Intractable Pain Due to Cancer

Posted by • May 29th, 2015

In the latest Case Record of the Massachusetts General Hospital, a 44-year-old woman with metastatic non–small-cell lung carcinoma with an EGFR mutation presented with severe pain, which was worsened by opioids other than hydrocodone and was unresponsive to most other analgesics. Management decisions were made.

The discomfort of most dying patients can be controlled with state-of-the-art palliative care, but there are rare patients whose symptoms cannot be controlled. In these rare cases, palliative sedation is considered.

Clinical Pearls

What is the World Health Organization “ladder” for cancer-related pain?

The World Health Organization (WHO) “ladder” for cancer-related pain is a well-validated and generally effective approach to pain management that recommends nonopioid therapy for mild pain and opioid therapy for moderate or severe pain. However, 12 to 14% of patients have poorly controlled pain despite adherence to WHO guidelines. For cancer-related pain that is unresponsive to systemic analgesics, a fourth step on the WHO ladder — interventional therapies — has been proposed. Data suggest that interventions such as neurolytic blocks and neuraxial drug delivery may yield improved pain control with fewer side effects.

Does opioid-induced hyperalgesia occur only with chronic exposure to high doses of systemic opioids?

Opioid-induced hyperalgesia is a phenomenon whereby exposure to opioids sensitizes a patient to a pain stimulus, causing a paradoxical increase in pain. The risk factor is chronic exposure to high-dose systemic opioids, but there have been reports of opioid-induced hyperalgesia in patients who have not previously received opioids, patients receiving low-dose opioids, and patients receiving intrathecal analgesia. Central activation of the N-methyl-D-aspartate (NMDA) receptor has been suggested as one possible cause, and administration of NMDA antagonists has been recommended when opioid-induced hyperalgesia is suspected.

Morning Report Questions

Q: What is palliative sedation?

A: Palliative sedation is an intervention to relieve intractable pain in terminally ill patients by means of continuous infusion of a sedation medication. Palliative sedation is distinct from other sedation interventions performed at the end of life, such as respite sedation, physician-assisted suicide, and euthanasia. In respite sedation, the patient is sedated for a predetermined period, after which sedation is lifted to assess the response. Respite sedation and palliative sedation are both ethically distinct from physician-assisted suicide and voluntary active euthanasia. In palliative sedation and respite sedation, the intention is to alleviate pain and suffering but not to hasten death. The intention in physician-assisted suicide and voluntary active euthanasia is also to relieve unacceptable suffering, but the intervention intentionally ends the patient’s life.

Q: What is the legal and ethical foundation of palliative sedation?

A: There is a robust legal foundation for the initiation of palliative sedation. When the U.S. Supreme Court ruled that physician-assisted suicide is not a constitutional right, it affirmed that patients with terminal illness who are experiencing great pain should have “no legal barriers to obtaining medication, from qualified physicians, to alleviate that suffering, even to the point of causing unconsciousness and hastening death.” The relevant ethical principles include autonomy, beneficence, nonmaleficence, and proportionality. [Beneficence, nonmaleficence, and proportionality] are embodied in the principle of double effect, which states that as long as the only intention of an intervention is to achieve a morally good outcome (e.g., alleviating intractable pain and suffering) through a morally good or neutral action (e.g., administering sedation medications), then even if there are unintended bad effects (e.g., the patient does not wake up from sedation and the patient’s life is shortened by a small amount), the intervention may proceed. The bad effects can be foreseen but cannot be intended.

Table 2. Features of Sedation Interventions.

Table 3. Principle of Double Effect.

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