Spironolactone vs frusemide for ascitic liver disease

RE: Spironolactone vs frusemide for ascitic liver disease

Aine Seavers — Thu, 24 Sep 2015 01:58:05 GMT

t also acts as an aldosterone inhibitor used to treat advanced heart failure when symptoms persist after other drug therapies are optimized

that is good to see in print as for a while some years ago-spiron was being used instead of lasix ie first or both started at same time.

A recent population-based case–control study has reported a 2.7-fold increase in risk of gastroduodenal ulcers or upper gastrointestinal bleeding (UGB) in patients taking spironolactone [7]. The strength of association increased with dose and with concomitant use of ulcerogenic drugs. The mechanism is believed to be inhibition of the formation of fibrous tissue by binding to mineralocorticosteroid receptors; the effect is modulated by 11β hydroxysteroid dehydrogenase enzymes [8]. Thus, aldosterone receptor antagonists, such as spironolactone, could impair the healing of gastric or duodenal erosions and result in the formation of gastroduodenal ulcers, with or without bleeding.

I checked the history of the GSD that bled out in front of me-no nsaids used, no liver disease as such (but how healthy is a liver in a cardiac patient), - was on lasix, vetmedin, fortekor and lanoxin with the spiron. 2nd GSD the same- the 3rd dog I became aware of was a chihuahua on vetmed.fortek/spiron, then phenobarb and potassium(not sure why the potassium..)- scoped , stomach full of blood-dog survived-but not kept on spiron afterwards.

So the cases are out there, my 2 gsd were not even considered for their breed ulcerogenic risk, the inappetance thought of as cardiac cachexia not impending stomach lesion issues. So if liver disease then maybe spirombut I still think more care needs to be paid to the breed and concurrent drugs when using it.. Even in liver disease, the USA vets talk about Zarolyn not spiron so is it just in Europe it is the drug of choice for liver ? I am aware coincidence is not causation but one when no one is even thinking of the drug's potential then a lot can be missed or blamed on other factors-i have had many Gsd with cardiac disease, gastrc ulceration is not something I commonly associate with the condition so when it starts to occur one has to ask what has changed- and for me- spirono was the new kid on the block.

RE: Spironolactone vs frusemide for ascitic liver disease

Martin Atkinson — Wed, 23 Sep 2015 14:08:01 GMT

Blimey that was quick 2 days Eleanor, I really must be getting old!

RE: Spironolactone vs frusemide for ascitic liver disease

Eleanor Raffan — Wed, 23 Sep 2015 13:44:24 GMT

Hi all,

The logic behind using spironolactone to treat the ascites of liver disease is that the pathogenesis specifically involves activation of the RAA system and the drug is a aldosterone receptor antagonist. Furosemide is often not effective and you run the risk of making the rest of the dog crispy without/before shifting the ascites.

Re risk of GI ulceration: there is no published evidence to support the contention that spironolactone causes GI ulceration in dogs. It is worth remembering, however, that dogs with liver disease and portal hypertension (predisposing to ascites) are very prone to GI ulceration and so true ulcerogenic drugs such as NSAID or steroids should be avoided completely/used with extreme caution. This also means that any association of spironolactone/GI bleed seen in dogs is as likely to be coincidence as causation.

In humans, there has been some statistical association between GI ulcers and spironolactone use mainly where concurrent heart disease and/or use of ulcerogenic drugs, but it remains the drug of choice to treat ascites due to liver disease.

Penny Watson (liver guru from Cambridge) had the following to say when I contacted her earlier:

'I have never seen a dog put on spironolactone with liver disease ulcerate - whereas I have seen plenty of vets put them on steroids and cause them to ulcerate! In addition, as you know, frusemide just doesn’t work (on its own) with the ascites of liver disease because the pathophysiology involves aldosterone. I HAVE seen dogs with liver disease on high doses of frusemide still having marked ascites while the rest of the dog becomes dangerously dehydrated. In addition, there is a paper showing spironolactone is anti-fibrotic in rats with liver disease (I’ll email you that one)

What we actually need is a proper dog trial and I am trying to persuade CEVA to let us do this.'

See this paper re fibrosis (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034230) and extract from this (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492928/) human paper regarding risk GI ulceration below:

'Spironolactone is a potassium-sparing diuretic mainly used to treat certain patients with hyperaldosteronism, low potassium levels, and patients with oedema caused by various conditions, including heart or liver disease. It also acts as an aldosterone inhibitor used to treat advanced heart failure when symptoms persist after other drug therapies are optimized [1]. When used in this manner, it is not as a diuretic to remove extra fluid from the body, but rather to reduce left ventricular hypertrophy in hypertensive patients and to decrease post-infarction collagen synthesis and improve left ventricular remodelling [2, 3]. It is considered the diuretic of choice in patients with liver cirrhosis.

Gastrointestinal (GI) bleeding in users of spironolactone has been reported in a few case reports [4–6]. A recent population-based case–control study has reported a 2.7-fold increase in risk of gastroduodenal ulcers or upper gastrointestinal bleeding (UGB) in patients taking spironolactone [7]. The strength of association increased with dose and with concomitant use of ulcerogenic drugs. The mechanism is believed to be inhibition of the formation of fibrous tissue by binding to mineralocorticosteroid receptors; the effect is modulated by 11β hydroxysteroid dehydrogenase enzymes [8]. Thus, aldosterone receptor antagonists, such as spironolactone, could impair the healing of gastric or duodenal erosions and result in the formation of gastroduodenal ulcers, with or without bleeding.'

Best wishes,

Eleanor

RE: Spironolactone vs frusemide for ascitic liver disease

Martin Atkinson — Wed, 23 Sep 2015 12:23:54 GMT

[quote user="Aine Seavers"]thanks Martin for doing that[/quote]Eleanor has promised to come back to me in a couple of days on this, I will update when she does.

RE: Spironolactone vs frusemide for ascitic liver disease

Aine Seavers — Wed, 23 Sep 2015 10:55:58 GMT

thanks Martin for doing that-the more info we have on spiron in at risk breeds the better- I have asked the question many times at meetings-certainly the trend some few years ago here to favour it over lasix in cardiac cases hasnow eased off so that has helped-my concern is the at risk of ulcer breeds may still exist-the liver debate is a whole other arena but whether zarolyn will prove to be better/safer for liver ascites will need the USA vets to comment- my only concern with it was the sulpha drug risk mentioned in the small print- does that make Doberman breed an issue for that? For me in cardiac cases and in resp coughing cases- lasix is not given the respect it deserves

RE: Spironolactone vs frusemide for ascitic liver disease

Martin Atkinson — Wed, 23 Sep 2015 10:37:13 GMT

[quote user="Andrew Kent"]I think that depends on the case - some dogs will be inappetent, nauseous and uncomfortable with significant ascites - in those cases using frusemide initially tends to improve things much more quickly than spironolactone alone.[/quote]I went to a talk in April by Eleanor Raffan from Cambridge Uni and in this she said she would avoid frusemide in dogs with liver disease and that spironolactone was more suitable for the reasons I've already suggested but I can't remember why she said we shouldn't use frusemide. In the light of Aine's reply I have emailed Eleanor and asked if she would like to add anything to the discussion.

RE: Spironolactone vs frusemide for ascitic liver disease

Aine Seavers — Wed, 23 Sep 2015 10:03:14 GMT

if all the work done by the specialist had failed to uncover liver disease I would be even crankier than them missing the signs of gastric pain-so again I would blame the spironolactone- it is just not common to have cardiac cases present with gastric ulceration- introduce a drug that can cause it- see it- stop using the drug- stop seeing it- its high up on my index of suspicion.

RE: Spironolactone vs frusemide for ascitic liver disease

Kate Richardson — Wed, 23 Sep 2015 09:20:45 GMT

I guess I have to ask if they would have bled with or without the spironolactone though if they had liver disease?

RE: Spironolactone vs frusemide for ascitic liver disease

Aine Seavers — Wed, 23 Sep 2015 09:15:59 GMT

3, 2 in GSD , so an ulcer risk breed waiting to happen which is why I was so cranky that no one thought to investigate the common causes of inappetence and reflux in a GSD regardless of its cardiac state. My concern is that gastric ulceration was not something I commonly associated with cardiac cases -then spironolactone becomes popular- and suddenly 3 pop up on the radar. Thats what made me go check the drug out- and not found or had any dogs on it either since once aware of it. Lasix in dogs works well, it takes a lot for them to be resistant to it and when are often they still respond to the injectable form-something the aussie vets here taught me- a weekly injection for many months when oral tabs not holding. Also Moduretic becoming popular rather than spironolactone last couple of years.

RE: Spironolactone vs frusemide for ascitic liver disease

Kate Richardson — Wed, 23 Sep 2015 08:58:54 GMT

[quote user="Aine Seavers"]Need to watch spironolactone in inappetant patients- I am aware of dogs getting significant gastric lesion issues on this drug[/quote]

How many cases have you seen with this as an issue? Do you know if they had any underlying GI ulceration predisposition prior to treatment? Liver disease itself can predispose to GI ulceration, so care with any potential ulcerogenic medications is warranted, but I wasn't aware of spironolactone being ulcerogenic. I haven't used spironolactone or frusemide in many liver patients only cardiac patients and have never had a clinical issue with it, so is it dose dependent or only an issue if they are inappetant? I worry more about the renal effcts of frusemide, have seen many a patient (mainly cats) go into renal failure from over judicious use of frusemide. I would personally physically drain the fluid via a large bore catheter as needed if its causing significant discomfort/respiratory compromise. I

RE: Spironolactone vs frusemide for ascitic liver disease

Aine Seavers — Wed, 23 Sep 2015 02:38:02 GMT

Need to watch spironolactone in inappetant patients- I am aware of dogs getting significant gastric lesion issues on this drug- saved because we advised stopping the drug but the first one- one my own patient a cardiac patient sent back from specialist center whose inappetance was put down to cardiac cachexia- owner presented the dog to me showing signs of subtle reflux - in view of spironlactone meds I got her onto all 3 anti-ulcer meds meds but she bled out shortly afterwards following a huge vomit of blood -no one had thought to remember that there can be a significant gastric ulceration risk with this med.=risk factors include high potassium concentrations can lead to gastric ulcerations and stenosis,2)ACE inhibitors, etc can increase the risk of hyperkalemia developing in patients receiving spironolactone, especially in the presence of renal impairment (renal disease, elderly patients).3) The postulated mechanism is that spironolactone's aldosterone antagonist activity delays gastro duodenal healing. Several papers in humans on this risk.

ACE inhibitors, angiotensin II receptor antagonists, trimethoprim, heparin, potassium supplements, potassium-containing medications (e.g., penicillin G potassium), can increase the risk of hyperkalaemia developing in patients receiving spironolactone, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are concurrently administered with spironolactone

Some american colleagues use a different drug for thisliver ascites-Zaroxalyn-Metolazone a thiazide like diuretic

use 5 mg/ per dog per day along with the Lasix they are already on.

Given daily until the ascites resolves then cut dose to every 2-3 days.

-also JSAP 2012 where an automated pump was inserted under muscle and with 2 catheters intra-abdomen to direct the fluid into the bladder- worked for a couple of months- only a prototype but has promise

Some vets do a small lap incision (~ 1cm) under local in severe ascitic patients, and the fluid just pours out. They don’t like trochars or 3-way taps because they take forever and block up with Omentum.

2) A 12 g. IV catheter, fenestrated it to help keep it from getting plugged with Omentum also used.

3) A 16 -18 gauge catheter in a big dog that needs some load of the diaphragm. Can fenestrate the 2.5 inch catheter if prefer to use over the shorter one .

DRAIN UNTIL THE animal breaths more comfortably and/or when the skin on the abdomen is no longer stretched like a drum head. passive drainage/aspiration to buy the dog some relief until main owners back off holiday etc-

but in the end best to stop totally and euthanise when dog still ticks most of the boxes on quality of life questionnaire forms not draw it out to its last painful breath.

RE: Spironolactone vs frusemide for ascitic liver disease

Andrew Kent — Tue, 22 Sep 2015 20:02:31 GMT

[quote user="Martin Atkinson"]you don't need instant action like in pleural effusion/pulmonary congestion[/quote]

I think that depends on the case - some dogs will be inappetent, nauseous and uncomfortable with significant ascites - in those cases using frusemide initially tends to improve things much more quickly than spironolactone alone.

Andy

RE: Spironolactone vs frusemide for ascitic liver disease

Martin Atkinson — Tue, 22 Sep 2015 18:22:55 GMT

Latest info I have is that you shouldn't use frusemide. Spironolactone is useful for its antifibrotic effects and as an aldosterone receptor antagonist. It is a much weaker diuretic than Frusemide but you don't need instant action like in pleural effusion/pulmonary congestion so I would choose spironolactone as a standalone agent.

RE: Spironolactone vs frusemide for ascitic liver disease

Andrew Kent — Tue, 22 Sep 2015 17:55:34 GMT

Spironolactone has been shown (at least in experimental rat models) to have some anti-fibrotic activity so the hope when we use it in fibrotic liver disease is that it may slow the progression of the disease.

My approach is often to use both to begin with and then drop the frusemide.

Andy

RE: Spironolactone vs frusemide for ascitic liver disease

Michael Woodhouse — Tue, 22 Sep 2015 17:43:22 GMT

I always found pentobarbitone most efficacious.

(Frusemide is a much more powerful diuretic, could use both. Prognosis generally hopeless in my opinion)