ACE inhibitors for AKI 2/2 CHF exac

[dozitgetchahi]

Do you guys continue/start ACE-is in the setting of AKI 2/2 CHF exacerbation?

I don't and had always been told to avoid them in the setting of AKI, but I got chastised big time by an attending today because I held someone's ACE-i after they came in with massively elevated SCr that was likely 2/2 a CHF exacerbation. "No knee-jerk response here - ACE inhibitors actually help with AKI 2/2 CHF" etc etc etc.

Took a look through the literature and opinion seems mixed at best...really the majority of articles are talking about why it probably isn't a good idea. So what gives?

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[jdh71]

Do you guys continue/start ACE-is in the setting of AKI 2/2 CHF exacerbation?

I don't and had always been told to avoid them in the setting of AKI, but I got chastised big time by an attending today because I held someone's ACE-i after they came in with massively elevated SCr that was likely 2/2 a CHF exacerbation. "No knee-jerk response here - ACE inhibitors actually help with AKI 2/2 CHF" etc etc etc.

Took a look through the literature and opinion seems mixed at best...really the majority of articles are talking about why it probably isn't a good idea. So what gives?

I don't and won't. I'll after load reduce in another way at presentation if I think that is what is needed. Sometimes the patients pump is just fine and the the renal injury is because if low volume and the patient just happens to have "CHF" and I'm not interested in a modality that could make the pre-renal situation worse when it's not clear on admit. Seems silly to continue.

 

[nephappl]

This in the setting of cardiorenal syndrome.
The mainstay of treatment is to diurese the patient with loop diuretics +/- thiazides and ultrafiltration should diuretics fail.
ACEIs / ARBs as well as aldosterone antagonist are therapies for the long term management of CHF and most people agree should be avoided
We always stop them because
1. they reduce renal perfusion and GFR making recovery harder in the acute setting
2. produce hyperkalemia
3. exacerbate hypotension
Very often ACEi / ARBs are held upon discharge until kidney function is more stable in the outpatient setting

 

[disorder]

I always hold it and have never been told otherwise. It seems more questionable to hold beta-blockers in CHF exacerbations this seems more of a "flavor-of-the-month" kinda thing-- have been told hold always to hold only if JVD is present to hold only if hypotensive (I believe literature only supports the last).

 

[dozitgetchahi]

Thanks everyone for confirming what I knew, down to the pathophys...being told to restart it seemed straight out of the twilight zone.

It was one of those "I'm always right and I know everything" attendings too, so when I tried to disagree with her on it she wasn't having it.

 

[Instatewaiter]

Do you guys continue/start ACE-is in the setting of AKI 2/2 CHF exacerbation?

I don't and had always been told to avoid them in the setting of AKI, but I got chastised big time by an attending today because I held someone's ACE-i after they came in with massively elevated SCr that was likely 2/2 a CHF exacerbation. "No knee-jerk response here - ACE inhibitors actually help with AKI 2/2 CHF" etc etc etc.

Took a look through the literature and opinion seems mixed at best...really the majority of articles are talking about why it probably isn't a good idea. So what gives?

I won't start them. Whether I continue them will depends on how significantly the creatinine increased. You need afterload reduction in acute systolic heart failure and whether you do this with ISDN/Hydral or ACEi depends on the rate of rise. If it's trivial I usually continue them. Otherwise, I like to see the cr dropping before I restart it.

 

[jdh71]

Alternatively consult palliative care and start nothing but morphine!!

FTW!

 

[timbuktu]

Alternatively consult palliative care and start nothing but morphine!!

FTW!

we had an entire grand rounds designed to demonstrate the cost-effectiveness of such a strategy!

 

[Cytarabine]

I won't start them. Whether I continue them will depends on how significantly the creatinine increased. You need afterload reduction in acute systolic heart failure and whether you do this with ISDN/Hydral or ACEi depends on the rate of rise. If it's trivial I usually continue them. Otherwise, I like to see the cr dropping before I restart it.

Going to jump onto this thread and see if I can get some clarification on something. Unless I misheard, I believe a cards guy told me to avoid hydralazine in acute heart failure d/t induced tachycardia & increased end diastolic pressure. Thoughts?

 

[jdh71]

Going to jump onto this thread and see if I can get some clarification on something. Unless I misheard, I believe a cards guy told me to avoid hydralazine in acute heart failure d/t induced tachycardia & increased end diastolic pressure. Thoughts?

Honestly, I simply don't see that much induced tachycardia with hydrazine. And I honestly wonder how much of a boogey man this phenomenon is. Though if you do have a lot diastolic function, restrictive physiology you obviously want to avoid tachycardia. Use with care. Monitor. This is why patients get admitted to special units. If you can't give hydralizine to a heat failure in the CICU then you shouldn't be giving it anywhere.

 

[Instatewaiter]

Going to jump onto this thread and see if I can get some clarification on something. Unless I misheard, I believe a cards guy told me to avoid hydralazine in acute heart failure d/t induced tachycardia & increased end diastolic pressure. Thoughts?

That tachycardia that everyone reports is both clinically insignificant except in states where you need to reduce HR (ie dissection) and rare. If they are so decompensated that they are terribly tachycardic, you're going to be in the CICU and they're going to be on nipride rather than hydralazine.

Hydralazine + Nitrates is a great combination in HF which reduces afterload and preload. Furthermore, the addition of hydralazine to nitrates reduces the nitrate tachyphylaxis. This is an incredibly common combination.

FYI I am talking about oral. I am a believer that IV hydralazine should almost never, ever be used.

 

[Cytarabine]

Honestly, I simply don't see that much induced tachycardia with hydrazine. And I honestly wonder how much of a boogey man this phenomenon is. Though if you do have a lot diastolic function, restrictive physiology you obviously want to avoid tachycardia. Use with care. Monitor. This is why patients get admitted to special units. If you can't give hydralizine to a heat failure in the CICU then you shouldn't be giving it anywhere.

That tachycardia that everyone reports is both clinically insignificant except in states where you need to reduce HR (ie dissection) and rare. If they are so decompensated that they are terribly tachycardic, you're going to be in the CICU and they're going to be on nipride rather than hydralazine.

Hydralazine + Nitrates is a great combination in HF which reduces afterload and preload. Furthermore, the addition of hydralazine to nitrates reduces the nitrate tachyphylaxis. This is an incredibly common combination.

FYI I am talking about oral. I am a believer that IV hydralazine should almost never, ever be used.

Thank you both for the input. The pt in question was an acute on chronic heart failure with improving course last we had observed, with new orders from IM for po hydralazine tid and vitals 170/110ish, 100ish bpm (both had been lower last we'd seen the pt), cards canceled the hydralazine. Would you have looked for alternative causes of the vitals change?

 

[Instatewaiter]

Depends on what the vitals were before- 160/100 and P95- probably wouldn't look for another cause.

BP 120/70 and P70, probably would look for another cause. Hydralazine usually doesn't cause hypertension. Was the guy in pain or withdrawing?

 

[Cytarabine]

Depends on what the vitals were before- 160/100 and P95- probably wouldn't look for another cause.

BP 120/70 and P70, probably would look for another cause. Hydralazine usually doesn't cause hypertension. Was the guy in pain or withdrawing?

Pt wasn't mine and is off service now, but from what I recall was afib w/RVR on admission w/flash pulmonary edema style dyspnea w/improving course after starting carvedilol and lasix, never any significant pain, just the dyspnea-anxiety. Really can't remember the course of the vitals, so the convo is probably heading toward a dead end, but I appreciate the education

 

[subtle1epiphany]

...If they are so decompensated that they are terribly tachycardic, you're going to be in the CICU and they're going to be on nipride rather than hydralazine...FYI I am talking about oral.
I am a believer that IV hydralazine should almost never, ever be used.

Agreed, particularly the point about IV hydralazine. I see it used for inpatient BP control and it drives me absolutely crazy.
You've got a drug that's indicated for hypertensive urgency, but not emergency. However, in the setting of hypertensive urgency intravenous administration is rather contraindicated, we very clearly prefer an oral route. So why administer an IV hypertensive urgency agent?
This is apart from the issues of this agent with respect to an inconsistent dose-response curve and prolonged effect.
So, we have a medication that is often incorrectly administered with regard to route in the context of the disease/condition, it is inconsistent in the response you get for a given dose, and lasts longer than you'd prefer. Who would like to receive this agent when they have the underlying condition?
Meanwhile, there are so many better agents when there is hypertensive emergency: esmolol for aortic dissection, nicardipine for the same or neurological catastrophes, nitroglycerin for pulmonary edema, assorted beta-blockers for ACS, etc. Then for hypertensive urgency, why are we treating this with anything but slow titration of oral agents increasing every day or two if admitted, less often if ambulatory. Perhaps it is an agent to consider parenterally in women with pre-eclampsia or eclampsia, although nicardipine may be a better choice still.
I'm certain that I'm preaching to the choir and not the congregation, but Instatewaiter mentioned precisely an issue that I see often with an incorrect reaction by medical physicians in training.

<steps down from soap box>

 

[dozitgetchahi]

Agreed, particularly the point about IV hydralazine. I see it used for inpatient BP control and it drives me absolutely crazy.
You've got a drug that's indicated for hypertensive urgency, but not emergency. However, in the setting of hypertensive urgency intravenous administration is rather contraindicated, we very clearly prefer an oral route. So why administer an IV hypertensive urgency agent?
This is apart from the issues of this agent with respect to an inconsistent dose-response curve and prolonged effect.
So, we have a medication that is often incorrectly administered with regard to route in the context of the disease/condition, it is inconsistent in the response you get for a given dose, and lasts longer than you'd prefer. Who would like to receive this agent when they have the underlying condition?
Meanwhile, there are so many better agents when there is hypertensive emergency: esmolol for aortic dissection, nicardipine for the same or neurological catastrophes, nitroglycerin for pulmonary edema, assorted beta-blockers for ACS, etc. Then for hypertensive urgency, why are we treating this with anything but slow titration of oral agents increasing every day or two if admitted, less often if ambulatory. Perhaps it is an agent to consider parenterally in women with pre-eclampsia or eclampsia, although nicardipine may be a better choice still.
I'm certain that I'm preaching to the choir and not the congregation, but Instatewaiter mentioned precisely an issue that I see often with an incorrect reaction by medical physicians in training.

<steps down from soap box>

Thank you for posting this re: both the hydralazine and IV dosing in general. IV hydralazine is dangerous and I've personally seen it crash peoples' BP with disastrous consequences.

As for hypertensive urgency...I switched to oral agents for it and people started looking at me funny. However, it simply makes sense. There is much less urgency for getting somebody's non-hypertensive emergency BP down.

 

[jdh71]

Yeah, but IV hydralizine is a great way to deal with PRN BP issues in a patient that can't take PO.

It's not poison. It's not stupid to use in the right situation.

Too much dogma in this thread.

 

[Raryn]

Yeah, but IV hydralizine is a great way to deal with PRN BP issues in a patient that can't take PO.

It's not poison. It's not stupid to use in the right situation.

Too much dogma in this thread.

The nurses freak out if the SBP is >160, even in an asymptomatic patient. I hate getting called from nurses. Putting on an IV 10mg hydralazine PRN helps me not get called from nurses.

I've never actually seen someone harmed from it, so I order it. Not because I think having the BP elevated for a few hours till the next PO dose of whatever I'm titrating off will harm the patient (given he's probably had a BP of 180 for months at a time), but because I hate phone calls. *shrug*

 

[Instatewaiter]

This past year alone, I have seen a handful of IV hydralazine related NSTEMIs... with respectable infarct size (MB ~50-100). It is a very rare circumstance when there are no better options than IV hydralazine.

 

[Raryn]

This past year alone, I have seen a handful of IV hydralazine related NSTEMIs... with respectable infarct size (MB ~50-100). It is a very rare circumstance when there are no better options than IV hydralazine.

I'd love to see how the determination was made that the hydralazine caused the patient's NSTEMI rather than it being caused by the underlying condition that the hydralazine was used for.

 

[flipmd]

This past year alone, I have seen a handful of IV hydralazine related NSTEMIs... with respectable infarct size (MB ~50-100). It is a very rare circumstance when there are no better options than IV hydralazine.

I've never heard of IV Hydralazine causing NSTEMIs before. Care to elaborate? (I'm not being snarky, I really would like to know. Only thing I can think of is if you drop their BP too much (which you should try not to do with any antihypertensive anyway most of the time) and they get a type 2 MI.. but I can't think of a reason why it would cause real NSTEMI).

Also, I can think of a LOT of circumstances where there are no other options (mostly in someone total NPO or not alert enough to even take SL). I can count with one hand the IV meds I can give push, and some of them are limited by renal function, HR, etc. Hydralazine's pretty much the only one that you can give almost anybody. I'd rather not put someone on a drip TBH, if they don't really need it.

 

[jdh71]

This past year alone, I have seen a handful of IV hydralazine related NSTEMIs... with respectable infarct size (MB ~50-100). It is a very rare circumstance when there are no better options than IV hydralazine.

Can someone say "confirmation bias"??

 

[Raryn]

Can someone say "confirmation bias"??

I hear confirmation bias doesn't exist at Hopkins. They're better than that.

 

[jdh71]

I hear confirmation bias doesn't exist at Hopkins. They're better than that.

Be nice!! Lol.

I mean I guess I get the general point he's trying to make but I just can't get on board that IV hydralizine is poison.

 

[Instatewaiter]

It has very idiosyncratic effects. Where 10mg IV may do nothing in one patient, it will cause severe hypotension in another. You are right, the NSTEMIs I have seen were type IIs. This is not a reason to discount it though. Each had a significant infarct size. When the MB leak is 100 that is a moderate infarct even for a "real" type I NSTEMi. The effect on the myocardium is the same.

In each of these instance, they were giving 10mg IV hydralazine as the initial dose and it caused severe hypotension. In terms of telling how the hydralazine caused it, the time course was obvious. In one instance it was surgery using it when there were better options. In another it was from an IM guy who lazily ordered it instead of an oral option.

Sure, there are occasions when it is the only option but I have seen enough **** go wrong with IV hydral that I use it as my second to last option (before IV enalaprilat).

 

[subtle1epiphany]

So, maybe I did come across a bit dogmatic, to which jdh alluded.
First, hypertension (and HTN urgency) in the hospitalized patient is over-treated to achieve euboxia, most of us will agree with this I imagine.
I will concede that hydralazine has uses in select circumstances, as many medications do.
However, I will also say that it is often the 'first-line' anti-hypertensive used in all-comers on the floor at both graduate medical centers where I have trained in two different regions of the country. It has many issues with regard particularly to pharmacokinetics and pharmacodynamics that make it a less than ideal or even suitable agent in said all-comers.
There are theoretical issues that have at times become realized with regard to the dose-response issues, ones that I have heard from many physicians and sources, delineated in Marik and Rivera Curr Opin Crit Care 2011; 17: 569-580. I realize that Marik can be rather contentious/controversial. However, given issues that include lack of ability to titrate easily, prolonged hypotension for that reason, reflex tachycardia, possible SLE and vasculitis, I'd prefer labetalol 5-20mg IVP or an infusion of nicardipine/clevidipine.

In agreement with Instatewaiter, the idiosyncrasies are a personal reason why I avoid it. A couple years ago I pushed 2.5mg aliquots, flushed with 10mL saline, separated by 5min each, into a veteran as a medicine resident (floor policy that a physician must push anti-hypertensives). After three separate 2.5mg aliquots there was no effect, then after 10mg his BP dropped precipitously, he had diaphoresis, tachycardia, T-wave inversion, and I transferred him to our step-down unit. This man did have a type 2 NSTEMI with cTnI release due to my decision and direct action.
Now I realize that my participation in the event that had adverse outcomes provides additional effect, that it is N=1 at most, that I was a trainee who had not been well trained in how to administer IV medications, etc are all confounding elements in this experience. However, as an Intensivist I like to think that I have other slicker medication/therapy choices in this issue and more latitude in realizing that my patients do not need to be euboxic while in the ICU. That's my story and disclaimer.
Would not mind thoughts from jdh or Instatewaiter, or any others.

Moving back to the OP's question, I agree with jdh/nephappl/Instatewaiter/etc, reasonable to hold ACE-i/ARB and aldosterone antagonist during the acute course and afterload reduce with another therapy such as NIV, nitroglycerine of choice, or oral hydralazine (less abrupt BP issues but remaining risk of SLE/vasculitis).

 

[jdh71]

Hm. Yeah. I guess my personal experience with the stuff has never had a bad outcome. Though I did have a patient in residency that we were pretty sure got an induced pulmonary-renal syndrome from the stuff and that has always given me pause. It's never been my "go to med" even for the floor nurses paging me for a SBP of 152. Though I have used it some with variable amounts of success in the past for floor patients who were NPO and still needing some BP help for higher ranges of SBP.

Since I work in an MICU now I basically never use it because I can push other meds or start infusions.

I think I've heard enough anecdotes in here to really avoid it going forward unless it's really the only option for whatever I'm trying to do.

 

[Instatewaiter]

So, maybe I did come across a bit dogmatic, to which jdh alluded.
First, hypertension (and HTN urgency) in the hospitalized patient is over-treated to achieve euboxia, most of us will agree with this I imagine.

Gonna be honest, I had to google euboxia. Hilarious.

We used to call it the white sign because abnormal things would show up as either red or yellow in the computer system. Normal things had a white box. I've got very little else to add.

 

[dozitgetchahi]

It has very idiosyncratic effects. Where 10mg IV may do nothing in one patient, it will cause severe hypotension in another. You are right, the NSTEMIs I have seen were type IIs. This is not a reason to discount it though. Each had a significant infarct size. When the MB leak is 100 that is a moderate infarct even for a "real" type I NSTEMi. The effect on the myocardium is the same.

In each of these instance, they were giving 10mg IV hydralazine as the initial dose and it caused severe hypotension. In terms of telling how the hydralazine caused it, the time course was obvious. In one instance it was surgery using it when there were better options. In another it was from an IM guy who lazily ordered it instead of an oral option.

Sure, there are occasions when it is the only option but I have seen enough **** go wrong with IV hydral that I use it as my second to last option (before IV enalaprilat).

Totally agree. The amount of BP drop and the duration are sometimes wildly unpredictable. Saw 10mg IV hydralazine get pushed by an intern on night float on some elderly dude with BP >180/110...3 hours later, BP was 85/50 and stayed there for hours. No other obvious cause of the hypotension aside from IV hydralazine. Second similar case happened with another elderly guy; this resulted in a 'watershed' stroke. I don't use it unless I have no other good options (which is rare).

Totally agree on over-aggressive inpatient BP management as well. After reading the data, I feel 'hypertensive urgency' is a whole hell of a lot less 'urgent' than most of us have been told to believe. Think of your clinic patients who walk in with these BPs. If they're not demonstrating symptoms of end-organ damage, treatment is purely outpatient. We overtreat and over-titrate BP meds in the hospital, and lots of these patients end up dizzy, falling, hypotensive etc after discharge. And if you're going to tx hypertensive 'urgency', PO is the way to go unless the pt is NPO etc.

 

[subtle1epiphany]

It's honestly gratifying to know that your observed non-RCT obtained observations are verified by another person's experience. It reassures me that it is less likely that I'm the aberrant part of the equation.

I've seen the same patterns in some subjects, some do well and there's a great and not too extreme reduction in pressure. In others, they manifest exaggerated responses to the same amount of drug. Perhaps it is predictable based upon body weight or surface area...but nothing I've been able to easily quantify.
Personally, labetalol boluses seem to be more predictable. I know that with 5mg I can slightly drop the pressure, with 10mg it will be modest and about where I'd prefer given hypertensive emergency, and with a total of 20mg I've gotten to a goal in that context.
Failing that outline, I can stack doses of 5 or 10mg and have no worry that I've screwed myself...or the patient to whom I've experimented upon (in best interest and intents).

Similarly, with nicardipine in residency I'd been able to get a good reduction without a high or low amount of drug. However, in a different region of the US I've noticed that a small amount without a loading dose (about 1mg/hr even) there is a precipitous drop in pressure.
Has anyone noticed a change in response to nicardipine over time or between regions of practice? It is something that more than slightly interests me.

Also, anyone been able to play with clevidipine? Observations or thoughts on it? As good as it claims to be?

 

[jdh71]

Also, anyone been able to play with clevidipine? Observations or thoughts on it? As good as it claims to be?

I've never been allowed to by a pharmacist in recent memory. And they have a good point: what's it really giving us that we are not getting with another medication that justifies the cost.

Though, I did my residency at a spot that was involved in a trial with the stuff post-SAH. It seemed fine.

Metabolism is cool. Might consider pushing for it in the right bad liver bomb patient.

 

[Instatewaiter]

It's honestly gratifying to know that your observed non-RCT obtained observations are verified by another person's experience. It reassures me that it is less likely that I'm the aberrant part of the equation.

I've seen the same patterns in some subjects, some do well and there's a great and not too extreme reduction in pressure. In others, they manifest exaggerated responses to the same amount of drug. Perhaps it is predictable based upon body weight or surface area...but nothing I've been able to easily quantify.
Personally, labetalol boluses seem to be more predictable. I know that with 5mg I can slightly drop the pressure, with 10mg it will be modest and about where I'd prefer given hypertensive emergency, and with a total of 20mg I've gotten to a goal in that context.
Failing that outline, I can stack doses of 5 or 10mg and have no worry that I've screwed myself...or the patient to whom I've experimented upon (in best interest and intents).

Similarly, with nicardipine in residency I'd been able to get a good reduction without a high or low amount of drug. However, in a different region of the US I've noticed that a small amount without a loading dose (about 1mg/hr even) there is a precipitous drop in pressure.
Has anyone noticed a change in response to nicardipine over time or between regions of practice? It is something that more than slightly interests me.

Also, anyone been able to play with clevidipine? Observations or thoughts on it? As good as it claims to be?

I've felt that nitroprusside is easier to titrate than nicardipine. I've never used clevidipine but the studies look promising. One even shows a mortality advantage over nitroprusside which I don't believe (mainly because the mortality rate for clevidipine was much lower in the ntp arm than in the nitro or nicardipine arms which accounts for the difference). The neuro guys at my place love nicardipine for htn emergency

 

[subtle1epiphany]

I have little experience with nitroprusside. Our unit here in Iowa is not a fan of arterial lines (of which I generally approve), so with such a rapidly changing output to your dose, titrating nitroprusside is rather difficult. Now, if it is my shift I'll place an arterial cannula to adjust my nitroprusside dose. Still many of the HTN emergency cases will go to the CVICU these days. They seem to have fewer beds, so we will get some.
Initially my preference is labetalol boluses up front, changing to an infusion of nicardipine/nitroprusside/etc thereafter depending upon the underlying condition. I find that labetalol infusions are not as helpful in these situations. Since we've got a great conversation going, any other thoughts are more than welcome.
Honestly, HTN emergency is a 'fun' condition to treat. In that it's satisfying, you get rapid results in response to each intervention. I think that you can reduce mortality and morbidity in this patient population (at least acutely), which is again satisfying. Personally I'd be interested in studying what specific end-organ symptoms, signs, or evidence are best to identify those who should be aggressively treated. For instance, should headache alone be considered end-organ effect, what about altered mental status, if so then how to measure/quantify it, etc.