What is Neuroexcitatory effects of opioids - Meaning and definition

Published by Roberto Wenk. Reviewed by Alison Ramsey. Last updated date: January 16, 2019.

Opioid-induced neurotoxicity describes a syndrome of neuropsychiatric toxicity consisting of cognitive impairment, severe sedation, hallucinosis, myoclonus, seizures, and hyperalgesia.
These features can exist singly or in combination; if any of them are present in a patient taking opioid medication, opioid-induced neurotoxicity should be suspected.

Myoclonus — the sudden, involuntary jerking of a muscle or group of muscles — can occur in patients on chronic therapy with most opioids including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. Higher doses more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur with all routes of administration. Current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects. Comorbid factors including renal failure, electrolyte disturbances, and dehydration can also contribute.
Myoclonus usually occurs in the extremities, starting with only an occasional random jerking movement. With continued administration, the jerking may increase in frequency; at the extreme, there is constant jerking of random muscle groups in all extremities.

As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and, eventually, grand mal seizures.

Assessment of a patient with possible opioid toxicity:

Physical examination
- Assess frequency of myoclonic jerks. Stand at the bedside and observe a patient for 30-60 seconds. Watch for and count the number of uncontrolled jerking movements.
- Determine if there is evidence of a new or worsening delirium. Complete a bedside mini-mental assessment.
- Assess hydration status.
- Estimate prognosis: hours, days, weeks, months, or years? A longer prognosis demands a more definitive change in treatment.

Chart review
- Review the recent opioid analgesic history. What is the current drug and dose? How has the dose changed over the past few days and weeks?
- Review the medication list for potentially exacerbating drugs (e.g., haloperidol, phenothiazines).
- Review recent laboratory studies; check renal and liver function, and for low magnesium, glucose, or sodium.

Adapted from Wilson RK and Weissman DE. Palliative Care Network of Wisconsin. Fast facts and concepts #57. Neuroexcitatory effects of opioids: patient assessment. Internet. Accessed on January 25, 2016.

Published by Roberto Wenk. Reviewed by Alison Ramsey. Last updated date: January 16, 2019.

Decisions about the most appropriate treatment approach need to take into account features of the physical examination (the frequency and intensity of symptoms, hydration status, and estimated prognosis) and information from the medical record (temporal pattern of opioid use and dose escalation, other medications, and the presence of electrolyte abnormalities and major organ dysfunction).
Whenever medically appropriate, easily treatable causes or exacerbating factors should be corrected (e.g., correct hypomagnesemia).

Options for management of opioid-induced neurotoxicity:

Observation
Mild myoclonus may trouble family members more than the patient. If the patient is satisfied with current therapy, explaining the cause/progression of symptoms may be all that is necessary.

Opioid dose reduction
Myoclonus may resolve over a few days with a decrease in opioid dose. Note: Do not reduce the opioid dosage solely to control myoclonus at the expense of good pain control.

Rotate to a dissimilar opioid
Rotating to a lower dosage of a structurally dissimilar opioid will often reduce myoclonus and other neuroexcitatory effects within 24 hours, while achieving comparable pain control.
Rotation is especially important in patients with opioid-induced hyperalgesia.
As a general rule, decrease the morphine equianalgesic dose by at least 50% when switching to a new medication. For patients on very high doses, rotate to a new opioid at 20-25% of the morphine equianalgesic dose. Historically, methadone and fentanyl have been considered to be better opioids to rotate to as they have no active metabolites. Note: When switching to methadone it is advisable to review recent methadone equianalgesic guidelines.

Adjuvant and other analgesic therapy
Adjuvant analgesics (e.g., anticonvulsants, antidepressants, corticosteroids) or nondrug therapies (e.g., acupuncture, TENS, heat, cold) may allow for opioid reduction with preservation of analgesia.

Benzodiazepines and other drugs to reduce myoclonus
The addition of a benzodiazepine may reduce myoclonus without alteration of the opioid dose, although increasing sedation may be an unwanted side effect. Start with clonazepam 0.5-1mg qhs or 0.5mg BID or TID. Alternative agents include lorazepam orally or sublingually, starting at 1-2mg q8. Continuous infusion midazolam is an effective option.
Alternatives to benzodiazepines include baclofen, gabapentin, and nifedipine.
Start baclofen at 5 mg 3 times a day and increase as needed/tolerated to 20 mg 3 times a day.
Start gabapentin at 100 mg 3 times a day and increase as needed to 900-3600 mg total a day. Nifedipine (10 mg 3 times a day) can also be used.

Adapted from Wilson RK and Weissman DE. Palliative Care Network of Wisconsin. Fast facts and concepts #58. Neuroexcitatory effects of opioids: treatment. Internet. Accessed on January 25, 2016.

Neuroexcitatory effects of opioids

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