crazy case of Tricyclic Overdose while on an overnight shift at Janus General.

Initial and Post-Treatment EKGs

Initial

Initial

Post-Treatment

Post-Treatment

List of Tricyclic Agents from Wikipedia.org

  • Amitriptyline (Tryptomer, Elavil)
  • Amitriptylinoxide (Amioxid, Ambivalon, Equilibrin)
  • Butriptyline (Evadyne)
  • Clomipramine (Anafranil)
  • Demexiptiline (Deparon, Tinoran)
  • Desipramine (Norpramin, Pertofrane)
  • Dibenzepin (Noveril, Victoril)
  • Dimetacrine (Istonil, Istonyl, Miroistonil)
  • Dosulepin/Dothiepin (Prothiaden)
  • Doxepin (Adapin, Sinequan)
  • Imipramine (Tofranil, Janimine, Praminil)
  • Imipraminoxide (Imiprex, Elepsin)
  • Lofepramine (Lomont, Gamanil)
  • Melitracen (Deanxit, Dixeran, Melixeran, Trausabun)
  • Metapramine (Timaxel)
  • Nitroxazepine (Sintamil)
  • Nortriptyline (Pamelor, Aventyl, Norpress)
  • Noxiptiline (Agedal, Elronon, Nogedal)
  • Pipofezine (Azafen/Azaphen)
  • Propizepine (Depressin, Vagran)
  • Protriptyline (Vivactil)
  • Quinupramine (Kevopril, Kinupril, Adeprim, Quinuprine)

Additionally…

  • Amineptine (Survector, Maneon, Directim) Norepinephrine-dopamine reuptake inhibitor
  • Iprindole (Prondol, Galatur, Tetran) 5-HT2 receptor antagonist
  • Opipramol (Insidon, Pramolan, Ensidon, Oprimol) ? receptor agonist
  • Tianeptine (Stablon, Coaxil, Tatinol) Selective serotonin reuptake enhancer
  • Trimipramine (Surmontil) 5-HT2 receptor antagonist and moderate-potency norepinephrine reuptake inhibitor.

And of course, the non-TCA agents…

  • Diphenhydramine
  • Cocaine
  • Cyclobenzaprine (I add this one to the list, b/c there can be TCA-like effects in toxicity, but it seems the potential for cardiac effects is markedly less though still possible. (J Emerg Med 1995;13(6):781-5) This one is from Bryan Hayes)

Pharmacologic Effects of TCAs

K+ Channel Blockade QTC Prolongation
NE & Serotonin Reuptake Inhibition Initial hypertension quickly followed by hypotension
Na+ Channel Blockade QRS Prolongation
Hypotension — depresses myocardial contractility
Ventricular dysrhythmias
Brugada-like findings on EKG
Muscarinic Anticholinergic Receptor Antagonism Anticholinergic Toxidrome
Antihistaminergic CNS stimulation or sedation
Alpha1 Adrenergic Antagonism Hypotension
GABA-A Receptor Blockade Seizures

This chart was taken from the excellent Resus Review Blog by Charles Bruen

Sodium Bicarbonate

Increases amount of drug in non-ionized form and may decrease binding to Na-channels (11482860)

May need many, many amps. For some reason the sodium and the bicarb don’t rise significantly in severe toxicity

My goals are QRS duration <100, hemodynamically stable, Na ~150, pH ~7.5

Electrolyte Abnormalities

Beware of hypokalemia and hypocalcemia

Send VBG with lytes at least Q1 hour

Hyperventilation

To promote alkalosis

Hypertonic Saline

If the patient is too alkalotic or out of amps of Bicarb

Sodium Acetate

Can substitute for NaBicarb. This article gives dosing recommendations and precautions. (23636658)

Intubation & Sedation

Be very careful the patient doesn’t become hypercapneic

Sedate with benzo or propofol to raise seizure threshold

Gastric Decon and/or Lavage

If time of ingestion <1 hour ago and airway is protected

We use a commercial device: the Easi-Lav system

Kimberly Clark Easi-Lav

Magnesium

May help, though risk of Torsades is low as long as the patient remains tachycardic

Lidocaine

Even though lidocaine is another Na-Channel Blocker, it actually antagonizes the effects of the TCA-like mediciations. As a Vaughan Williams Class IB agent, For additional information, this review discusses the pertinent issues.(20507243)

VasoPressors

Norepi or Epi

Intralipids

Certainly for cardiac arrest and probably for hypotension/increasing pressor necessity

For this or any other Lipid Question, you need to go immediately to the Lipid Rescue Site

You can find the Lipid Administration Instruction Sheet there, which should be hanging somewhere on the wall of your ED.

ECMO

The last resort for tox instability

Want More?

My friends Sean Nordt and Stu Swadron did a great EM:RAP episode on this 2 months ago

Here is a review and guideline article.

Shout-Outs

Medcalc sent me some freebie codes for their new IOS version of the app. Join the mailing list to be in the running (see the area below to sign up for the mailing list)

Daren Lewis of leadingvisually.com designed the wonderful Janus General logo; consider him if you need any message design.

Janus_General_400px_TransparentBG

Now on to the podcast…

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Comments

  1. R. Garrett Hanzel writes:

    Hey Scott, I didn’t see cyclobenzaprine (Flexeril) on your list. I’ve heard that its 3-ringed structure can give you +TCA on a drug screen, but I can’t find much solid evidence of whether it causes sodium channel blockade and would be managed like any other TCA overdose. Thanks for any thoughts on this.?

    • The literature is scant, but at least 1 article: Am J Emerg Med. 2011 Jul;29(6):645-9, indicates no TCA-like effects despite the false + on urine drug testing.

    • Bryan Hayes says:

      Although the cyclobenzaprine structure is similar to TCA and it has the potential to cause TCA-like toxicity, overdoses usually don’t cause TCA-like cardiovascular effects. Lethargy and anticholinergic toxicity predominate. Still check in ECG. J Emerg Med 1995;13(6):781-5.

  2. Good podcast Scoot, I’m EP from Colombia and everytime I share your Podcast with students, residents and collegues. Thank you!
    relucho@gmail.com

  3. Great stuff as always. If you pop in an ILMA after ketamine without a paralytic, is that truly RSA? I always thought RSA was defined as induction + paralysis + SGA (without any attempt at laryngoscopy).

    That antidysrhythmic rap was pure gold. Reminded me of Schoolhouse Rock!

  4. Charlie Moore says:

    What is the drip rate you usually use with the bicarb drip with a TCA OD?

    Great podcast as always! Thanks!

  5. Mike Sherriff says:

    Excellent podcast.
    Say I responded to an altered patient, and did not see pill bottles indicative of a TCA-like OD laying around. And I obtained the initial ECG you posted above. I’m betting my first thought would be hyperkalemia. (Not that I’m correct and I understand the significant of the R in aVR, but to me at least it has a hyperkalemia-like QRS widening and one could convince oneself that (ie V1) the sine wave is coming.)
    By our EMS protocol I would give 1 G CaCl and 1 mEq/kg Sodium Bicarb, along with possibly some Albuterol; then more CaCl and Bicarb if there was no narrowing of the QRS. So my treatment may be beneficial for the TCA OD, but could potentially contribute to some intracellular shift of the K+.
    (If I was aware of TCA OD, then the ECG would prompt me to give 1-2 amps of Sodium Bicarb without the CaCl and albuterol).

    Any thoughts on considering hyperkalemia from the first ECG? And the effect our hyperkalemia regimen would have on the TCA OD?

    Living in the dialysis belt, I have seen much more bad hyperkalemia than TCA OD (only one comes to mind).

    Thanks,
    Mike

    • Hey Mike,

      Hyperkalemia generally would not give the AMS or seizures, but if in doubt give CaCl and bicarb with no loss for either dx.

  6. Renee Garcia says:

    Hi Scott,

    Had a bad case of TCA overdose last month ( 400 tabs of 25mg nortriptylene, AND Ace inhibitor, B Blocker, Quitiapine on top of those. Walked to ambulance, on arrival to ED GCS 10ish. Was maximally aggressive, intubation, gut decontamination, Bicarb, Pressors, insulin-glucose, glucagon, Intra-lipids. Unfortunately ECMO not option. Despite all of this patient died after 9 hours of maximal therapy after transfer to ICU. All of my training suggested we should be able to win when we do everything right. Really frustrating. Apparently sometimes these overdoses are bigger than us. Noticed in all review articles except this post Intra-lipids aren’t on algorthym, but having tried to keep up with this emerging therapy I was aware of case reports of success, and lipiphilic nature and potential benifit in both the TCA and the BB so as last ditch after convential therapy was failing and refractory hypotension and a persistant accelerated Junctional rhytm despite quadrupal strenth Adrenoline/ Nor Ad, Na, Bicarb, insulin-glucose and glucagon we gave it a go. Later found some vague referances to Intralipids less effective in setting of high dose pressors. Any thoughts? Should probably post case on lipid rescue as most posts there relate success in face of death but unfortunately no response with my patient. Thanks again for all your great blog posts Hope to see you at SMACC 2014 (loved SMACC 2013!)
    Cheers,
    New Yorker turned Kiwi

    • Cheers Renee. At this stage the tox folks feel intra-lipids should be given a shot for any tox-induced cardiac arrest.

      Your case sounds horrible and short of ECMO, probably not much else would work.

  7. Chad Garmany says:

    I’ve also read about phenytoin (good and bad). What’s your opinion on this?

    • The article on lidocaine above goes through the evidence for phenytoin as well. Lidocaine as edged it out as the preferred agent.

  8. Winnie says:

    Thanks for the interesting review. I was surprised when you said you RSI-ed this pt with succs, given the wide QRS, which could lead to a sine wave rhythm cardiac arrest. Did you consider roc or another agent?

    • It is a great question. The EKG didn’t look like hyperK and there was no clinical context to suspect it. If you had doubt, sure give roc. Problem with a case like this is you lose the ability to know if the pt is seizing again (which she turned out to do soon afterwards).

  9. Hi,
    Was wondering where you found your evidence for hyperventilation these patients. I know this is still common place in many hospitals and EMS services but very little evidence exists to prove it’s worth – some studies even suggest it results in poorer outcomes. Current guidelines on up to date don’t mention it…

Trackbacks

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