Case Published: November 2021
Diagnosis: Baclofen toxicity in a patient with end stage kidney disease (ESKD)
Case Summary: Well done! Short case – with a very important teaching point for patients with ESKD. Altered mental status (AMS) has a wide differential diagnosis in any patient – drug intoxication, electrolyte derangements, infection, metabolic encephalopathy, etc. Based on the history and physical examination of this patient, it is likely that this patient has altered mental status due to impaired kidney clearance of baclofen (it’s primarily excreted by the kidneys!) – a well described toxicity of this commonly used medication that is generally described as a “muscle relaxant” and prescribed for pain, muscle spasms/stiffness. While our patient has some mild lab abnormalities (mild anemia, mild hyponatremia, mild hyperkalemia), they are unlikely to lead to AMS in this patient. In a patient receiving chronic dialysis, uremic encephalopathy is unlikely as the last treatment was 3 days ago.
Back to the culprit here, baclofen. Baclofen is a highly prescribed drug, the 125th most prescribed drug in the United States in 2019! It’s mechanism of action: a γ-aminobutyric acid (GABA) receptor agonist. Recently, baclofen has received considerable attention for its association with altered mental status, coma, and sedation in patients with impaired kidney function (advanced chronic kidney disease or requiring dialysis). A 2020 study of “baclofen-users” on dialysis in Canada found that hospitalization with encephalopathy occurred in about 7% of users (compared to 0.1% in non-users) and that hospitalization occurred 3 days after baclofen dispensing (median time). A 2021 analysis of another cohort found that older adults with chronic kidney disease who started baclofen at ≥20 mg/day compared to <20 mg/day were at higher risk for hospitalization with a fall and hypotension (our patient here was prescribed 20 mg).
So…what do we do? Stop the baclofen! Since the problem here is impaired kidney function, should we perform hemodialysis to remove the drug? Baclofen actually is a fairly “dialyzable” drug – given it’s relatively small molecular weight, low volume of distribution, and low binding to protein. Recent recommendations from the EXTRIP workgroup on extracorporeal treatment (ECT) for baclofen poisoning suggest that “in patients presenting with toxicity from therapeutic baclofen in kidney impairment…performing ECTR in the presence of an associated coma requiring mechanical ventilation (weak recommendation, very low quality of evidence).” Further, they suggest intermittent hemodialysis rather than peritoneal dialysis or continuous kidney replacement therapy (CKRT). Finally, they recommend “stopping ECTR based on clinical improvement (strong recommendation, very low quality of evidence).” Of note, the group does not recommend dialysis for patients with normal kidney function and acute baclofen poisoning, given the short elimination half-life in these patients.
In summary, avoid baclofen (particularly doses ≥ 20 mg/day) in patients with CKD and ESKD! Want to raise awareness for this problem by wearing one of the pins below? Reach out to Dr. Matthew Sparks. Check out these additional references on baclofen toxicity in patients with kidney disease as well as a post from our friends at the Renal Fellow Network.
Case 52 Index