ECG Pointers: Poisoned Sodium Channels

Authors: Michael Bieszard (Resident, Hackensack University Medical Center); Khizer Rizvi (Medical Toxicologist, Hackensack University Medical Center); Alyssa Berns (Staff EM and Critical Care Physician, Hackensack University Medical Center); Lloyd Tannenbaum (Staff Physician, Hackensack University Medical Center) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

This case is presented as a collaboration between the ER, ICU, and a medical toxicologist.  The story is told from the point of view of the ER team with the ICU and Toxicologist weighing in and giving their expert opinion at times.  Our resident weighs in at the bottom with some tips for other residents that he learned for the case and some takeaways.

During a busy ED shift with multiple critically ill patients, EMS calls and tells you that they just pulled a 24-year-old female out of a car.  She is becoming less responsive.  She’s telling them that she took “a lot” of pills in a suicide attempt.  She has a complex history of several psychological conditions and is taking multiple different psych meds.  EMS gets her on the stretcher and gets IV access, an EKG, and a first set of vitals:

HR 139, BP 105/82, Temp 99.5 (oral), SpO2 98% RA, RR 20, Glucose 120, EKG obtained at 1522.

As they transport her to you, she gets progressively more obtunded.  EMS notices a change in her EKG, so they transmit a second EKG to you at 1537:

Notice here how the EKG is changing.  Before, your patient had a narrow QRS at 118 msec.  Now, the QRS has stretched out to 144 msec.  The paramedics are asking if you want to give any medications or if they should continue to monitor and transport. You’re not quite sure, so you tell them to monitor, transport, and drive fast.

She’s now become unresponsive, and EMS is asking you for medications to intubate her.  Vitals are HR of 130, BP 100/59, RR 25, SpO2 92 RA.  You tell them to use 150 mg rocuronium and 50 mg ketamine.

Success! The patient is intubated and almost here, but the EKG changed again, and EMS sent you one more to look at (EKG obtained at 1549):

Yikes. This looks less good. Notice here how the QRS has stretched out to 174 msec.  That’s impressively wide. And very bad. EMS has arrived, and you and your resident hustle over to go see the patient.  As you walk over to go see her, you order a repeat EKG.

Before you move on to the next EKG, look back at the EMS EKGs and note the time between them. The first one was done at 1522.  Then 1537 for the second and 1549 for the last.  In the course of 15 minutes, her QRS duration went from 118 msec to 144 msec, and then in the next 12 minutes, her QRS went to 174 msec.  I know your staff sometimes think you are a crazy person asking for serial EKGs, but this is why!  You can watch her QRS widen in front of you!  If you see acute changes on the tele monitor, which these excellent paramedics did, get a repeat EKG!  Please.  Ok, now take a look at the next EKG obtained at upon arrival:

When the patient arrives, you recognize the widened QRS complexes and immediately order 2 amps of sodium bicarbonate and a bicarb drip to chase it.  Remember, if you ever had to make your own sodium bicarbonate drip, it’s 3 amps in a liter of D5W.  This little fact has been known to show up on standardized exams.  Take a look at the EKG after just 2 amps of bicarb:

Nice work!  The QRS is now down to 92 msec.

Luckily, a medical toxicologist was standing next to us this whole time and helping with the case.  He recommended q1H EKGs to monitor for changes and that we perform gastric lavage (thanks…).  Given that the patient took a lot of psych medications, we’d expect the QTc to stretch out, which is exactly what it did:

Now what?  Would more bicarb help?  What are we worried about with a prolonged QTc?

Tox sidebar:  What do we do with an EKG with a widened QRS or a prolonged QTC? Let’s start with a widened QRS.  There are many causes of a widened QRS, but we aren’t talking about boring things like a bundle branch block or VT.  We’re talking about a really really wide (Greater than 1 big box or 200 msec) [2,3].  Take 10 minutes and watch this video of Amal Mattu explaining how to avoid a kill with a wide complex tachycardia, It’s fantastic: 

How do you avoid a clean kill with wide complex tachycardias?

So, from a tox point of view, what stretches out the QRS complexes to make it look like this?  A sodium channel blocker.  TCAs are the classic boards answer, but now, since we don’t use a ton of TCAs, think of BENADRYL/DIPHENHYDRAMINE causing QRS prolongation.  And it’s readily available in club-sized bottles without a prescription.  Keep in mind you need a massive amount of benadryl to cause QRS prolongation (a toxic dose is 25 mg/kg or about 1 pill per kg).  What numbers should we be aware of for a widened QRS in the setting of an overdose?  100 msec.  That’s right, it’s not a typo.  100 msec.  Why is that?  If we look at the data behind it, young people were often the ones overdosing on TCAs.  And the number 120 for “wide” QRS was based on an average of EKGs of people of all ages, it’s not specific for certain ages.  So for people 20 and under, we’d expect a much narrower QRS than people 80-85.  If you take a ton of TCAs and your QRS stretches out to 100, you’re at a higher risk of seizing.  If your QRS goes to 160, you’re at a higher risk of VT.  Yikes.  Breakout that sodium bicarb. But why? Two main reasons: the sodium and the bicarb [2,3].

ICU Corner: TCA overdose poisons the myocytes by blocking the fast sodium channels and prolonging the repolarization and refractory periods, which is the part of the cardiac cycle where bad things can happen- the heart is at risk of ventricular arrhythmia. Giving extra sodium helps to overcome this by trying to overwhelm the receptors with sodium so that, even if many of them are blocked, there is plenty of sodium around waiting for the opportunity to interact with the myocytes.

Why not just give sodium? We have lots of kinds of sodium and can even give 23% sodium in really special circumstances to raise sodium in other situations, such as patients who are trying to herniate. The reason is related to acid base status, the best part of medicine. TCAs that are floating around in the plasma are the ones that can wreak havoc, but if you cause an alkalosis, you can actually increase the amount of drug bound to plasma proteins and reduce the amount that is available to poison the heart. This is the reason that we start with sodium bicarb amps, which have high amounts of sodium, and then continue with a bicarb drip (which is nearly normonatremic and iso-osmolar) afterwards- to maintain a bit of alkalosis, and continue to supply sodium (the sodium content of an isotonic bicarb drip is 150mEq/L, which is slightly higher than physiologically normal levels).

How much sodium is an amp of bicarb? 50mEq in 50mL. There is also 50mEq of bicarb in there. This means that it is extremely concentrated and you can raise the sodium as much as 2mEq on the chemistry with one push! How concentrated? 2000mosm per liter- almost twice the osmolarity of 3% saline. But what about 23% saline? It has even more sodium per mL- the osmolarity is more than 8000mosm/L!

So why don’t we use hypertonic saline? Well, it is rarely first line. The pH of saline solutions is below 6 whether we are talking about 0.9%, 2%, 3%. If our goal by alkalinizing the sodium is to increase plasma protein binding of the drug, solutions will do the opposite. That being said, there are case studies and animal models where hypertonic saline has been used successfully, and you can consider also that your patient is likely at the upper limit of tolerable alkalosis (above 7.50-7.55). While your critical patients can tolerate a remarkable level of acidosis, they cannot tolerate severe alkalosis [4,5].

So that’s why the QRS stretched out and how to beat it, what about the QTc?  Here is a cool picture from the American Psychiatric Society.  Try not to have too many flashbacks to med school when you realize you’re looking at electrolytes and transporters:

What are we looking at?  Remember, with cardiac myocytes, depolarization occurs when there is an influx of sodium and then calcium from the cells. To balance that and help the cells repolarize, potassium leaves the cell.  Drugs that prolong the QT interval often block a certain type of potassium channel, the hERG [6].

Tox Sidebar: Also, sometimes Na channel blocking medications that can cause QRS prolongation can also prolong QT overall because it slows phase 0, so it can overall slow conduction, without changing ST segment duration. Maybe that’s what happened to this patient, but we aren’t sure what Na blocking medication she took. I guess that’s why 1a and 1c antidysrhythmics (procainamide/quinidine and flecainide can cause TDP) [2,3].

Now look at frame C for a second.  Notice the small Mg2+ that’s gray on gray and you may have overlooked.  Your initial drug of choice to narrow that QTc is magnesium!  Why is that?

Tox side bar: Prolonged QT can predispose to early afterdepolarizations (essentially starting a new depolarization during the refractory period). This can induce early afterdepolarization contractions (R on T phenomena), which can trigger ventricular dysrhythmias. [2,3].

The role of magnesium is highly debated- there is a divergence of opinions from toxicologists. Some believe that it should only be given if the patient develops ventricular dysrhythmias such as TDP or if they are hypomagnesemic (as magnesium can stabilize the cardiac membrane). Many toxicologists do not believe in “empiric/prophylactic magnesium”. The literature is uncertain of its full use in QT prolongation, but it is postulated to reduce early afterdepolarizations, which reduces QT variation and risk of ventricular dysrhythmias.

I think the takeaway from a toxicologist would be: treat the underlying etiology if possible, replete magnesium as necessary, monitor for ventricular dysrhythmias. But the answer is not always magnesium. [2,3].

Resident tips:

Please spend as much time with this patient at the bedside as you need. Cases like this are rare, extremely complex, and your brain will hurt, but you’ve got this!

Just to re-paint the picture; we suspected an ingestion and she came in intubated because she rapidly decompensated in the ambulance! Now we have so much to do and such little time.

First: ABC’s and is the tube in the correct place? How is our IV access? What is our post-intubation sedation of choice here?

Next: What medications did she take? Go through her gigantic plastic bag of medications bottles that EMS brought, count the pills, look at her pharmacy records, consider co-ingestions, consider the timing of ingestion, review her recent psychiatry notes, and obtain collateral information from the frantic family outside of the resuscitation room. Quickly, recognize any “dangerous” medications and try to remember the complex pathophysiology and tiny little cellular transporters and think of how we can fix the very scary EKG findings.

Pro tip: Delegate tasks! Order your charcoal early even if you don’t need it. Send a friend to run and find the gastric lavage kit (wipe off the dust), and maybe refresh your memory on how to lavage.

Lastly: Take some deep breaths, control your own tachycardia, wipe the sweat from your brow, and remind yourself that you are a capable Emergency Medicine Doctor who can do all of this at the same time in order to save your patient!

Case resolution:

Luckily for us, the patient got accepted by the ICU team with Tox following closely.  The patient was extubated 2 days later and made a full recovery

Key Points:

• In an unknown overdose, make sure to get an EKG early in your assessment to evaluate for a widened QRS complex or prolonged QTc
• These patients should be kept on the telemetry monitor to watch for any EKG changes
• Repeat EKGs can help assess for EKG changes too
• QRS narrowing can often be obtained with sodium bicarbonate
• Magnesium is often the drug of choice for a prolonged QTc, but there is debate on whether it should be given empirically

References

1. Michael Simpson, Linda Johnson & Charlotte Goldfine (2023) Sodium bicarbonate treatment for QRS widening in bupropion overdoses, Clinical Toxicology, 61:6, 436-444, DOI: 10.1080/15563650.2023.2218029
2. Bailie DS, Inoue H, Kaseda S, et al. Magnesium suppression of early afterde- polarizations and ventricular tachyarrhythmias induced by cesium in dogs. Circulation. 1988;77:1395-1402.
3. Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med. 1985;313:474-479.
4. McKinney, P. E., & Rasmussen, R. (2003). Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution. Annals of Emergency Medicine, 42(1), 20–24. https://doi.org/10.1067/mem.2003.233
5. ‌UpToDate. (2023). Uptodate.com. https://www.uptodate.com/contents/tricyclic-antidepressant-poisoning
6. Margo C. Funk, M.D., M.A., Scott R. Beach, M.D., et al.  Resource Document on QTc Prolongation and Psychotropic Medications. https://www.psychiatry.org/psychiatrists/search-directories-databases/resource-documents