Chemical Cardioversion with Amiodarone part... - AF Association

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Chemical Cardioversion with Amiodarone part 2: Reporting progress

In a previous post, I reported on an unusual method of cardioversion: the use of 1200mg Amiodarone, then 800mg, each as a 'bolus' to hit the AF hard, and reset the circuitry. I was treated by a French trained surgeon/general cardiologist. This surgeon knew how to handle life threatening rate and rhythm problems, and this probably influenced his use of this unusual method.

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Post chemical-cardioversion, I stayed on Amiodarone for 5 weeks. The official schedule was 400mg as a daily bolus for 5 days, then a pause over the weekend. After two weeks I noticed the irregularities on Monday were low, but were high on Tuesday. Therefore, the Amiodarone was stimulating the irregularities so I reduced it to 200mg daily. It definitely felt fragile.

The doctor wanted me to stay on Amiodarone for six months. The compromise was 1-2 months. Here is how I negotiated.

** Since I now refused Amiodarone, and we were agreed on Flecainide, He said 100/100mg. I replied with my case history. I knew from several years of experience that for me, the maximum dose is 50/50 and that sometimes even that is too much. He seemed unaware of how variable this medicine is. The patient has the best memory of case history.

So he sort of agreed to 50/50.

** I replied, that was too high, because in patients on Amiodarone, the dosage of Flecainide is halved. I learned that from one of the drug interactions sites.

So, 25/25. But he still wrote down 100/100 on the prescription. Maybe he was tired.

He did not like the idea of taking Bisoprolol. He did well to be cautious. He was nervous about my blood pressure, and wanted to start me on a new drug, one I had never taken before. And, worst, he wanted to start at a high dosage instead of starting slowly, building up with time if needed.

When I got home, I did not feel comfortable. I knew that taking nothing was an option for three days, so I decided to set out various scenarios, and see which was best when I was calmer.

My eventual reasoning was this: the doctor was clearly wrong about the dosage of Flecainide.

Bisoprolol WAS safe in small amounts, and Bisoprolol was closest to treating the current causes. It also nicely put a damper on the blood pressure without adding yet another medicine. The problem of blood pressure could also wait a few months. It went down a few weeks later, as my stress went down.

So, I began with bisoprolol 1.25mg ONLY. After about two weeks I felt some irregularities kicking in, so started in addition, Flecainide, 25/25. After two weeks I found I needed a booster mid afternoon, so I am now experimenting with 50/25. I noticed the INR is going back to normal faster than last time which is a marker of how much Amiodarone is in my system, so I can expect to be on normal prophylaxis of 50/50 fairly soon.

** Lessons learned **

1/ In February I had missed the warning signs: I should have gone back on prophylaxis for several weeks/months at a time when I had tachcardia twice in a week. In years past, I never had an incident of tachycardia while on Flecainide.

2/ The benefits of low dose Bisoprolol (1.25mg) especially to counter the high adrenaline in the early evening. A few weeks of this from time to time and when stressed could be beneficial.

3/ The sympathetic system and the parasymathetic system must not be viewed as opposites which are alternating. The traditional view is that when you are high on adrenaline you are low on calm factors. Reality is that you can be high on adrenaline and highly calm, high sympathetic AND high parasympathetic. [I am in my element lecturing for 100 minutes non stop and I reckon to hold the attention of the students that long. It is exhausting extremely high pleasure for me but my friends say it would terrify them]. As long the adrenaline and calm sheer pleasure are in equal strength there are few problems. But when I relax while adrenaline is high, then I get problems.

4/ Would I take Amiodarone as PIP? Would I do so on my own initiative? I have not ruled it out if the normal Flecainide/bisoprolol PIP fails. Would I do it without medical supervision? With hesitation, now I know how I react, I say yes, provided I was not alone, and it was morning not evening and I had given time (24 hours) for the short acting meds I was on to significantly diminish.. The big danger is that the blood pressure will get too low at the peak of the bolus of Amiodarone (around 10 hours after taking the medication). I would want to have regular blood pressure readings, and regular ECG.

5/ I have seen that Amiodarone, when taken as a bolus, has a massive influence on rate not just rhythm. It is incorrect to say that Amiodarone 'is' a rate controller.

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Well, after having read this 3 times I can only say that it is a good job you know what you are doing!

I had a (simple?) Chemical cardioversion with Amiodarone in cardiac unit over 2/3 days about 23 years ago and was discharged on the drug......stayed on it for about 18 months and then changed to Disopyramide. A lot of water under the bridge......more recently 24hr iv Amiodarone couldn't budge my AF.

Sandra

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Sorry to hear that 24 hours of intravenous Amiodarone failed.

That is certainly one method -- it is documented somewhere in the methods used when people need treatment for life threatening rate and rhythm problems. The sort of thing that Cardiologists in the Emergency department use.

The key difference with my doctor was he used the method of the 'bolus' of Amiodarone. He wanted a sudden high dose to hit the heart, like a diffuse electrical hit. He knew from experience this could be achieved orally. He knew from experience that oral is safer than iv. He knew from my experience that I could tolerate (stomach etc) a high dose orally.

In this case, it is a good job my doctor knew what he was doing, and that (with difficulty) I had broke through to trusting him enough to try it. Disagreements what to do afterwards were another story.

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The reason for a high initial dose when administering Amiodarone is because it has a very long half life of about a month. If you were to start out on the maintenance dose without an initial loading dose first, it would take several weeks before you reached a high enough blood concentration to actually do anything.

When the crash team put me on Amiodarone in 2014 they used IV for the initial loading dose. The first 500cc bag was emptied into my arm in 20 minutes flat, with the drip pump whining like a banshee instead of the usual 'tick....tick...tick'. That was followed by another bag over the next 24 hours, by which time my arms were sore, and bulging like Popeye's.

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I follow you. They did put in a high initial dose, fast, which creates a bolus that hit the heart. In your case, it unfortunately had little effect. Loading is important for Amiodarone, when you want it in your system. With tablets there are two ways of doing loading: short sharp shock, and spaced.

You got your 'bolus' intravenously, I received it orally.

Bolus, and Loading, are two different concepts.

My doctor said that if the second bolus had failed he would then have used the 'last resort' which is the shocks. I would also have been prepped, by having the Amiodarone in my system. If the electrical shocks then fail, the Amiodarone would be discontinued. If the NSR is achieved, then my doctor likes to keep me on Amiodarone as long as possible. At that point, it becomes a matter of judgement when to stop.

I think there is a case for using Amiodarone as another type of PIP, without using it for prophylaxis afterwards.

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Little effect? The Amiodarone worked fine for me, my heart rate was down to a safe level within about half an hour, and back to normal after a couple of days.

Amiodarone isn't practical as a PIP because the half life is too long, you would have to scoff a whole packet to get anywhere near a therapeutic dose.

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Yes, the first attempt had little effect on me.

There is a major difference between hitting the heart hard, with a bolus of medicine, and achieving a therapeutic dose! For my first bolus I took 1600mg! The doctor would have given me more, but he feared that I would over-react, and the heart rate would drop too low, along with low blood pressure. He might have given me more if it was started in the morning but I was started in the evening.

In your case, it seems like you had a high initial dose. That was NOT just for the loading. It was to speedily send a wave of this chemical into your system, like a tidal wave. It worked first time for you.

For me, he did that wave orally. And it did not work the first time. I know, I was resting in hospital all night, watching the ECG, heart rate, and hourly blood pressure readings. I saw when the Amiodarone began to have an effect. I then saw the battle, to reduce the rate and to regularise the rhythm. I saw my heart rate get to a normal 55 (normal for 3am) then the irregularities increased and the rate increased in compensation. Therefore, the first tidal wave had shown signs of working, and we agreed a second attempt.

Maintaining NSR is another matter. There is no medical reason why having had Amiodarone like PIP, that other drugs cannot be used, such as the traditional flecainide/bisoprolol mixture. Having done it once in hospital, I could DIY at home, when other methods fail, as a last resort.

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The half life of Amiodarone is 50days, so that means that after 24 hours there will be 98.62% of the drug remaining in your system (0.9862 is the 50th root of 0.5), so if you start taking a daily dose of say 200mg:

After the first 24 hours there will be 98.62% of the first tablet left (197mg), and you then take another 200 making a total of 397mg in your system.

Next day the same happens: 0.9862*397+200= 592mg

Then again and again each day:

0.9862*yesterday+200 = 784,

and then 973,1159, 1343, 1525, 1704 etc etc.

This has already exceeded 1600mg after just 8 days, and it's still rising at nearly 200mg per day. In each successive 24 hour period the level drops by 1.38% of the total, and then rises by 200mg with the next pill, so whilst the total grows at about 200 per day to start with, it will grow more slowly as 1.38% of the total becomes a bigger number.

Eventually you will reach a point where 1.38% of the total already in your system is equal to the 200mg you're taking each day, and at that point you have reached an equilibrium where the concentration in your system will stabilise. That concentration is 200/0.0138= 14500mg, so even a 1600mg dose is just 9% of the level that would be in your system if you were taking 200mg daily, and 200mg as a single dose would only be 1.4%, so would that really have any effect?

(Continuing the progression above, after 50 days you will still have reached only half the equilibrium dose of course.)

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I love it! Yes, I can follow the calculations. I miss this level of discussion. Thanks for doing the sums.

But, there is something else happening. Either intravenously or orally with a single dose there will be a peak. If that peak is sharp and concentrated, there will be an effect.

That is why with PIP such as Flecainide, they recommend one high dose, not two small doses. It is the peak that gives the kick.

That is why my doctor prescribed repeated kicks, after the 1200mg (sorry, I incorrectly said 1600mg) it was 800mg, then repeated daily kicks of 400mg, with a rest at the weekend so that the body could get rid of some of the drug.

Steady state is one thing. Reset Kicks are another.

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If you take a big dose the concentration in your system will be higher than if you take a small dose of course, but if you take a single dose the concentration can't be any higher than it will be after the first of many doses. Your body doesn't have a crystal ball to predict the future, so if you take a dose of a drug it has no way of knowing whether it is the first of many, or the only one.

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The point about the big dose is that it is all taken at once. So, 1200mg taken as one dose, will give a peak concentration. That peak will be sudden. If the 1200mg is taken as say three doses of 400mg over 24 hours, then you will get slow steady loading.

The peak concentration of 1200mg in one go, will be higher than the maximum level of 2 times 400mg over 24 hours.

This peak dose would usually be considered to be dangerous. But in this case, the desire was to create a peak. The same effect could be done using an intravenous injection (lower amounts of course!!) with all the risks of intravenous. The peak, taken orally, was blunter than taken intravenously, but was still a definite peak. One peak had a similar effect to an electrical shock.

It is the same principle in any PIP. This is an important point. I used to take Flecainide as my PIP, and to space it. There is benefit in a PIP in the sudden peak which hits the electrical circuits and cleans them out. Therefore, for instance, if your stable prophylaxis dosage for Flecainide is 50/50, and you were off flecainide for a while then suddenly needed it, you would use 100mg as PIP, NOT 50mg.

It was very interesting. My doctor after the initial 1200 then 800, asked me to repeat the hitting daily, five times a week, and stop for a rest at the weekend. I was asked to take 400mg in ONE dose each day. The doctor wanted repeated hits. The weekend off was there to give time to get rid of some of the loading which was hindering the hits.

After the second weekend I found that the irregularities were LESS on the Monday than the other days, which showed me the drug was now creating irregularities, and I reduced the dosage and stopped.

... Just following the centuries old tradition of self-experimentation of scientists!!

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