Muscle Relaxant Tied to Severe Confusion in CKD Patients

WASHINGTON -- Patients with chronic kidney disease (CKD) prescribed baclofen (Lioresal) were at an increased risk of being hospitalized with delirium, disorientation, or other manifestations of encephalopathy, a Canadian researcher said here.

Among about 15,000 patients with lower kidney function (<30% eGFR) those prescribed ≥20 mg of baclofen per day in the outpatient setting were at a significantly higher risk of being hospitalized for encephalopathy in the subsequent 30 days than patients prescribed <20 mg per day (weighted rate ratio 3.54, 95% CI 2.24-5.59), reported Amit Garg, MD, PhD, of Western University in Ontario.

When comparing patients with low kidney function who were and were not prescribed the muscle relaxant, a baclofen prescription was associated with an increased risk of encephalopathy at both the high (RR, 19.8, 95% CI 14.0-28.00) and low (RR 5.90, 95% CI 3.59-0.70) doses, Garg said at the American Society of Nephrology annual meeting. The findings were simultaneously published in JAMA.

"Overall, if you look at the pharmacokinetics of this drug ... it is almost entirely filtered by the kidney, so it makes good biological sense that if your kidney function is not working well, the drug levels would accumulate, and you would be at a high risk of toxicity," Garg told MedPage Today. "Now, we're seeing this large population-based study corroborating that."

In 2016, there were >8 million baclofen prescriptions in the U.S. CKD has been estimated to affect between 10%-20% of adults across the country. Garg said he would like to see updates to computer systems, warning labels, and physician education resources to include information about this risk. Providers should also be aware of this symptom when considering prescribing baclofen to patients who are older or who have limited kidney function, he said.

"Patients should never stop their drug without talking to their primary care providers, and I wouldn't want patients to be alarmed about this," Garg said. "But having said that, we think this is highlighting an important consideration."

Garg and colleagues linked prescription and patient data from the Institute for Clinical Evaluative Sciences (ICES) database to hospital admission data from 2007-2018. Patients, ages ≥66, with eGFR <60 mL/min/1.73m² who were not on dialysis were included.

In total, 15,942 individuals (median age 77; 61% female) were prescribed baclofen, typically by primary care providers (86%). Patients in both the baclofen low and high dose groups were similar across 98% of characteristics measured, the authors noted.

Two-thirds of the group had an eGFR between 45 and 59 mL/min/1.73 m², while 27% had eGFRs between 30 and 45 mL/min/1.73 m², and 7% had eGFRs <30 mL/min/1.73 m².

Overall, the proportion of patients hospitalized after being prescribed baclofen was small in both the high (1.11%) and low (0.42%) dose groups, though typically the hospitalization occurred within 3 days. Patients with lower kidney function were also at an higher risk for encephalopathy than those with higher kidney function.

Specifically, the higher versus lower dose of baclofen was associated with an increased risk of hospitalization due to delirium (RR 3.48, 95% CI 1.88-6.45) and all-cause hospitalization (RR 1.49, 95% CI 1.29-1.72), but not all-cause mortality (RR 0.96, 95% CI 0.68-1.35), the authors reported.

Garg and colleagues cautioned against inferring a causal association and noted the observational nature of the study was a limitation. Also, while the rate at which baclofen was prescribed was known, it was not possible to determine how many patients were actually taking their prescriptions in the study. They also relied on International Classification of Diseases (ICD) codes to classify hospitalizations, so some cases of encephalopathy may have been missed. Lastly, serum concentrations were unavailable, so the causal mechanisms by which baclofen may be affecting hospitalizations are speculative, they added.

"This study was not designed to answer the question of whether the potential benefits of baclofen outweigh its risks, and clinicians will need to judge this on a patient-by-patient basis," the authors concluded.

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