Drugs crystallizing inside therapeutically induced hypothermic patients.

[ethyl]

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Has anyone out there seen this happen? It seems more like a thought exercise to figure out since unfortunately nobody is purposely trying to crystallize drugs in people. 😉 I can't really think of any other drugs that crystallize at somewhat high temperatures... so I think Mannitol will be the best example.

If you have a patient with a core temperature of ~89 degrees F, but receiving cold saline of about 40 degrees F through a peripheral line, is there much potential for a drug like Mannitol to crystallize in the person's body especially in their fingers and toes?

I figure it's likely because of how much colder their appendages will be compared to their core temp, and I can imagine mannitol just chillin in some small vasculature, crystallize and go stabbing everywhere like a crazy latina ex-gf.

 

[metrarx]

....

 

[Praziquantel86]

Good food for thought. I don't think that the majority of drugs at therapeutic concentrations are close to their saturation points, but there are a few notable exceptions. Sulfa antibiotics come to mind, and maybe ceftriaxone (probably a stretch).

I would definitely be interested to see if there are any cases out there.

 

[WVUPharm2007]

Does Rimington's have solubility info?

 

[njac]

that is an interesting thought.

Just thinking of the therapeutic hypothermia patients I've worked with - it's initiated when they first show up so they haven't acquired their ICU infection yet so we don't need abx.

 

[Praziquantel86]

Does Rimington's have solubility info?

Yes, but it isn't very in-depth. I'd think that somethink like the Merck Index might almost be better, it would be able to cover a pretty wide range of possible physiologic precipitates.

 

[powertoold]

ceftriaxone (probably a stretch).

I doubt it. Have you thawed one of those ceftriaxone Baxter bags? You can't see any precipitation of the drug 🙂

 

[Pianopooh]

UPENN medical has this:

Caution: Do not administer any medication to hypothermic patient if medication is labeled "Do not refrigerate". (Example: Mannitol)

Source: http://www.med.upenn.edu/resuscitation/hypothermia/documents/WakeMed.pdf

Information located on page 3. This is for "Adult Induced Hypothermia and/or Re-warming Status Post Cardiac Arrest Orders"

 

[Pianopooh]

This article speaks of using mannitol via a console in mild hypothermia patients (decrease 3-4 C per hour) as treatment to minimize secondary brain injury after a traumatic brain injury event. From this CoolGard console, 55% of hypothermia group had favorable results.

Source: http://www.aann.org/ce/pdf/0610b.pdf

 

[njac]

UPENN medical has this:



Source: http://www.med.upenn.edu/resuscitation/hypothermia/documents/WakeMed.pdf

Information located on page 3. This is for "Adult Induced Hypothermia and/or Re-warming Status Post Cardiac Arrest Orders"

nicely done!

 

[Aznfarmerboi]

Has anyone out there seen this happen? It seems more like a thought exercise to figure out since unfortunately nobody is purposely trying to crystallize drugs in people. 😉 I can't really think of any other drugs that crystallize at somewhat high temperatures... so I think Mannitol will be the best example.

If you have a patient with a core temperature of ~89 degrees F, but receiving cold saline of about 40 degrees F through a peripheral line, is there much potential for a drug like Mannitol to crystallize in the person's body especially in their fingers and toes?

I figure it's likely because of how much colder their appendages will be compared to their core temp, and I can imagine mannitol just chillin in some small vasculature, crystallize and go stabbing everywhere like a crazy latina ex-gf.

This topic reminds me of gouts in the joints where the oldies massage it so that the crystals will dissolve.

 

[Praziquantel86]

I doubt it. Have you thawed one of those ceftriaxone Baxter bags? You can't see any precipitation of the drug 🙂

I was thinking that the calcium levels in the body might speed the process (precaution with calcium-containing products). Still a stretch, but who knows.

I've seen a few articles saying that there's a moderate incremental benefit to the mannitol/hypothermia combination vs. either alone in increased ICP, but nothing about precipitation. If anything would do it, I would think mannitol would probably be the most likely candidate based on clinical scenario alone. I agree with aznfarmerboi, too, you'd think that gouty symptoms would be the first to appear (maybe the kidneys as well).

 

[njac]

I was thinking that the calcium levels in the body might speed the process (precaution with calcium-containing products). Still a stretch, but who knows.

that was in <10 neonates 15-20 years ago.

I'm not convinced it's an issue with the circulatory volume of an adult.

 

[ethyl]

I looked at the two NEJM studies that boosted the induced hypothermia into the guidelines... but neither mentioned excluding any drugs. The university of Pennsylvania and University of Southern California have guidelines that say not to give drugs like mannitol or 'do not refrigerate drugs', but none cite why. I think these protocols are all from institutions being cautious with only anectodotal evidence. There's no primary literature out there that I can find that mentions any kind of crystallization of mannitol or dilantin in the body of hypothermic patients. It makes sense to me though that it may be possible... I wish I could get a sense of just how cold a patient's periphery gets.

As far as any antibiotic instability, sepsis is an exclusion criteria for therapeutic hypothermia.

And some more food for thought, there's a recent animal study that's brought up the possibility of reduced CYP enzyme activity in hypothermic patients. 😉

 

[ethyl]

This article speaks of using mannitol via a console in mild hypothermia patients (decrease 3-4 C per hour) as treatment to minimize secondary brain injury after a traumatic brain injury event. From this CoolGard console, 55% of hypothermia group had favorable results.

Source: http://www.aann.org/ce/pdf/0610b.pdf

Thanks for bringing that up. I had looked at that article too. I was a bit concerned that the section on mannitol infusion wasn't cited, so I looked through every reference for the article and still didn't see anything that mentioned mannitol. So I have no idea where they came up with that other than the logic of not infusing mannitol at the same time through a catheter that's running saline at 4 degree celcius. 👍

I've seen other protocols online for therapeutic hypothermia that don't mention any exclusions for 'do not refrigerate' drugs... so coupled with that article, I suspect there's plenty of places using these drugs in hypothermia, including mannitol. The whole thing is just so new I doubt we'll know for sure for another few years till this treatment rolls out in more places.

 

[ethyl]

Does Rimington's have solubility info?

http://books.google.com/books?id=NF...6-USifqvm&dq=remington's solubility&pg=PA1422

meh

 

[npage148]

Based on the large vol of dist (>3L), the effects of plasma proteins/lipids in reducing free fraction and solubilizing drugs, and the relatively low doses of drugs I don't foresee this happening

a 200g dose of mannitol in a 70kg man would probably be about a peak plasma conc of 13mg/ml, using extracellular volume as the Vd. Way below the remington's solubility of it in water at room temp.