Blogs to Boards: Question 8

This is the fourth in a series of 41 posts from both GeriPal and Pallimed to get our physician readers ready for the hospice and palliative medicine boards. Every week GeriPal and Pallimed will alternate publishing a new question, as well as a discussion of possible answers to the question (click here for the full list of questions).  

We welcome comments about any aspects of the questions or the answers/discussions.  The feedback that we hope to get in the comment sections of the post will help us all learn important aspects for the boards. We also welcome an interdisciplinary viewpoint when answering these questions, so even if you are not taking the medical boards, your input is still very much welcome.

Mr. Smith is a 72 year old patient was admitted to hospital from his nursing home for respiratory distress due to CHF exacerbation. Despite aggressive diuresis attempts, his respiratory distress continued and his urine output remained minimal (~30ml/day). 

PMH: heart failure, moderate dementia, renal insufficiency 

Home medications: furosemide 40mg po bid, metoprolol 25mg bid, donepezil 10mg daily, olanzapine 5mg qhs.

After a conversation with his son (health care proxy) the patient was "made CMO" (comfort measures only) by the hospitalist service and resident team two days ago. He was then started on a morphine drip “titrate by 1mg as needed for pain or shortness of breath”, his donepezil, olanzapine and diuretics continued, other medications stopped. 

His intern calls in a panic: “We promised to make him comfortable, that he would die in 2 days, but he is still alive and the family does not know why he is in such pain – even with light touch – crying out & jerking.”

What is your recommendation? 

a) Stop morphine drip and start fentanyl and lorazepam prn

b) Increase morphine and olanzapine

c) Increase morphine and add lorazepam prn

d) Stop morphine drip and start fentanyl, increase olanzapine

Discussion:

Answer and Discussion:

The correct answer is A.

KEY POINTS

• Opioid neurotoxicity in the setting of renal failure/azotemia is the most likely answer. Morphine metabolites build up disproportionately in the setting of renal failure. Morphine 3-glucoronide is a neurostimulant that can lead to agitated delirium, myoclonus, hyperalgesia, and even seizures. Morphine and hydromorphone are the most common culprits. Morphine 6-glucoronide is a metabolite that is active on the mu-opioid receptor, and thus is not a major player in terms of inducing agitated neurotoxicity.
• Fentanyl does not have the same metabolites and thus has a lower risk of agitated neurotoxicity. Since there are no active metabolites that build up in renal failure, it is the safest of the “pure” opioids for patients on dialysis or who are oliguric. Methadone is another opioid that is nearly ~100% excreted in the stool.
• The treatment for this is to rotate off current opioid. Fentanyl is safer option in renal failure.
• Antipsychotics can worsen the symptoms
• Benzodiazepines can help treat myoclonus and prevent seizures

References:

• Robin K Wilson, David E Weissman; Neuroexcitatory effects of opioids: patient assessment, 2nd ed. EPERC# 057
• Smith, H. S. (2009). Opioid metabolism. Mayo Clinic proceedings. Mayo Clinic, 84(7), 613-24.

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Palliemd test blogs to boards

This is the fourth in a series of 41 posts from both GeriPal and Pallimed to get our physician readers ready for the hospice and palliative medicine boards. Every week GeriPal and Pallimed will alternate publishing a new question, as well as a discussion of possible answers to the question (click here for the full list of questions).  

We welcome comments about any aspects of the questions or the answers/discussions.  The feedback that we hope to get in the comment sections of the post will help us all learn important aspects for the boards. We also welcome an interdisciplinary viewpoint when answering these questions, so even if you are not taking the medical boards, your input is still very much welcome.

You visit a patient at home receiving hospice care for cancer. Her pain has been well controlled with long acting morphine 60mg BID and occasional PRN doses of short acting liquid morphine (10mg) over the past few weeks: she had been tolerating this well. She has had recent progressive functional decline and is currently at a PPS of 20%. In the last 24 hours the patient has vomited and has been more lethargic and having difficulty swallowing pills. She appears uncomfortable. In your examination you see a very thin patient who appears to be dying with a prognosis in the few days to a week range.

The patient’s son is a respiratory therapist at a hospital and is insisting you change the patient’s opioid to a fentanyl patch because “it is less sedating than morphine.”

The best response is:

a) Because the patient is cachectic, you tell the family that fentanyl transdermal patches are not indicated because the medication will not be absorbed.

b) Agree with the son and convert the patient to a 37.5mcg/hr fentanyl patch with oral morphine liquid 10mg q1 hour PRN

c) Because the fentanyl will not be effective for over 24 hours, continue the long acting morphine sulfate 60mg BID but give it rectally instead of by mouth

d) Suggest starting a morphine infusion via her port at 1.7mg/hr basal with a 3mg q30min bolus PRN after talking with the son about his concerns about sedation.


Discussion:

Answer and Discussion:

The correct answer is D.

a) Cachexia has not been show to be a CLINICALLY RELEVALANT factor in absorption of transdermal fentanyl. Cachexia will decrease the amount of subcutaneous fat which is where fentanyl is stored AFTER absorption through the dermal layers. In 2009 Heiskanen did a study comparing blood levels between cachectic and non-cachectic volunteers and found no significant difference, although cachectic patients had a slightly lower mean concentration. There was no difference in VAS score.

b) Fentanyl is not less sedating than morphine at equianalgesic doses. Also there is no 37.5mcg/hr patch or 12.5mcg/hr patch. As written, and described by the manufacturer, the “12.5mcg/hr patch” is labeled and Rx’d as a “12mcg/hr” patch to prevent confusion with Rx’ing 125mcg/hr. As for the conversion, it could be acceptable to use a 25mcg/hr & 12mcg/hr patch (total 37mcg/hr) per the Fentanyl transdermal product insert. It recommends 25mcg/hr for someone on OMDD of 60-134mg and 50mcg/hr for someone on OMDD 135-224, so this is right in the middle. The Breitbart/Donner conversion of 2mg morphine = 1mcg/hr transdermal fentanyl which would be 60mcg/hr of fentanyl (You could choose 50 or 75 depending on other clinical circumstances).

c) The pharmacokinetics of fentanyl do not warrant switching to it if otherwise indicated. Morphine still has time to circulate and get out of her system, and fentanyl begins to reach significant blood concentrations 8-12 hours after application. If needed, she can be bridged with a few doses of liquid morphine. In addition, people do not prefer rectal administration if it could be avoided.

d) A morphine continuous infusion allows for the continuation of the current effective opioid in a patient who is likely not going to regain swallowing function. The conversion is most direct (120mg OMDD = 40mg daily IV = 1.7mg/hr (1.5 if your pumps are limited in decimal rates). A 3 mg IV morphine bolus most closely replicates the 10mg oral morphine doses that were effective prior. If you did not choose this answer because your hospice doesn’t use continuous infusions (expense, nurse familiarity, not available from local pharmacy) then start talking with your hospice to decrease these barriers to an effective and essential tool to good pain management.

References:

• Cachexia and Transdermal Abosrption of Fentanyl - Pallimed
• Heiskanen, Tarja. (2009-7) Transdermal fentanyl in cachectic cancer patients. PAIN, 70(1-2), 928-222. DOI: 10.1016/j.pain.2009.04.012
• Mercadante, Sebastiano. (2012-01-09) Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management. European Journal of Pain, 7(Suppl. A), 320-1046. DOI: 10.1016/j.ejpain.2008.01.013
• Weissman DE. Converting to/from Transdermal Fentanyl, 2nd Edition. Fast Facts and Concepts. July 2005; 2. Available at: http://www.eperc.mcw.edu/fastfact/ff_002.htm.
• Tatum IV WO. (2002) Adult patient perceptions of emergency rectal medications for refractory seizures. Epilepsy & behavior : E&B, 3(6), 535-538. PMID: 12609248
• Colbert SA, O'Hanlon D, McAnena O, & Flynn N. (1998) The attitudes of patients and health care personnel to rectal drug administration following day case surgery. European journal of anaesthesiology, 15(4), 422-6. PMID: 9699099
• Mercadante, Sebastiano. (2012-01-09) Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management. European Journal of Pain, 7(Suppl. A), 320-1046. DOI: 10.1016/j.ejpain.2008.01.013

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@ctsinclair Will you be interacting with the Mass General#hpm folks next month?7 minutes ago via web in reply to ctsinclair

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