Intrathecal drug delivery: selection, safety and complications

Intrathecal therapy is for severe pain that systemic drugs cannot control or that causes dose-limiting side effects. Board questions focus on emergencies: granuloma, baclofen withdrawal and ziconotide neuropsychiatric toxicity, plus anticoagulation before implant.

1. Indication: severe pain or dose-limiting side effects. ASPN states an implanted intrathecal pump is indicated when cancer pain remains severe despite adequate conventional medication or when side effects limit dosing; trials show efficacy and fewer opioid side effects ¹.
2. New myelopathy suggests a catheter-tip granuloma. Inflammatory masses are an uncommon complication of chronic intrathecal opioid infusion that can cause devastating neurologic injury, so early detection with imaging is essential ².
3. Granuloma risk tracks dose and concentration. These sterile masses are usually linked to high doses and concentrations of intrathecal morphine or hydromorphone and are rare with fentanyl ³.
4. Baclofen withdrawal can kill. Abrupt interruption can cause high fever, altered mental status, rebound spasticity and rigidity, progressing to rhabdomyolysis, multi-organ failure and death; restore intrathecal baclofen at or near the prior dose ⁴.
5. Ziconotide toxicity: stop it. Ziconotide carries a boxed warning for severe psychiatric symptoms and neurologic impairment, is contraindicated with a history of psychosis, and can be interrupted or stopped abruptly without withdrawal when serious signs appear; other causes of confusion still need evaluation ⁵.
6. Implantation is high bleeding risk. ASIPP classifies intrathecal pump implants, like stimulator implants, as high risk; warfarin is held until the INR normalizes, with bridging for high thromboembolic risk ⁶.

If intrathecal baclofen cannot be restored quickly, oral baclofen or benzodiazepines may prevent fatal sequelae, but oral baclofen alone cannot be relied on to stop the syndrome ⁴.

• A catheter at an intrathecal rather than epidural location does not lower neuraxial bleeding risk ⁶.
• Hallucinations occurred in about 12% of ziconotide-treated patients ⁵.
• Ziconotide is an N-type calcium channel blocker ⁵.
• Intrathecal delivery can allow oral opioids to be reduced or eliminated, with large falls in serum opioid levels ¹.
• Catheter-tip masses can cause progressive myelopathy at the catheter level ².
• With a mechanical valve, ASIPP supports LMWH bridging, stopped about 24 hours before the procedure ⁶.
• Cost-effectiveness of intrathecal therapy for cancer pain has been shown in a large US payer database ¹.
• Granulomas are noninfectious inflammatory masses; the PACC stresses early detection to prevent permanent deficits ².

• Continuing ziconotide through new confusion or hallucinations ⁵.
• Treating fever and rigidity in a baclofen pump patient with antipyretics alone ⁴.
• Assuming fentanyl carries the same granuloma risk as concentrated morphine ³.
• Continuing warfarin for a pump implant because the catheter is intrathecal rather than epidural ⁶.