Adverse Events and Complications Associated With Intrathecal Drug Delivery Systems: Insights From the Manufacturer and User Facility Device Experience (MAUDE) Database

Abstract

Background: Modern intrathecal drug delivery systems (IDDS) are technologically advanced to deliver medication through various automated and patient-controlled programs. They also are associated with unique complications ranging from post-operative complications, medication-related adverse events (AE), device malfunction, to refill associated AE.

Objectives: To systematically analyze real-world complications and AE reported on the Food and Drug Administration's Manufacturer and User Facility Device Experience database (MAUDE) associated with IDDS among patients predominantly with chronic pain disorders.

Materials and methods: MAUDE database was sampled for a month four times a year during the study period, February 2018 to February 2019. The database was resampled every six months till August 2020 to evaluate for any additional reported cases during the index months. The two FDA approved IDDS, were included. AE were broadly classified into causes related to catheter malfunction, pump malfunction, biologic, and medication-related AE.

Results: A total of 1001 reports were included in the final analysis. The top three reasons for adverse report are infection/erosion (15.7%, n = 157), motor stall (12.4%, n = 125) and adverse medication reactions (11.8%, n = 119), respectively. There were five deaths among patients with IDDS. Epidural hematoma (n = 3) after IDDS surgery resulted in a death and residual neurological deficits after surgical evacuation. Programming errors, medication concentration discrepancy, and failure to turn on the pump after reprogramming are various preventable causes of medication-related IDDS AEs.

Conclusions: Analysis of AE associated with IDDS from the MAUDE database provided a real-world perspective different from reported registry complications. Awareness and vigilance of preventable IDDS-related complications is the first step toward mitigating risks to provide safe and effective intrathecal drug delivery for chronic pain management.

Keywords: Chronic pain; FDA; complications; implantable devices; intrathecal drug delivery system.

Figure 1.

Summary of the study design. The database was resampled every six months until August 2020 to evaluate any additional cases during the index months. SynchroMed (Medtronic) and Prometra (Flowonix).

Figure 2.

CONSORT style flow chart of cohort derivation. MAUDE, Manufacturer and User Facility Device Experience.

Figure 3.

The figure illustrates AE from various studies. Panel a shows how we would like to make inferences to a target population from a study population that was performed on a source population that can be enumerated. Panels b and c reveal case reports and case series from patients with IDDS. Notice that they often highlight cases with more severe AE (red circles) than milder AE (green circles). Panel d shows AE from clinical registries, which are a subset of all the IDDS patients. There may be a selection bias associated with clinical registries. Panel e shows AE from clinical trials. Often the AE rates are low and are not representative of the real-world practice. Panel f shows AE from passive surveillance systems like MAUDE. They represent real-world data, and the limitations are concerns with follow-up and lack of standardization of data reporting.