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Late Stage
Pain Medications - End Stage


Pain Medications - End Stage
The Merck Manual
Section 21. Special Subjects 

Patients perceive pain differently, depending on such factors as fatigue, insomnia, anxiety, depression, and nausea. Addressing these factors together with a supportive environment can help control pain.

Analgesic choice depends largely on pain intensity, which can be determined only by talking with and observing the patient. All pain can be relieved by an appropriately potent drug at the right dosage, which may also produce sedation or confusion.

Commonly used drugs are aspirin, acetaminophen, or NSAIDs for mild pain; codeine or oxycodone for moderate pain; and hydromorphone or morphine for severe pain. For a detailed discussion of analgesic use, see Ch. 167. Aspects of particular significance to patients with terminal illness are discussed below.

Opioid analgesics:

In terminal illness, oral administration of opioids is the most convenient and cost-effective route. Rectal administration provides slower absorption but with very little first-pass effect; morphine suppositories or pills may be given rectally at the same dose as used orally and titrated as needed. IV or sc administration of opioids is preferred to IM injections, which are painful and have variable absorption.

The usual effective dosage interval for opioid analgesics is 3 to 4 h, except for long-acting preparations. Always give opioids around the clock to avoid onset of pain.

When opioids are indicated, the physician should prescribe them with confidence, in adequate dosage, and on a continuous basis to prevent pain. Public and professional reticence often tragically limits their appropriate use.

Pharmacologic dependence is part of regular use but causes no problems except the need to avoid inadvertent withdrawal. Psychologic dependence is so rare as to be irrelevant in pain patients using prescribed opioids.

Morphine is the most commonly used opioid in terminal illness. Possible adverse effects include nausea, sedation, and confusion. Constipation should be treated prophylactically (see below). The patient usually develops substantial tolerance to the respiratory depressant and sedative effects of morphine but much less tolerance to the analgesic and constipating effects.

When morphine is given orally, a controlled-release form is preferred because it provides steady levels of morphine with twice-daily dosing (instead of dosing every 3 to 4 h for immediate-release morphine); however, it has a slow onset of action.

Patients are usually converted to equianalgesic dosing of controlled-release morphine based on initial attempts to control pain with short-acting opioids. Immediate-release morphine should be kept available for breakthrough pain.

Two dosing rules are useful. First, if any dose will seriously depress respiratory function, it is usually much more than twice the stable tolerated dose. Second, reestablishing pain control when a stable dose becomes inadequate ordinarily requires >= 1.5 times the previous dose.

When the oral route is not feasible, morphine may be given by suppository or parenterally (or even sublingually or in the buccal space, by tablet or 20 mg/mL solution).

In the hospital, morphine is commonly administered IV via patient-controlled analgesia (PCA) pumps.

Morphine, continued

More common to hospice care is the use of sc PCA pumps, thereby avoiding the difficulties of maintaining venous access while providing steady levels of analgesia. An indwelling 25-gauge sc needle with catheter attached can be left in place for 3 to 7 days. Morphine at concentrations of up to 50 mg/mL can be pushed through the catheter intermittently in 1-mL amounts or supplied continuously via a PCA pump the size of a portable cassette player. Continuous sc infusion rates are generally maintained at 0.1 to 1 mL/h. Rates of several milliliters per hour have been used successfully; however, maintaining the needle site is more difficult. Pumps can be maintained at home with a visiting nurse changing the sc site twice a week.

Hydromorphone is about five times more potent than morphine and can be given in a more concentrated solution (up to 100 mg/mL), allowing more convenient dosing in a patient receiving continuous sc infusion.

Fentanyl is the only opioid administered topically via a patch, which releases opioid steadily for about 72 h and then is changed. At least 24 h is needed to attain maximum analgesia, and the dose should not be increased for at least 3 days.

Patients must be given short-acting opioids while awaiting fentanyl's steady state. Fentanyl can cause confusion and delirium. Once the patch is removed, it takes 18 h for serum levels to decline 50%, thus untoward effects may continue for more than a day.

Meperidine is not recommended for management of persistent pain because it is short-acting, does not provide steady levels of analgesia, and produces a toxic metabolite that causes psychosis and CNS hyperexcitability at relatively low doses.

Similarly, pentazocine, butorphanol, and other mixed agonist-antagonist drugs should not be used because of their low potency, erratic oral and IM absorption, and greater incidence of adverse effects, especially psychosis.

Adjuvant analgesics: Use of adjunctive drugs for pain control often allows for reduction in opioid dosing. Corticosteroids are widely used in the terminally ill to decrease the pain of inflammation and swelling. Tricyclic antidepressants such as amitriptyline, nortriptyline, and doxepin help manage pain. Anticonvulsants like valproate, carbamazepine, and, most recently, gabapentin have been helpful adjuncts, especially for the management of neuropathic pain. Benzodiazepines are useful for patients whose pain is worsened by their anxiety.

Anesthetics: For severe pain in localized body regions, an anesthesiologist experienced in pain management may provide relief with few adverse effects. Indwelling epidural or intrathecal catheters may be placed to provide continuous infusion of analgesics, often mixed with anesthetic drugs. A pain management team may also provide various nerve-blocking techniques.

Nondrug treatments:

Pain-modification techniques such as guided mental imagery, hypnosis, and relaxation are useful for some patients.

Counseling for stress and anxiety, or spiritual support from a chaplain, may be very useful.