As with systemic opioid administration, the dose range for intraspinal opioid therapy varies widely, depending on the level of pain and tolerance (Du Pen and Williams, 1992). Any agent delivered into the epidural or intrathecal space should be free of preservatives because some preservatives and antioxidants can produce neurotoxicity when used intraspinally (Du Pen, Ramsey, and Chin, 1987; Wang, Hillman, Spielholz, et al., 1984). All patients treated with intraspinal drugs should have access to rescue medications (oral or parenteral) for periods of breakthrough pain or in the case of catheter or drug delivery system malfunction. The coadministration of systemic opioids (which generally is not recommended for postoperative pain management) is safe in most cancer patients because they are tolerant to the respiratory-depressant effects of the drugs.
Morphine is the most commonly used intraspinal drug. Alternative opioids such as hydromorphone, fentanyl, or sufentanil have been used intraspinally to manage cancer pain and may be useful substitutes when the patient experiences side effects from morphine. Intraspinal morphine may produce the same side effects of nausea, mental clouding, and sedation as in oral, rectal, or parenteral dosing, because epidural or subarachnoid morphine is absorbed into the circulation by way of the rich epidural vascular plexus and is also carried in the normal flow of cerebrospinal fluid (CSF) from spinal levels to the brain (Bromage, Camporesi, Durant, et al., 1982; Chauvin, Samii, Schermann, et al., 1982; Cousins, 1988; Max, Inturrisi, Kaiko, et al., 1985). Single-dose epidural administration of 10 mg of morphine produces levels in blood comparable to an intramuscular injection of the same dose (Max, Inturrisi, Kaiko, et al., 1985). Very lipophilic opioids such as fentanyl and sufentanil have a more limited CSF distribution, but these drugs also gain access to the blood and are delivered to the brain via the systemic circulation.
In some patients, it is possible to give relatively small doses of opioid spinally and produce pain relief while avoiding the side effects that can limit prior oral or parenteral dosing. However, patients with a high degree of tolerance to systemic opioids may require large doses of spinal opioids (Cousins and Bridenbaugh, 1987), which may negate the advantages of this targeted approach because side effects may still be prominent at high dosage levels.
The main indication for the long-term administration of intraspinal opioids is intractable pain in the lower part of the body, particularly when pain is bilateral or midline (Du Pen and Williams, 1992). With proper selection and screening, good to excellent pain relief can be expected in up to 90 percent of patients (Krames, Gershow, Glassberg, et al., 1985; Onofrio and Yaksh, 1990). Opioids (sometimes maladministered with other agents such as dilute local anesthetic) (Akerman, Arwestrom, and Post, 1988; Fraser, Chapman, and Dickenson, 1992; Maves and Gebhart, 1992; Tejwani, Rattan, and McDonald, 1992) are delivered to the epidural or subarachnoid space via percutaneously placed catheters connected to ports, reservoirs, or infusion pumps (Table 12). For short-term treatment of weeks to a few months, externalized catheters (tunneled or untunneled) can be used. For more prolonged treatment, the delivery system (catheter plus port or pump) can be internalized. Adverse sequelae include the development of tolerance, urinary retention, constipation, pruritus, device failure, and infection (Du Pen, Peterson, and Williams, 1990; Hogan, Haddox, Abram, et al. 1991).
Intraspinal drug delivery systems
General comments and cautions regarding the use of opioid analgesics
Adjuvant analgesic drugs for cancer pain
Drugs and routes of administration not recommended for treatment of cancer pain
Neuraxial Opioid Infusion