Over many years I have seen several cases where upon hospital admission, the house staff and emergency clinicians mistakenly assign blame to opioids, the diagnosis of which is in their minds indubitably an opioid overdose. Imagine the outcome when a family member makes a B-line to the nearest attorney with intent to sue the prescribing clinician.
It seems that much like the untrained journalist, it is easiest to lay blame on opioids without a proper differential diagnosis. Far be it from me to make or second guess a diagnosis upon hospital admission because as a doctor of pharmacy that is outside my scope of practice – or is it? When blame is specifically misplaced because of a drug overdose, the lines between who is qualified to ascertain causation become less clear.
Below is a typical example which is based on a real case. Names, dates, and specifics have been changed to protect the guilty.
Ms. Smith is a 62 year old Caucasian female who was seen in the hospital for purposes of continuity of care, and per notification from the in house clinical pharmacist and house staff. She was seen at bedside by the Pharmacy Pain Team.
OUTPATIENT pain and pain-related related medications included many as listed below:
- AMITRIPTYLINE HCL 10MG TAB PO AT BEDTIME
- BACLOFEN 20MG TAB TAKE ONE TABLET PO TID PRN FOR MUSCLE RIGIDITY
- BUPROPION HCL 150MG 12HR SA TAB PO BID FOR DEPRESSION
- DULOXETINE HCL 60MG EC CAP TAKE ONE CAPSULE BY MOUTH EVERY MORNING FOR PAIN/DEPRESSION
- ETODOLAC 300MG CAP PO TID PRN FOR ARTHRITIC STUMP PAIN
- PREGABALIN 150MG ORAL CAP PO TID FOR PAIN
- ZOLPIDEM TARTRATE 10MG TAB PO AT BEDTIME AS NEEDED
- FENTANYL MATRIX 25MCG/HR PATCH APPLY 1 PATCH TO SKIN EVERY 48 HOURS FOR PAIN
- LEVORPHANOL TARTRATE 4MG TAB PO QID FOR PAIN
The patient was followed by our service for severe diabetic neuropathy and phantom limb pain. She was admitted through our neighboring hospital with a diagnosis of “opioid overdose”.
ALLERGIES: CEFAZOLIN (RASH)
Active inpatient medications included:
- AMITRIPTYLINE TAB, Give: 10MG PO QHS
- ASPIRIN E.C. TAB,EC, Give: 81MG PO DAILY
- BACLOFEN TAB, Give: 20MG PO TID PRN
- DOCUSATE/SENNOSIDES TAB, Give: 2 TABLETS PO TID
- DULOXETINE CAP,EC, Give: 60MG PO QAM
- ETODOLAC CAP,ORAL, Give: 300MG CAPSULES PO TID
- HEPARIN SODIUM INJ,SOLN, Give: 5000UNIT/1ML SC BID
- LISINOPRIL TAB, Give: 40MG PO DAILY
- MULTIVITAMIN CAP/TAB, Give: 1 TABLET PO DAILY
- OMEPRAZOLE CAP,EC, Give: 20MG PO QAM
- PREGABALIN CAP,ORAL, Give: 150MG PO TID
- TROSPIUM TAB, Give: 20MG PO BID
- BUPROPION 12HR TAB,SA, Give: 150MG PO BID
- OXYCODONE TAB, Give: 10MG PO Q4H PRN severe pain
- OXYCODONE TAB, Give: 5MG PO Q4H PRN moderate pain
- DOCUSATE/SENNOSIDES TAB, Give: 2 TABLETS PO TID PRN constipation
The patient had quite a long medical problem lest including:
- PMH of DM2
- Neuropathy and foot ulcer
- Depressive Disorder
- Hip Joint replacement Status (Prosthetic or Artificial Device)
- Phantom limb pain
- Peripheral vascular disease
- Below knee amputation
- Other: Iron Deficiency Anemia, Nicotine Dependence, Lymphadenopathy
Ms. Smith was admitted with a reported pain level of 5 out of 10, with 10 being the most severe and 0 being no pain. She was admitted for presumed opioid overdose. On day of event, patient states that she was in her kitchen when she “lost balance” with her prosthesis and fell on her back, and was aided by her husband after the fall. He moved her to the bedroom to lay her down, and her husband called for help.
This patient has always been a delight to work with and an excellent medication complier. Upon admission she denied taking any extra doses of her pain medications while at home as she uses a “pill box/organizer”. She denied any episodes of loss of consciousness from home to being admitted through our Emergency Room. She confirmed last applying a fentanyl patch on 3 days earlier and self-removed it following the incident d/t feeling “scared” of what was happening. She acknowledged storing her medications in a safe area away from others.
All too often, patients similar to this are labeled (diagnosed) as an “opioid overdose”. Even at the point of death, I have seen medical examiners label the cause of death as “opioid overdose” without checking the medical records to ascertain whether or not a patient was opioid naïve or tolerant.
In this case, the patient’s fentanyl and levorphanol were discontinued upon admission and prior to transfer. Of note, 2mg of levorphanol is equivalent to 15mg of oral morphine (or 10mg oral oxycodone) and 25mcg/hour of transdermal fentanyl is equivalent to 90mg of oral morphine (or 60mg oral oxycodone). The patient was placed on oxycodone IR 5-10mg PRN and left on pregabalin 150mg TID, duloxetine 60mg daily, amitriptyline 10mg QHS, etodolac 300mg TID PRN, baclofen 20mg TID PRN. Since being admitted three days earlier, the patient stated that she received “rapid detox/Narcan”, and has been in “more pain”, acknowledged having “sweats” and abdominal cramps while off of her levorphanol and fentanyl likely consistent with opioid withdrawal symptoms.
For educational purposes, it’s worth noting that most traditional opioids carry a higher risk of gastrointestinal bleed when combined with certain SNRIs, especially duloxetine. Since the patient is on heparin, that too elevates this risk. But, etodolac is actually more COX-2 specific than even celecoxib as seen HERE.
In the previous 12 hours, the patient had received 45mg of oxycodone (67.5mg MEQ) which is subtherapeutic in comparison to her outpatient regimen. She denied any lightheadedness, dizziness, drowsiness, excessive sedation, peripheral edema, nausea, vomiting, or headache. Her most recent labs indicated normal renal and hepatic function. A urine drug screen performed on admission in ER was appropriately positive for opiates and negative for other screened substances while on fentanyl and levorphanol prior. This is consistent and expected.
To clarify, we do agree that neuromodulators would be the first choice line medications here, but the patient failed to respond adequately to several trials with various combinations.
A state prescription drug monitoring program (PDMP) report was performed on upon admission and no DEA Controlled Schedule II-IV prescription medications were found. The patient reported no new allergies to any medications. She denied any OTC analgesics, herbal products, or dietary supplements.
There is more to the history, but for the sake of this discussion, it was relatively inconsequential.
No doubt that all sedating drugs could enhance lethargy from opioids. These included at minimum, amitriptyline, pregabalin, and zolpidem. But it is not appropriate for a chart to reflect an opioid overdose as a definitive diagnosis at the previous hospital or the one to which the patient was transferred. In fact, statements such as…
“Especially in light of her recent narcotic overdose, it is important to focus on pain management without long-acting opioids. The adverse effects of polypharmacy are a concern in this individual.”
Reality Check #1: While I do agree with the statement regarding polypharmacy, that is not synonymous with “narcotic overdose”. The recommendation was for “…may give oxycodone 5mg qid PRN and only short supply (a week at a time)”. Note also, that had the dose been appropriate, IR formulations provide higher serum peaks that could prove even more problematic in terms of side effects and lethargy.
Reality Check #2: I DO NOT believe that opioids were the PRIMARY cause of this “overdose”, nor that it was an overdose. I do acknowledge that opioids could be additive in sedating effect to other underlying medical cause(s) considering the multiple co-morbid conditions and polypharmacy. THIS SHOULD BE NOTED IN THE MEDICAL RECORD BY A PHARMACIST OR A MEDICAL PROVIDER THAT UNDERSTANDS!
Six months earlier, the patient came to us on fentanyl transdermal 50mcg/hour changed Q48HOURS (200mg PO morphine equivalent – MEQ) plus methadone 15mg PO TID (110 MEQ), for a total daily PO MEQ of 310mg. At the time the patient presented to the ER, presumably found “to be obtunded from opioids”, the pharmacy pain clinic, in collaboration with Primary Care Provider had her on fentanyl 25mcg/hour (100mg MEQ) + levorphanol 4mg PO QID (120mg MEQ), for a total daily MEQ of 220mg.
Compared to the 310mg she was on at the time she was originally seen in six months ago, she is now actually on MEQ 310mg – 220mg = 90mg of morphine equivalent LESS than the patient was taking previously. While I acknowledge that the notes from our sister institution stated that the patient responded to Narcan, I submit that any patient that is sedated for physiological or medication reasons other than opioids, who remains on long term high dose opioids and are injected with Narcan, will in fact have ADRENERGIC OVERSTIMULATION, which could “jolt” someone into an awakened state even if the overall cause is not narcotization. So in this case, reversal alone cannot be confirmatory especially without considering that the patient was also noted to be orientated to time and place just minutes before.
The plan was to send this patient home with only oxycodone 5mg qid PRN.
Reality Check #3: This is 90% less opioid equivalent than this patient had been receiving over the last several weeks and would undoubtedly result in discomfort from withdrawal and tremendously increased pain. I anticipated overt withdrawal to begin within the next 24-30 hours based on the half-life of transdermal fentanyl (following patch removal) and the 16 hour half-life of levorphanol. This would have been additional patient suffering and possibly a readmission.
In the end, we made recommendations as outlined below. The patient was thoroughly counseled on fall risk medications with advanced age, instability with prosthesis, and rationale behind discontinuation of her sedating medications. The patient was provided with education on being a possible candidate for a naloxone kit/EVZIO.
MEDICATION RECOMMENDATIONS, for remainder of inpatient admission and continued after discharge…
- Discontinue fentanyl 25mcg/hr transdermal patch, oxycodone PRN, zolpidem, amitriptyline, and baclofen.
- Increase pregabalin to 200mg PO TID for phantom limb pain (max dose).
- Continue therapy with levorphanol 4mg PO QID for BLE neuropathic pain.
- Continue therapy with duloxetine 60mg PO QD for pain/depression.
- Continue therapy with etodolac 300mg PO TID PRN for arthritic shoulder/stump pain.
- Obtained signed consent for Long-Term Opioid Therapy (DONE).
- Discussed and provided a handout for “Taking Opioids responsibly” education as well as naloxone kit/EVZIO (naloxone HCl auto-injector) education, with a printed copy of the former being provided to the patient.
- PCP to order naloxone kit/EVZIO (naloxone hcl auto-injector) if available; will provide re-education to patient and husband to demonstrate competency. THIS SHOULD BE COMPLETED PRIOR TO DISCHARGE!
So there you have it – one of the longest blogs here ever. But, I hope this encourages my medical and pharmacy colleagues to work together as a team and to clarify whenever possible the morphine equivalent doses in similar situations and note [IN THE MEDICAL RECORD] the chronic prescribed opioid history. To have notes that state the cause as an “opiate overdose” without any indicators or clarification to the contrary opens the door to liability. Unfortunately I’ve seen it and as my attorney says, “people can sue for anything – the paper won’t reject the ink”. In this case, ambulatory care clinicians must rely on savvy hospitalists and clinical pharmacists to document the reality and to mitigate against liability for their community counterparts.
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