Recommendations from the EXTRIP workgroup on extracorporeal treatment for baclofen poisoning

Abstract

Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation.

Keywords: baclofen; hemodialysis; overdose; pharmacokinetics; poisoning; toxicity.