Morphine and low dose naltrexone...useful?

[turkish]

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I am currently managing a terminal cancer patient's pain in the ICU because this person has recently been having severe respiratory depression while at the same time requiring massive amounts of narcotics/ketamine/intrathecals for pain control.

I was wondering if anyone here has had good luck with co-administration of naltrexone with morphine for better pain control/lower dosing of morphine.

I have done some looking around, and it seems to be helpful, but I wanted a "real-world" perspective. Thanks for any help.

 

[Tenesma]

what...???

 

[turkish]

http://www.paintrials.com/publications/Capasso8.pdf

also http://www.biospace.com/news_story.aspx?StoryID=20670120


Basically co-administration can greatly enhance pain relief while reducing both side effects and receptor-switching (tolerance). At least in some trials.

Was wondering if anyone has used this clinically.

 

[Tenesma]

read those studies a bit better...
this is the prelude for methylnaltrexone coming on the market as the "eliminator" of all bad side-effects - just what our druggies needed...

 

[drusso]

I am currently managing a terminal cancer patient's pain in the ICU because this person has recently been having severe respiratory depression while at the same time requiring massive amounts of narcotics/ketamine/intrathecals for pain control.

I was wondering if anyone here has had good luck with co-administration of naltrexone with morphine for better pain control/lower dosing of morphine.

I have done some looking around, and it seems to be helpful, but I wanted a "real-world" perspective. Thanks for any help.

What's running in the epidural? Are you dealing with opioid induced hyperalgesia??

 

[Kwijibo]

What's running in the epidural? Are you dealing with opioid induced hyperalgesia??

Unless the patient is a rodent, there is minimal to no evidence that opiod induced hyperalgesia exists.

 

[Aether2000]

Hmmm....and how would you propose we test the theory in pain patients?

 

[jsaul]

Unless the patient is a rodent, there is minimal to no evidence that opiod induced hyperalgesia exists.

concur,


everyone screams opioid hyperalgesia--- folks does that really exist-- not much true evidence for it

 

[drusso]

Hmmm....and how would you propose we test the theory in pain patients?

It's a tough nut to crack. I think that there is pretty good evidence (including human experimental models) that the phenomenon exists. There are still a lot of details and pharmacogenomics to work out.

What to do about it clinically is another matter. I love it that people will jump all over OIH screaming there is "no evidence!" as if the rest of the interventions in the field have been backed innumerable by "Framingham-esque" trials.

 

[Mister Mxyzptlk]

I'm a believer. I think when they get to the point where they can't sleep at night but are drowsy all day, the dosing interval keeps getting shorter, and pain persists despite dose escalation you are well into the hyperalgesia phase. They don't even realize how bad the drugs are making them feel until you put in a pump or do something else that gets the PO meds way down.

Has anyone else noticed that if you put a pump or stim in someone on high dose opioids they come back stating that their back pain is ok but they complain bitterly about the incisional pain for the next 2 weeks? A comparable operation for a pacemaker needs Tylenol #3 for a day or two, if at all. I think that is classic hyperalgesia.

 

[Kwijibo]

Opiod-induced Hyperalgesia, A Qualitative Systematic Review
Angst, M.D., J. David Clark M.D Ph.D
Anesthesiology 2006; 104:570-87

there are a couple of other articles pertaining to the subject in that issue as well.

 

[Tenesma]

hyperalgesia: just look at heroin addicts or any of your high-opioid consumers - try sticking an IV in them. They literally will cry like babies... if that isn't hyperalgesia then i don't know what is...

 

[Aether2000]

I have seen this in my own patients, especially the examples of incisional pain, that are mediated by AMPA and not by NMDA. Interesting....

 

[lobelsteve]

It's a tough nut to crack. I think that there is pretty good evidence (including human experimental models) that the phenomenon exists. There are still a lot of details and pharmacogenomics to work out.

What to do about it clinically is another matter. I love it that people will jump all over OIH screaming there is "no evidence!" as if the rest of the interventions in the field have been backed innumerable by "Framingham-esque" trials.

In the aforementioned review article, I counted 9 case reports and 4 studies with n of 60, 60, 60, and 50.

I am finding a lot of the "data" is what people heard from an attending. Our program is working around that by gathering a large collection of PDF's on all topics. BTW, DP did a great job on his first Celiac.

 

[drusso]

In the aforementioned review article, I counted 9 case reports and 4 studies with n of 60, 60, 60, and 50.

I am finding a lot of the "data" is what people heard from an attending. Our program is working around that by gathering a large collection of PDF's on all topics. BTW, DP did a great job on his first Celiac.

I'd still like to know what's running in the intrathecal or epidural catheter...Our practice is use Robivacaine/sufentanil when the patient has a known history of opioid tolerance.

Re: DP--That's good news. He has a "special interest" in pelvic floor tension myalgia and, back in the day, was the preferred provider for the entire south-eastern minnesota region; so maybe you should be giving him the superior hypogastric plexus blocks instead. I'll let him fill you in on the details...

 

[wonthurtabit1]

thanks for the review article Kwijibo

 

[drrinoo]

I'd still like to know what's running in the intrathecal or epidural catheter...Our practice is use Robivacaine/sufentanil when the patient has a known history of opioid tolerance.

Could you clarify what you mean by hx of opioid tolerance [most patients with an IT pump have been on po narcotics....or alternatively, are you talking about IT opioid tolerance]

In any case, are you using sufenta/rop as the index drug for some of your new IT implants or are you switching from another opioid?

Sufenta, in my experience, requires that the catheter be in a specific location in the IT space, given the lipophillicity....e.g., in someone with perineal pain, the catheter should be near the conus or in someone with thoracic pain, the catheter should be located near that thoracic spinal cord segment.

Thus, if you use sufenta as an index drug during the implant...you can plan the placement of the your catheter....but if you use it as a second line drug, you are dependent on the original catheter location...and the quality of analgesia may suffer.

Finally, what is your daily rate of sufenta and what conversion are you using, when switching from another opioid, such as MSO4 (1:1000?)

 

[drusso]

Sufenta, in my experience, requires that the catheter be in a specific location in the IT space, given the lipophillicity....e.g., in someone with perineal pain, the catheter should be near the conus or in someone with thoracic pain, the catheter should be located near that thoracic spinal cord segment.

Thus, if you use sufenta as an index drug during the implant...you can plan the placement of the your catheter....but if you use it as a second line drug, you are dependent on the original catheter location...and the quality of analgesia may suffer.

Finally, what is your daily rate of sufenta and what conversion are you using, when switching from another opioid, such as MSO4 (1:1000?)

Dr. Shah,

I should clarify that my comments pertain only to management in the acute pain hospital setting...not chronic pain management.

 

[PainDr]

everyone screams opioid hyperalgesia--- folks does that really exist-- not much true evidence for it

I'm not sure why more studies haven't been done, but ask anyone who treats alot of malignant pain...it is an accepted phenomenon.

I am finding a lot of the "data" is what people heard from an attending.

After personally dealing with it many times during fellowship, I'm a believer as well. Rotation DOES work.

To the OP, you only mentioned morphine. I'm assuming you've exhausted all other options...dilaudid, fentanyl, methadone, etc.?

 

[neurodoc]

Two possible explanations of this "phenomenon" are:

1) OH is essentially a manefestation of opioid tolerance +/- addiction; and,

2) OH reflects an opioid induced dysfunction of the descending pain modulation pathways and intraspinal interneuronal circuits.

Nick