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Objective 5: Identify and effectively prevent/treat common opioid side-effects.

For more information on side-effects see International Association for the study of pain

A. Constipation
B. Nausea and Vomiting
C. Sedation
D. Delirium
E. Respiratory Depression
F. Less Common Reactions

A. Constipation [back to top]

Constipation is a very common side effect of opioids.  It is caused by decreased gut motility as a result of direct effects in the myenteric (gut) plexus as well as effects on the brain and spinal cord. 

Tolerance does not develop to this side effect, so most patients should be started on a bowel management regimen when opioids are initiated.  As Cicely Saunders said, “The hand that writes the opioid prescription should write the laxative prescription.”

Stimulant (e.g. senna) or osmotic (e.g. milk of magnesia) laxatives are needed by most patients.  The value of adding stool softeners (e.g. docusate) is debatable.  In more active patients, exercise, fluids, and bulk laxatives may be helpful.   However, "fiber" generally will not resolve opioid-induced constipation, and it may even be detrimental in debilitated patients.  Injectable methylnaltrexone (an opioid antagonist that does not cross the blood-brain barrier, thus does not interfere with analgesia) is available, but there is no evidence yet comparing it to less invasive and less costly oral medications.

Untreated constipation can be highly symptomatic (distention, pain, cramping),  and it can ultimately even lead to intestinal obstruction.  Prevention of these problems should be a high priority when treating patients with opioids.

B. Nausea and Vomiting [back to top]

Nausea and associated vomiting are also common side effects of opioids. This is caused by multiple mechanisms, but the most important are direct stimulation of the chemoreceptor trigger zone as well as inhibition of GI motility.  Interestingly,  unrelieved pain can also cause nausea.  In contrast to constipation, tolerance often develops to this side effect. 

There are no controlled studies evaluating the best approach to the treatment of opioid-induced nausea. Experts generally concur that the first step in treatment should be use of a dopamine-2 blocking anti-emetic, such as:

  • haloperidol (Haldol)
  • prochlorperazine (Compazine)
  • metoclopramide (Reglan)

Do not simply assume that opioids are the cause of nausea - assess the patient for other etiologies as well.  And address non-pharmacologic treatments for nausea as well. 

Article: Intractable Nausea and Vomiting in Patients at the End of Life
Fast Fact: Opioids and Nausea

C. Sedation [back to top]

Remember that many patients, when first getting adequate pain relief, are exhausted from enduring pain and sleeping poorly for an extended period of time. They may have accumulated a considerable “sleep debt” and need to catch up. “Catch-up" sleep (sleeping an unusually long time, but able to fully awaken) must be distinguished from sedation (unable or difficult to fully awaken).
Patients often develop tolerance to the sedative side effect of opioids quite rapidly.  If it continues to be a problem, adjusting the dose or the time interval at which it is given may be helpful. Small trials have shown  possible benefit to adding stimulants, such as dextroamphetamine 2.5 - 7.5 mg  q AM.

Patients with persistent sedation should be evaluated thoroughly for other contributing factors, particularly medications. Opioid-resistant pain should also be considered. (See Objective 8)

Rarely, it may be necessary to balance the benefits of pain control against  the cost of sedation. Patients and their families should guide decisions based on their goals; no one can better evaluate the relative cost/benefit ratio than the person directly experiencing both the cost and the benefit!

D. Delirium [back to top]

Delirium from opioids is not uncommon.  Patients with other risk factors for delirium (advanced age, pre-existing dementia, electrolyte imbalances, hypercalcemia, etc.) are most likely to experience this problem when imitating opioid treatment.  If it does not clear soon after the initiation of the medication, the patient should be assessed for possible opioid excess and should also tried on a different opioid. 

The development of delirium during ongoing treatment is most often due to other clinical change (decreased renal function, sepsis, medication changes, metabolic problems, etc.). 

Article: Diagnosis and Management of Delirium near the End of Life
Fast Fact: Treating Terminal Delirium

E. Respiratory Depression [back to top]

Respiratory depression is rarely of clinical significance when opioids are appropriately titrated.  Nonetheless it is the side effect that most anticipated and feared by clinicians.

The threshold for respiratory depression is usually above the threshold for analgesia, and appropriate titration will prevent its occurrence.

If naloxone (Narcan) is ever used in a patient on opioids for serious pain, it should be diluted and administered cautiously to avoid precipitating a major pain crisis.   Signs of impending death (hypotension, respiratory changes, etc.) should not be confused with respiratory depression from opioids.

F. Less Common Reactions [back to top]

Urinary retention can be a problematic side effect of opioids, especially for older men with prostatic hypertrophy.  Its management is no different than that of other causes.

Opioid-induced histamine release is the usual cause of itching, urticaria, and sweating.  This is typically not an allergic reaction (not IgE mediated).  It may be relieved with antihistamines, or the patient may benefit from using an opioid from a different chemical class.

Various other idiosyncratic reactions may also benefit from a trial of a different opioid.

Next: Pain in the Active Dying Process

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