Azotemia in 13yr old Labrador

Re: Azotemia in 13yr old Labrador

Anthony Dennison — Sat, 01 Jun 2013 04:02:07 GMT

[quote user="Evelyn Barbour-Hill"]What's the mechanism of the nephrotoxicity?[/quote]

COX-1 and COX-2 are involved in prostaglandin production which help regulate of renal blood flow, expressed in differing amounts depending where on the nephron you look. I presume even with the highly selective -coxibs, their use long term could affect renal blood flow, which is where you'd get problems with nephrotoxicity? Or is there are more direct action?

(Another reason why robenacoxib is good - not in the plasma long enough to cause an issue renally)

I'll leave it to the experts to give the proper answer

Re: Azotemia in 13yr old Labrador

Michael Woodhouse — Sat, 01 Jun 2013 00:21:37 GMT

I honestly wonder where some of these ideas make their way into vet medicine as gospel and you look to the medics and they pretty much ignore these so called 'rules'.

Steroids in serious infections esp pneumonia.

Bacteriocidal and static antibiotics together

Not using NSAIDS in renal patients

I pulled the NICE guidelines of patients with chronic kidney disease:

In people with CKD the chronic use of NSAIDs may be associated with progression and acute use is associated with a reversible fall in GFR. Exercise caution when treating people with CKD with NSAIDs over prolonged periods of time. Monitor the effects on GFR, particularly in people with a low baseline GFR and/or in the presence of other risks for progression.

Spoke to a neighbours son who was visiting (consultant gasteroenterologist) who says they use NSAIDS 'all the time' in people with kidney disease.

I don't disagree that very occasionally animals may be harmed by NSAIDs effect on their kidneys. I do suspect that even I as a mere mixed vet with no certificate to wave (yet) have seen far more dogs and cats helped by giving them NSAIDs than you have ever seen harmed by them. I also think you are neglecting the anti-inflammatory effects.

Re: Azotemia in 13yr old Labrador

Evelyn Barbour-Hill — Sat, 01 Jun 2013 00:06:40 GMT

[quote user="Christopher Saul"]

I would agree Onsior might be the NSAID to go for but ONLY if you've decided upon NSAIDs first with the consent of the owner as I have explained in my previous posts. Onsior might well be slightly less nephrotoxic than the other NSAIDs but ANY NSAID can be nephrotoxic

[/quote]

What's the mechanism of the nephrotoxicity, Christopher?

Re: Azotemia in 13yr old Labrador

Christopher Saul — Fri, 31 May 2013 23:58:14 GMT

Re: Azotemia in 13yr old Labrador

Anthony Dennison — Fri, 31 May 2013 21:33:56 GMT

Onsior (robenacoxib), as mentioned in one of the posts may be an option. It has a really short plasma half life (30 minutes? Definately less than 2 hours) and is very tissue specific, so will mainly head for areas of inflammation.

My mum was involved in the larger scale clinical trials of it (as a prescribing vet, not a patient I may add!) and she rates it.

Re: Azotemia in 13yr old Labrador

Christopher Saul — Thu, 30 May 2013 19:07:59 GMT

I have definitely and on a number of occasions now seen acute nephrotoxicity due to NSAIDs in well hydrated patients, so I think there's a little more to it than the effect of dehydration. Having said that, I would say it's acceptable to use NSAIDs in CKD patients if other less nephrotoxic agents have failed to control the animal's pain and it's apparent there is no other option - and of course you've got full and informed consent from the owner...

Chris

Re: Azotemia in 13yr old Labrador

mariette asselbergs — Thu, 30 May 2013 17:31:45 GMT

I have the same approach Sarah, because I thought that the harmful effect of NSAIDs on kidneys is not a direct toxic effect, but comes about in case of dehydration where the COX protects the kidneys against the toxic effect of dehydration, and NSAIDs reduce this protection by inhibiting the COX. As long as there is no dehydration, I am not so worried about nephrotoxicity from NSAIDs. Maybe I am wrong, anybody?

Mariette

Re: Azotemia in 13yr old Labrador

Sarah Keir — Wed, 29 May 2013 21:05:46 GMT

Hi Emily,

If you do diagnose CRF (ie azotaemia with a reduced urine concentration, or a persistent low urine SG) then consider Hills j/d. I couldn't believe a diet could make that much difference until I used it on my own dog. Of course, with renal disease you may want to go with a restricted protein/phosphate diet but then you have to balance the risks with the benefits. If you do go with NSAIDS in mild renal disease (and I do sometime with owners full consent) then make sure the animal doesn't become dehydrated eg if it has vomiting or diarrhoea for an reason then stop the NSAID immediately.

Sarah

Re: Azotemia in 13yr old Labrador

John Flynn — Wed, 29 May 2013 20:19:48 GMT

[quote user="Christopher Saul"]

If you read the paper in full regarding the side effects, you'll see that the majority are pretty theoretical with no known reported clinical cases

[/quote]

I was tongue-in-cheek with the omega side effects - I'm not actually expecting that dogs are dying from omega-therapy

I would be interested in your thoughts on their use however and what conditions and products you advocate them for and your level of confidence that they are beneficial - I'm currently in the skeptics corner on omegas, but willing to shift if good reason to - I'll maybe start another thread for omega-3 chat as will be getting off topic otherwise...

[quote user="Christopher Saul"]Regarding the concept that patients on CKD live longer with NSAIDs[/quote]

I was only posting these abstracts (without commentary) to be helpful as I think they were the ones Mark was referring to above.

[quote user="Christopher Saul"]How do we know this dog has CKD? [/quote]

I think with a SG of 1.036 it's pretty damn unlikely.

[quote user="Christopher Saul"]could it be acute renal failure?[/quote]

I may have missed something in the history, but I don't think there was any history of PUPD suggestive of chronic kidney disease, nor any suggestion that the dog may be in ARF. I understand that NSAID administration can cause ARF, but I think it's overkill to investigate every dog I start on NSAIDs in case this happens. I have personally only seen this once (obviously I could have missed other cases unwittingly) on which occasion the dog had been injected with steroids, flunixin and at least one other NSAID repeatedly intravenously for a few days in a patient that was probably hypovolaemic; I'm sure in your line of work you see many more cases including ones where a more 'conventional' approach to NSAID use has been applied!

[quote user="Christopher Saul"]It could even have GI haemorrhage, or be severely dehydrated [/quote]

I don't think it sounded like the patient was severely dehydrated, but I could have missed that. I do think that GI toxicity is an issue with NSAID use - agreed.

[quote user="Christopher Saul"]

[quote user="Christopher Saul"]I would agree there are on occasion times when one may use NSAIDs in azotaemic patients, for instance if you have a patient with mild CKD, you've first tried other analgesics, qualitiy of life is unacceptable on those other analgesics, you've explained the risks/benefits to the owners and they've come to an informed decision. [/quote]

[/quote]

I agree, I jsut think that lower doses of NSAIDs tend to work better than "other analgesics" and that the risk with respect to mild CKD and responsible dosing with NSAIDs doesn't (in my limited experience, nor in cats when investigated) appear to be a problem. Certainly in a patient with CKD mild enough to not be clinically evident and require extensive investigation to detect, I don't know I'd worry too much, but that may reflect a combination of my personality and ignorance of small animal medicine rather than be a good approach. I wasn't trying to suggest that I knew more than a dedicated small animal medic re small animal medicine - I clearly don't - and sorry if I came across like that

Re: Azotemia in 13yr old Labrador

Christopher Saul — Wed, 29 May 2013 10:18:04 GMT

[quote user="John Flynn"]

Omega-3's potential adverse effects: Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions

[/quote]

If you read the paper in full regarding the side effects, you'll see that the majority are pretty theoretical with no known reported clinical cases

Regarding the concept that patients on CKD live longer with NSAIDs: How do we know this dog has CKD? Have we got serial urea/creat?Have we ultrasounded the dog's kidneys? could it be acute renal failure? It could even have GI haemorrhage, or be severely dehydrated ( in which case you certainly wouldn't want to give NSAIDs)

Have a quick look back to my previous point:-

I am not totally 100% against the use of NSAIDs in CKD, I am just replying to a legitimate request for advice.

Ultimately it is up to Emily who's advice she buys, this is essentially a question about small animal medicine, and I am a certificate holder in that area with a fair bit of experience........

Re: Azotemia in 13yr old Labrador

Christopher Saul — Wed, 29 May 2013 10:14:09 GMT

[quote user="Emily Herskind Nightingale"]To follow up urinalysis in house was done yesterday with trace protein, no blood/glucose/ketones with acc spec gravity of 1.034[/quote]

This is good; there is likely to be a pre-renal component to the dog's azotaemia. It would still be worth repeating the urea/creat in a few days on the same day as another urinalysis. I'd also do a protein : creatinine ratio, urine cytology ( formalin sample) as well a c and s. I'd also ultrasound the kidneys. See if the azotaemia is transient or not, and if not if it's progressive.....

hope this helps

Chris

Re: Azotemia in 13yr old Labrador

Christopher Saul — Wed, 29 May 2013 10:04:53 GMT

[quote user="Emily Herskind Nightingale"]And I've been prescribing this drug bid albeit rarely at top whack 4mg/kg since I qualified!! I am mortified!!!![/quote]

Don't worry too much Emily, I think there's a fair therapeutic margin on most of these drugs.

Re: Azotemia in 13yr old Labrador

John Flynn — Wed, 29 May 2013 08:27:43 GMT

[quote user="Christopher Saul"]IMO would be better to spend the money on omega 3s[/quote]

IMO better on a low-dose of meloxicam

Wow, sounds scary and reads much like the insert to meloxicam! I think I should check blood clotting, scope the stomach for any pre-existing ulcers and run a baseline fructosamine before starting these

Seriously though, which omega-3 product do you recommend out of interest? Thoughts on http://www.vetenox.com/?

Re: Azotemia in 13yr old Labrador

Emily Nightingale — Wed, 29 May 2013 08:15:50 GMT

Thank you for all your informative and helpful replies. Yes I agree I should have been worked up the cough beforehand however this dog gets extremely stressed (barks nonstop)in the surgery setting and therefore a trial of medication was elected before looking at admitting her. As for the Rimadyl dose am very embarrassed to report that I thought genuinely the dose range was 2-4 mg/kg SID or BID!!! I have a feeling that this is what it says in NOAH and remember reading it thinking that's a bit ambiguous but will check. Have looked up the official literature on Rimadyl and it says 2-4mg/kg once daily or divided into 2 doses. Yikes!!!!! And I've been prescribing this drug bid albeit rarely at top whack 4mg/kg since I qualified!! I am mortified!!!! To follow up urinalysis in house was done yesterday with trace protein, no blood/glucose/ketones with acc spec gravity of 1.034 (just to put you in the picture the labstick results for SPG were 1.010 highlighting the importance of always using a refractometer!!!) Awaiting prot:crea and sediment ex and further work up next Tues. thank you for your help everyone. Am so unbelievably embarrassed re the Rimadyl!! Hope someone has done something similar in the past and will confess to make me feel better!!!! Lastly apols for any weird typos. Am writing this on my phone and can only see small bit of screen at a time :-)

Re: Azotemia in 13yr old Labrador

John Flynn — Wed, 29 May 2013 08:09:36 GMT

[quote user="Mark Holmes"]A recent study referred to at BSAVA and somewhere on here demonstrated animals (cannot remember species probably cats ) with CRF living longer on NSAIDS. I am not convinced the pathogenesis of NSAID associated renal failure can necessarily be applied to a dog in CRF taking NSAIDS as they are different entities. If you want a quick check for pyelonephritis spin a urine sample dry and quick dip the sediment. If here are no bugs I wouldn't worry. I have had dogs on NSAID with CRF and found an improvement but similar to others I have also found paracetamol very effective.[/quote]

A retrospective analysis of the effects of meloxicam on the longevity of aged cats with and without overt chronic kidney disease.

Gowan, R. A.; Baral, R. M.; Lingard, A. E.; Catt, M. J.; Stansen, W.; Johnston, L.; Malik, R.; Sage Publications, Thousand Oaks, USA, Journal of Feline Medicine and Surgery, 2012, 14, 12, pp 876-881, 24 ref.

The study sought to examine the effect of long-term meloxicam treatment on the survival of cats with and without naturally-occurring chronic kidney disease at the initiation of therapy. The databases of two feline-only clinics were searched for cats older than 7 years that had been treated continuously with meloxicam for a period of longer than 6 months. Only cats with complete medical records available for review were recruited into the study.The median longevity in the renal group was 18.6 years [95% confidence interval (CI) 17.5-19.2] and the non-renal group was 22 years [95% CI 18.5-23.8]. The median longevity after diagnosis of CKD was 1608 days [95% confidence interval 1344-1919] which compares favourably to previously published survival times of cats with CKD. In both groups the most common cause of death was neoplasia. Long-term treatment with oral meloxicam did not appear to reduce the lifespan of cats with pre-existent stable CKD, even for cats in IRIS stages II and III. Therefore, to address the need for both quality of life and longevity in cats with chronic painful conditions, meloxicam should be considered as a part of the therapeutic regimen.

Retrospective case-control study of the effects of long-term dosing withmeloxicam on renal function in aged cats with degenerative joint disease.

Gowan, R. A.; Lingard, A. E.; Johnston, L.; Stansen, W.; Brown, S. A.; Malik, R.; Elsevier Ltd, Oxford, UK, Journal of Feline Medicine and Surgery, 2011, 13, 10, pp 752-761, 36 ref.

Medical records (2005-2009) of a feline-only practice were searched for cats with degenerative joint disease (DJD) treated using meloxicam. DJD was diagnosed by the presence of at least two of the following: (i) altered mobility (observed by the owner), (ii) abnormal physical findings, (iii) characteristic radiographic changes. The primary study cohort consisted of cats older than 7 years that had received meloxicam for variable intervals in excess of 6 months, and for which complete records were available. These cats were subdivided according to whether detectable chronic kidney disease (CKD) was present ('renal group'), or not ('non-renal group'), and, for the 'renal group', according to the cat's IRIS category. Serum biochemistry, urinalysis (including urine specific gravity [USG]), body mass and condition score were monitored regularly. Progression of CKD in the 'renal group' and 'non-renal group' of cats was compared to two groups of age- and IRIS-matched control cats not receiving meloxicam (from the same clinic, over the same time period). The study was thus a case-control design, with two study groups. Thirty-eight cats with DJD receiving long-term meloxicam therapy met the inclusion criteria. Of these, 22 cats had stable CKD at the start of treatment (stage 1, eight cats; stage 2, 13 cats; stage 3, one cat). No cats initially had an elevated urinary protein to creatinine ratio. The remaining 16 cats initially had normal renal analytes and adequately concentrated urine. The median age of the 'renal' and 'non-renal' meloxicam groups was 15.5 and 13.4 years, respectively. The median treatment duration was 467 days in the 'renal group' and 327 days in the 'non-renal group'. After titration (to the lowest effective dose), the median maintenance dose was 0.02 mg/kg/day in both groups (range 0.015-0.033 mg/kg/day). There was no difference in sequential serum creatinine concentration or USG measurements between the 'non-renal group' treated with meloxicam compared to control cats not treated with meloxicam. There was less progression of renal disease in the 'renal group' treated with meloxicam compared to the age- and IRIS-matched cats with CKD not given meloxicam. These results suggest that a long-term maintenance dose of 0.02 mg/kg of meloxicam can be safely administered to cats older than 7 years even if they have CKD, provided their overall clinical status is stable. Long-term meloxicam therapy may slow the progression of renal disease in some cats suffering from both CKD and DJD. Prospective studies are required to confirm these findings.

Re: Azotemia in 13yr old Labrador

Michael Woodhouse — Tue, 28 May 2013 23:55:49 GMT

Pretty much my point, Mark. I have given you 5 stars as Mr 1 star is out tonight with vengeance.

Re: Azotemia in 13yr old Labrador

Mark Holmes — Tue, 28 May 2013 23:40:04 GMT

A recent study referred to at BSAVA and somewhere on here demonstrated animals (cannot remember species probably cats ) with CRF living longer on NSAIDS. I am not convinced the pathogenesis of NSAID associated renal failure can necessarily be applied to a dog in CRF taking NSAIDS as they are different entities. If you want a quick check for pyelonephritis spin a urine sample dry and quick dip the sediment. If here are no bugs I wouldn't worry. I have had dogs on NSAID with CRF and found an improvement but similar to others I have also found paracetamol very effective.

Re: Azotemia in 13yr old Labrador

Christopher Saul — Tue, 28 May 2013 23:12:50 GMT

[quote user="Michael Woodhouse"]Honestly how common is pylonephritis? I have had a hell of a lot of negative urine cultures......[/quote]

not very common, but certainly not rare either, and it IS a differential for azoaemia. You can get false negatives because baceria will lyse in transit in dilute urine, hence why it's important to get urine cytology also, as well as looking at the kidneys on ultrasound. I was simply giving an example of why it could be a bad idea to blindly continue NSAIDs without first investigating the cause. After all, having taken the decision to run bloods, would it not be unwise to ignore the results?

[quote user="Michael Woodhouse"]What I am saying is we don't have to outright panic that the dog has a mild elevation in U&C when we haven't even checked the urine.[/quote]

Who's panicking? I have merely given appropriate advice in response to a legitimate request for advice (i.e. a potentially temporary discontinuation of NSAIDs in favour of other more appropriate analgesics)

Re: Azotemia in 13yr old Labrador

Michael Woodhouse — Tue, 28 May 2013 22:56:57 GMT

[quote user="Christopher Saul"]Let's say for the sake of argument (I concede this may very well not be the case in this dog) that the dog actually has pyelonephritis, you continue blindly continue NSAIDs and drive the poor dog into complete renal failure, completely unnecessarily of course because you could have temporarily stopped NSAIDs and cleared up the infection with antibiotics. Would that increase QOL and bring renal parameters back to normal?[/quote]

Honestly how common is pylonephritis? I have had a hell of a lot of negative urine cultures....... Compare that to almost every single older dog that will suffer some renal dysfunction before death.

I am a big fan of checking urine SG and doing a dipstick before starting NSAIDS, but less excited by bloods. We have a VetTest, but I lost all confidence in it. It went to Holland twice and I was spending stupid money running controls to find it was a random number generator. I'd rather wait 24 hours and decent quality results back. What it does mean is that it is rarely possible to check kidneys before the dog goes onto an NSAID.

I'm not saying that I would put a dog with a urea of 50, creatinine of 350 and a USG of 1010 on high doses of NSAID. What I am saying is we don't have to outright panic that the dog has a mild elevation in U&C when we haven't even checked the urine.

How some of you guys sleep at night without worrying amazes me at times.

Re: Azotemia in 13yr old Labrador

Christopher Saul — Tue, 28 May 2013 22:44:26 GMT

[quote user="John Flynn"]A midstream, first thing in morning urine test for "SG" is surely more helpful and significantly cheaper?[/quote]

John you make a nice point, I have often used this method for monitoring NSAIDs especially if the owners cannot afford more monitoring, as a low SpG is more sensitive (though not very specific) then urea/creat for detection of renal disease - you lose concentrating ability when about 66% GFR lost whereas azotaemia won't occur until 75% or so of GFR is lost.

[quote user="John Flynn"] don't think you've documented kidney disease as yet[/quote]

Quite correct, but we might have renal disease, hence why it is so important to investigate further, and pending the results of these investigations it is advisable to discontinue NSAIDs in the short term..

I agree I doubt the vivitonin is doing a lot, IMO would be better to spend the money on omega 3s

I'm sorry, when I first read the post I hadn't noticed the cough. +1 vote for chest x rays,

In general though Emily, good case management so far

hope this helps,

Chris

Re: Azotemia in 13yr old Labrador

Christopher Saul — Tue, 28 May 2013 22:32:39 GMT

I would agree there are on occasion times when one may use NSAIDs in azotaemic patients, for instance if you have a patient with mild CKD, you've first tried other analgesics, qualitiy of life is unacceptable on those other analgesics, you've explained the risks/benefits to the owners and they've come to an informed decision. But.........

Emily, your approach with regards to the kidneys ( i.e. to withdraw the NSAID for the time being while you work up the azotaemia) has been quite correct, and continuing with NSAIDs at this juncture without having first at least tried the dog on more renal-friendly medications would be quite inappropriate.

[quote user="Michael Woodhouse"]I have put dogs onto Carprieve with similar renal parameters and the increased QOL and appetite has brought renal parameters back to normal.[/quote]

and I have seen a number of cases of NSAID associated renal failure.

Let's say for the sake of argument (I concede this may very well not be the case in this dog) that the dog actually has pyelonephritis, you continue blindly continue NSAIDs and drive the poor dog into complete renal failure, completely unnecessarily of course because you could have temporarily stopped NSAIDs and cleared up the infection with antibiotics. Would that increase QOL and bring renal parameters back to normal?

Re: Azotemia in 13yr old Labrador

John Flynn — Tue, 28 May 2013 22:25:42 GMT

[quote user="Emily Herskind Nightingale"]My question is, what painrelief/ antiinflammatory could I consider to help her mobility that is going to be kind on her kidneys[/quote]

I usually use meloxicam.

Why the blood test before urine?

A midstream, first thing in morning urine test for "SG" is surely more helpful and significantly cheaper? (although I apprecaite can be difficult to get on occasions...) Could the dog have been dehydrated when you took the blood sample? I don't think you've documented kidney disease as yet, and even if have then I don't see why can't benefit from NSAIDs, perhaps just at a lowest effective dose if wanting to be cautious.

What is dog's weight?

I'd be surprised if corvental and vivitonin are doing much, but I'm a die-hard cynic about these drugs, so probably best ignored

Re: Azotemia in 13yr old Labrador

Michael Woodhouse — Tue, 28 May 2013 21:03:05 GMT

Emily - I have put dogs onto Carprieve with similar renal parameters and the increased QOL and appetite has brought renal parameters back to normal. I'd be a lot less worried if the dog is adequately concentrating urine. This is true especially in cats.

If you look at a lot of human medics they use loads on NSAIDs in people with renal problems. We can worry too much. .

Quality of life beats duration. If the dog is happy I'd be very reluctant to change anything at the moment and monitor bloods. If things deteriorating then alter your course of treatment.

[I may consider adding in Catrofen injections with the hope of dropping the carprofen dose right down, or even weaning off.]

Re: Azotemia in 13yr old Labrador

Richard Sanderson — Tue, 28 May 2013 18:55:21 GMT

[quote user="Emily Herskind Nightingale"]

Dottie is owned by our accounts manager, and at a recent booster 2wks ago was noted to be quite stiff, with reduced ROM in elbow (R worse than L), reluctant to extend hips and stifles and generally a bit creaky. Chest and heart were fine, bright in self, often coughs at home and roars if gets excited but this is generally short lived.

I have put her on 100mg Rimadyl BID, 500mg Corvental and 150mg Vivitonin BID with a follow up 14d later with blood test.

The owners today have reported a HUGE improvement all round, keener to go for walks, better mobility, breathing better ( cough 99% resolved) and they are delighted. However, in the light of wanting to continue with the Rimadyl (albeit was thinking orf reducing dose from 3.3mg/kg to nearer 2mg/kg BID I ran her inhouse bloods (starved sample) which have shown BUN 10.5 (2.5-8.9) CREA 153 (27-124) and mild hyperkalemia 5.9 (3.7-5.8).

My plan is to stop the Rimadyl, continue with the Corvental and Vivitonin, get a freecatch urine sample for labstick, accurate spec gravity + prot:crea ratio and sediment exam, and have booked her in provisionally for next Tues 4th June for rpt bloods, radiograph abdo and ultrasound of kidneys etc.

My question is, what painrelief/ antiinflammatory could I consider to help her mobility that is going to be kind on her kidneys..She's a lovely old dog and is much loved and her owners have been so thrilled that she is now literally taking them for walks, I'd like to be able to keep her comfy!

Thanks

[/quote]

Just to check - are you using carprofen at 4mg/kg SID then attempting to go down to 2mg/kg SID? I assume a typo re BID at this dose rate?

Re: Azotemia in 13yr old Labrador

Richard Sanderson — Tue, 28 May 2013 18:53:44 GMT

The previous information here covers most of it. I would definately consider the a thoracic radiograph series as well as abdominal radiography/ultrasound. I would probably give light sedation for abdominal imaging and collection of cystocentesis then induce light GA for inflated thoracic radiography to rule out neoplastic issues (esp if abnormal on ultrasound). Regarding the pain relief, my systematic review paper on the management of canine OA (Vet Record, 2009) goes through the evidence base for most reported treatments of canine OA and rates them. I would commence a fatty acid/omega 3 supplement - my first choice is Nutradyl given the concentrations it has. In addition you have the main 3 options (in my order of preference) 1) tramadol slow release at 2-5mg/kg BID 2) gabapentin starting at 10mg/kg TID and increasing as required 3) pardale using the dose of paracetamol to be 10mg/kg BID. I usually use a combination where NSAIDs can't be used. Other option if the azotaemia is shown not to be renal in origin, and the liver is not compromised at all would be a -coxib e.g. robenacoxib but need assess the azotaemia first properly.