ABSTRACT: Many individuals with advanced malignancy continue to suffer from pain and, consequently, impaired quality of life. The clinical scenarios in advanced cancer pain are complex, and successful management may require a more sophisticated and individualized approach than suggested by the World Health Organization guidelines. In patients referred to the Harry R. Horvitz Center for Palliative Medicine in Cleveland, numerous commonly occurring errors in opioid use have been noted. This article describes these errors and offers strategies with which to improve outcomes for patients suffering with cancer pain.
The classic approach to analgesia in cancer patients is both opioid and adjuvant medication prescribed in a stepladder fashion, as established by the World Health Organization (WHO). Since its inception, these guidelines have been validated and are now applied worldwide.[ 1] Given that over 80% of patients living with advanced cancer experience pain, it is one of the most common and severe problems in this population.[2,3] Oncologists must therefore be familiar with the effective use of analgesics. Many individuals with advanced malignant disease continue to suffer with pain and, consequently, impaired quality of life.[4-6] Why do those who complain of pain to their physician and receive treatment still suffer? In reviewing the literature and observing physician management decisions in patients referred to us in a tertiary care hospital, we have noted numerous gaps between theory and practice.
In practice, clinical scenarios involving pain in advanced cancer are complex and require more sophisticated individualized approaches than those addressed by the WHO guidelines. Proper opioid management takes into account the quality and severity of pain as well as the time course-whether pain is constant, incident, or breakthrough in nature. Medically sound strategies for initiating opioids are based on the pharmacokinetic and pharmacodynamic properties of these agents, in addition to general prescribing principles.
Finding the right opioid for an individual requires trial and error. Reassessment for response may identify problems with the current opioid regimen. Even with dose titration, an opioid may not control the pain or cause persistent adverse effects. Assuming a sufficient trial of the original regimen has been attempted, this may require rotation to a new opioid or a new route of administration. To rotate opioids effectively, the physician must have an understanding of equianalgesic dosing for different opioids and routes. Appropriate prescribing, coupled with frequent reassessment and rotation if necessary, will provide effective analgesia for most patients with advanced cancer pain.
In patients referred to us for the management of cancer pain, we have recognized several commonly occurring errors in opioid use prior to the referral. As reported here, these observations are based on collective and collaborative clinical experience at our dedicated palliative medicine inpatient unit, as well as the inpatient and outpatient consulting services. The errors may be grouped into three categories: (1) errors in strategy, (2) errors in titration, and (3) errors in conversion.
In this article, we describe these errors, why each may occur, and the consequences. In accordance with the basic principles of opioid management that guide our practice, we also offer strategies to avoid these errors and improve outcomes for patients suffering with cancer pain. Morphine sulfate is the opioid of first choice in our practice. For illustrative purposes in this report, we will use morphine sulfate as the model opioid.
Error #1: Rescue or As-Needed Prescribing for Constant Pain
Given constant pain, it is appropriate to start regular repeated doses of opioids. It is inadequate to leave a patient on rescue, or as-needed (prn), dosing alone. If only rescue dosing is employed, patients will be continuously trying to catch up with their pain. As a result, life revolves around not only the pain but also frequent medication. Rescue dosing for continuous pain at 3- to 4-hour intervals will also disturb sleep, as individuals will awaken during the night with pain and to take medication.
• Correction—This situation first requires a careful assessment of the temporal pain patterns. A general rule is that continuous pain needs continuous analgesia. This may be accomplished with (1) oral sustained-release (SR) medications, (2) transdermal medication, (3) parenteral continuous infusion, or (4) oral immediaterelease (IR) medications scheduled around-the-clock (ATC). The option of choice is an oral SR medication, which is easily prescribed in the outpatient setting.
If pain is severe, requiring rapid dose titration, then continuous parenteral (subcutaneous or intravenous) infusion- usually in the inpatient setting-is recommended to establish quick control. Although used less often since the development of SR opioids, regularly scheduled IR opioids are an alternative. A double-dose of the IR medication at bedtime is safe and can usually avoid the need to wake for dosing during sleep.
Error #2: Scheduled Prescribing Without Rescue Dosing
While continuous pain calls for ATC medication, pain levels vary. Breakthrough pain is an unpredictable exacerbation of baseline pain.[8-10] Failure to identify breakthrough pain causes inappropriate management. Individuals not given IR rescue opioids to take as needed may have significant pain before their next scheduled ATC dose. They will mistakenly believe their SR medication is ineffective. In response, physicians may increase SR dosing, producing adverse effects such as delirium, nausea, and sedation. Patients may also use or be given SR opioids to take as needed but, given the delayed analgesic onset, find them ineffective.
• Correction—Always prescribe a prn rescue opioid dose when initiating SR opioid therapy. The rescue dose should be an IR preparation, usually the same opioid as the sustained- release drug. SR medications should never be dosed prn. If rescue medication is required more than four times in 24 hours, the SR dose may be increased in an effort to prevent the breakthrough pain. An example of this process follows.
Mr. T. is taking 60 mg of SR morphine sulfate every 12 hours. He has required eight 15-mg doses of IR morphine for breakthrough pain, with good relief and no side effects. Over 24 hours, he used an additional 120 mg of IR morphine. His SR dose is increased by 120 mg, for a new total daily SR morphine dose of 240 mg, or 120 mg every 12 hours. Because his rescue dose has been effective, it is not changed.
Error #3: Not Using Prophylactic Rescue Dosing for Incident Pain
Incident pain is brought about by a specific action or event, which may be voluntary (moving, walking, eating) or involuntary (cough, defecation). Specific identification of incident pain is important, as it limits activity and creates a high probability of suboptimal pain control. Incident pain will not be effectively managed by SR medications alone, and oral rescue doses may not take effect rapidly enough for adequate control.
• Correction—As incident pain, by definition, is usually predictable, it is more effective to give rescue dosing before a known precipitating event. The rescue dose should be enough to control the incident pain and may often be larger than that required for breakthrough pain. Parenteral administration is sometimes needed for quick action. Buccal fentanyl (Actiq) is an alternative in this situation.[11,12]
Error #4: Use of Multiple Opioids and/or Formulations
We commonly encounter simultaneous use of both transdermal fentanyl (Duragesic) and SR morphine sulfate for continuous pain, and both IR oxycodone and IR morphine for breakthrough pain. That is, instead of titrating the initial SR opioid dose to pain relief, a second opioid was added. Multiple opioids complicate a regimen and risk confusing patients and caregivers. Usually neither medication is being given at adequate doses.
• Correction—Only one extendedrelease opioid should be used and increased until either adequate pain control or toxicity occurs. Whenever possible, the same opioid should be used for the IR dosing (ie, SR and IR morphine sulfate or SR and IR oxycodone). If a new opioid is required- for example, in the setting of unacceptable side effects-an equianalgesic dose of the new opioid is calculated. The original opioid is discontinued, and the new medication initiated and titrated until analgesia achieved.
Error #5: Not Prescribing Adjuvant Analgesics
The WHO guidelines recommend the addition of adjuvant analgesics at each step on the ladder if needed to achieve adequate analgesia, yet this is often not done. Common adjuvants include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, tricyclic antidepressants, anticonvulsants, corticosteroids, and antiarrhythmics. Adjuvants may be particularly helpful for neuropathic pain, which is often incompletely controlled with opioids alone.
• Correction—The appropriate use of adjuvant analgesics requires a careful pain assessment. Typically, NSAIDs or corticosteroids are used in bone pain and antidepressants or anticonvulsants in neuropathic pain. Whether opioids or nonopioids are used as the primary analgesic, an adjuvant medication may contribute to improved pain control. If opioid toxicity occurs with titration, the addition of an adjuvant medication may improve pain control enough to allow an opioid dose reduction and elimination of the unacceptable side effect.
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