Mortality Associated with Implantation and Management of Intrathecal Opioid Drug Infusion Systems to Treat Noncancer Pain

Abstract

Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients.

The Enduring Vitality of Implausible Claims for Neurostimulation and Psychosurgical Therapies

“…When we analyzed how implantable device-based pain therapies had zero efficacy, disagreements over the quality of evidence were of limited consequence in public health terms [23,24] . However, as data have emerged that undermine the notion that spinal cord stimulation and intrathecal opioid drug delivery are safe [ 26,27 , http://www.wsj.com/articles/SB10001424052702 304512504579493843647492538] a subset of implanting physicians have collaborated with industry to generate publications that misrepresent efficacy and underestimate (or deflect attention from) relative risks [28,29] . Readers may not be aware that with the exception of ziconotide (Prialt, Jazz Pharmaceuticals, Dublin, Ireland), and despite pre-1976 legacy status and other historical factors, no FDA-approved neurostimulation or intrathecal drug therapy for noncancer pain has successfully undergone formal clinical trial programs to establish safety and efficacy.…”

Intrathecal drug delivery for the management of pain and spasticity in adults: an executive summary of the British Pain Society’s recommendations for best clinical practice

“…Mortality rates of patients treated with ITDD were higher when compared with patients treated with SCS after 1 month (0.39% vs 0.09%, respectively) and after 1 year (3.89% vs 1.36%, respectively). 3 The main cause of mortality for ITDD patients was respiratory depression due to opioid or central nervous system depressant drugs as a primary or contributing factor. It should be noted that from the nine index cases reported, seven patients received an initial intrathecal opioid dose that exceeded the 0.2-1 mg/day dose recommended on the drug manufacturer's label and two patients had a history of prescription drug abuse or overuse, and the two patients with an initial intrathecal opioid dose within the suggested range were obese, which may contribute to decreased respiratory reserve.…”

Naloxone Treatment of Opioid Overdose

“…The concomitant medications that increase overdose risk include CNS depressants (benzodiazepines) and medications that alter cytochrome P450 metabolism. Other opioid-related issues include morphine equivalent dose greater than or equal to 100 mg daily, initiation/titration/rotation/poly-opioid use, and the use of extended-release opioid preparations, transdermal fentanyl use, and intrathecal opioid administration [6][7][8][9][10][11][12][13].…”