Bupropion is Not a Forgiving Medicine.

One minute, I was patiently waiting for my burrito bowl at Chipotle, and the next, I was en route to a female with AMS, sans said bowl... Such is the life of a paramedic.

En route we got an update from dispatch, "P1 be advised, police on scene requesting you step it up, the patient is actively seizing." As if we weren't already driving with a purpose... 

Anyway, we were about 5 minutes away.

When we showed up, we found the patient in her living room. She was post-ictal, with some vomit being cleared by a firefighter. Her mom handed me an empty pill bottle, "It was filled last week, but I don't know if she's been taking it."

Bupropion HCl SR, 150 mg, 90 tabs.

She also took ziprasidone and escitalopram however, it didn't appear that any of those were missing and they weren't found in the patient's room.

The patient was a 21-year-old female who had recently moved back in with her parents after having some issues living alone. She had a history of bipolar disorder, some substance abuse issues, depression, and anxiety with previous suicide attempts.

Bupropion (commonly known in the US by a prevalent name brand, Wellbutrin) is an atypical antidepressant that can treat depression among a few other things. Basically, it inhibits the reuptake of dopamine and norepinephrine, keeping them in the synapse longer which can increase things like motivation, pleasure, alertness, learning, memory, etc. Structurally and mechanistically, it's very similar to amphetamines... But is not technically a stimulant. It comes in a variety of forms (at least in the US) with this patient taking the sustained-release variety.
It's very toxic.

Bupropion is known to cause seizures, usually the tonic-clonic kind, even at therapeutic doses. In fact, for a while, it was taken off the shelf because even the stand dose at the time (around 450 mg a day) was causing seizures. Now, again, at least in the US, you shouldn't be prescribed more than 400 mg daily.

Today, around 2-3 hours ago (per her Facebook), she ingested presumably the rest of the bottle - More than 12,000 mg of it - while her parents were shopping.

We didn't mess around on scene... Bupropion is not a forgiving med and overdoses can lead to agitation and amphetamine-like effects (think stimulant intoxication), then seizures, and then cardiopulmonary collapse. We scooped her up using a blanket carry and got her into the truck.

There are 2 big things to care about in bupropion toxicity: Neurotoxicity and cardiotoxicity and she already had signs of the former.

She was minimally responsive at this point and tachycardic, but normotensive. We placed an IV, obtained a 12-lead, and then decided to intubate her for airway protection given her neuro depression and seizures - That all went fine. We then placed an OG tube.

The ECG was very concerning and already showed cardiotoxicity with both a widened QRS and QTc.

Normally in tox when you see a widened QRS you should immediately think "Na channel blockade" and then "bicarb." However, this is actually not the case here, oddly enough. Bicarb doesn't tend to work in bupropion toxicity. Bupropion isn't a Na channel blocker... It inhibits gap junctions. Gap junctions are well taught in paramedic school, unfortunately, so a lot of us may not know why that's significant.

Gap junctions are small channels between cells that allow direct diffusion of ions between them - it's how myocytes work so quickly and in tandem. They are largely responsible for the speed and direction of cardiac conduction. The signal goes SA node -> AV node -> Bundles -> Purkinje fibers, right? And then myocytes. Gap junctions are what allow myocyte A to propagate the signal to myocyte B, then C, then D, etc. In toxic doses, bupropion inhibits these slowing the signal - which is what causes the prolonged QRS (and less prominently, the prolonged QTc).

Bupropion kills via its cardiotoxic effects. The ability of the heart to squeeze becomes nil and the ECG gets wider and wider. Ultimately, at least in my experience, they become refractory hypotensive and go into PEA.

With all that said, we did try an amp of bicarb just to see... It didn't work.

We reached the ED within a few minutes. There, over the course of several hours, she got worse. She ended up suffering multiple seizures, her QRS widened even more, and her pressure dropped. She arrested 3 times.

The name of the game in bupropion toxicity, like much of tox, is supportive care.
She ended up getting activated charcoal via OGT for attempted decontamination. She got multiple doses of benzos, a midazolam drip, a high-dose propofol drip, and Keppra for her seizures. Despite bicarb not really working in bupropion toxicity, she got 8 amps of it... And then they started Intralipid once the tox folks got involved.

Intralipid is a 20% IV fat emulsion therapy. No one really knows why it works, but the leading theory is that of a "lipid sink." Basically, Intralipid is made of triglycerides and phospholipids. These like to stick together in little Intralipid spheres that float around in the blood. These little spheres form a new compartment. Lipophilic drugs (like bupropion) will concentrate in that compartment - pulling the drug away from the body. It's super cool! There are some other theories out there too, though, this is just the most prominent.

Anyway, she also ended up on norepi, epi, neo, vaso, and dobutamine... So things got a bit spicy there... She also got magnesium for the QTc (though these patients don't go into Torsades).

Before long the patient was transferred by helicopter to another hospital for VA-ECMO. Our hospital was an ECMO and tox center however, they already had their maximum number of ECMO patients already admitted. I spoke to the flight crew later on who told me she coded again during the flight.

Ultimately, she survived! She was on ECMO for a few days, the drug wore off, she got better and after a moderately long hospital course she was back home - I know this because I subsequently picked her up no less than 20 times for various reasons in the months following this ordeal. It was cool to play a small role in that outcome!

So big takeaways for bupropion outside of this case: It's sneaky... Bupropion can come in extended-release forms where symptoms can be delayed up to 10-24 hours. The patient can be totally fine and then - BOOM - Actively dying. Bupropion is also known to cause tachycardia, agitation, hallucinations, and essentially, Meth/cocaine-like symptoms. For this reason, it's sometimes referred to as "poor man's cocaine" where people will crush them up and snort them... It's very similar to amphetamine and can cause all the stimulant issues including serotonin syndrome and the like. The patient can present as a danger to themselves and others - these can all be early warning signs of neurotoxicity. Finally, any ingestion >4.5 to 9 grams puts the patient at high risk of seizures and true toxicity, but keep in mind, that seizures can still happen far below this dosing.

EMS's role is largely supportive. Some agencies have activated charcoal and Intralipid on their trucks (mine didn't). Some agencies have standing orders for bicarb in toxicity. So some things can be considered additionally.

For those wondering, I did eventually get my cold Chipotle…

Anyway, have you ever responded to a bupropion OD case? How did they present? Let me know below!

-Dean Stockley