An Unclear Mechanism of Wide-Complex Tachycardia

Written by Matthew Behrens MD

Reviewed by Sage Wiener MD

Case:

A 31-year-old man was brought in by EMS after passing out while getting off the bus. 

Prehospital vitals were:

EMS placed a peripheral venous catheter, gave NS, and placed the patient on 15L O2 NRB. They reported “runs of VT and PVCs”. Here’s what they show you:

ECG performed by EMS

This single lead ECG appears to show a regular, sinus, wide-complex rhythm at a rate of ~125/min with prolonged QT.

Triage vital signs are:

The patient’s SpO2 is 70-80’s% on RA. 

Initial Assessment and Interventions:

• • Airway: unprotected (lethargy)
• • Breathing: Tachypnea
• • Circulation: Tachycardia, warm extremities

This patient has life-threatening respiratory failure and tachydysrhythmia. The next steps were:

• • Cardiac monitor (wide-complex tachycardia)
• • 2nd peripheral venous catheter, additional IVF (LR bolus) 
• • Rapid-sequence intubation (etomidate, rocuronium)
• • ECG 

Now that the airway is secure and the patient is being oxygenated/ventilated, we can resume our secondary survey: 

Secondary Exam

Lung/cardiac ultrasonography showed no pericardial effusion and lung sliding bilaterally.

Initial Differential Diagnosis:

We have a 30-year-old male who presented with AMS, respiratory distress, tachycardia, and an ECG performed in the field that shows a wide QRS. We have very little history of present illness. In cases like this, we typically start very broadly in our peri-arrest/arrest differential.

A wide QRS complex (as opposed to a narrow QRS complex) pushes metabolic causes further up in our differential. We have already resolved one of our H’s, hypoxia, with supplemental O2, intubation, and mechanical ventilation. Hypoglycemia is also ruled out. Based on the secondary survey findings of tachycardia/hypertension, mydriasis, diaphoresis, and tactile hyperthermia, this case strongly suggests a sympathomimetic toxidrome. Bedside ultrasonography ruled out tamponade and tension pneumothorax. Acidosis and hyper/hypokalemia are all still possible.

After intubation, the ECG is performed:

Initial ECG

ECG Interpretation: 

Regular, wide-complex tachycardia at 170/min; right axis deviation and possible negative precordial concordance. Notice the very brief pause in the rhythm.

A wide QRS (>120 ms) represents prolonged ventricular depolarization and can be created by several pathologies:

• • Impulse is not transmitted through the rapidly conducting His-Purkinje fibers and spreads slowly through non-specialized ventricular tissue
• • Impulse is traveling the His-Purkinje fibers, but there is pre-existing conduction disease and the impulse takes longer to propagate
• • A toxin acts on myocardial ion channels, prolonging time for Na+ influx, or producing triggered activity through early or delay afterdepolarizations

A regular wide-complex tachycardia in the setting of a sympathomimetic toxidrome can be:

• • Sinus tachycardia in the setting of sodium channel blockade: SA node with enhanced automaticity (sympathomimetic effects) and QRS is prolonged due to the effect of the toxin
• • “SVT” (other than sinus tachycardia) with aberrancy: AVNRT, AF/AFL, and AVRT  induced by catecholamines with an abnormally functioning His-Purkinje system (structural or toxin-induced)
• • Monomorphic VT: Re-entrant, triggered, or automatic focus arising from the ventricles

This tachydysrhythmia may be monomorphic VT. For further information about  VT see:

“You make my heart race: Ventricular Tachycardia as a Consequence of Triggered Activity”

“First-line treatment for Ventricular Tachycardia? What the Guidelines and Evidence Say”

Monomorphic VT can be induced by several toxins, particularly Class 1C antiarrhythmics, but also other sodium channel blocking, sodium channel opening, and Na+/K+ ATPase inhibiting agents, including TCAs, lithium, cocaine (sodium channel blockers), and cardiac glycosides (Na+/K+ ATPase inhibitor). 

Clinical Course:

A repeat ECG is performed:

Second ECG

ECG Interpretation: 

Irregular, wide complex rhythm (unchanged QRS morphology) with indeterminate N/NW axis, unifocal PVC

Since the QRS morphology is unchanged and remains wide, this is likely toxin-induced rather than solely from triggered activity.  

Since there was no definitive response to electrocardioversion, it is probable that the wide-complex tachycardia in this patient previously was not reentrant but due to abnormal automaticity. The anti-adrenergic effect of amiodarone may have suppressed the automatic focus uncovering AF with slow ventricular response. 

The patient becomes bradyasystolic despite push-dose pressors and norepinephrine drip, and CPR is initiated. Epinephrine, calcium, naloxone, and dextrose are given. Cardiac standstill is noted 30 minutes into the arrest without other obvious reversible causes, and the patient is pronounced. 

Discussion:

We have two overlapping differentials to work with: 1) peri-arrest state and 2) monomorphic VT. Both of these overlap with toxins, hyperkalemia, and MI. A toxin-induced mechanism was most likely given the sympathomimetic toxidrome A lack of improvement with calcium gluconate also makes hypokalemia less likely. While this may be a co-ingestion with multiple toxins, there is one agent that can cause both a sympathomimetic toxidrome and is a class I/III antidysrhythmic (sodium channel and potassium channel blocker) effect. It’s cocaine!

Cocaine has been reported to cause a variety of dysrhythmias.

Types of arrhythmia caused by cocaine [7]

In order to understand how cocaine can change what we find in an ECG, we have to dive deeper and review some basic cardiac electrophysiology. Below you’ll find a figure of the ventricular cardiac action potential and the corresponding voltage-gated channels responsible for each phase. Note that I’ve excluded other important ion channels and antiporters to simplify:

Fig.1 Phases of AP

Fig.2 Phases of AP

Phase 0 in ventricular myocytes is mediated by voltage-gated sodium channels. This channel is in the resting state when the membrane potential is around -90 mv (phase 4). When an action potential raises the threshold to about -70 mv, the sodium channels open en masse for a few milliseconds, allowing for Na+ ions to flow into the cell before quickly becoming inactivated by another conformational change. It is this 3rd conformational state on which cocaine is believed to act. In vitro studies show that cocaine has little affinity for resting sodium channels, but a much higher affinity once they’ve been activated. Cocaine prevents sodium channels from returning to the resting state, leaving fewer sodium channels in the resting state ready to fire during the next cycle. This in turn decreases the velocity at which Na+ ions can enter the cell, increasing the time it takes to complete phase 0 of the AP. Phase 0 in the ventricular myocardial AP is our QRS complex on the ECG. This is how it leads to the increase in QRS duration that we see in sodium channel blockade. In addition, the effect is modulated by rate, meaning the faster the patient’s heart rate, the more prolonged the QRS becomes due to the increased relative amount of time the sodium channel spends in its inactivated state.  

These effects alone allow cocaine to produce a wide-complex tachycardia. The sinus tachycardia or precipitated SVT from catecholamine excess and the prolonged QRS from sodium channel blockade can be mistaken for monomorphic VT but can resolve with hypertonic bicarbonate alone (more on that later). A non-specific finding of the presence of sodium channel blockers on the ECG is a terminal R in aVR and S wave in I and aVL. Although not completely explained, right-sided conduction is more impaired by sodium channel blockers than left, leading to a slight rightward axis. See this example ECG: 

Fig.5 ECG with Sodium Channel Blockade [6]

When cocaine acts on K+ channels, It prolongs phase 2 and 3, and prevents the cell from returning to the resting membrane potential. When the influx of extracellular Ca++ is not balanced with the efflux of K+, this creates a positive inflection in the membrane potential during phase 2 and 3, known as an Early AfterDepolarization (EAD). It also allows for increased intracellular Ca++ accumulation. As Ca++ levels become too high, Ca++ also begins to leak from the sarcoplasmic reticulum and create excess + charge within the cell. This can in turn create fluctuations in membrane potential during phase 4, creating a Delayed AfterDepolarization (DAD). Excess catecholamines can produce DADs through a similar mechanism of Ca++ accumulation through modification of L-type Ca++ channels. Both EADs and DADs can trigger an additional AP if a sufficient number of Na channels are in the resting conformation. If sequential EADs/DADs reach threshold, then each AP can induce another, creating a cycle that results in VT. These are likely some of the sources of triggered activity in cocaine toxicity. 

Fig.6 Mechanism of Triggered Activity [10]

This explanation leaves us with some salient clinical points:

• • Heart rate is a major modulator of cocaine’s affinity for sodium channels; the tachycardia from excessive catecholamines worsens the sodium channel blockade
• •Tachycardia may be somewhat protective when there are predominantly potassium channel blocking effects. As the heart rate increases, the relative refractory period decreases. This decreases the likelihood of Torsades de Pointes

Interventions:

Now that we’ve discussed the complex pharmacology of cocaine on cardiac sodium and potassium channels, we can explore treatment options for a critically poisoned patient.

Treating Catecholamine Excess:

• • Benzodiazepines: This should be used when there are signs of tachycardia, psychomotor disturbances, or agitation. Benzodiazepines act on GABA channels and act as a CNS depressant, counteracting the stimulation caused by excess dopamine, norepinephrine, and serotonin.
• • Cooling: Catecholamine excess can lead to hyperthermia through several mechanisms, including impaired heat dissipation through vasoconstriction, increased muscle tone, and hypothalamic activation. Elevated temperature in cocaine toxicity is associated with significant mortality⁸ and should be treated directly. This can be done through one of several ways:
  • • Immersive Cooling: ice bath
  • • Evaporative Cooling: mist and fans
  • • Chilled Crystalloid

• • Volume Resuscitation: Patients who are diaphoretic or increased respiratory drive may have increased insensible losses, and volume should be replaced.

Treatment of Sodium Channel Blockade: 

• • Hypertonic Sodium Bicarbonate: This directly increases the gradient of Na ions flowing from outside to inside the cell. The addition of bicarbonate also alkalinizes the serum, shifting cocaine from sodium channels on the myocardium to binding proteins in the plasma. This is our first-line therapy for any patients with an ECG suggestive of sodium channel blockade (wide QRS). Boluses are given at 1-2 mEq/kg. Add 150 mEq of sodium bicarbonate to 1 L D5W and infuse at 150 ml/hr. Titrate to a serum pH of 7.45 to 7.55.
• • Lidocaine (class 1B antiarrhythmic (also a sodium channel blocker)): This is recommended if sodium bicarbonate fails. Lidocaine is believed to exert its effects by competing with cocaine at the site of binding on the cardiac sodium channel. While cocaine is slow to rebind sodium channels, lidocaine quickly dissociates and is rarely able to cause QRS prolongation. This allows the sodium channel to recover. In cardiac arrest, the dose is 1 – 1.5 mg/kg IV bolus, then repeat dosing of 0.5 – 0.75 mg/kg IV bolus up to 3 times. In stable ventricular tachycardia, the dose is 30-50 mcg/kg/minute. 

Treatment of Potassium Channel Blockade:

• • There is no direct treatment for cocaine’s effect on K+ channels
• • Consider giving 2-4 mg magnesium sulfate empirically (After giving sodium bicarbonate)
• • Hypokalemia/Hyperkalemia, if present, should be addressed as well. 

Other Antiarrhythmics:

• • Class 1A and 1C antiarrhythmics: Prolong both the QRS and QT interval, enhancing the toxicity of cocaine and should be avoided. (remember Lidocaine is 1B.) 
• • Beta-blockers: While demonstrated in animal models, the use of beta-blockers in cocaine-induced catecholamine excess is feared to produce unopposed alpha-adrenergic tone, leading to coronary vasoconstriction. Elevated blood pressure should be managed with direct-acting vasodilators such as nitroglycerin or phentolamine.
• • Amiodarone, while not expressly contraindicated, has been relatively unstudied in the setting of cocaine toxicity. It has anti-adrenergic effects and is not recommended

References:

1. 1. Antzelevitch C, Burashnikov A. Overview of Basic Mechanisms of Cardiac Arrhythmia. Card Electrophysiol Clin. 2011;3(1):23-45. doi:10.1016/j.ccep.2010.10.012
2. 2. Edhouse, J., & Morris, F. (2002). Broad complex tachycardia–Part I. BMJ (Clinical research ed.), 324(7339), 719–722. https://doi.org/10.1136/bmj.324.7339.719
3. 3. Edhouse, J., & Morris, F. (2002). ABC of clinical electrocardiography: Broad complex tachycardia-Part II. BMJ (Clinical research ed.), 324(7340), 776–779. https://doi.org/10.1136/bmj.324.7340.776
4. 4. Tse G. Mechanisms of cardiac arrhythmias. J Arrhythm. 2016;32(2):75-81. doi:10.1016/j.joa.2015.11.003
5. 5. Grant, A. (2009). Cardiac Ion Channels. Circulation. Arrhythmia and Electrophysiology, 2(2), 185–194. https://doi.org/10.1161/CIRCEP.108.789081
6. 6. Hoffman RS. Treatment of patients with cocaine-induced arrhythmias: bringing the bench to the bedside. British Journal of Clinical Pharmacology. 2010 May;69(5):448-457. DOI: 10.1111/j.1365-2125.2010.03632.x.
7. 7. Lange RA, Hillis LD. Cardiovascular complications of cocaine use. N Engl J Med. 2001 Aug 2;345(5):351-8. doi: 10.1056/NEJM200108023450507. Erratum in: N Engl J Med 2001 Nov 8;345(19):1432. PMID: 11484693.
8. 8. Marzuk PM, Tardiff K, Leon AC, et al. Ambient Temperature and Mortality From Unintentional Cocaine Overdose. JAMA. 1998;279(22):1795–1800. doi:10.1001/jama.279.22.179.
9. 9. O’Leary ME, Hancox JC. Role of voltage-gated sodium, potassium, and calcium channels in the development of cocaine-associated cardiac arrhythmias. Br J Clin Pharmacol. 2010;69(5):427-442. doi:10.1111/j.1365-2125.2010.03629.x
10. 10. Proven Doctor . [Internet]. 2020 [cited 2020 Nov 5];Available from: https://www.youtube.com/watch?v=htCLGEHaVZU
11. 11. Riera, A. R., Barros, R. B., de Sousa, F. D., & Baranchuk, A. (2010). Accelerated idioventricular rhythm: history and chronology of the main discoveries. Indian pacing and electrophysiology journal, 10(1), 40–48.
12. 12. RILEY, M., & MARCHLINSKI, F. (2008). ECG Clues for Diagnosing Ventricular Tachycardia Mechanism. Journal of Cardiovascular Electrophysiology, 19(2), 224–229.

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