A Complication of the COVID Era

Submitted and written by Gia Coleman MD and Roshan Givergis DO, edits by Meyers and Smith



A woman in her 30s was found crawling in the streets, altered on arrival to the ED. Here is her presenting ECG:

How would you interpret this EKG and what is on your differential?

At first glance, it appears to be a sinus rhythm with PR prolongation at a rate of about 75 bpm. The QRS may appear narrow but is in fact slightly wide (see figure below). The computer measured it to be 136 ms.

Perhaps the most striking finding in this EKG is the almost complete loss/flattening of the T waves. The computer calculated the QTC to be 427. Looking closer, the P waves, particularly in the precordial leads, are not of uniform morphology. Taking the flattened T waves into consideration, this made me question whether the P waves were only P waves, OR were P waves with superimposed U waves, OR only U waves. Most likely these are sinus P waves with superimposed U waves.

Meyers comment: I agree, I cannot tell where the T and/or U wave is or where it ends. I don't think a QT interval can be meaningfully calculated here.

Taking a global look at this EKG, everything just looks long, regardless of the computer calculations. The top two things on my differential when I see EVERYTHING stretched out like this is electrolyte abnormalities or toxins.

The patient then progressed into an irregular wide complex rhythm which unfortunately was not captured on paper. She was treated with an amp of bicarb and an amp of calcium with normalization of her rhythm. She did not lose a pulse.

This is her EKG after calcium and bicarb:

Likely back in sinus rhythm however the U waves are more discernible so it is difficult to see the P waves. The QRS is now narrow and it is regular. Compared to the first ECG, V2 and V3 now show more recognizable T and U wave morphology, showing that there are indeed U waves superimposed on the P waves. The QU interval, if calculated, would be extremely long, in the range of 600 msec.

The patient managed to tell the team through her stupor just prior to intubation that she had taken a bottle of hydroxychloroquine, estimated later to be approximately a 50-gram ingestion. She was given activated charcoal post intubation and started on high dose diazepam, as well as epinephrine for refractory hypotension.


Initial labs returned with a potassium of 3.2; calcium and magnesium were all normal. On repeat labs, potassium dropped to 1.6 with EKG as below.

Ignoring the digital conversion artifact in the inferior leads, there is likely atrial bigeminy. QRS is narrow and QTC by computer is 629 ms (not sure which algorithm) which results from the computer incorporating the U wave into the calculation. To measure the QTc, we must first differentiate the T wave from the U wave, which is easiest to do using V3. See the enlarged view of V3 below. The first beat in V3 is a sinus beat followed by a premature atrial beat resulting in a U wave and a P wave that are superimposed. This becomes more evident when looking at the second beat in V3 where you can clearly see a T wave and a separate U wave.

(Blue arrow = P wave, Red arrow = U wave, Green arrow = T wave)

Below is the most recent EKG, taken four days later.

You can see the P waves are much smaller now, and likely her normal P waves when compared to prior EKGs.

This confirms that what we saw previously were likely U waves superimposed on P waves. The patient was transferred from the Medical ICU down to the floor the following day.


In the COVID era, we should be familiar with signs of potential hydroxychloroquine toxicity if providers are still using and patients are still taking this medication as it has a very narrow therapeutic window and can be lethal.

Hydroxychloroquine/chloroquine are potassium and sodium channel blockers which can lead to QRS widening, ST changes, QTC prolongation and dysrhythmias.

Hypokalemia is a hallmark feature and degree of hypokalemia is associated with mortality risk. Exact mechanism is unclear but is thought to be due to an intracellular shift. While repleting the potassium may be necessary, Goldfrank’s advises caution with aggressive repletion as hyperkalemic complications have been noted later in the course when the potassium then shifts out of cells. Use of bicarb for widened QRS is controversial as it may exacerbate hypokalemia but is reasonable to use if the potassium level is normal taking into consideration the patient’s entire clinical picture.

Management is mainly supportive with early intubation, glucose therapy for refractory hypoglycemia, and epinephrine for hypotension. Several small human and animal studies have shown a benefit in using high dose diazepam (2mg/kg IV over 30 minutes followed by a high dose drip).

If you have a patient with a possible overdose, call your local poison control center at 1-800-222-1222.

For a more in-depth analysis of the QTc interval and U waves in another similar case, check out this article by Dr. Smith, in which cardiac arrest due to Hydroxychloroquine was treated with intravenous fat emulsion. 




Take home:
1. Know how to measure QTC, the computer is often wrong.

2. Pay close attention to QRS and QTC in potential tox patients.

3. Know the possible EKG findings of hydroxychloroquine as ubiquitous use in the COVID era can cause serious complications.




Resources:

Barry, James David. "Antimalarials." Goldfrank's Toxicologic Emergencies, 11e Eds. Lewis S. Nelson, et al. McGraw-Hill, 2019, https://accessemergencymedicine.mhmedical.com/content.aspx?bookid=2569§ionid=21027 3082.

Crouzette, J et al. “Experimental assessment of the protective activity of diazepam on the acute toxicity of chloroquine.” Journal of toxicology. Clinical toxicology vol. 20,3 (1983): 271-9. doi:10.3109/15563658308990070

Riou, B et al. “Treatment of severe chloroquine poisoning.” The New England journal of medicine vol. 318,1 (1988): 1-6. doi:10.1056/NEJM198801073180101

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MY Comment by KEN GRAUER, MD (7/24/2020):

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GREAT case, with superb explanation and dissection of serial ECGs in this case by Drs. Coleman, Givergis, Meyers & Smith. My comments are brief:

• I’ll repeat the emphasis that was made on the importance of accurate assessment of QRS duration. As noted above — at 1st glance, the QRS complex appears to be “normal”. However, as was shown by the magnified view (2nd figure above) — vertical BLUE lines clearly document significant QRS prolongation (ie, to >0.13 sec). This is highly relevant — because QRS prolongation >100 msec is a most important predictor of serious sodium channel blocker toxicity (especially as a predictor of potential seizures).
• PEARL #1: The reason the QRS complex “looks normal” in the 1st ECG shown above (which I’ll call ECG #1) — is that: i) QRS morphology does not resemble any known form of conduction block in ECG #1 (ie, not RBBB nor LBBB); and, ii) The initial portion of the QRS complex is completely normal (ie, it looks virtually identical to the initial portion of the QRS complex in serial tracings after QRS duration returned to normal). This terminal prolongation effect is commonly seen with sodium channel blockade and with selected other toxicities — in which QRS widening is primarily a result of widening of the latter portion of the QRS complex.
• PEARL #2: Hydroxychloroquine/chloroquine is a sodium channel blocker. Prominent for its absence in ECG #1 are 2 of the characteristic signs of sodium channel toxicity = i) Right axis deviation; and, ii) Development of a terminal tall and wide R wave in lead aVR (felt to be due to delay that occurs predominantly in the right bundle branch). It should be appreciated that these 2 ECG signs should be specifically looked for when suspecting sodium channel toxicity — and, it’s insightful to know that despite ingestion of a very large amount of a potent sodium channel blocker (ie, hydroxychloroquine) — that these 2 characteristic ECG signs of sodium channel blockade were absent.

The 3rd 12-lead ECG shown above manifests a bigeminal rhythm. I found this to be the most fascinating tracing in this case.

• As shown in the magnified view of lead V3 — the KEY that reveals “The Answer” to a problematic tracing will often be found within the pause in the rhythm (even when this pause is brief, as it is here). U waves are really only seen well in lead V3 of this 3rd 12-lead tracing. It is because of the pause that occurs after the early beat — that the P wave in front of the 3rd (and last) beat in this V3 lead becomes isolated, and clearly identified ( = the last BLUE arrow in this magnified view).
• Knowing that this last BLUE arrow lies over the last P wave in this magnified V3 lead — tells us that the 2nd RED arrow lies over a U wave that is no longer superimposed on the next P wave. Therefore, it is only because of this short pause (that results from this bigeminal rhythm) — that we are finally able to establish with certainty where the U wave ends.
• Rather than the T wave — I believe the 2nd GREEN arrow in this magnified V3 view lies over a coved (but not elevated) ST segment. I believe the T wave itself has a negative component, that falls in-between the 2nd GREEN and RED arrows, blending imperceptibly with the U wave.
• Finally — Beyond-the-Core: This 3rd 12-lead ECG shows a bigeminal rhythm. Although difficult to tell because of the electrical interference artifact in the baseline and because each of the early-occurring P waves is superimposed upon a U wave — P wave morphology in all 12 leads for both the 1st and 2nd P waves in each group looks to be virtually the same. IF we could clearly identify a difference in P wave morphology between sinus P waves and the P waves preceding the early-occurring beats — then we could identify this rhythm as atrial bigeminy. But, when there is a bigeminal rhythm with each beat preceded by P waves with the same morphology — we need to include 3:2 SA block of the Wenckebach (Mobitz I) type in our differential diagnosis of the rhythm.

Chest pain in high risk patient. Are these Hyperacute T-waves? What is going on here?

A 40-something woman with h/o obesity, hyperlipidemia, smoking, as well as cocaine and alcohol abuse presented with intermittent chest pain for 2-3 weeks that became constant in the last day.  There is also some generalized weakness.   There is some associated SOB, but no nausea and vomiting.


Here is the initial EKG:

What do you think?

There is sinus rhythm, a bit of ST depression (II, aVF, III, V2-V6) and apparently very wide and large T-waves.  However, if one looks closely, one sees a distinct and prominent U-wave in leads II, III, aVF.  Whether a T-wave or a U-wave, the interval (QT or QU) is very long.  I measure it at 700 ms.  The computer measured and QT interval of 450 ms and did not mention U-waves.

Look at V1 and V2:

Now notice that there are 2 tiny humps in these waves.  I point it out in the first complex with these arrows:

Here I draw a blue line down from the clear U-waves in II and III to lead II across the bottom (it is also obvious in lead aVF).    Then, I draw red lines from the same part of the QRSTU complex in lead II across the bottom up to the same part of the QRS complex in leads: (aVR, aVL, aVF), (V1-V3), (V4-V6).

This shows that those enormous T-waves are really TU-waves.
Is there a long QT?  Or only a long QU?
The QT interval appears to be measurable in lead III.



See lead III here:

Where does the T-wave end?  What is the QT interval?

The arrow points to what appears to be the end of the T-wave.
The QT interval is 480 ms, which is slightly long, but not dangerously so.
Thus what appears in other leads to be a long QT is a long QU!

As it turns out, the K was 2.6 mEq/L.

There was a previous ECG for comparison:

Normal

Ondansetron was given for nausea and vomiting AFTER this initial EKG.


Here are 2 more ECGs recorded before the K could be adequately repleted:

No significant difference

The computer measured this QT as 452 ms, QTc = 443 ms.
The computer made no mention of U-waves

Again, the "QT" is really a QU-wave.

U-waves are still prominent, and again, I measure the QU interval as very long at 640 ms

Computers are terrible at measuring the QT and QU!

--No ECG was recorded after K was replenished to 4.1 mEq/L. There was no EKG recorded confirming normalization of the QT/QU interval.
--The long QU was not recognized as a long QU.
--The supposed "long QT" was partly attributed to ondansetron, but this was given AFTER the first EKG.  

She ruled out for MI by serial troponins.

Found to be on methadone, and I was worried that this might be methadone effect, so we contacted the patient to have another ECG recorded with a normal K.  Here it is:

Normalized.
Thus, the long QU was probably all due to hypokalemia.

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MY Comment by KEN GRAUER, MD (12/18/2019):

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We have seen this picture that appears in the initial ECG in this case ( = ECG #1 in Figure-1) — more than a few times before on Dr. Smith’s ECG Blog. The “picture” that I refer to is the following:

• The patient is a “set-up” for developing an electrolyte disorder (most notably low serum K+ and/or Mg++) — due to poor nutrition, neglect, recent nausea/vomiting; hypothermia, and all-too-often from alcohol abuse. Generalized “weakness” typically figures prominently in the recent history.
• The ECG shows diffuse ST-T wave abnormalities — usually in the form of some ST-T wave flattening and/or depression, sometimes with some T wave inversion.
• The QTc (or QU interval) is obviously prolonged.
• Prominent U waves are present in a number of leads. These U waves may be readily visible as a distinct “hump” that follows the T wave — or U waves may be more subtle because they so gradually blend in with the preceding T wave. KEY Point — with practice looking for them — you will usually be able to find these U waves deforming, or at least producing some indentation in the preceding T wave. Learn to recognize U waves!

Figure-1: The first 2 ECGs shown in this case (See text).

I'll ADD the following thoughts to comments made above by Dr. Smith:

• “My Take” on the subject of HypoKalemia appears in My Comment at the bottom of the November 18, 2019 Post in Dr. Smith’s ECG Blog. Many of my observations regarding today’s case are THE SAME as I described on November 18 — so I will refer to that post here.
• As was the case on November 18 — a distinct U wave was only seen in 1 or 2 leads. In most leads, the U wave fused with the terminal portion of the preceding T wave — and could therefore be easy to miss. Therefore — it's important to always assess all 12 leads when trying to determine if U waves might be hidden within the T waves that precede them.
• My PEARL #1 from the Nov. 18 Post holds for today’s case. In my 30+ year experience of closely monitoring serial electrolyte levels in such patients — serum Mg++ is so very often also reduced when there is hypokalemia. I believe low serum Mg++ produces similar clinical effects (including weakness) and ECG changes as does hypokalemia. Correction of low serum K+ may be problematic until serum Mg++ is also corrected. We are not told what the serum Mg++ level was in this case ...
• My PEARL #2 from the November 18 Post also holds true: Some patients with hypokalemia develop a “pseudo-P-pulmonale” pattern. Note that the P waves in each of the inferior leads in ECG #1 (especially in lead II) — are tall, peaked and pointed. This P wave pattern was not present in the previous tracing ( = ECG #2), which was obtained when K+ was normal.

OTHER Points that I’d Make:

• I’m surprised that the computerized interpretation in this case missed the U waves in ECG #1. I suspect the computer in this case used lead III, or possibly lead aVF for its calculation of the QTc. Dr. Smith and I both (independently) used lead III — but selection of lead aVF by the computer (considering the bradycardia) would yield a corrected QTc value close to the 450 msec reported. In my experience — the computer is generally quite good in estimating the QTc — because this is a calculated value, and the computer excels at calculations. That said — errors are possible if the wrong data point for the end of the T wave is selected by the computer. BOTTOM LINE — It is essential to always oversee what the computer says. It should be obvious in ECG #1 that either the QT and/or the QU interval is markedly prolonged. This finding of a long QT (QU) interval should not be overlooked. STEP BACK a few inches, and look at ECG #1 from a short distance away. Then “fix in your brain” the picture we see in ECG #1 of a disproportionately long QT (or QU) interval.

PEARL #3 — The easiest way to ensure that you never forget to assess the QT interval — is to use a Systematic Approach in your interpretation of each-and-every ECG you encounter. Failure to comply with this recommendation — is a guarantee that you will periodically forget critical ECG findings, such as a long QTc. (I illustrate use of a Systematic Approach to ECG Interpretation in My Comment at the bottom of the June 28, 2019 SSmith Post).

• Once a long QT (or QU) interval is recognized — Remember the simple LIST that I suggested in the November 18 Post for the causes of a long QTc. In a patient with a history like the one in this case — the presumed diagnosis in ECG #1 (until you prove otherwise) should be low K+/Mg++.

FINAL Points:

• Although the possibility of ischemia should enter into your differential diagnosis for the cause of the ST-T wave flattening/depression that we see in ECG #1 — given this patient’s history, the very long QT (or QU) interval, and our presumed diagnosis of low K+/Mg++ until proven otherwise — I would not have activated the cath lab at this point. My rationale for saying this, is that even IF this patient did have an acute coronary syndrome — IF serum K+/Mg++ are dangerously low — then performing an invasive procedure such as emergency cardiac cath is not advised until you’ve improved serum electrolyte status. Slight delay for this purpose allows: i) A little time to see if chest discomfort lessens, and ECG abnormalities begin to correct as you replace serum electrolytes; and, ii) A chance to follow the patient closely to better assess IF new-onset cardiac chest pain is truly the principal problem (Sounds like it may not have been in this case ...).
• Did you note that voltage criteria for LVH are met in both ECGs #1 and #2? Small and narrow q waves are also seen in multiple leads on both tracings. These narrow q waves are unlikely to be clinically significant (they are probably “septal” q waves, which can also be seen in inferior leads when the frontal plane axis is relatively vertical, as it is in ECG #2).
• Of interest — Comparison of ECG #1 with the previous tracing on this patient obtained when serum electrolytes were normal ( = ECG #2) showed that: i) the QTc was previously normal; ii) Other than perhaps a tiny U wave in lead V2 — U waves were absent in the previous tracing; and, iii) ST-T wave flattening and depression was not seen in the previous tracing. These differences between ECG #1 and the prior (baseline) tracing confirm that ECG changes of electrolyte imbalance in ECG #1 are new!

Our THANKS to Dr. Smith for presenting this case!