ROUTES OF ADMINISTRATION
The route selected for administering an analgesic agent (Table 13-3) depends on the patient’s condition and the desired effect of the medication. Analgesic agents can be administered by par-enteral, oral, rectal, transdermal, transmucosal, intraspinal, or epidural routes. Each method of administration has advantages and disadvantages. The route chosen should be based on the pa-tient’s needs.
Parenteral administration (intramuscular, intravenous, or subcu-taneous) of the analgesic medication produces effects more rapidly than oral administration, but these effects are of shorter duration.
Parenteral administration may be indicated if the pa-tient is not permitted oral intake or is vomiting. Medication ad-ministered by the intramuscular route enters the bloodstream more slowly than medication given intravenously and is metabo-lized slowly. The rate of absorption may be erratic; it depends on the site selected and the amount of body fat.
The intravenous route is an alternative to intramuscular injec-tion for many but not all analgesic medications. The intravenous route is the preferred parenteral route in most acute care situations because it is much more comfortable for the patient. In addition, peak serum levels and pain relief occur more rapidly and reliably. Because it peaks rapidly (usually within minutes) and is metabo-lized quickly, an appropriate intravenous dose will be smaller and prescribed at shorter intervals than an intramuscular dose.
Intravenous opioids may be administered by IV push or slow push (eg, over a 5- to 10-minute period) or by continuous infu-sion with a pump. Continuous infusion provides a steady level of analgesia and is indicated when pain occurs over a 24-hour pe-riod (eg, after surgery for the first day or so, or in a patient with prolonged cancer pain who cannot take medication by other routes). The dose of analgesic agent is calculated carefully to re-lieve pain without producing respiratory depression and other side effects.
The subcutaneous route for infusion of opioid analgesic agents is used for patients with severe pain such as cancer pain; it is par-ticularly useful for patients with limited intravenous access who cannot take oral medications, and patients who are managing their pain at home. The dose of opioid that can be infused through this route is limited because of the small volume that can be administered at one time into the subcutaneous tissue. How-ever, this route is often an effective and convenient way to man-age pain.
If the patient can take medication by mouth, oral administration is preferred over parenteral administration because it is easy, non-invasive, and not painful. Severe pain can be relieved with oral opioids if the doses are high enough (see Table 13-2).
In terminally ill patients with prolonged pain, doses may gradually be increased as the disease progresses and causes more pain or as the person builds up a tolerance to the medication. If these higher doses are increased gradually, they usually provide additional pain relief without producing respiratory depressionor sedation. If the route of administration is changed from a par-enteral route to the oral route at a dose that is not equivalent in strength (equianalgesic), the smaller oral dose may result in a withdrawal reaction and recurrence of pain.
The rectal route of administration may be indicated in patients who cannot take medications by any other route. The rectal route may also be indicated for patients with bleeding problems, such as hemophilia. The onset of action of opioids administered rec-tally is unclear but is delayed compared with other routes of administration. Similarly, the duration of action is prolonged.
The transdermal route has been used to achieve a consistent opi-oid serum level through absorption of the medication via the skin. This route is most often used for cancer patients who are at home or in hospice care and who have been receiving oral sustained-release morphine. Fentanyl (Duragesic) is the only commercially available transdermal medication. The preparation is a patch consisting of a reservoir containing the medication and a membrane.
When the transdermal system is first applied to the skin, the fentanyl, which is fat-soluble, binds to the skin and fat layers. Then it is slowly and systemically absorbed. Therefore, there is a delay in effect while the dermal layer is being saturated. A drug reservoir actually forms in the upper layer of skin. This results in a slowly rising serum level and a slow tapering of the serum level once the patch is removed (see Fig. 13-8). Because it takes 12 to 24 hours for the fentanyl levels to gradually increase from the first patch, the last dose of sustained-release morphine should be given at the same time the first patch is applied (Donner et al., 1996). Transdermal fentanyl is associated with slightly less constipation than oral opioids. Absorption is increased in the febrile patient. A heating pad should never be applied to the area where the patch is applied. Transdermal fentanyl is much more expensive than sustained-release morphine but less costly than methods that de-liver parenteral opioids.
Once it is determined that switching from other routes of morphine administration to the patch is appropriate, the correct dosage for the patch must be calculated. If the patient uses an opioid other than morphine, conversion to milligrams of oral morphine is the first step. After determining how many mil-ligrams of morphine (or morphine equivalents) the patient has been using over 24 hours, an initial dose of transdermal fentanyl can be calculated.
Pasaro (1997) suggests one method of calculating the initial dose of fentanyl: the patient’s daily dose of morphine is divided by two. Thus, the equivalent of 400 mg morphine used per day would be equivalent to 200 g fentanyl per hour. Patients switched from morphine to fentanyl need to be assessed not only for pain and potential side effects but also for dependence, reflected by withdrawal symptoms, which may consist of shivering, a feel-ing of coldness, sweating, headache, and paresthesia (Puntillo, Casella et al., 1997). Patients may require short-acting opioids for breakthrough pain before the systemic fentanyl level reaches a therapeutic level.
These conversions and the conversion-type table in the trans-dermal fentanyl packet insert should be used only to establish the initial dose of fentanyl when the patient switches from oral mor-phine to fentanyl (and not vice versa). These tables and equationsare not meant to be used to determine the dosages of oral mor-phine for a patient who has been receiving transdermal fentanyl. Many patients will not achieve satisfactory analgesia from the initial dose of transdermal fentanyl and will require an increase in their fentanyl dose to treat breakthrough pain. If the table or equation is used incorrectly to calculate a morphine dose, there is a risk of overdose. If the patient requires a change from trans-dermal fentanyl back to oral or intravenous morphine (as in the case of surgery), the patch should be removed and intravenous morphine supplied on an assessed need basis.
Before applying a new patch, the patient should be carefully checked for any older, forgotten patches. These should be dis-carded. Patches should be replaced every 72 hours.
The person with cancer pain who is being cared for at home may be receiving continuous opioids using sustained-release morphine, hydromorphone, oxycodone, transdermal fentanyl, or other med-ications. These patients often experience short episodes of severe pain (eg, after coughing or moving), or they may experience sud-den increases in their baseline pain resulting from a change in their condition. These periods, called breakthrough pain, can be well managed with an oral dose of a short-acting transmucosal opioid that has a rapid onset of action. Currently the only transmucosal opioid available is fentanyl, a lozenge on an applicator stick (often referred to as a lollipop by patients).
Currently the only approved and commercially available transmucosal opioid analgesic agents in a nasal spray form are bu-torphanol (Stadol) and fentanyl. Butorphanol is a complex med-ication that simultaneously acts to induce or promote (agonist) and inhibit or reverse (antagonist) opioid effects. It works like an opioid agonist and an opioid antagonist at the same time. Butor-phanol in any form cannot be combined with other opioids (eg, for cancer breakthrough pain) because the antagonist com-ponent will block the action of the opioids the patient is already receiving. The principal use of this agent is for brief, moderate to severe pain, such as migraine headaches.
Intranasal fentanyl is useful in cancer-related breakthrough pain. Given in this form, analgesia is achieved within 5 to 10 minutes and was rated as achieving analgesia superior to oral morphine by 50% of patients in one study (Zeppetella, 2000).
Infusion of opioids or local anesthetic agents into the subarach-noid space (intrathecal space or spinal canal) or epidural space has been used for effective control of pain in postoperative patients and those with chronic pain unrelieved by other methods. A catheter is inserted into the subarachnoid or the epidural space at the thoracic or lumbar level for administration of opioid or anes-thetic agents (Fig. 13-9). With intrathecal administration, the medication infuses directly into the subarachnoid space and cerebrospinal fluid, which surrounds the spinal cord. With epidural administration, medication is deposited in the dura of the spinal canal and diffuses into the subarachnoid space. It is be-lieved that pain relief from intraspinal administration of opioids is based on the existence of opioid receptors in the spinal cord.
Infusion of opioids and local anesthetic agents through an in-trathecal or epidural catheter results in pain relief with fewer side effects, including sedation, than with systemic analgesia. Adverse effects associated with intraspinal administration include spinal headache resulting from loss of spinal fluid when the dura is punc-tured. This is more likely to occur in younger (less than 40 years of age) patients. The dura must be punctured with the intrathecal route, and dural puncture may occur inadvertently with the epidural route. When dural puncture inadvertently occurs, spinal fluid seeps out of the spinal canal. The resultant headache is likely to be more severe with an epidural needle because it is larger than a spinal needle, and therefore more spinal fluid escapes.
Although respiratory depression generally peaks 6 to 12 hours after epidural opioids are administered, it can occur earlier or up to 24 hours after the first injection. Depending on the lipophilic-ity (affinity for body fat) of the opioid injected, the time frame for respiratory depression can be short or long. Morphine is hydro-philic, and the time for peak effect is longer compared to fentanyl, which is a lipophilic opioid. All patients should be monitored closely for at least the first 24 hours after the first injection, longer if changes in respiratory status or level of consciousness occur. Opioid antagonist agents such as naloxone must be available for intravenous use if respiratory depression occurs.
The patient is also observed for urinary retention, pruritus, nausea, vomiting, and dizziness. Precautions must be taken to avoid infection at the catheter site and catheter displacement. Only medications without preservatives should be administered into the subarachnoid or epidural space because of the potential neurotoxic effects of preservatives.
During surgery, intrathecal opioids are used almost exclusively after a spinal anesthetic agent is administered. For patients under-going large abdominal surgical procedures, especially those at risk for postoperative complications, a combination of a general in-haled anesthetic agent for the surgery and a local epidural anes-thetic agent and epidural opioids administered after surgery results in excellent pain control with fewer postoperative complications.
Patients who have persistent, severe pain that fails to respond to other treatments, or those who obtain pain relief only with the risk of serious side effects, may benefit from medication administered by a long-term intrathecal or epidural catheter. After the physician tunnels the catheter through the subcutaneous tissue and places the inlet (or port) under the skin, the medication is injected through the skin into the inlet and catheter, which delivers the medication di-rectly into the epidural space. The medication may need to be in-jected several times a day to maintain an adequate level of pain relief.
In patients who require more frequent doses or continuous in-fusions of opioid analgesic agents to relieve pain, an implantable infusion device or pump may be used to administer the medica-tion continuously. The medication is administered at a small, con-stant dose at a preset rate into the epidural or subarachnoid space. The reservoir of the infusion device stores the medication for slow release and needs to be refilled every 1 or 2 months, depending on the patient’s needs. This eliminates the need for repeated injec-tions through the skin.
Headache resulting from spinal fluid loss may be delayed. There-fore, the nurse needs to assess regularly for headache after either type of catheter is placed. Should headache occur, the patient should remain flat in bed and should be given large amounts of fluids (provided the medical condition allows), and the physician should be notified. An epidural blood patch may be carried out to reduce leakage of spinal fluid.
Cardiovascular effects (hypotension and decreased heart rate) may result from relaxation of the vasculature in the lower ex-tremities. Therefore, the nurse assesses frequently for decreases in blood pressure, pulse rate, and urine output.
For patients experiencing urinary retention and pruritus, the physician may prescribe small doses of naloxone. The nurse ad-ministers these doses in a continuous intravenous infusion that is small enough to reverse the side effects of the opioids without re-versing the analgesic effects. Diphenhydramine (Benadryl) may also be used to relieve opioid-related pruritus.
The patient who receives epidural analgesic agents at home and the family must be taught how to administer the prescribed med-ication using sterile technique and how to assess for infection. The patient and family also need to learn how to recognize side effects and what to do about them. Although respiratory depres-sion is uncommon, urinary retention may be a problem, and pa-tients and families must be prepared to deal with it if it occurs. Implanted analgesic delivery systems can be safely and confi-dently used at home only if health care personnel are available for consultation and, possibly, intervention on short notice.
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