Adult Cancer Pain: Part 2 -- The Latest Guidelines for Pain Management

Laura A. Stokowski, RN, MS


December 06, 2010

In This Article


Pain Agent Updates

The short-acting opioids most frequently used in cancer pain management are morphine, hydromorphone, fentanyl, and oxycodone. The guidelines advise against meperidine and propoxyphene -- particularly for long-term or high-dose use -- because of toxicity.

NCCN v.2010 incorporates new information about several pain management agents, including buprenorphine and 2 formulations of fentanyl (transdermal and transmucosal).

Buprenorphine. Pain-management products are being introduced all the time, according to Paice, and NCCN v.2010 attempts to be inclusive. Although not new, buprenorphine has been removed from the "not recommended" list. Buprenorphine is a partial mu and ORL-1-receptor agonist and kappa-delta receptor antagonist. Because it interacts with different G proteins than more potent mu agonists, buprenorphine may not be fully cross-tolerant to standard opioids. Laboratory studies suggest that buprenorphine may block central sensitization (hyperalgesia) that is commonly found with neuropathic pain, although more studies in humans are needed.[3]

Transdermal fentanyl. Transdermal fentanyl is most useful in patients who have chronic pain and cannot take oral medications or who have experienced unmanageable toxicity from morphine, oxycodone, or hydromorphone.[4]

NCCN v.2010 provides more guidance about the use of this agent. In "Special Notes Regarding Transdermal Fentanyl" it is noted that:

  • Patches are not recommended for unstable pain that requires frequent dose changes. Fentanyl patches are to be used only in patients who are tolerant to opioids.

  • Dose titration of the fentanyl patch may be necessary in some patients.

  • A statement in NCCN v.2009 that "thin body habitus" may accelerate the absorption of transdermal fentanyl and is a contraindication for transdermal fentanyl, was removed as new studies suggest even very thin patients have sufficient blood levels of fentanyl.

Transmucosal fentanyl. In addition, transmucosal soluble film fentanyl was added to the list of fentanyl products for the management of brief episodes of acute exacerbation of pain not attributed to inadequate dosing of around-the-clock opioid. Oral transmucosal fentanyl citrate has been shown to be an excellent therapy for breakthrough pain in patients whose pain control is maintained with transdermal fentanyl.[4]Data do not support a specific transmucosal fentanyl dose equianalgesic to other opioids, so this drug should be initiated at the lowest dose (200 µg lozenge, 100 µg buccal tablet, or 200 µg buccal soluble film) and titrated to effect.

Placebo. Previous versions of the pain guidelines have emphasized that the use of placebos in pain management is not recommended. In explanatory material of NCCN v.2010, this concept is taken a step further with the statement, "use of placebo in the treatment of pain is unethical."

Judith Paice explains that "placebos should never be used in cancer pain management except in the context of a randomized control trial when the patient has signed a consent form and knows that he or she might receive a placebo. Placebos are rarely a problem anymore, but if a nurse or pharmacist was faced with a physician who ordered a placebo, they would have this guideline to back them up by saying that it is unethical to give a placebo in cancer pain management."

Routes of Administration

NCCN v.2010 includes a new principle concerning preferred and available routes for administration of pain medications: "Generally, oral route is most common; however, other routes (IV [intravenous], subcutaneous, rectal, transdermal, transmucosal, buccal) can be considered as indicated to maximize patient comfort." This is a helpful reminder to clinicians of the wide array of available routes for the administration of pain medications beyond the traditional oral or IV routes. The most effective route of administration can vary for different pain relief agents.

For ongoing care in pain management, it is now recommended that, if feasible, medication be converted to oral formulations, including extended-release agents and rescue doses.

Opioid Maintenance

A recommendation was added to "add extensive release or long-acting formulation to provide background analgesia for control of chronic, persistent pain controlled on stable doses of short-acting opioids." The concept of "background analgesia" is new to the guidelines.

When possible, it is recommended that the same opioid be used when short-acting and extended-release formulations are used together. An ongoing need for repeated rescue doses may indicate a need for dose adjustment of the patient's regularly scheduled opioid.

Errors and breaks in continuity of care are most likely to occur during transitions from one care setting to another, including discharge to home.[5] For patients with hard-to-control pain, it is especially important to avoid inadequate pain management during these transitions. In NCCN v.2010, this concept was emphasized with the new recommendation to "ensure adequate access to prescribed medications, especially between sites of care."

Drug Conversions

It is not unusual for oncology clinicians to switch the opioid in a patient whose pain is proving difficult to manage, or who is having unacceptable side effects from the current opioid. NCCN v. 2010 maintains that, "No single opioid is optimal for all patients." Changing the patient's pain medication to a different opioid or a different formulation is often referred to as "opioid rotation." Although this switch may prove beneficial for the patient, it can also pose a risk of overdosing or underdosing if equianalgesic conversions are not calculated correctly.

Feedback from clinicians on a previous version of the adult cancer pain guidelines revealed that calculating conversions for switching or rotating patients from one opioid to another is challenging. To improve both the ease and safety of opioid drug conversions, NCCN v.2010 includes step-by-step instructions for converting or rotating from one opioid to another drug, and patient case examples are provided for:

  • Converting IV morphine to IV hydromorphone;

  • Converting from one opioid (any route) to transdermal fentanyl; and

  • Converting from oral morphine to oral methadone.

Equianalgesic doses used in these conversions are derived from a table of oral and parenteral opioid equivalences supplied in the guidelines.

Opioid Side Effects

Adverse effects commonly experienced with opioid therapy include constipation, nausea, vomiting, pruritus, delirium, respiratory depression, motor and cognitive impairment, and sedation. To provide truly effective pain therapy that meets the patient's goals for both comfort and function, it is essential to assess and manage the side effects of opioids.

In the last version of the adult cancer pain guidelines, the NCCN said, with respect to opioid side effects, that with opioid use "tolerance generally develops, except with constipation." In NCCN v.2010, this was changed to the more specific statement "opioid side effects generally improve over time, except constipation."

Because it doesn't subside over time, constipation is one of the most bothersome side effects of opioid therapy, according to Judith Paice. "It is a huge barrier to effective pain management." Opioid-induced constipation does not always respond easily to treatment.[6]Typically, stimulant laxatives and stool softeners are introduced prophylactically when opioid therapy is initiated. Recently, the peripherally acting mu antagonist methylnaltrexone bromide has been approved for the treatment of opioid-induced constipation in patients who do not respond adequately to standard laxative therapy.

In the previous version of the guidelines, the use of methylnaltrexone was recommended for constipation in patients with advanced illness who were receiving palliative care. With increasing recognition of the problem of constipation and its often refractory nature, the recommendation was changed to consideration of methylnaltrexone "when the patient's response to laxative therapy has been insufficient."


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