Blogs to Boards: Question 8

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? 

  1. Stop morphine drip and start fentanyl and lorazepam prn
  2. Increase morphine and olanzapine
  3. Increase morphine and add lorazepam prn
  4. Stop morphine drip and start fentanyl, increase olanzapine

Discussion: 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