title: Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain.
abstract: BACKGROUND
  In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery.
  
  
  METHODS
  After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality.
  
  
  RESULTS
  Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Divisions of Neuromodulation Clinical Research, Regulatory Vigilance, and Biostatistics, Medtronic Inc., 7000 Central Avenue NE, Minneapolis, MN 55432, USA. robert.coffey@medtronic.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: Mary L
authors.initials: ML
authors.lastname: Owens
authors.forename: Steven K
authors.initials: SK
authors.lastname: Broste
authors.forename: Michel Y
authors.initials: MY
authors.lastname: Dubois
authors.forename: F Michael
authors.initials: FM
authors.lastname: Ferrante
authors.forename: David M
authors.initials: DM
authors.lastname: Schultz
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Stearns
authors.forename: Michael S
authors.initials: MS
authors.lastname: Turner
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D002423:Cause of Death; D016208:Databases, Factual; D017586:Diskectomy; D004343:Drug Implants / Q000009:adverse effects*; D062787:Drug Overdose; D004599:Electric Stimulation Therapy / Q000401:mortality; D004868:Equipment Failure; D006323:Heart Arrest / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D015918:Infusion Pumps, Implantable / Q000009:adverse effects*; D017116:Low Back Pain / Q000188:drug therapy / Q000401:mortality; D006278:Medicare / Q000706:statistics & numerical data; D010146:Pain / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D012042:Registries; D012307:Risk Factors; D013116:Spinal Cord; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D004343:Drug Implants