Update: cancer pain management
Eric W. Anderson, MD
Practitioners' ability to control cancer pain is advancing at a fast pace, and in tandem with our expertise in the broader realm of palliative care. A decade ago, adequate dosing of opioids was the major clinical challenge in cancer pain, but this is not the case today. Now that we understand the importance of aggressive analgesia, our challenge is to address the full spectrum of cancer patients' pain and suffering.
In this review, we will focus on four areas of controversy and research: patients' expectations about pain management, the use of newer opioid formulations, methadone hydrochloride's reemergence as an analgesic, and palliative care for the patient who is actively dying.
What do patients want from pain management?
Patients value attentiveness of care, as much as they value pain relief itself. Several studies in the postoperative setting have demonstrated high patient satisfaction ratings for pain management, even though a majority of patients described their pain as moderate or severe.1,2 Experiences with cancer patients echo these findings. A hospice patient with widespread metastatic thyroid cancer experienced severe boney pain with the slightest movement. Despite this level of pain over many months, he expressed gratitude for the pain-control efforts of his physician and hospice team.
Patients also value perceived control over pain.3 Any interventions that increase a sense of control contribute to a good patient experience.
What does this mean in practical terms?
First, we must treat pain on an around-the-clock schedule before it becomes severe. This creates a successful "early win" when the pain is less severe, conferring to the patient a sense of control.
Second, we need to show patients how to use non-drug modalities such as the relaxation response to modify their pain.
Finally, we should ask patients about their pain on a regular basis throughout the illness.
The message is clear: Patients want us to listen to them and be attentive to their pain needs. Our attitude of caring is as important as the resulting pain relief.
The 'new' opioids
We now have at our disposal sublingual, highly concentrated preparations of morphine (Roxanol Intensol, 20 mg/mL), oxycodone hydrochloride (Roxicodone Intensol, 20 mg/mL), and lorazepam (Lorazepam Intensol, 2 mg/mL). These formulations are absorbed either transmucosally or via swallowing of small volumes of liquidreplacing the rectal or injection methods for patients who are unable to swallow pills.
A new, once-a-day formulation of morphine is also available.4 It may be useful in home situations where misuse of opioids is a concern, because the drug can be dosed entirely by visiting staff. This is also the only long-acting opioid that can be opened, and the contents given via a feeding tube of 16 French diameter or larger.5
Despite the continued popularity of morphine for cancer pain, use of slow-release oxycodone in this country has surpassed long-acting morphine sulfate. In contrast to slow-release morphine, which requires 8-hour dosing in some patients, the oxycodone preparation has true 12-hour kinetics. It may also cause less confusion, particularly in the elderly. Geriatric patients may accumulate morphine-6-glucuronide and normorphine metabolites because of reduced renal function, predisposing them to agitated confusion. Opioid rotation replaces one drug with equianalgesic doses of another; this practice has been shown to alleviate morphine-induced confusion.6
Conversion among the opioids is relatively simple. Long-acting morphine is converted to oxyocodone at an equianalgesic ratio of 2:1. For example, 60 mg of MS Contin every 12 hours would be converted to 30 mg of Oxy Contin every 12 hours.
To convert oral opioids to transdermal fentanyl citrate, the "1:2:3 Rule" is useful (Miles Belgrade, MD, personal communication, 1996). The 1:2:3 Rule enables calculation of dose conversions by equating 1 mg per 24 hours of parenteral morphine with a 2-µg-per-hour fentanyl patch, and with 3 mg per 24 hours of oral morphine. As an example, a patient getting 1 mg/hour of morphine intravenously receives about 25 mg of morphine per day. This equates with a 50-µg-per-hour fentanyl patch or 75 mg/day of oral morphine. Package insert conversion tables were designed to avoid oversedation of opioid-naïve patients, but they are too conservative for patients already taking regular opioids.
Methadone, alone among the commonly used opiods, blocks the N-methyl-D-aspartate (NMDA) receptors in the central nervous system and spinal cord. These receptors, when activated by painful stimuli, can produce an amplifying effect, termed "wind up," through release of the gaseous neurotransmitter nitric oxide.7,8 Widespread regional neuropathic pain may result.
In a recent series of four patients with intractable cancer pain, intravenous (IV) methadone produced good pain relief. In this series, patients required less than 4% of their calculated dose of methadone, using the standard opioid conversion.9 The mechanism of pain relief at this low dose is postulated to involve blockage of the NMDA receptors.
Methadone's role in palliative care is evolving, and we can expect to see more studies in the coming year. In the interim, we should disregard the published conversion ratio (approximately 1:1 methadone to morphine10) and give 1 mg of oral methadone for each 3 mg of oral morphine. In contrast to its use for opioid addiction maintenance, methadone must be dosed every 6 hours when employed as an analgesic.
As death approaches, pain diminishes. Its incidence drops from 52% to 30% in the 2 weeks prior to death.11 During this time, patients may withdraw; they may stop eating and drinking altogether; and they may have a variety of dreams and visions related to dying. Such visions often involve travel metaphors and contacts with deceased family members.12 These final days may be a time of intense personal and spiritual work, and the focus of palliative efforts needs to change.
Symptoms that patients will complain of most at this time are dry mouth, anorexia, confusion, and general weakness. Dry mouth is a symptom that appears to be unrelated to hydration state.13 Relief is accomplished by moistening the mucosa. Salivart and similar products are available for this purpose. Water-soluble gels such as K-Y may be used for dry tongue in mouth-breathing patients.
It is unnecessary to give fluids to relieve the symptom of dry mouth, beyond what the patient spontaneously ingests. Indeed, IV fluids infused at the usual rates can worsen suffering by stimulating gastrointenstinal and respiratory secretions.
A dying patient's need for pain medication often diminishes, but may occasionally escalate. In those instances where very high doses of opioid are needed (that is, in the range of 30 mg to 1,000 mg/hr morphine), some patients develop an agitated confusion that requires aggressive treatment with benzodiazepines and/or large doses of a neuroleptic such as haloperidol at doses of 10 mg to 30 mg/24 hours.14
Renally excreted metabolites of morphine may inhibit Renshaw cell activity in the spinal cord. Loss of this inhibitory neuron effect leads to myoclonuscontractions often misinterpreted as seizure activity.15
The first step in combating opioid-induced agitation and myoclonus is to lower the dose of opioid, if possible. Benzodiazepines, often delivered as an infusion of midazolam or lorazepam, are also helpful in combating this untoward opioid side effect. Benzodiazepine infusions may also be useful in the treatment of restlessness, pain, and nausea. Incremental titration of these agents under medical direction by experienced IV or hospice nurses is often successful in the home setting.
This brief overview of cancer pain management has emphasized several points:
Patients expect attentive care for their pain, before it becomes severe.
Use of newer opioid formulations can simplify dosing.
Rotation of analgesics is often effective in treating opioid side effects.
Methadone has reentered cancer pain management as an opioid with unique effects on neuropathic pain.
Pain generally diminishes as death approaches, and our palliative efforts need to shift to the other concerns for bodily comfort that afflict the dying patient.
Dr Anderson is medical director, HealthSpan Hospice, Minneapolis.