Antiarrhythmic confusion.........

[ekgpress]

Fair enough.

I like to discuss to physiology and pharmacology because they interest me, and I have a fair bit of education in these areas. While this is probably an unpopular opinion, I think that doing so has made me a better paramedic. But we're all in the same boat here. I can't deliver a therapy that's not available on my ambulance. And while I may have been able to move outside of the medical control guidelines from time-to-time, I can't just decide they're wrong and outright violate them without good cause. I don't think anyone is suggesting that you should either.

Granted the topic of this thread has drifted far away from amiodarone maintenance infusions, but at some point we started discussing the pharmacology of nitroglycerin. Feel free to contribute to that discussion, if you'd like.

If we steer this thread back to the original topic -- I'd always wondered why we use maintenance infusions with an antiarrhythmic like amiodarone that has such a long t1/2. It seems like if we get high enough plasma concentrations to convert / suppress an arrhythmia, that if we're waiting 50 days for he concentration to half, there's not going to be a pressing need to administer more in the next couple of hours (days?).

Then I looked at some research, and saw that amiodarone rapidly redistributes to the adipose tissue from the bloodstream. So I think that after a bolus injection, we see a rapid movement of amiodarone from the bloodstream to the adipose tissue compartment. So in the initial period following IV administration, the plasma concentration actually falls much much more rapidly. The apparent half-life during this period is much shorter. One the amiodarone has redistributed, and the vascular and adipose compartments are in equilibrium, the longer 50 day half-life is seen. So I think the maintenance infusion may be designed to ensure that plasma [amiodarone] stays higher than it would otherwise.

I've got to say though -- given amiodarone's multiple complex, and perhaps not fully understood actions, I think it's surprising that we use a drug with such a long half-life. Once it's in, we're stuck with relatively high levels for a couple of months. Seems like that might present some potential for drug interactions and proarrhythmic effects.

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Wow- It's difficult for a newcomer to follow the energized flow of EMTLIFE conversation . . . . Re Amio - my impression is that the 30-90 day half-life following oral loading is as you say different from initial IV loading which has more rapid redistribution - so there is a rationale for IV bolus and initial IV maintenance infusion on those occasions with potential life-threatening arrhythmias (when it is indicated). I think we are on the same page as to "IF" amio infusion is indicated - with KEY to this decision being whether it was the IV amio bolus that converted the patient - and whether there may be other underlying/contributing factors to having caused the VT/V Fib in the first place. Amio IV infusion is not necessarily indicated in all cases, esp. if something "fixable" is found and corrected after conversion to sinus rhythm.

As to Nitro - I'd summarize what I'm getting as the "gist" of your conversation flow by adding the following thoughts/comments:
i) the physiologic effects of IV nitro differ from nitro given by any other route in that there clearly is more arterial vasodilatation with IV NTG (vs predominant venous/preload effect when NTG is given by other routes). This is why IV NTG has been a drug of choice for acute pulmonary edema (great afterload reduction effect in this situation). IV NTG also offers the advantage of immediately "turn on/turn off" effect for hospitalized patients with acute ischemic chest pain.
ii) NTG given by any formulation may lower BP. Caution (at the least) if not contraindication is advised if your starting BP is very low. How low is "very low" may be a matter of judgement depending on the situation. When one is dealing with a volume dependent situation like acute RV MI - my tendency had been not to use NTG (because of the expected potentially dangerous BP drop you anticipate). Whether to say NTG can "never" be tried in such situations is a difficult call since one rarely has "pure" RV MI (it is usually associated with inferior LV MI also - and how much RV vs LV involvement effect is operating may be difficult to determine . . . ).
iii) The problem of course with sublingual administration of NTG is that IF you do get a big BP drop - you "can't take the sublingual pill back . . . " - vs a more controlled situation with cautious initiation of a low-dose IV drip that can be much more rapidly titrated (which obviously is NOT something EMS will be able to do in the field . . . ).
iv) I agree that even if you as EMS personnel are working in a situation where you are compelled to "follow protocols" - that it is still good to think about "Why?". Hopefully the situation will allow some conversation with the Medical Director (at least at some point . . . ). Your input should (in a good system) be heard and at least considered . . .
v) My impression (if memory serves me - since it has been a while ... ) - the big ISIS-4 study on use of IV NTG did not show benefit for acute ACS patients - BUT that huge study was FLAWED since it did not control for the use of sublingual NTG prior to administration of IV NTG in the study . . . ergo despite wide publicity in cardiology circles - I don't know that it has truly ever been established as to whether there may be some positive effect of NTG in ACS. Physiologically - it makes sense to me that there may be, if ischemia is a contributing mechanism - but I don't know that this is known for sure. So like almost everything else in medicine - the question of whether or not to use NTG (sublingual and/or IV, depending on circumstance) is a "balance" depending on specific circumstances of the case at hand plus baseline BP and clinical status - without any rigid "yes" or "no" answers. I personally loved the drug when I was in practice - but I had a healthy respect for potential adverse effects of its use . . .
HOPE the above sheds some light from the perspective of this MD - : ) Ken