Kadian

Find out if an alternative administration route can help you control your patient's pain better.

YOU'RE FAMILIAR with administering opioid analgesics by the oral and intravenous (IN.) routes. But how much do you know about less-- commonly used options, such as the rectal, oral transmucosal, or subcutaneous (S.C.) continuous infusion routes? In some cases, these alternatives can provide effective and safe pain relief when other routes aren't available.

Being aware of the various administration options for such opioids as morphine, hydromorphone (Dilaudid), and fentanyl will help you identify the least invasive and most effective route for each patient, depending on his pain control needs. We'll start by reviewing traditional routes, then discuss how alternative routes stack up against them.

Preferred routes

Oral Inexpensive, noninvasive, and easy for patients to self-- administer, oral medication is the first choice for managing both acute and chronic pain. The oral route is inappropriate for severe, escalating pain because opioids administered orally take effect slowly and don't reach peak effects for 90 to 120 minutes after ingestion. Once pain is under control, however, an oral opioid administered regularly at a high enough dose may effectively maintain control of severe pain. Giving a dose that's too low is a common reason oral opioids fail to achieve analgesia.

Oral opioids, such as oxycodone, codeine, or hydrocodone, are commonly formulated in fixed combinations with acetaminophen. But these are appropriate only for mild to moderate pain because acetaminophen limits the number of tablets that can be given in 1 day. The maximum recommended dose for acetaminophen in a 24-hour period is 4,000 mg. Single-entity opioids such as plain oxycodone (OxyIR) are used for moderate to severe pain.

The relatively new controlledrelease opioids, such as morphine (MS Contin, Oramorph SR, Kadian) and oxycodone (OxyContin), make using the oral route more convenient. They can maintain pain control with only one or two doses a day. The slow, uniform absorption of these opioids is ideal for managing continuous acute or chronic pain. MS Contin, Oramorph SR, and OxyContin may be given every 12 hours, but not more often than every 8 hours. Kadian may be given once or twice a day. When prescribing these drugs, practitioners should also order supplemental doses of immediate-release opioids for breakthrough pain.

The controlled-release formulations of morphine have a delayed onset of 2 to 3 hours. But, OxyContin releases oxycodone immediately (onset in about 45 minutes) as well as over 12 hours for ongoing analgesia. It's now used more frequently to manage acute pain.

Many opioids are available in tablet and liquid forms. Crushing tablets and putting them into concentrated suspensions may be an option when liquid forms aren't available. However, be careful: Some medications, such as controlled-release tablets, shouldn't be altered.

I.V. Most opioids are available for parenteral administration. Given I.V, opioids have a rapid onset of action (5 to 10 minutes) and can be rapidly titrated to fit the patient's needs. So this route is best when patients need immediate relief from severe or escalating pain. Methods of administration include continuous infusion, bolus, and patient-- controlled analgesia (PCA).

Hospitalized patients who require short courses of therapy, such as surgical patients, often receive opioids I.V. This route is also ideal as a temporary measure for patients with cancer pain or chronic nonalignant pain who require rapid titration. Once pain is controlled, the patient may switch to oral opioids. For patients with chronic pain who can't take oral opioids, such as terminally ill patients with intestinal obstruction, long-term I.V. infusions may be indicated.

Intraspinal The intraspinal route encompasses epidural and intrathecal (spinal) administration. Medication can be delivered via bolus or continuous infusion or both.

Intraspinal routes are recommended for major abdominal, thoracic, and joint surgeries when severe, acute pain is anticipated. Studies have shown that compared with IX PCA, intraspinal analgesia in these situations provides much better analgesia and improved outcomes, such as shorter lengths of stay.

Morphine (Astramorph PF, Duramorph), fentanyl, and hydromorphone are commonly prescribed by this route. Increasingly, intraspinal opioids are combined with low doses of local anesthetics, such as bupivacaine. These combinations provide analgesia, not anesthesia, and allow you to give lower doses of opioid, which reduces opioid-- induced adverse reactions.

Patients with chronic pain are rarely candidates for the intraspinal route because they can be treated effectively with oral opioids. Routes to avoid

Intramuscular (I.M.) Once standard, the I.M. route is no longer recommended for pain management. Intramuscular injections are painful, can damage tissues and nerves, and increase the risk of infection with abscess formation. Most importantly, drugs given I.M. are absorbed slowly and at an unpredictable rate, so pain control is unreliable. The I.M. route is a particularly poor choice for the elderly, who've lost muscle mass from aging, and for children, who dread painful injections.

The I.M. route is especially inappropriate for postoperative pain: Hypovolemia, hypothermia, and lack of muscle activity further delay drug absorption. Poor pain relief because of slow absorption likely results in administering additional doses, which leads to more opioid accumulation in the tissues. Then as circulation improves and absorption increases, the patient may experience adverse reactions, such as sedation and respiratory depression. Unreliable absorption makes it difficult to predict peak effect and to know when to monitor for respiratory depression. This is probably the reason that the risk of respiratory depression with the LM. route is five times greater than for I.V. administration.

Intermittent S.C injections

Like the I.M. route, intermittent S.C. injections of opioids are no longer recommended. Although the S.C. route offers better opioid absorption than the I.M. route, S.C. injections have a slow onset of action and are painful, time-- consuming, and potentially damaging to tissue.

Alternative routes

Some opioids are formulated for administration by alternative routes, such as the rectal route. As a second-- line approach, a pharmacist may also compound some opioids for administration by alternative routes, such as the transdermal route. Don't use compounded preparations as first-line therapy because their absorption, peak effects, and duration of action usually haven't been studied adequately. Absorption could be minimal or nonexistent. Following are routes that may be considered when patients can't take opioids by the oral route or, in the case of S.C. continuous infusion, by the LV. route. Use more caution with routes for which commercially available formulations don't exist, such as the vaginal route.

Transdermal Fentanyl

(Duragesic), available via adhesive patch in 25-, 50-, 75-, and 100-- mcg/hour doses, currently is the only opioid available for use by the transdermal route.

The skin under the patch absorbs fentanyl and depots drug concentrate in the upper skin layers, fat, and skeletal muscles. From these depots, fentanyl is gradually released into systemic circulation.

Once in place, the transdermal system can release fentanyl at a nearly constant rate for up to 72 hours, although some patients require a new patch after 48 hours. Practitioners should also prescribe an immediate-release opioid for breakthrough pain.

Transdermal fentanyl may be an option for patients with stable, moderate to severe chronic pain who are unable to take opioids orally.

Patients with pain that varies in severity throughout the day aren't good candidates because they'd need additional opioid doses by another route for breakthrough pain, negating the transdermal route's advantage of infrequent dosing.

Transdermal fentanyl shouldn't be the primary analgesic when pain isn't under control. The current formulation doesn't substantially relieve pain for 12 to 16 hours after a first dose. And, titration to an effective dose may take days, which requires the patient to take an opioid by another route during this period.

Also, you can't easily adjust the dose to manage adverse reactions, such as nausea and vomiting. Even after patch removal, a depot of fentanyl remains and serum concentrations decline at the slow rate of about 50% in approximately 17 hours.

Another shortcoming: External or internal heat sources may increase transdermal fentanyl's absorption. A fever of 104 deg F (400 deg C) can increase serum fentanyl concentration by one-third, increasing the risk of adverse reactions and possibly requiring a dosage decrease. Advise patients not to take excessively hot showers, sleep on a heated water bed, or put a heating pad over the patch.

Transdermal fentanyl isn't safe for managing acute or postoperative pain, especially in the outpatient setting. These patients are usually opioid-naive; that is, not tolerant to the respiratory depressant effect of opioids. The smallest dose of transdermal fentanyl (25 mcg/hour) may be too high for them, and it can't be adjusted downward. Patients who are opioid-naive require a route of administration that allows for rapid onset and titration. Transdermal fentanyl is inappropriate because of the delay in onset of analgesia (12 to 16 hours). In the outpatient setting, it's dangerous to send patients home on opioid doses that haven't yet taken effect and may be too high.

S.C continuous infusion

Practitioners are increasingly using the S.C. route for continuously infusing opioids via PCA pump for patients with chronic cancer pain who can't take oral medications and who don't have central venous access. Hydromorphone and morphine are the most common opioid analgesics administered this way.

Patients receive small volumes of opioid (often highly concentrated formulations) for S.C. infusion. Most patients can absorb between

2 and 5 ml/hour. When necessary, some patients can even tolerate an infusion of up to 8 ml/hour for a few hours. Patients receive rescue doses as S.C. PCA boluses.

Rectal The rectal route offers an excellent, but frequently overlooked, alternative to the oral route for patients who can't take oral medications. The effective dose of opioids by the rectal route is approximately equal to oral dosing; however, some researchers suggest reducing the starting dose by approximately 25%. The most common reason for failure to achieve adequate analgesia is insufficient dosing.

The rectal route is particularly useful when other routes are unavailable and you expect a delay in establishing alternative treatment. For example, the rectal route may be used temporarily when a patient taking oral opioids can no longer swallow and arrangements are being made to insert a central line for IX PCA administration. The rectal route may be contraindicated in patients who are neutropenic or thrombocytopenic (platelet count of 50/mm3 or below) because of the risk of rectal bleeding from drug insertion.

Drugs commercially available as rectal suppositories are morphine, methadone, hydromorphone, and oxymorphone, although theoretically, patients can absorb any opioid rectally. A pharmacist or someone in the home may compound opioids for rectal administration. Oral tablets, oral solutions and suspensions, and injectable products have been given rectally, sometimes without altering the medication. Studies show that the intact tablets of oral controlled-release opioids, such as MS Contin, can be given rectally.

Vaginal Although no opioid is formulated for vaginal administration, the body can absorb drugs given by this route. One study found controlled-release morphine (Oramorph SR) is safe and effective when administered every 12 hours by the vaginal route to patients with cancer pain.

Patients reported no consistent changes from the oral route in the frequency of adverse experiences, morphine requirements, or pain intensity ratings.

Oral transmucosal Sublingual, buccal, and gingival tissues are available for oral transmucosal administration. These areas are considered separate routes of administration. Research on these routes, except for administration of oral transmucosal fentanyl citrate, is limited.

Sublingual administration involves placing the drug (tablet or liquid) under the tongue for absorption through the oral mucosa into the systemic circulation. No opioids are formulated for this route. Those given sublingually for pain control are seldom administered properly because the patient must hold the drug in his mouth without swallowing for at least 5 minutes. Since pain relief probably occurs because the drug is swallowed, the sublingual and oral doses are the same. Use of liquefied opioids in this manner is common and useful when swallowing is difficult, but isn't literally sublingual administration.

Opioids are sometimes administered via the buccal route (placing a tablet inside the mouth between the cheek's mucosal surface and the gum of the upper molars) and the gingival route (placing a tablet between the upper lip and the gum of the incisors). However, formulations specifically designed for these routes aren't available.

Some evidence suggests that patients absorb morphine by the buccal and gingival routes; however, research findings vary significantly, and patients complain of an extremely unpleasant bitter taste with morphine tablets. Also, these routes require leaving the tablet in contact with the gum for a long period, sometimes up to 6 hours, which makes this approach uncomfortable and impractical for most patients. However, the buccal or gingival routes may be useful to temporarily administer opioid to patients who are no longer able to swallow tablets or who vomit their oral medications.

N Intranasal The mixed agonist-- antagonist opioid butorphanol (Stadol) is the only opioid formulated and available for intranasal administration. A small aerosol device delivers a set dose of the drug into a nostril.

Intranasal butorphanol is easy for patients to use, has a consistent absorption pattern, and provides adequate analgesia for some types of postoperative pain. However, because it's an agonist-antagonist (not a mu agonist, or morphinelike drug), this drug may reverse the analgesia in patients taking morphinelike drugs. In patients with physical dependence on morphine or morphinelike opioids, such as oxycodone, intranasal butorphanol may cause withdrawal.

Nebulized morphine administered by face mask is reportedly safe and effective for treating dyspnea associated with end-stage chronic obstructive pulmonary disease, heart failure, and lung cancer. But it isn't recommended for pain relief because current techniques result in limited absorption of the drug. Besides morphine, several other opioids, such as fentanyl, hydromorphone, and codeine, can be nebulized.

Although opioids aren't formulated as nasal drops, you can instill the parenteral formulation of sufentanil intranasally in droplet form or via a swab. But this can cause burning and stinging, especially in children who often object to any form of nose drops, which produce a sensation similar to drowning.

Stomal Opioids aren't formulated for stomal administration, and no one knows how effective this route is. However, temporary use of the stomal route may be an alternative when proven routes are unavailable. Formulations that are used orally or rectally may also be administered stomally. The starting dose is usually the same as for oral or rectal administration.

Sigmoid colostomies (left-sided), which produce formed stool, are more likely than other ostomies to allow for absorption of opioids. Ostomies that are constructed in other areas of the colon and produce wet, liquid, or semisolid effluent generally have more rapid transit times. Constant pressure of watery effluent pushes out the drug before it absorbs.

The choice makes a difference

Your knowledge of the many ways of administering opioids will help match your patient's pain control needs with the most effective and least invasive route.

SELECTED REFERENCES

Coyle, N., et al.: "Pharmacologic Management of Cancer Pain," in Cancer Pain Management, 2nd edition, D. McGuire, et al. (eds). Boston, Mass., Jones and Bartlett Publishers, 1995.

Liu, S., et al.: "Epidural Anesthesia and Analgesia. Their Role in Postoperative Outcome," Anesthesiology. 82(6):1474-1506, June 1995.

McCaffery, M., et al.: "Analgesic Administration Via Rectum or Stoma," Journal of E. T Nursing. 19(4):114-121, July-August 1992.

Pasero, C., et al.: "Opioid Analgesics;' In Pain: Clinical Manual, 2nd edition, M. McCaffery and C. Pasero. St. Louis, Mo., Mosby, Inc., 1999. Schug, S.: "Intramuscular Opioids-the Slow Extinction of a Dinosaur!" Acute Pain: The International Journal of Acute Pain Management. 2(2):5668, June 1999.

BY MARGO McCAFFERY, RN, MS, FAAN Consultant in the Nursing Care of Patients with Pain Los Angeles, Calif.

CHRIS PASERO, RN, MS Pain Management Educator and Consultant Rocklin, Calif.

Copyright Springhouse Corporation Dec 2000
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