title: Primary Hydromorphone-Related Intrathecal Catheter Tip Granulomas: Is There a Role for Dose and Concentration?
abstract: BACKGROUND
  Intrathecal drug delivery therapy has been used effectively in treating patients with intractable chronic pain. The development of an intrathecal catheter tip granuloma (ICTG) related to delivery of intrathecal opiates is a relatively infrequent, but potentially devastating complication. While there are many morphine-related ICTG cases described, reports of hydromorphone-related ICTG are limited. In addition, studies suggest a strong correlation between the use of higher doses and concentrations of intrathecal opiates and ICTG formation.
  
  
  OBJECTIVE
  The objective of this study is to determine the incidence and the association of intrathecal hydromorphone dose, concentration, duration of treatment and concomitant agents with ICTG formation.
  
  
  METHODS
  This is a retrospective analysis of 101 consecutive patients implanted with intrathecal infusion delivery devices. Data were collected from chart review, and records of pump refills from the division of Pain Medicine of University Hospitals or outsourced to a home pump refill service.
  
  
  RESULTS
  From a cohort of 101 consecutively implanted patients, 69 were treated with intrathecal hydromorphone and followed up postimplant for an average of 33.5 ± 24 months (range 0-93 months; 95% CI of 27-39 months). The incidence of ICTG in our patient population was 8.7% during this period of time postimplant with mean time to granuloma detection 35.1 ± 7.9 months. Patients developing granuloma (n = 6) were treated with a combination of intrathecal hydromorphone and bupivacaine infusion. Exposure time to intrathecal agents was not different between the granuloma and nongranuloma group. Monthly dose increase of hydromorphone was higher in granuloma group vs. non-granuloma group (58 ± 34 mcg/month n = 6 vs. 25 ± 8 mcg/month n = 63). Four out of six granuloma cases occurred with low dose and concentration of IT hydromorphone (160-370 mcg/day; 0.75-1.0 mg/mL concentration). Intrathecal bupivacaine dose was not different between groups. A subset of patients was treated with intrathecal fentanyl and bupivacaine. No intrathecal granulomas occurred in this patient cohort.
  
  
  CONCLUSIONS
  This is the first clinical report demonstrating an association of hydromorphone with intrathecal granulomas, particularly at low doses and concentrations of hydromorphone. This study supports the notion that using low dose of IT opioids might not protect against ICTG development but that the level of exposure and type of opioid used in IT space might be highly correlated with ICTG development. Further research and recommendations related to chronic intrathecal opioid infusions are necessary to raise awareness of significant incidence of ICTG and development of tests to isolate patient populations at high risk.
authors: Case Western Reserve University, Cleveland, OH, USA.|Louis Stokes Veterans Administration Medical Center, Cleveland, OH, USA.
authors: I Elias
authors: IE
authors: Veizi
authors: Case Western Reserve University, Cleveland, OH, USA. Salim.hayek@uhhospitals.org.|University Hospitals Case Medical Center, Cleveland, OH, USA. Salim.hayek@uhhospitals.org.
authors: Salim M
authors: SM
authors: Hayek
authors: University Hospitals Case Medical Center, Cleveland, OH, USA.
authors: Michael
authors: M
authors: Hanes
authors: University Hospitals Case Medical Center, Cleveland, OH, USA.
authors: Ryan
authors: R
authors: Galica
authors: University Hospitals Case Medical Center, Cleveland, OH, USA.
authors: Sivakanth
authors: S
authors: Katta
authors: University of California, San Diego, La Jolla, CA, USA.
authors: Tony
authors: T
authors: Yaksh
mesh_terms: D000368:Aged; D002045:Bupivacaine / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006099:Granuloma / Q000000981:diagnostic imaging / Q000209:etiology*; D006801:Humans; D004091:Hydromorphone / Q000009:adverse effects*; D007278:Injections, Spinal / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000009:adverse effects*; D012189:Retrospective Studies; D013116:Spinal Cord / Q000000981:diagnostic imaging; D013997:Time Factors
chemical_list: D009294:Narcotics; D004091:Hydromorphone; D002045:Bupivacaine
keywords: Complication; fentanyl; granuloma; hydromorphone; inflammatory mass; intraspinal; intrathecal; pain pump