Photo courtesy of Matthew Sparks @Nephro_Sparks

Most practicing nephrologists have seen cases of baclofen toxicity in patients on dialysis; in severe cases, this can even mimic brain death. Some nephrologists on Twitter (eg @Nephro_Sparks) have taken up the call to educate clinicians about the use of medications such as baclofen in patients on dialysis. An article by Mina et al published in AJKD examines the association between muscle relaxant use and altered mental status. AJKD Social Media Editor Timothy Yau (AJKDBlog) interviews authors Diana Mina and Julie Ishida (Authors) on their research:

AJKDBlog: Most nephrology clinicians have had some experience of seeing patients with altered mental status who improved after dialyzing off these medications. What were the main reasons your group chose to study this problem?

Authors: As clinicians, we know that patients on dialysis commonly complain of pain and that many are prescribed muscle relaxants. While there are many case reports and a call to educate clinicians about the use of baclofen in patients with renal failure, there has been a lack of epidemiologic data regarding the safety of these medications in this unique population.

AJKDBlog: Your article looked at several medications, some of which are common (baclofen, carisoprodol, cyclobenzaprine) and others less so (dantrolene, chlorzoxazone). In your research, for which disorders were these drugs being used?

Authors: Using data from the United States Renal Data System (USRDS), we determined diagnoses associated with muscle relaxant use based on ICD-9-CM codes among patients receiving hemodialysis. We found that the most common indication was musculoskeletal pain other than neck or back pain, followed by back pain, muscle spasticity, neck pain, and headache. Less common indications were fibromyalgia, cramps, cerebral palsy, and multiple sclerosis.

AJKDBlog: What outcome did you study, and how did you decide to choose this for your study?

Authors: We wanted to study outcomes for which it was plausible that there could an association with muscle relaxants and that were clinically meaningful to patients. Muscle relaxants have been associated with altered mental status, fall, and fracture in the general population, and patients receiving hemodialysis may be at particularly high risk of these unfavorable outcomes.

AJKDBlog: What percentage of patients in the USRDS were on these medications? Did this number surprise you?

Authors: We found that 10% of dialysis patients received a muscle relaxant prescription in 2011. Based on clinical experience, this was not surprising.

AJKDBlog: Can you summarize what you found with regards to muscle relaxant exposure?

Authors: Muscle relaxant use was associated with a higher risk of altered mental status and fall compared to no muscle relaxant use. Although the association between muscle relaxant use and fracture did not reach statistical significance, we could not rule out a clinically meaningful association.  Cyclobenzaprine was the most commonly prescribed muscle relaxant, and we performed additional analyses focused on this medication. Cyclobenzaprine was associated with a higher risk of altered mental status (Adjusted HR 1.24) and fracture (Adjusted HR 1.31):

Table 2 from Mina et al, AJKD, © National Kidney Foundation.

AJKDBlog: Did you find a difference between the antispasmodic (e.g. cyclobenzaprine) and the antispastic (e.g. baclofen) classes of these drugs? Is the distinction important?

Authors: Cyclobenzaprine was the only muscle relaxant with sufficient prevalence to warrant an individual analysis, so we were unable to directly compare associations between different classes of muscle relaxants. Among patients receiving hemodialysis, a key factor to consider is the degree of renal excretion. Because baclofen relies on intact kidney function for clearance, not surprisingly, most case reports about muscle relaxants in renal failure have described the harmful effects of baclofen. However, in our study, even cyclobenzaprine, which is extensively hepatically metabolized prior to renal excretion, was associated with adverse outcomes. So regardless of mechanism of action, it appears that muscle relaxants are associated with harms among patients receiving hemodialysis.

AJKDBlog: What’s your big takeaway point for our readers?

Authors: Providing the best care to our patients is not limited to providing the best dialysis prescription. Pain is common among our patients and the risks and benefits of each treatment we provide must be carefully considered for each patient. This is the first study to use epidemiologic data from dialysis patients in the US to assess whether muscle relaxants are associated with harm. Based on our data, we cannot make definitive recommendations about the use of muscle relaxants among hemodialysis patients, and further research is required in this area. Obviously, individual patients need to be counseled and monitored appropriately, and clinicians need to be aware of the potential adverse effects.

AJKDBlog: Thanks to both of you for taking part in this interview!

Follow Diana Mina @DiMiRenalMD 

To view Mina et al (subscription required), please visit AJKD.org.

Title: Muscle Relaxant Use Among Hemodialysis Patients: Prevalence, Clinical Indications, and Adverse Outcomes
Authors: D. Mina, K.L. Johansen, C.E. McCulloch, M.A. Steinman, B.A. Grimes, and J.H. Ishida
DOI: 10.1053/j.ajkd.2018.11.008