Perioperative Augmentin doses

Re: Perioperative Augmentin doses

John Flynn — Thu, 25 Sep 2014 21:53:39 GMT

[quote user="Michael Woodhouse"]I appreciate that if you give IV it will be eliminated faster.[/quote]

Just picking up on this - is that an advantage other than for urinary surgery?

For gut surgery, then presumably the main risk is direct contamination of the peritoneal cavity and contents with significant levels of intestinal flora bugs. If my antimicrobial lasts for the duration of surgery only before being rapidly eliminated, is that really a good thing? Surely if I'm using an antibacterial that, say, only kills bacteria during cell division, then one presumably wants that drug to persist in tissue levels for a good while after surgery - enough to allow for the cell division process to commence for any contaminant bugs?

Re: Perioperative Augmentin doses

John Flynn — Thu, 25 Sep 2014 21:32:30 GMT

Looks like Michael has spotted the dearth of evidence for any of the proposals suggested thus far in the thread.

Unless someone can explain in terms I understand the reasoning behind any specific dogma they follow re choice/route of prophylactic antimicrobial for the surgery in question, then I'll continue to believe that it's largely a matter of personal preference based on your own intuitive logical thought.

Anthony, if you haven't come across a decent explanation for what other people use, then I'd suggest that it's because no such clear explanation exists. There is certainly expert-led material recommending the intramuscular route out there as well (though less than in favour of intravenous), as well as differences in recommendation of choice, timing, duration etc of antimicrobial.

If what you're aiming for is the "what do most people do in practice" approach, and you're aiming simply to have serum levels of 2-3times the MIC90 for amoxicillin for the duration of surgery while throwing in some clavulanate for good measure, then I suspect you'll find with relation to intravenous augmentin for prophylactic gut surgery that a wide variation in dose levels and frequency are out there and it is probably quite sensible to not overthink it and use a "vial"-type dose where your dose rate falls between the lower (8mg/kg?) and higher (25mg/kg?) doses commonly recommended - just remember to inject slowly and that some other amox/clav intravenous preparations anecdotally have been associated with unreasonable levels of anaphylaxis in dogs (perhaps don't dissolve as well initially?)

Repetition of this dose would then depend on the half-life via the method of administration, with presumably half the original dose repeated for each elapse of the half-life of the drug, or, in practical terms, perhaps half a vial every hour or so.

To answer these most basic of questions (while skipping all the inherent assumptions on aims of such therapy in the first place etc), then one needs to venture to the pharmacokinetics side, I found only one published study related to the intravenous adminsitration of clavulanate in the dog (from 1987) at a dose similar to your 8.75mg/kg augmentin dose which estimated the half-life at 40mins - thought I'd throw that in there as a bit of PK trivia ;-)

Re: Perioperative Augmentin doses

Michael Woodhouse — Thu, 25 Sep 2014 17:59:47 GMT

Peritonitis and even death are accepted complications of surgery. So long as you weren't negligent then your choice of antibiotic should hardly be relevant. If there was a big pool of evidence IV was better then we wouldn't be having this discussion and the answer would be clear cut.

Just because a referral hospital do something doesn't mean it's OK or even best practice. I remember a RCVS DC where pin relief was discussed and Dan Brockman (super surgeon) had not heard of Pardale V.........

More likely is the owners discovered you used an unlicensed human medicine without a signed consent form and that is why the dog died

(there was a VDS case not that long ago where they paid out because the vet used buprenorphine, bitch (or maybe pups) died, the owners pulled the data sheets online and saw an absolute contraindication on the data sheet for caesers.)

Re: Perioperative Augmentin doses

Anthony Dennison — Thu, 25 Sep 2014 15:21:31 GMT

I'm not arguing your point at all Michael - it's a very good one, my responses have just been me thinking aloud, trying to see if there is a way of applying the cascade to Augmentin.

The other way to think of it is this; if there was a post-op peritonitis in the case I mentioned in the OP, the dog died and the client complained to the RCVS and the case went to DC (not that it probably would). Would giving a single dose of Synulox s/c at the time of pre-med be seen inferior to repeated doses of I/v Augmentin because referral centres use Augmentin?

Re: Perioperative Augmentin doses

Michael Woodhouse — Thu, 25 Sep 2014 15:13:05 GMT

I appreciate that this was done in pigeons, but I am struggling to find anything that compares different routes of admin:

http://www.ncbi.nlm.nih.gov/pubmed/9769077

The blood levels were maintained significantly longer if given IM versus IV. Synulox is formulated in a slower release oily base so that it can be given once daily.

I appreciate that if you give IV it will be eliminated faster. What I don't see is why you can justify it. Why the profession can justify it. (I know it is commonly done.)

(I've said before on here - the cascade is a pain in the arse, but whilst it exists and is law I will follow it. Wanting to give something by a different route on a whim would seem hard to defend. Good sound evidenced based judgement is irrefutable. I just can't find any. I looked before and I looked now. The best I could find were pigeons.....)

Re: Perioperative Augmentin doses

Anthony Dennison — Thu, 25 Sep 2014 14:54:25 GMT

[quote user="Michael Woodhouse"](It was said on here, may have been Malcolm Ness, but not 100% sure, I apologise if I miss quote - that they compared the two routes and found Synulox at pre-med did the same job).[/quote]

Yes I remember this, and yes it did reach similar plasma levels, but this was as a single dose, not looking at the half life of synulox in the system. During longer soft-tissue and orthopaedic surgeries, the level of antimicrobials needs to remain effective. To be at appropriate concentrations at the time of tissue manipulation/incision in longer surgeries, repeated doses are needed, in which Synulox is not licensed, but Augmentin is in humans, so the cascade can be applied.

Re: Perioperative Augmentin doses

Michael Woodhouse — Tue, 23 Sep 2014 14:18:43 GMT

[quote user="Robin Grimmer"]

Surely as there is no licensed iv preparation then it is fine to use augmentin.

[/quote]

Back at you - can you give me any evidence that is any better than using a licensed product by the s/c route?

(It was said on here, may have been Malcolm Ness, but not 100% sure, I apologise if I miss quote - that they compared the two routes and found Synulox at pre-med did the same job).

Re: Perioperative Augmentin doses

Robin Grimmer — Tue, 23 Sep 2014 13:16:21 GMT

Surely as there is no licensed iv preparation then it is fine to use augmentin.

Re: Perioperative Augmentin doses

Tim Charlesworth — Tue, 23 Sep 2014 09:51:03 GMT

Without getting drawn into the whole cascade/pharmokinetics debate we (and most other soft tissue surgeons I know) use perioperative augmentin @20mg/kg iv q 90-120 minutes when indicated,

Tim

Re: Perioperative Augmentin doses

Anthony Dennison — Tue, 23 Sep 2014 00:30:25 GMT

I'm sorry, I can't see what part would indicate using Augmentin is breaking the law; either at the dose in the formulary or at the dose wirrten in literature.

An awful lot of vets use Augmentin for this purpose, so I'm unsure if a case would ever come up against someone for doing so.

Re: Perioperative Augmentin doses

Michael Woodhouse — Sat, 20 Sep 2014 01:09:36 GMT

The Cascade is based on the principle that, if there is no veterinary medicine
authorised in the UK for treating a disease, the veterinary surgeon responsible for the
animal may, in particular to avoid unacceptable suffering, treat the animal with a
product from one of the following categories in descending order of suitability:

a) A veterinary medicine authorised in the UK for the same condition in another
animal species or for another condition in the same animal species;
b) Either:
(i) a medicine authorised in the UK for human use; or
(ii) VMP not authorised in the UK but authorised in another Member State
(MS) for use in any animal species in accordance with an import certificate
issued by the VMD (for further information on the Import Certificate Scheme
please refer to VMGN 5 Import Certificate Schemes, which is published on
the VMD website:
http://www.vmd.defra.gov.uk/public/vmr_vmgn.aspx
c) A medicine prescribed by the veterinary surgeon responsible for treating the
animal and prepared extemporaneously by a veterinary surgeon, a
pharmacist or a person holding an appropriate manufacturer’s authorisation (so
called “specials manufacturer”). Under exceptional circumstances medicines
may be imported from third countries in accordance with a VMD Import
Certificate.

The aims of the existing legal provisions are to ensure that unauthorised medicines
are used only when there is no authorised product for the condition and species
concerned

Dosage Considerations - Sometimes a veterinary surgeon may consider that the
effective treatment of a particular condition in a particular animal requires a different
dosage regime from that on the label of a product. In such circumstances recourse
to the Cascade would be appropriate and the veterinary surgeon may compare the
merits of using that product with a dosage regime different from that described on the
product’s SPC with an alternative authorised veterinary medicine. If neither can
safely be administered at the dosage required, the veterinary surgeon should
consider further options under the Cascade.

You are breaking the law routinely using Augmentin, by my reading of the cascade.

Re: Perioperative Augmentin doses

Sammy82 — Sat, 20 Sep 2014 00:49:22 GMT

Does any antibiotic have a perioperative licence for this matter? Following the cascade we are still supposed to use the veterinary formulation before the human one.

Re: Perioperative Augmentin doses

Rob Loxley — Fri, 19 Sep 2014 19:37:50 GMT

[quote user="Michael Woodhouse"]A bigger question would be why you couldn't achieve that target MIC using a licenced veterinary version of amoxicillin......[/quote]

strictly Synulox RTU does not have a perioperative licence...

but yes, we have done this debate before e.g. http://www.vetsurgeon.org/forums/p/6714/27641.aspx

Re: Perioperative Augmentin doses

Anthony Dennison — Fri, 19 Sep 2014 17:07:53 GMT

[quote user="Michael Woodhouse"]A bigger question would be why you couldn't achieve that target MIC using a licenced veterinary version of amoxicillin......[/quote]

Fair point - again, I used it because generally Augmentin was the antibiotic in these situations whilst I was at university, and it is what is used at my practice routinely for surgical antibiotic prophylaxis.

Re: Perioperative Augmentin doses

Anthony Dennison — Fri, 19 Sep 2014 14:55:57 GMT

[quote user="Martin Atkinson"]I would probably have used IV metronidazole in the OP's case anyway rather than Augmentin and sent it home with pot. amox. tablets.[/quote]

Why send it home with antibiotics? There was no contamination of the abdomen, surgery went well. Again, most literature on GI surgery says unless there is marked contamination therapeutic antimicrobials aren't needed.

Re: Perioperative Augmentin doses

Andrew Mellor — Fri, 19 Sep 2014 10:39:53 GMT

I suppose a lot comes from human literature and use which is up to 30mg/kg in what they call serious infections every 6 hours - from the BNF

Re: Perioperative Augmentin doses

Martin Atkinson — Fri, 19 Sep 2014 09:04:43 GMT

I have to say that I just follow the logic that the dose would be the same as if it was being given orally so I work that out at the upper end of the range and give that IV. If there is an argument re. whether you should be giving a higher dose then my logic again suggests to me that its given IV then its going straight to the target organ at maximum dose rather than a slow build up over a few hours if its got to be absorbed through the gut. Seems logical to me anyway!

That said, if anything, I would probably have used IV metronidazole in the OP's case anyway rather than Augmentin and sent it home with pot. amox. tablets.

Re: Perioperative Augmentin doses

Michael Woodhouse — Fri, 19 Sep 2014 08:59:56 GMT

Remembering that amoxicillin is time based killing rather than concentration dependant. So long as you achieve MIC for your chosen pathogen in your chosen tissue.

A bigger question would be why you couldn't achieve that target MIC using a licenced veterinary version of amoxicillin......

Re: Perioperative Augmentin doses

Mark Hedberg — Fri, 19 Sep 2014 08:52:33 GMT

[quote user="Anthony Dennison"]

why would a dose rate of 20mg/kg be repeated so often in literature if it wasn't appropriate?

[/quote]

I would be suspicious that it was a 'we've always done it like that' approach that's crept into the papers. Quite often when a generation of distinguished greybeards do things their own way, it just seeps into general usage. Take flank spaying, for instance - you can argue the merits but the fact is, it's an incredibly frequent op here, and comparatively rare overseas. 'More is better' was a great fashion in antibiotics for a long time (still is in some quarters!) and it could just be another case of 'Eminence based medicine'.

Re: Perioperative Augmentin doses

Anthony Dennison — Fri, 19 Sep 2014 08:29:32 GMT

Vert good questions John, unsure about the second one I'm afraid.

My aim is to provide appropriate antibiosis for the duration of the surgery, so that levels of the drug are present at the time of first incision and stay at an effective concentration for the duration of the surgery. In the case of this dog, he received a dose 30 minutes prior to first incision and then another dose 20 minutes after surgery finished (90 minutes after the first dose). No further antimicrobials were given as there was minimal/no contamination.

What are effective levels though - formulary or literature doses? We haven't had any complications using the formulary dose as far as I'm aware, but why would a dose rate of 20mg/kg be repeated so often in literature if it wasn't appropriate?

Re: Perioperative Augmentin doses

John Flynn — Thu, 18 Sep 2014 17:42:40 GMT

not an answer, but 2 questions:

1) What is your aim? Is it to reach normally-considered effective levels of the amoxicillin and the clavulanate in the tissues being cut, say 2-3 times the MIC for the most common small intestinal or skin bugs, for the duration of surgery? Or is it to reach tissue levels vastly in excess of normally-considered therapeutic levels for the duration of surgery? Or if for longer, then how much longer?

2) What phamacokinetic/pharmacodynamic data is there for amoxicillin and, in particular, clavulanate in the dog when administered intravenously?

Re: Perioperative Augmentin doses

Andrew Mellor — Thu, 18 Sep 2014 17:14:30 GMT

Ginerally for orthopaedics I would go for higher end of range something like 15mg/kg but in septic joints / septicaemic patients I have used up to 25mg/kg four times daily for 1-2 days, generally all I would say is the higher you go the worse the gut fallout tends to be!