title: An in vivo canine study to assess granulomatous responses in the MedStream Programmable Infusion System (TM) and the SynchroMed II Infusion System®.
abstract: OBJECTIVE
  A rare, but consistently reported complication of intrathecal (IT) delivery of opioids via programmable implantable infusion pumps is aseptic granuloma formation around the tip of the IT catheter. In the current study, the incidence and severity of IT granuloma formation was assessed for the MedStream Programmable Infusion and SynchroMed II Infusion pumps when delivering saline, baclofen, or morphine at varying concentrations and daily doses.
  
  
  METHODS
  Randomized study with six groups: 1) MedStream with 0.9% saline; 2) SynchroMed II with 0.9% saline; 3) MedStream with morphine sulfate; 4) SynchroMed II with morphine sulfate; 5) MedStream with baclofen; or 6) SynchroMed II with baclofen. The groups receiving morphine received either low or high concentrations (6 or 12.5 mg/mL) delivered in rates resulting in low to high (1.25-12 mg/day) daily doses. Animals receiving baclofen began at low dose/low concentration and underwent stepwise increases in concentration and dose to a maximum of 2 mg/mL/day. Animals receiving saline received a constant flow rate through either a silicone or a polyurethane IT catheter.
  
  
  METHODS
  The study was set as in vivo laboratory experiment.
  
  
  METHODS
  52 (21-32 kg) canines.
  
  
  METHODS
  Delivering IT saline, baclofen, or morphine through SynchroMed II and MedStream Programmable Infusion pumps.
  
  
  METHODS
  The incidence and severity of IT catheter tip granuloma formation was assessed with paraffin-embedded spinal cord sections by a pathologist without knowledge of treatment and compared between drug type, drug concentration, daily dose, and pump type.
  
  
  RESULTS
  Granuloma formation occurred only in animals receiving morphine, with zero incidence in baclofen or saline infusion, regardless of catheter type. Granuloma incidence increased with increasing morphine concentration or daily dose (one [12.5%] low dose/low concentration, 3 [37.5%] low dose/high concentrations, 4 [50%] high dose/low concentration, and 7 [100%] high dose/high concentration). A granulomatous response to morphine was observed in 10 (63%) animals with SynchroMed II pumps and 5 (33%) animals with MedStream pumps, P = 0.156.
  
  
  CONCLUSIONS
  In this in vivo canine model of IT drug delivery, catheter tip granuloma formation was associated with higher concentrations and daily doses of morphine infusion while none were seen with baclofen or saline, and was not associated with catheter type. For both pumps, granulomas were only produced in the presence of morphine infusion. These results suggest that the MedStream Programmable Infusion System has a granuloma safety profile at least equivalent to that of the SynchroMed II pump.
authors.affiliation: Codman & Shurtleff, Inc., 325 Paramount Drive, Raynham, MA 02767, USA. amichae2@its.jnj.com
authors.forename: Aileen
authors.initials: A
authors.lastname: Michael
authors.forename: Elaine
authors.initials: E
authors.lastname: Buffen
authors.forename: Richard
authors.initials: R
authors.lastname: Rauck
authors.forename: William
authors.initials: W
authors.lastname: Anderson
authors.forename: Matthew
authors.initials: M
authors.lastname: McGirt
authors.forename: H Vince
authors.initials: HV
authors.lastname: Mendenhall
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002408:Catheters, Indwelling / Q000009:adverse effects*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006099:Granuloma / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D015918:Infusion Pumps, Implantable / Q000009:adverse effects*; D011897:Random Allocation
chemical_list: D000701:Analgesics, Opioid