GI prophylaxis in critical care: Protonix vs. Carafate

[Back34]

Just finished the GI prophylaxis chapter in the "I.C.U. Book" (Marino) (I know, I know...shouldn't be reading now but that's beside the point) and it made a great argument for using Carafate over Protonix (or anything else which decreases acid in the gut) in the ICU.

First, it's cheaper, significantly so. Second, it has no effect on acid production. I never really thought of acid as the effective antibiotic that it is; rather, it was simply bad stuff that aggravated stress ulcers. The author's reasoning made perfect sense, i.e., a more basic environment allows the overgrowth of all kinds of nasty critters (E. coli, etc) which can go on to cause pneumonia and/or sepsis.

In my two years of clinical experience, I've never seen Carafate ordered and am just wondering if this happens anywhere else.

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[southerndoc]

We use H2 blockers almost exclusively in our ventilated patients (for >48 hours ventilation). We use PPI's only for active GI bleeds or in those who cannot tolerate H2 blockers.

H2 blockers do not cause as much acid suppression as PPI's.

 

[AJM]

Surprisingly, there's very little data on the benefits of any type of GI prophylaxis in the ICU. Most data is in the form of very small trials and a few older retrospective studies, many of which had several flaws. There is almost nothing on head-to-head comparison of the different types of GI prophylaxis.

But yes, there is some thought that carafate may be superior to PPIs because of the acid issue. That said, I have never ordered it or have had any patient on it. As far as what our practice is in our units, it is highly variable. One of my attendings recently took a cross-sectional survey of the 30 or so patients that happened to be in our MICU on a particular day -- it was all over the board as to what type of prophylaxis they were on, ranging anywhere from high-dose PPI, low-dose PPI, IV H2 blocker, po H2 blocker, and no prophylaxis. There really didn't seem to be any rhyme or reason to it. Apparently even having all of our patients in a single unit still did not make it easier for us to make up our minds....

 

[sdn1977]

Sorry - as a pharmacist, I don't agree with the rationale of using sulcralfate as a prophylatic agent. Its mechanism is that it binds with exudates the the ulcer site & makes a sulcralfate-albumin complex which covers the site to allow healing underneath. There is some pepsin inhibitory activity, but not much. If there is no ulcer....then...no purpose...

If there is no ulcer (which would negate the prophylactice theory), there is not reason for its use. However, selective H2 blockers do make sense - they sit on the histamine receptor which prevents the histamine release which triggers the pepsin/acid/bile acid release. Of these - famotidine is the best in the ICU (IMO) - fewer drug interactions, but you do need to decrease the dose if Crcl < 50. Cimetidine has LOTS of drug interactions - has no place in the ICU at all (again - my opinion). Ranitidine - ok.

PPI's are becoming more cost effective as they become generic. They have few drug interactions & are only an issue in those folks who have trouble metabolising them (altho you do need to watch for the P450 system drugs - erythromycin, ketoconazole, etc). They actually decrease the proton pump from putting out acid, so you don't have to worry about something with more affinity knocking your H2 blocker off the receptor.

Also...heliobacter profilerates in an acidic environment...so I'm not sure where you're coming from when you say acid is the "antibiotic".....The standard heliobacter tx is 2 antibiotics & a PPI.

 

[Samoa]

We can speculate all day on which is better or worthless or whatever...until I see a head-to-head trial, I won't be convinced.

That said, I've seen all three agents used with equal success. And what I mean by that is that I've never seen a stress ulcer in someone on any form of prophylaxis, as long as they were actually getting the medication in appropriate doses. Including carafate.

What I do think is stupid is using carafate in addition to a PPI or H2 blocker. You might as well just roll up $2 and shove it down their NG tube.

 

[Winged Scapula]

We typically use Protonix here (although some attendings have a preference for Pepcid) and the only time I've used Carafate is in the PICU and SICU as part of tx for gastric ulceration (on recommendation of GI), never for prophylaxis.

 

[southerndoc]

Also...heliobacter profilerates in an acidic environment...so I'm not sure where you're coming from when you say acid is the "antibiotic".....The standard heliobacter tx is 2 antibiotics & a PPI.

I think he is referring to non-Helicobactr bacteria proliferating and its association with ventilator-associated pneumonia.

We only use H2 blockers here (famotidine), and only on patients who are ventilated and expected to be ventilated for >48 hours.

A 2004 article in Annals of Internal Medicine recommended sulcrulfate for VAP prophylaxis. Check out Dodek, et al. Evidence-based clinical guidelines for prevention of ventilator-associated pneumonia. Ann Intern Med, 141(4): 305-313.

I think the best way to prevent stress-induced ulcers is not PPI's, H2 blockers, or sulcrulfate, but early initiation of enteral feeds, even if only in small amounts. Of course, not every patient is eligible for early enteral feeds.

 

[southerndoc]

By the way, shouldn't this be in the Critical Care Forum now?

 

[AJM]

However, selective H2 blockers do make sense - they sit on the histamine receptor which prevents the histamine release which triggers the pepsin/acid/bile acid release. Of these - famotidine is the best in the ICU (IMO) - fewer drug interactions, but you do need to decrease the dose if Crcl < 50. Cimetidine has LOTS of drug interactions - has no place in the ICU at all (again - my opinion). Ranitidine - ok.

Unfortunately, at most hospitals you don't get to choose which specific agent in a certain class to use -- it all depends on what's on formulary at the hospital. If you want to use a nonformulary agent you have to have an extremely compelling reason to use it.

 

[sdn1977]

I think he is referring to non-Helicobactr bacteria proliferating and its association with ventilator-associated pneumonia.

We only use H2 blockers here (famotidine), and only on patients who are ventilated and expected to be ventilated for >48 hours.

A 2004 article in Annals of Internal Medicine recommended sulcrulfate for VAP prophylaxis. Check out Dodek, et al. Evidence-based clinical guidelines for prevention of ventilator-associated pneumonia. Ann Intern Med, 141(4): 305-313.

I think the best way to prevent stress-induced ulcers is not PPI's, H2 blockers, or sulcrulfate, but early initiation of enteral feeds, even if only in small amounts. Of course, not every patient is eligible for early enteral feeds.

Thanks for the clarification on the non-Heliobacter proliferation!

I pulled the Annals article you referred to I don't see how you come to your conclusion. In their conclusion, it states "On the basis of evidence from two level 2 trials (76,77), we conclude that the use of sucralfate does not influence the incidence of VAP compared with placebo"

My objection to this article is that the pharmacologic strategies it evaluated were sucralfate, intratracheal antibiotics, intravenous antibiotics, and intravenous and topical antibiotics. Perhaps these are the pharmacologic options available in Canada, but I'd suggest the standard in the US is an H2 blocker or ppi. But...I admit, I've not done a recent journal search.

 

[sdn1977]

Unfortunately, at most hospitals you don't get to choose which specific agent in a certain class to use -- it all depends on what's on formulary at the hospital. If you want to use a nonformulary agent you have to have an extremely compelling reason to use it.

Thats true...but thats what P&T committees are for! There is a physician representative from every service on the committee in addition to the Director of Pharmacy & usually (hopefully) a clinical pharmacist. I cannot think of any compelling reason to justify the use of cimetidine. Ranitidine & famotidine are comparable, so either one is ok. Perhaps I misunderstood your point. But...if you want a drug on the formulary..take it to the chief of your service - he/she should then take it to the P&T.

For an urgent situation, most pharmacists can order anything if available for the short term, but that is just my experience in the facilities I've worked in.

 

[AJM]

Thanks for the clarification on the non-Heliobacter proliferation!

I pulled the Annals article you referred to I don't see how you come to your conclusion. In their conclusion, it states "On the basis of evidence from two level 2 trials (76,77), we conclude that the use of sucralfate does not influence the incidence of VAP compared with placebo"

My objection to this article is that the pharmacologic strategies it evaluated were sucralfate, intratracheal antibiotics, intravenous antibiotics, and intravenous and topical antibiotics. Perhaps these are the pharmacologic options available in Canada, but I'd suggest the standard in the US is an H2 blocker or ppi. But...I admit, I've not done a recent journal search.

H2 blockers and PPIs are not used for prophylaxis against VAP -- they're used for stress ulcer prophylaxis. This article was looking specifically at VAP prevention strategies, so there would be no reason for them to test H2 blockers and PPIs.

 

[AJM]

Thats true...but thats what P&T committees are for! There is a physician representative from every service on the committee in addition to the Director of Pharmacy & usually (hopefully) a clinical pharmacist. I cannot think of any compelling reason to justify the use of cimetidine. Ranitidine & famotidine are comparable, so either one is ok. Perhaps I misunderstood your point. But...if you want a drug on the formulary..take it to the chief of your service - he/she should then take it to the P&T.

For an urgent situation, most pharmacists can order anything if available for the short term, but that is just my experience in the facilities I've worked in.

Yes, but a committee is just that -- a committee. It's like pulling teeth to get them to change their mind about anything once they've come up with a decision. At least that's how it is at all of the hospitals I've worked at. Proposals to change formularies are almost always shot down, even if they make sense, usually because the powers that be don't want to change the pharma contracts the hospital has already established. (no, I'm not bitter, this has just been my observation over the years....)

As far as middle of the night urgent situations, the ease of getting a short-term supply of a nonformulary medication greatly depends on the pharmacist who happens to be on at that time, and it also depends on the specific non-formulary medication that one would like to use.

 

[southerndoc]

H2 blockers and PPIs are not used for prophylaxis against VAP -- they're used for stress ulcer prophylaxis. This article was looking specifically at VAP prevention strategies, so there would be no reason for them to test H2 blockers and PPIs.

We actually use H2 blockers for both stress ulcer prophylaxis as well as VAP prophylaxis. Although the best VAP prophylaxis is elevating the head of the bed to 30 degrees.

 

[AJM]

We actually use H2 blockers for both stress ulcer prophylaxis as well as VAP prophylaxis. Although the best VAP prophylaxis is elevating the head of the bed to 30 degrees.

Really? GI acid reduction is used to decrease the incidence and severity of aspiration pneumonitis, which is a chemical pneumonitis, but it does not do anything to prevent VAP, which is caused by bacterial pathogens.

Unless there's a study out there that I'm not aware of....

 

[sdn1977]

The last information I read on this was a year ago...Am J Resp & Crit.Care Med 171:388-416. Altho they do refer to sucralfate, it appears there is not a uniform consensus.

"In one multicenter study of VAP in patients with ARDS, sucralfate and duration of exposure to sucralfate were associated with an increased risk of VAP. A large, double-blind, randomized trial comparing ranitidine with sucralfate demonstrated a trend toward lower rates of VAP with sucralfate, but clinically significant gastrointestinal bleeding was 4% higher in the sucralfate group. Thus, if stress ulcer prophylaxis is indicated, the risks & benefits of each regimen should be weighed before prescribing either H2 blockers or sucralfate."

I recognize the pH effects, but it appears there are greater risk factors than pH & from a practical standpoint - sucralfate is a pia for nurses to administer!

On the other issue - sorry about your experience with your P&T. Drug contracts are only for a year....Since the bulk of the committee members are physicians - you need to get out and lobby your colleagues! - Just my opinion.

 

[southerndoc]

Really? GI acid reduction is used to decrease the incidence and severity of aspiration pneumonitis, which is a chemical pneumonitis, but it does not do anything to prevent VAP, which is caused by bacterial pathogens.

Unless there's a study out there that I'm not aware of....

No, you are correct. I guess I should have said aspiration pneumonitis instead of VAP.

Our ventilator bundle includes: prevention of peptic ulcer disease, prevention of deep venous thrombosis, head of bed elevation, daily trial of weaning, sedation breaks and glycemic control.

 

[Adcadet]

Do you guys suspect P450 interaction problems when using H2 blockers, or is this thought to be a rare occurence?

 

[Dimoak]

Do you guys suspect P450 interaction problems when using H2 blockers, or is this thought to be a rare occurence?

Most in vitro tests have proven that Zantac does endup binding ever so weakly to P450, but as long as you don't exceed the recommended dosing, P450's activity with the liver's oxygenase enzymes will remain uninhibited. From what I've read, much of the issues in some H2 blockers are how drug interactions modify bioavailabilities, which could then lead to problems.

 

[Crypt Abscess]

The important thing to know here is that significant stress ulcers are pretty rare in your standard ICU patient, so therefore no prophylaxis is needed. The exceptions are burn patients and neuro cases.

There is some emerging data that PPIs are associated with C dif colitis (stomach acid normally kills the spore) which is really becoming a significant problem at many hospitals. I only give GI ulcer prophylaxis to burn and neuro patients as well as anyone who is on ASA to keep stents open, or who has a history of PUD. PPIs are the standard of care for anyone with active upper GI bleeding.

My .02. Crypt