Drug 1/2 dose limits in the elderly obese patient

M

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G'Day all

Pondering a bit of a dilemma at the moment. The situation is this.

Under our adult guidelines a number of drugs such as Midazolam are given under dose for weight parameters with which everyone will be familiar. eg with Midaz its 0.1mg/kg. You'll use that parameter for treating seizures and the same one for sedation to intubate etc.

Makes sense so far?

Now there are further restrictions. If you have patient who is >= 60yo or under 60kg in weight you give a half dose. eg a 50kg 18yo girl gets 0.05mg/kg and a 75yo nanna gets the same.

Also makes sense yeah?

The last restriction is the max dose you can give - 10mg. (with a couple of exceptions eg the agitated patient)

So whats the dilemma you say?

It all makes perfect sense doesn't it? - Midazolam is a powerful sedative and does wonders for gag, respiration and blood pressure when you start pumping it in hence the restrictions and half dose for fragile (elderly) or small patients.

It's all about lean muscle mass (or lack thereof) in the older or smaller patient, hepatic and renal function, drug distribution and absorption, circulating free drug yada yada yada. Drug actions versus risk of side effects, therapeutic range and toxicity levels etc.

In summary, risky or susceptible patients=smaller doses. Pharmacokinetics and dynamics 101

Fine.

So what happens to the "smaller" (1/2) dose when your patient is say 75yo and weighs say 120kg.

Well half dose age >=60 - - 6mg IV (120 x 0.05mg). A shade above the half the absolute maximum but not too much. 5mg versus 6mg. Seems Okay.^_^

Well what about the morbidly obese patient say 180kg who is >=60yo?

Half dose, right? 9mg (180kg x 0.05mg)

Hang on. The absolute maximum full dose is 10mg and that's for the young adult in the normal weight range (apparently most drug doses are determined based on average weight ranges for adults stats -obese ranges don't come into the picture).

So this 75yo nanna who happens to be bariatric as well gets nearly the same maximum dose a strapping 75kg 20yo body builder would.;)

Hence the problem. There is no half dose maximum because the dose is calculated on weight to begin with.

So set a maximum half dose of 5mg for all circumstances, easy.

Based on what evidence?

I can't seem to find any and that's the problem. Dose for weight calculations are all based on the average adult weight stats I mentioned earlier and there's no mention of setting specific levels. All the articles I've found so far just say "smaller" doses for the elderly.

There a plenty of articles expressing great concerns about dose calculations for obese patients particularly in areas like antibiotic therapy and cancer therapy. But what about obese elderly patients where dose for weight applies?

Your ponderings on zis matter meine dammun und herrun would be much appreciated.

MM
 
I got confused halfway through your post and I'll say this, hoping it's relevant :D


Just because a person is bigger doesn't mean the extra tissue metabolizes the drug, and you still stick the the maximum dose, even if it is lower then the weight-decided dose.

Hence why a pedi will still get a max of .3mg Epi, the adult dose, even if the dose based on kg is higher than .3mg
 
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Linuss said:
I got confused halfway through your post and I'll say this, hoping it's relevant :D


Just because a person is bigger doesn't mean the extra tissue metabolizes the drug, and you still stick the the maximum dose, even if it is lower then the weight-decided dose.

Hence why a pedi will still get a max of .3mg Epi, the adult dose, even if the dose based on kg The OP is talking about basing the dose on presumed lean body mass. It makes a lot of sense and you are more or less correct that it has to do with not letting the amount of fat a person is packing around change the dosages for drugs that are not going to act upon that tissue.
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Something else to consider is that Midazolam is metabolized by the liver. So as the liver's ability to metabolize decreases with age and disease, the half life of the drug will increase.
 
Hmm our clinical newsletter had a bit on drugs in obese patients recently, *wheels to other side of room to get it ... aw man, it says where the normal dose is proving ineffective to consult with a Medical Advisor (ala the Metro Clinician) as dosing may need to be 25-30% larger.
 
Context

Your'e all champions for having a dig. Perhaps I need to explain a little better.

First the numbers again.

Normal adult gets 0.1mg/kg IM provided they are >60kg and less than 60yo.

Now if you are >60yo or less than 60kg you get half doses ie 0.05mg/kg.

(That's for safety reasons and well supported by clinical evidence and relative contingencies for the pre-hospital situation - eg risk of resp depression, loss of consciousness, hypotension etc and how well we can manage these things in the back of rig with what we have in the kit)

Now some examples about doses. (and this is where the plot thickens so they say!!)

eg1. 20yo weighing 80kg would get 8.0mg IM (80 x 0.10) [av. weight & age]
eg2. 40yo weighing 50kg would get 2.5mg IM (50 x 0.05) [small person]
eg3. 70yo weighing 70kg would get 3.5mg IM (70 x 0.05) [old person]

now:

eg4. 70yo weighing 200kg would get 10mg IM (200 x 0.05)

That's the maximum dose allowed for a normal adult weight (>60kg) with an age less than 60yo.

We have a set maximum dose for Midaz as explained above. 10mg

Unfortunately there is no set maximum half dose so when you throw in the dose/weight spanner you are giving potentially toxic doses to little old ladies just because they are actually not that little.

You can't give an elderly pt the same amount of midaz as a youngun just because they are large. It doesn't work that way. And this is where the problem arises. Where does the half dose limit stop and why that amount?

Midaz in its salt form (which is how we all get it) is water soluable (fat soluable in its pure form).

Lean muscle mass is the big factor here because the elderly have a much lower proportion of lean muscle mass and muscle contains a lot more water than fat. (They also have a higher proportion of fatty tissue)

Hence Midaz is well absorbed in muscle tissue and very little finds its way unaltered into the central circulation where it can become toxic. Normal grown ups of average weight and age get full doses because they can handle it.

But if the pt is old irrespective of whether they are bariatric they cannot handle large doses of this drug without dire consequences. They have lots of fat yes but still very little lean muscle and reduced renal function and other common issues associated with ageing.

So little of the drug gets absorbed into the fatty tissue but there isn't much muscle to take it up so instead it finds its way into circulation and the problems begin.

Now some of our observant ambos here came across such a situation. What dose should they give? The pt was 80yo but weighed 130kg, not common but it happens especially in an era of growing obesity problems.

They want answers and the answers have to be right, they have to be safe and they have to meet rules of evidence to get past our medicos and not cause the service to wind up in court when we kill someone because we recommended the wrong dose. And our education department has to find the answer.

But bariatric pts and especially bariatric old people weren't put into the mix when the chemistry gurus worked out the safe doses from studies.

I cannot find any information which solves this problem and allows me to go back to our department (and our staff) and say you give this maximum half dose and no more. The ambos I mentioned covered their arses by consulting -the docs told them to give a small dose. Why? - Because they don't know the answer either. There just doesn't seem to be anything specific out there.

As I mentioned in my first post this issue is arising in lots of areas, like antibiotic prescribing and cancer therapy doses for bariatric pts. Nobody I guess ever thought we would need studies which took into account 40% of the population being grossly obese.

Once again chaps your thoughts.

MM
I hope that makes in clearer - sorry for the long windedness (as usual).
 
Soem extras

Midaz is lipid soluable in normal physiologic PH. (this changes with ageing or certain disease processes like COPD?)

Also it is easily taken up by the central nervous system but has a pronounced extension of half life in the elderly. One article I read states the doses in the elderly should be reduced by at least a factor of two. (Hence our half doses).Still no mention of the dose per weight issue and where you set your limits on the half dose.

Elderly pts with hepatic disease, renal dysfunction, dementia, COPD etc are all at far greater risk of toxicity or side effects in both degree and length of effect.

MM
 
So why not just start at arbitrarily say 0.25 and titrate up to the desired effect?

I think I understand your point, but when you start dealing with water/fat ratios you would also have to take into account sex of the patient, as women generally have more lipid than men physiologically. They also have a lower hepatic function, which is why you see lower alcohol limits for women than men. It is not just about size. From there you have to add into the mix a host of other pathologies, which could further alter your dosing regimen.

If you are referring to the volume of distribution, as fat increases so will distribution, Which would mean the drug would remain active longer. I don't see how this is really an EMS concern. If you are talking about subsequent doses, you will probably have to reduce dose as well as frequency.


http://www.drugs.com/pro/midazolam-injection.html

I don't think you are going to be able to create a hard/fast standard dosage. Like I said in the begining, start low and titrate.
 
I think the key point we are missing here is, have you ever seen a fat elderly person? :P
 
Vexing

Veneficus said:
So why not just start at arbitrarily say 0.25 and titrate up to the desired effect?

I think I understand your point, but when you start dealing with water/fat ratios you would also have to take into account sex of the patient, as women generally have more lipid than men physiologically. They also have a lower hepatic function, which is why you see lower alcohol limits for women than men. It is not just about size. From there you have to add into the mix a host of other pathologies, which could further alter your dosing regimen.

If you are referring to the volume of distribution, as fat increases so will distribution, Which would mean the drug would remain active longer. I don't see how this is really an EMS concern. If you are talking about subsequent doses, you will probably have to reduce dose as well as frequency.


http://www.drugs.com/pro/midazolam-injection.html

I don't think you are going to be able to create a hard/fast standard dosage. Like I said in the begining, start low and titrate.
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Thanks Venny

I take your point and agree entirely. A titrated dose is a logical approach to take with an arbitrary starting point and plenty of the papers I have looked at say pretty much the same thing. Some suggested starting dose limits are 1-3mg IM/IV eg. (I'm not quite sure about your suggested dose - as I said we administer on the basis of mg/kg hence the weight issue and the over 60yo problem combination when calculating.)

In the end I think our real issue is less about giving too much but actually holding back too much and not reaching therapeutic threshold. This is because our first dose is in the emergency setting of a time critical patient. Our first dose is a loading dose designed to reach serum levels for effect as quickly as possible. That makes sense when you look at seizures in particular. You don't want to have to keep repeating doses too much in older patients or head traumas for example.

However, there is clearly no question the elderly should get smaller doses for all the reasons mentioned and it's also certainly true the obese elderly patient cohort is likely to be a small one. But there are future considerations in this as we all know obesity is on the rise.

We have quite a few indications for Midaz in our CPG's, 8 in total. 6 of them involve exploiting the sedative properties of the drug eg induction for tubes, pyschostimulant overdose, agiatated pt, cardioversion etc. The other two involve the anticonvulsant properties for seizures.

A lot of the pts who fall into our categories would be young enough or small enough to get full doses. Head traumas needing RSI could be any age MVA's, falls, assaults and the like and you could certainly get fitting elderly CVA patients however.

Realistically the problem area I see is the 60 something year old who is obese (realistically still a possibility around that age) and requires induction following head trauma or has a seizure following a sub arach. It's hard to envision many 80yo people being bariatric pts.

In the end though, there still won't be many who test the calculation issue.

We are looking at recommending to our docs a maximum 1/2 dose limit of half the normal maximum ie 5mg IM/IV (normal max 10mg) with the caveat of titrating to response and suggesting a consult for extra doses if needed. That way staff can still give 0.05mg/kg even in bariatric elderly pts and if they ever get a stupendously large pt they just give 5mg max and then ask someone else to decide about more!

Should be enough to keep us out of trouble.

Thanks again Venny

MM
 
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