When it's OK to give opioids

Although opioids are often dangerous, they can be the best option for patients with advanced cancer.


Opioids have earned their reputation for being addictive and dangerous.

However, for patients with advanced cancer and at the end of life, opioids often present the best form of pain control, said Suresh K. Reddy, MD, a professor and director of the palliative care fellowship program at the University of Texas MD Anderson Cancer Center in Houston.

For cancer pain, nonopioids have their place—for example, NSAIDs or bisphosphonates for bone pain, antidepressants for neuropathic pain, corticosteroids for compression neuropathy and bone metastases, he said. “But the mainstay of cancer pain is going to be opioid management. That's what you need.”

Dr. Reddy explained how to simply yet comprehensively assess cancer pain, as well as manage opioid side effects, during his session at Internal Medicine Meeting 2017.

Evaluating the pain

Pain is extremely common in advanced cancer patients, reaching almost 100% incidence in those with stage IV cancer, and about 30% of all cancer patients have pain that severely interferes with their function, Dr. Reddy explained.

Suresh K Reddy MDslashPhoto by Kevin Berne
Suresh K. Reddy, MD/Photo by Kevin Berne.

Physicians ask patients to assess their pain on a numerical scale, but “pain is not like a number where we can measure objectively.” The pain scale is only capturing how patients express their pain, which is modified by many factors, he said.

“This is not just a sensory experience; it is predominantly an emotional experience in some patients. I want you to understand this more than anything else....This is the reason why two patients with the same cancer report differently,” Dr. Reddy said.

Even though validated pain assessment tools still only capture subjective pain expression, their methodological consistency acts as a quality control measure, according to Dr. Reddy. “We have shown that when you employ tools on a consistent basis, you capture more symptoms than not...and you can follow symptoms over time when you have the appropriate tool,” he said.

In addition to the 0 to 10 scale, a longstanding evaluation tool is the Edmonton Symptom Assessment Scale, which takes two minutes for patients to fill out and captures such symptoms as nausea, depression, and anxiety, said Dr. Reddy.

He said another commonly used tool is the four-part CAGE questionnaire (Cut down? Annoyed? Guilty? Eye-opener?), which is typically also used to screen for alcohol use disorder. “We found, again and again, this is a marker for chemical coping, not just alcohol....Even in cancer patients, this is not uncommon: In 20% of our patients, we see some kind of chemical coping,” said Dr. Reddy.

Although there may be many false negatives and false positives, a score of two “yes” answers on the CAGE is the best marker of chemical coping, which is a complicated issue that requires multidisciplinary team management, he said. “Once you have this, you are careful not to escalate medications unnecessarily; otherwise, you'd be putting them into opioid-induced neurotoxicity.”

A fairly new concept in pain treatment is asking patients for a personalized pain goal: On a 0 to 10 scale, where do they want their pain to be so that they can be comfortable and be functional? “Generally, on average, people say 4 and below. But some, they have pain [at] 10 all the time—8 is good enough,” he said.

To assess pain in patients at the end of life may require a deeper look at nonverbal clues, such as facial expression, restlessness, tossing in bed, protective movements, and increased confusion, said Dr. Reddy. “But we need to be careful. Sometimes delirium masquerades as pain, and it can make delirium worse if you give higher doses of opioid medications, which are causing delirium in the first place.”

Keep in mind that constipation can also masquerade as pain, he noted. “You routinely prescribe laxatives because every patient walking into any cancer hospital on even mild-pain opioids is constipated unless otherwise proved. Constipation presents as nausea, vomiting, and abdominal pain so many times,” Dr. Reddy said. “Every time I don't want to believe it, it ends up being constipation. I eventually end up being aggressive on laxatives, including giving [an] enema, and symptoms subside.”

Using opioids wisely

By the time patients with cancer come to the hospital, “they usually come with strong opioids,” Dr. Reddy said, noting that morphine remains the gold standard for treating cancer pain.

Opioids with a short half-life include morphine, hydrocodone, oxycodone, and hydromorphone, and those with a long half-life include methadone, levorphanol, and transdermal fentanyl (which works for 72 hours after taking up to 18 hours to form a depot on the skin), he noted. “You prescribe a long-acting every eight to 12 hours, or you can prescribe short-acting every four hours,” said Dr. Reddy. “Both are good, by the way. You don't really need to use long-acting,” which offers convenience but no better analgesia and the same side effects at a higher cost.

For strong opioids, which have similar effects and toxicity, he reviewed potency ratios relative to morphine: Hydromorphone is five times more potent, oxycodone is 1.5 times more potent, fentanyl is 100 times more potent, oxymorphone is three times more potent, and methadone is variable and depends on the previous opioid dose (the higher the morphine dose, the less methadone is needed). “It becomes important when you rotate from one opioid to another,” Dr. Reddy said.

He cautioned, “Opioid conversion is not a mathematical game. The calculated opioid dose will put you in the safe ballpark, but one needs to use clinical judgment for the right dose of a new opioid.” The patient's frailty, renal function, hydration status, and other concomitant treatments (e.g., NSAIDs, radiation, steroids) may alter the conversion dose, Dr. Reddy said.

He offered a pearl for the fentanyl patch: Dosing is roughly equal to half of a morphine equivalent daily dose, at a maximum of 150 μg per hour as a safety valve. “I wouldn't go more than that; it's very risky and dangerous. Same thing with methadone: If you really have to use methadone, my safety valve is no more than 10 mg twice a day of methadone,” said Dr. Reddy.

Opioid rotation can be considered for patients who don't achieve relief on one medication and who are experiencing dose-limiting side effects, said Dr. Reddy.

He offered five general steps for opioid rotation:

  1. 1. Calculate the total daily/24-hour dose of the previous opioid.
  2. 2. Calculate the new opioid daily dose using an equianalgesic conversion table to avoid overdosing or underdosing.
  3. 3. When rotating from a low-potency to a high-potency opioid, decrease the new opioid dose by 25% to 50% to adjust for incomplete tolerance between opioids.
  4. 4. Divide the daily dose by the number of scheduled doses per day. One can use a combination of extended-release and short-acting opioids, or a short-acting opioid used every four hours. Breakthrough pain is very common in cancer, and a breakthrough dose equals about 10% to 15% of the total daily 24-hour dose every two to four hours as needed.
  5. 5. Based on patient response, titrate the new opioid dose until adequate analgesia is achieved.