Thread by @AvrahamCooperMD, 1/Ever wonder why magnesium (Mg) is used to treat Torsades de Pointes?The [...]

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Ever wonder why magnesium (Mg) is used to treat Torsades de Pointes?

The answer is fascinating, elegant, and also explains why Mg treats another clinical entity - eclampsia

#medthread #tweetorial #medtwitter

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First, let& #39;s find how torsades was originally described (and named!):

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Francois Dessertenne noted "ventricular tachycardia with two variable foci" in a patient in 1966

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">He coined the arrythmia torsades de dointes, connoting "twisting peaks"

https://bit.ly/2XN9Hp5 ">https://bit.ly/2XN9Hp5&q...

2/ First, let& #39;s find how torsades was originally described (and named!):https://abs.twimg.com/emoji/v2/... draggable=

Francois Dessertenne noted "ventricular tachycardia with two variable foci" in a patient in 1966https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">He coined the arrythmia torsades de dointes, connoting "twisting peaks" https://bit.ly/2XN9Hp5&q..." title="2/ First, let& #39;s find how torsades was originally described (and named!):https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Francois Dessertenne noted "ventricular tachycardia with two variable foci" in a patient in 1966https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">He coined the arrythmia torsades de dointes, connoting "twisting peaks" https://bit.ly/2XN9Hp5&q...">

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To understand how Mg treats torsades we need to understand the pathophys of the arrythmia itself.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="▶️" title="Right-pointing triangle" aria-label="Emoji: Right-pointing triangle">Torsades is a ventricular arrythmia of repolarization, occurring in patients with prolonged QT intervals (usually acquired from drugs, ischemia, or

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow">electrolytes)

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There are 4 phases of repolarization of cardiac myocytes

1: K efflux
2: Ca influx
3 and 4: K efflux

Calcium influx in phase 2 "stalls" repolarization as in/out charge flow is balanced (more on this later)

https://bit.ly/34khj4T ">https://bit.ly/34khj4T&q...

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Torsades arises from a specific sequence of events that disrupts repolarization.

https://abs.twimg.com/emoji/v2/... draggable="false" alt="✅" title="White heavy check mark" aria-label="Emoji: White heavy check mark">Sinus beat

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Prolonged QT

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Ventricular ectopic beat during depol (aka an "early after depolarization" or EAD, thought to be calcium-mediated)

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Re-entrant arrythmia

https://bit.ly/2ruAj1R ">https://bit.ly/2ruAj1R&q...

5/Torsades arises from a specific sequence of events that disrupts repolarization.https://abs.twimg.com/emoji/v2/... draggable=

Sinus beathttps://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Prolonged QThttps://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Ventricular ectopic beat during depol (aka an "early after depolarization" or EAD, thought to be calcium-mediated)https://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Re-entrant arrythmia https://bit.ly/2ruAj1R&q..." title="5/Torsades arises from a specific sequence of events that disrupts repolarization.https://abs.twimg.com/emoji/v2/... draggable="false" alt="✅" title="White heavy check mark" aria-label="Emoji: White heavy check mark">Sinus beathttps://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Prolonged QThttps://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Ventricular ectopic beat during depol (aka an "early after depolarization" or EAD, thought to be calcium-mediated)https://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">Re-entrant arrythmia https://bit.ly/2ruAj1R&q..." class="img-responsive" style="max-width:100%;"/>

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It turns out that seeing torsades on the monitor is literally watching a re-entry circuit circulate

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Terrifying but also striking to see

https://bit.ly/2OKJdjL ">https://bit.ly/2OKJdjL&q...

6/ It turns out that seeing torsades on the monitor is literally watching a re-entry circuit circulate https://abs.twimg.com/emoji/v2/... draggable=

Terrifying but also striking to see https://bit.ly/2OKJdjL&q..." title="6/ It turns out that seeing torsades on the monitor is literally watching a re-entry circuit circulate https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Terrifying but also striking to see https://bit.ly/2OKJdjL&q..." class="img-responsive" style="max-width:100%;"/>

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Now that we understand torsades, how did Mg come to be preferred therapy?

The original description was in 1984 when Mg infusion treated 3 patients w/ torsades who had acquired long QT.

All had normal serum Mg levels, the QT intervals didn& #39;t shorten

https://bit.ly/2OhCm2q ">https://bit.ly/2OhCm2q&q...

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It is not totally clear how they figured out that this might work, but they cite a paper from 1968 where 2 patients w/ Vfib from low Mg (which was actually torsades) were treated with overdrive pacing.

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So how does Mg actually work?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">It turns that Mg, as a cation, is an effective Ca channel blocker.

https://bit.ly/2OkFt9H ">https://bit.ly/2OkFt9H&q...

9/So how does Mg actually work?https://abs.twimg.com/emoji/v2/... draggable=

It turns that Mg, as a cation, is an effective Ca channel blocker. https://bit.ly/2OkFt9H&q..." title="9/So how does Mg actually work?https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">It turns that Mg, as a cation, is an effective Ca channel blocker. https://bit.ly/2OkFt9H&q..." class="img-responsive" style="max-width:100%;"/>

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https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Blocking Ca channels suppresses the EADs, allowing the re-entrant arrythmia to terminate. This was first described in dogs who had torsades-like arrythmias induced by cesium infusions with magnesium rescue.

https://bit.ly/2XKz7DK ">https://bit.ly/2XKz7DK&q...

10/ https://abs.twimg.com/emoji/v2/... draggable=

Blocking Ca channels suppresses the EADs, allowing the re-entrant arrythmia to terminate. This was first described in dogs who had torsades-like arrythmias induced by cesium infusions with magnesium rescue. https://bit.ly/2XKz7DK&q..." title="10/ https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Blocking Ca channels suppresses the EADs, allowing the re-entrant arrythmia to terminate. This was first described in dogs who had torsades-like arrythmias induced by cesium infusions with magnesium rescue. https://bit.ly/2XKz7DK&q...">

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This was described by @PulmCrit as naloxone for torsades (I really like that description)

He also advocates for protocol-driven, continuous Mg infusions to make sure the serum levels stay up (goal 3.5-5 mg/dl) and those Ca channels stay blocked.

https://bit.ly/2OLEJcK ">https://bit.ly/2OLEJcK&q...

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Calcium channel blockade also explains why Mg treats eclamptic seizures:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Eclamptic seizures are driven by dysregulated cerebral vasoconstriction

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Mg blocks Ca channels and induced vasodilation

https://abs.twimg.com/emoji/v2/... draggable="false" alt="✅" title="White heavy check mark" aria-label="Emoji: White heavy check mark">Seizures stop

https://bit.ly/2KUupxX ">https://bit.ly/2KUupxX&q...

12/Calcium channel blockade also explains why Mg treats eclamptic seizures: https://abs.twimg.com/emoji/v2/... draggable=

Eclamptic seizures are driven by dysregulated cerebral vasoconstrictionhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Mg blocks Ca channels and induced vasodilationhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="✅" title="White heavy check mark" aria-label="Emoji: White heavy check mark">Seizures stop https://bit.ly/2KUupxX&q..." title="12/Calcium channel blockade also explains why Mg treats eclamptic seizures: https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Eclamptic seizures are driven by dysregulated cerebral vasoconstrictionhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Mg blocks Ca channels and induced vasodilationhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="✅" title="White heavy check mark" aria-label="Emoji: White heavy check mark">Seizures stop https://bit.ly/2KUupxX&q..." class="img-responsive" style="max-width:100%;"/>

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To sum up:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Torsades is a re-entrant ventricular arrythmia in the setting of a prolonged QT interval

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Early after depolarizations, triggered by Ca influx, lead to torsades

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Mg blocks Ca channels and

https://abs.twimg.com/emoji/v2/... draggable="false" alt="❌" title="Cross mark" aria-label="Emoji: Cross mark">the arrythmia

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Electric light bulb" aria-label="Emoji: Electric light bulb">Mg treats eclamptic seizures by a similar mechanism

What do you think #medtwitter?

CC: @laxswamy @ChrisWorsham @virenkaul @grecoa3 @dina_khateebDO @AdamRodmanMD @tony_breu @ETSshow @cjchiu @gbosslet @aoglasser

This is the correct source for tweet #8

https://www.ahajournals.org/doi/pdf/10.1161/01.CIR.37.2.210">https://www.ahajournals.org/doi/pdf/1...

Props to @downsjw2000 @ElizaMillerMD and others who pointed out that, in eclampsia, Mg has other effects besides vasodilation including NMDA blockade (also by blocking calcium channels!) and neuromodulatory effects

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