August CCU 2014

Does Amiodarone Cause Torsades de Pointes?
Stephanie DeFiores Corey, PGY3
CCU Rotation

CC: Vomiting and Chest Pain

HPI: The patient is a 50 yo female with h/o diabetes, hypertension, cervical cancer s/p complete hysterectomy (many yrs ago), IV drug abuse, now on 170 mg methadone, hepatitis C, bipolar disorder (on seroquel) presenting with 2 days of vomiting and chest pain. She cannot even keep her methadone down.

Physical Exam:
VS: T 99.4, HR 89, RR 18, BP 168/90, SpO2 98% on RA, FSG 266
Gen: In mild distress, yelling, actively vomiting
CV: RRR, normal S1/S2, no murmur
Abd: soft, non-tender, non-distended, no guarding, no rebound
Ext: 2+ distal pulses, no edema, warm
Neuro: alert, oriented x3

ED Course: EMS called ahead and sent rhythm strips. The rhythm strips demonstrated non-sustained runs of ventricular tachycardia. EMS noted a systolic bp of 100 and treated her with a load of amiodarone prior to ED arrival. A 12 lead EKG was done in the ED on arrival which demonstrated non-sustained ventricular tachycardia (NSVT) and bigeminal premature ventricular contractions (PVCs). The rhythm strips from EMS were further examined and demonstrated runs of non-sustained NSVT. The patient was noted to have a prolonged QTc in the current and previous ekgs. The ED ekgs did not demonstrate torsades, but especially given the history of methadone and seroquel use, the patient was treated with magnesium in attempt to avoid reentry into torsades.

Cardiology was consulted. Based on the long QTc and the concern for torsades, they recommended discontinuing amiodarone and starting the patient on lidocaine.

CCU Course: Methadone, clonidine and seroquel were held. PVCs/NSVT resolved. The patient complained of withdrawal symptoms and was restarted on a lower dose of methadone without further QTc prolongation (QTc stabilized at 414). She was transferred to the floor and is awaiting a Cardiac CT scan to further evaluate her coronary vessels.
Torsades de pointes:

torsades word

Image courtesy of

Torsades de Pointes (TdP) is a polymorphic ventricular tachycardia with a prolonged QT interval that characteristically appears like a twisted ribbon. It is usually preceded by an ectopic ventricular beat followed by a pause followed by a sinus beat. It is often self terminating as in this case, but can be a lethal arrhythmia.

Does amiodarone cause torsades de pointes?

Based on an Ovid and Pubmed searches, there is very little evidence of amiodarone causing torsades. A handful of case studies were found, but notably most case studies mention that the cases involved electrolyte abnormalities as well as the use of amiodarone. Rajpal (2013) is a case study of torsades in a methadone patient that resolved with discontinuation of amiodarone and treatment with iv magnesium, potassium, and lidocaine. Jhuo (2014) described a case of a patient with heart failure who was s/p mitral valve replacement surgery who developed torsades while taking amiodarone and digitalis in combination and suggests that the combination was the cause.

One study also noted that between 1983-1999, 47 cases of amiodarone associated cases of TdP were reported with one fatality according to data collected by the World Health Organization. This paper is cited in many articles and papers, but the original article was not accessible through Ovid or Pubmed databases and could not be more thoroughly examined.

There is a theoretical risk of amiodarone causing QTc prolongation and leading to torsades. One of our cardiologists referred me to the website to view a list of QT prolonging drugs.

To further understand this theoretic risk of QT prolongation from amiodarone and the preferential use of lidocaine in this particular case, lets briefly review the mechanism of action of each medication.

Mechanism of Action: amiodarone

Amiodarone is a class III anti-arrhythmic. It is unique because it has class I, II, and IV anti-arrhythmic activity. It alters the lipid membrane on which the ion channels and receptors are located, thereby altering all of their activities. Its action on Ca channels preferentially at the SA and AV nodes (similar to the activity of a calcium channel blocker) are the basis of the theoretical risk of prolonged QT leading to TdP.

Mechanism of Action: lidocaine
Lidocaine is a class Ib anti-arrythmic. It blocks sodium channels of ventricular myocardial cells, preferentially at overactive tissue sites (without affecting normal cardiac tissue), increasing the threshold for action potentials in myocytes and decreasing the slope of phase 4 depolarization. It rapidly dissociates from Na channels and carries no known risk of QT prolongation and repolarization is actually shortened by its use.

Should amiodarone be avoided in patient’s with prolonged QTc?

In conclusion, amiodarone does carry a risk of QT prolongation. Although case studies demonstrating amiodarone therapy leading to torsades de pointes are rare and may be confounded by electrolyte abnormalities and a variety of other factors that may have lead to TdP, lidocaine or an alternative anti-arrhythmic may be preferential in a situation in which a patient already has a prolonged QT interval. Since amiodarone does have a known risk of QT prolongation, a prospective study would not be ethical to determine if amiodarone is more efficacious and safer than alternative therapies in these situations. In my practice I think I will avoid it in patients who have already had runs of TdP and who have prolonged QT intervals. What will you do?


Armstrong, E. “23: Pharmacology of Cardiac Rhythm.” Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2012. N. pag. Accessed via Einstein remote access library 8/14/14.
Jhuo, Shih-JieLai, Wen-Ter et al. “Torsade de pointes induced by amiodarone in a patient with heart failure.”
The Kaohsiung Journal of Medical Sciences 30.2 (2014): 108 – 109. Pubmed. Web. 15 Aug. 2014.
Rajpal, S. “Treatment of Methadone-induced Torsades De Pointes with Lidocaine.” J La Sate Med Soc 165.6 (2013): 338-41. Pubmed. Web. 15 Aug. 2014.
Yap, Y. G. “Drug Induced QT Prolongation and Torsades De Pointes.” Heart 89.11 (2003): 1363-372. Pubmed. Web. 15 Aug. 2014. accessed 8/14/14 5:50pm. accessed 8/14/14 5:50pm.

4 Comments on "August CCU 2014"

  • Good Job Steph,
    This is definitely a difficult topic to tackle – TdP and Vaughn-Williams antidysrhythmics… I think you do a great job of breaking down some of the difficult-to-understand points.
    Most simply put (and Cardiologists would probably frown on my simplified explanation), the repolarization of the myocardium (the ST and T-wave on the EKG) can thought of as the closing of the Ca++ channels. It should be divided into an “absolute refractory period” (when the Ca++ channels are inactive) and a “relative refractory period” (when Ca++ channels are closed, but ready to be activated/opened again). This “relative refractory period” corresponds with the second half of the T-wave. Any ectopic beat that lands on this portion of the EKG may lead to TdP.
    Amiodarone is quite a special Class III anti-dysrhythmic. It blocks Na and K channels, thus prolonging the QT interval. You would think that this would increase your chance of getting TdP. But amiodarone also block L-type Ca++ channels. You can essentially think of it as making the “relative refractory period” more like the “absolute refractory period”. Giving magnesium, essentially a calcium-channel blocker, also does the same thing…
    I think there is a lot of data out there that suggest that TdP with amiodarone alone is quite rare.
    I don’t disagree with the use of a Class Ib like lidocaine for the treatment of TdP, it makes sense. But I don’t think that the prolonged QT produced by amiodarone leads to that much TdP. Furthermore, ED physicians and EMS might be more familiar with amiodarone rather than using lidocaine for dysrhythmias.
    Open to thoughts…

  • I don’t know that there is a definite answer to the question you raise. As you have stated – there is little evidence of TdP induced by Amiodarone (perhaps because of the mechanism cited by Vince). I share concern about using Amiodarone in frank cases of established TdP with marked QT prolongation – but I don’t think the issue comes up very often. Treatment of choice for established TdP with prolonged QT is IV Magnesium (and lots of it – up to 8-10 gm if/as needed). In the absence of frank TdP with marked QT prolongation – I don’t know that there is contraindication to Amiodarone – especially when QT prolongation is not excessive. NICE write-up by Dr. Corey!

  • Super-chief Steph! Awesome follow-up. I was quick to read your post because this question has been weighing on my mind since…well… I was head-of-bed for this exact notification a couple months back. Thanks for doing the heavy-lifting in chewing this over. And thanks for the contributors that prolonged* the dialogue.

    *yes, that was a pun

    My thoughts for the case: Right, there was no clean rhythm strip that showed us hallmark “twisting of the points,” but we recognized that the risks were there with the methadone, vomiting (e-lyte imbalances) and anti-psychotics. And despite the NSVT she was markedly brady-also prolongs QT. Mag was an easy choice for all those reasons. And Amio was really to treat the EMS strip–NSVT. It took us 15-20min to get any good EKG as patient was flailing and vomiting in the trauma bay and the monitor looked like an etch a sketch. She was almost immediately Sinus after the mag.

    All said, I would not start amio for clear-cut TdP or prolonged QT. But after reading all this, I think it was still the appropriate decision to start the amio drip after the Mag based on what we saw-or didn’t see-on the strips. And I also do not think it did any harm as long as mag was on board.

    Needless to say, we did not give this patient Zofran for her vomiting.

    So prolonged QT can cause the phenomena of early afterdepolarization and TdP, but from what I have read, it is mostly attributed to changes in potassium channel conductance during depolarization. All those QT-prolonger drugs blocks one of the many subtypes of potassium channels. The calcium channels go through stages of activity and inactivity during the refractory periods but the potassium current brings everything back down to the proper resting potential and sodium conductance is what will kick-up the next one. I get Vince’s point though, amiodarone works on all these channels, and although some of it’s action might further prolong, part of its action likely has similar effects to the magnesium.

  • in the spirit of the jacobi festivities lately here at acep14, here’s my 2 cents as i’m nursing a headache.

    they say things come in 3s, and recently i had 4 vtac cases, 4 different causes, 3 within a week’s time, so i had some chance to practice. i’ll share the cases and things i learned.

    1. octagenarian in vtac. no family member. slightly confused. unclear if this was baseline or 2/2 poor perfusion. i gave him mag. lidocaine. didn’t break. then decided to cardiovert him. turns out, he had an underlying LBBB and was in SVT.
    i know there’s a way to tease this out. but i’m a simple guy and when it smells like vtac, i just treat it as such. i also usually go big. 200j. re: his mental status, he was confused from the vtac. he also spoke russian, and i spoke none. 200J fixed the first issue, and translator confirmed it.

    2. etoh-er with iodine allergy in vtac. again, started with mag. lido drip. i especially picked lido on this one because her qtc was in mid 500s. then again, most vtac i’ve seen will have electronic reading of qtc in 500s. failed. i got cards involved and he recommended amio, aware of the qtc. when doing something that i know has some contraindications, i involve the experts =) amio worked. then she went to torsades. gave more mag. broke. continued amio gtt. kept on going into torsades. more mag. electric cardioversion. when the pt was in sinus rhythm (on amio gtt), she had u waves. her K was normal though, and by this time, her mag was nl/hi-nl. then some smart guy mentioned the nernst equation. i’m not smart enough to understand this (i know vince will be), but apparently, even though the K is normal, she was hypokalemic. they gave more K in the CCU, and she stopped going in and out of vtac. what about the iodine allergy which can be triggered by amio? it’s like pcn in syphilis. unless it’s anaphylactic rxn, especially in vtac cases, treatment trumps potential allergy.

    3. this was the mother of all vtacs that week. recently admitted for MI, now with vtac with good bp, good mentation. again, tried mag+lido. tried overdrive pacing. then she lost pulse. shocked. goes back to sinus rhythm, then back to vtac. after 2 rounds of cardioversion, decided to intubate her, put an a-line, and it was cool to see that whenever she went into vtac, the a-line would flat line. at this point, i had 2 cardiologists on the line at 4am, one being an electrophysiologist. recommendation was to give amio. and lots of it. so i bolused her with amio 6 times. (150mg x 6!) and shipped her to the CCU. she continued to be in vtac for the next day, but eventually what worked was procainamide. now i use procainamide in afib patients, but don’t like it in vtac because 1. takes too long, 2. pressure can drop. 3. in nonsustained vtac, it can also cause torsades. underlying problem for this patient was an LV aneurysm that was arrhythmogenic after her MI. learning point. ok to give high doses of amio. but again, with blessing from cards.

    4. old guy in vtac. has aicd. supratherapeutic on dilantin. tried precordial thump. no dice. mag. lido gtt. turns out, dilantin toxicity had nothing to do with it. his aicd just died. lido did the trick.


Leave a Reply