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American Journal of Kidney Diseases

Muscle Relaxant Use Among Hemodialysis Patients: Prevalence, Clinical Indications, and Adverse Outcomes

Published:January 10, 2019DOI:https://doi.org/10.1053/j.ajkd.2018.11.008

      Rationale & Objective

      Muscle relaxants are often used to treat musculoskeletal pain or cramping, which are commonly experienced by hemodialysis patients. However, the extent to which muscle relaxants are prescribed in this population and the risks associated with their use have not been characterized.

      Study Design

      Observational cohort study.

      Setting & Participants

      140,899 Medicare-covered adults receiving hemodialysis in 2011, identified in the US Renal Data System.

      Exposure

      Time-varying muscle relaxant exposure.

      Outcomes

      Primary outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, or fracture. Secondary outcomes were death and composites of death with each of the primary outcomes.

      Analytical Approach

      Multivariable Cox regression analysis.

      Results

      10% of patients received muscle relaxants in 2011. 11%, 6%, 3%, and 13% had an episode of altered mental status, fall, fracture, and death, respectively. Muscle relaxant use was associated with higher risk for altered mental status (HR, 1.39; 95% CI, 1.29-1.51) and fall (HR, 1.18; 95% CI, 1.05-1.33) compared to no use. Muscle relaxant use was not statistically significantly associated with higher risk for fracture (HR, 1.17; 95% CI, 0.98-1.39). Muscle relaxant use was associated with lower hazard of death (HR, 0.85; 95% CI, 0.76-0.94). However, hazards were higher for altered mental status or death (HR, 1.17; 95% CI, 1.10-1.25), fall or death (HR, 1.14; 95% CI, 1.06-1.22), and fracture or death (HR, 1.10; 95% CI, 1.01-1.20).

      Limitations

      A causal association between muscle relaxant use and outcomes cannot be inferred, and residual confounding cannot be excluded. Exposure and outcomes were ascertained using administrative claims.

      Conclusions

      Muscle relaxant use was common in hemodialysis patients and associated with altered mental status and falls. We could not rule out a clinically meaningful association between muscle relaxant use and fracture. The lower risk for death with muscle relaxants may have been the result of residual confounding. Future research to define the appropriate use of muscle relaxants in this population is warranted.

      Index Words

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      References

        • Dillon C.
        • Paulose-Ram R.
        • Hirsch R.
        • Gu Q.
        Skeletal muscle relaxant use in the United States: data from the Third National Health and Nutrition Examination Survey (NHANES III).
        Spine. 2004; 29: 892-896
        • Kantor E.D.
        • Rehm C.D.
        • Haas J.S.
        • Chan A.T.
        • Giovannucci E.L.
        Trends in prescription drug use among adults in the United States from 1999-2012.
        JAMA. 2015; 314: 1818-1831
        • Chou R.
        • Peterson K.
        • Helfand M.
        Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review.
        J Pain Symptom Manage. 2004; 28: 140-175
        • See S.
        • Ginzburg R.
        Skeletal muscle relaxants.
        Pharmacotherapy. 2008; 28: 207-213
        • Toth P.P.
        • Urtis J.
        Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone.
        Clin Ther. 2004; 26: 1355-1367
        • American Geriatrics Society 2015 Beers Criteria Update Expert Panel
        American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults.
        J Am Geriatr Soc. 2015; 63: 2227-2246
        • Spence M.M.
        • Shin P.J.
        • Lee E.A.
        • Gibbs N.E.
        Risk of injury associated with skeletal muscle relaxant use in older adults.
        Ann Pharmacother. 2013; 47: 993-998
        • Golden A.G.
        • Ma Q.
        • Nair V.
        • Florez H.J.
        • Roos B.A.
        Risk for fractures with centrally acting muscle relaxants: an analysis of a national Medicare Advantage claims database.
        Ann Pharmacother. 2010; 44: 1369-1375
        • Brkovic T.
        • Burilovic E.
        • Puljak L.
        Prevalence and severity of pain in adult end-stage renal disease patients on chronic intermittent hemodialysis: a systematic review.
        Patient Prefer Adherence. 2016; 10: 1131-1150
        • Cook W.L.
        • Tomlinson G.
        • Donaldson M.
        • et al.
        Falls and fall-related injuries in older dialysis patients.
        Clin J Am Soc Nephrol. 2006; 1: 1197-1204
        • McAdams-DeMarco M.
        • Suresh S.
        • Law A.
        • et al.
        Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study.
        BMC Nephrol. 2013; 14: 224
        • Goldsmith D.
        • Kothawala P.
        • Chalian A.
        • Bernal M.
        • Robbins S.
        • Covic A.
        Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of fracture and need for parathyroidectomy in CKD.
        Am J Kidney Dis. 2009; 53: 1002-1013
        • Wolf E.
        • Kothari N.R.
        • Roberts J.K.
        • Sparks M.A.
        Baclofen toxicity in kidney disease.
        Am J Kidney Dis. 2018; 71: 275-280
      1. Methocarbamol (tablet) [package insert]. Endo Pharmaceuticals, Inc, Malvern, PA2016
        • El-Husseini A.
        • Sabucedo A.
        • Lamarche J.
        • Courville C.
        • Peguero A.
        Baclofen toxicity in patients with advanced nephropathy: proposal for new labeling.
        Am J Nephrol. 2011; 34: 491-495
        • Chen K.S.
        • Bullard M.J.
        • Chien Y.Y.
        • Lee S.Y.
        Baclofen toxicity in patients with severely impaired renal function.
        Ann Pharmacother. 1997; 31: 1315-1320
        • Niehaus M.T.
        • Elliott N.C.
        • Katz K.D.
        Baclofen toxicity causing acute, reversible dyskinesia.
        J Med Toxicol. 2016; 12: 406-407
        • Wu V.
        • Lin S.
        • Lin S.
        • Fang C.
        Treatment of baclofen overdose by haemodialysis: a pharmacokinetic study.
        Nephrol Dial Transplant. 2005; 20: 441-443
        • Lee J.
        • Shin H.S.
        • Jung Y.S.
        • Rim H.
        Two cases of baclofen-induced encephalopathy in hemodialysis and peritoneal dialysis patients.
        Ren Fail. 2013; 35: 860-862
        • Radhakrishnan H.
        Baclofen-induced neurotoxicity in a patient with end-stage renal disease.
        Saudi J Kidney Dis Transpl. 2016; 27: 595-597
        • Justo-Ávila P.
        • Fernández-Antuña L.
        • Compte-Jove M.T.
        • Gállego-Gil C.
        Baclofen neurotoxicity in a patient with end-stage chronic renal failure.
        Nefrologia. 2014; 34: 536-538
        • Ijaz M.
        • Tariq H.
        • Kashif M.
        • Marquez J.G.
        Encephalopathy and hypotonia due to baclofen toxicity in a patient with end-stage renal disease.
        Am J Case Rep. 2015; 16: 232-235
        • Meillier A.
        • Heller C.
        • Patel S.
        Baclofen-induced encephalopathy in end stage renal disease.
        Case Rep Med. 2015; 2015: 1-3
        • Mousavi S.S.B.
        • Mousavi M.B.
        • Motemednia F.
        Baclofen-induced encephalopathy in patient with end stage renal disease: two case reports.
        Indian J Nephrol. 2012; 22: 210-212
        • Porter L.M.
        • Merrick S.S.
        • Katz K.D.
        Baclofen toxicity in a patient with hemodialysis-dependent end-stage renal disease.
        J Emerg Med. 2017; 52: e99-e100
        • Quintana L.F.
        • Lladó A.
        • Butjosa M.
        • Santamaría J.
        • Torras A.
        • Poch E.
        Baclofen-associated encephalopathy in a hemodialysis patient with hiccups.
        Nefrologia. 2006; 26: 486-488
        • Wu C.C.
        • Lin S.H.
        A possible baclofen-induced neurotoxicity in a CAPD patient who recovered with long-duration hemodialysis.
        Perit Dial Int. 2002; 22: 279-280
        • Roberts J.K.
        • Westphal S.
        • Sparks M.A.
        Iatrogenic baclofen neurotoxicity in ESRD: recognition and management.
        Semin Dial. 2015; 28: 525-529
        • Ishida J.H.
        • McCulloch C.E.
        • Steinman M.A.
        • Grimes B.A.
        • Johansen K.L.
        Opioid analgesics and adverse outcomes among hemodialysis patients.
        Clin J Am Soc Nephrol. 2018; 13: 746-753
        • Andrade S.E.
        • Kahler K.H.
        • Frech F.
        • Chan K.A.
        Methods for evaluation of medication adherence and persistence using automated databases.
        Pharmacoepidemiol Drug Saf. 2006; 15 (discussion 575-577): 565-574
      2. Baclofen (tablet) [package insert]. Aspen Pharma Pty Ltd, St. Leonards, NSW, Australia2009
      3. Cyclobenzaprine (tablet) [package insert]. McNeil-PPC, Inc, Fort Washington, PA2013
      4. Dantrolene (capsule) [package insert]. JHP Pharmaceuticals, LLC, Rochester, MI2011
      5. Tizanidine (tablet, capsule) [package insert]. Elan Pharma Int, Ltd, Athlone, Ireland2006
      6. Carisoprodol (tablet) [package insert]. Meda Pharmaceuticals Inc, Somerset, NJ2009
      7. Metaxalone (tablet) [package insert]. Mallinckrodt Inc, Hobart, NY2008
      8. Chlorzoxaone (tablet) [package insert]. Vertical Pharmaceuticals, LLC, Bridgewater, NJ2017
      9. Orphenadrine citrate (tablet, injection) [package insert]. 3M Pharmaceuticals, Northridge, CA2006
        • See S.
        • Ginzburg R.
        Choosing a skeletal muscle relaxant.
        Am Fam Physician. 2008; 78: 365-370
      10. US Renal Data System Coordinating Center. USRDS 2013 researcher's guide to the USRDS database. 2013. https://www.usrds.org/2013/rg/A_intro_sec_1_13.pdf. Accessed April 19, 2018.

        • Nair S.S.
        • Lenihan C.R.
        • Montez-Rath M.
        • Lowenberg D.W.
        • Chertow G.M.
        • Winkelmayer W.C.
        Temporal trends in the incidence, treatment and outcomes of hip fracture after first kidney transplantation in the United States.
        Am J Transplant. 2014; 14: 943-951
        • Saran R.
        • Robinson B.
        • Abbott K.C.
        • et al.
        US Renal Data System 2017 Annual Data Report: epidemiology of kidney disease in the United States.
        Am J Kidney Dis. 2018; 71: S1-S672
        • Collins A.J.
        • Foley R.N.
        • Chavers B.
        • et al.
        US Renal Data System 2013 annual data report.
        Am J Kidney Dis. 2014; 63: e1-e420
        • Yusuf A.A.
        • Howell B.L.
        • Powers C.A.
        • St Peter W.L.
        Utilization and costs of medications associated with CKD mineral and bone disorder in dialysis patients enrolled in Medicare Part D.
        Am J Kidney Dis. 2014; 64: 770-780
        • Davison S.N.
        The prevalence and management of chronic pain in end-stage renal disease.
        J Palliat Med. 2007; 10: 1277-1287
        • Nahin R.L.
        Estimates of pain prevalence and severity in adults: United States, 2012.
        J Pain. 2015; 16: 769-780
        • Vestergaard P.
        • Rejnmark L.
        • Mosekilde L.
        Fracture risk associated with the use of morphine and opiates.
        J Intern Med. 2006; 260: 76-87
        • Jamal S.A.
        • Leiter R.E.
        • Jassal V.
        • Hamilton C.J.
        • Bauer D.C.
        Impaired muscle strength is associated with fractures in hemodialysis patients.
        Osteoporos Int. 2006; 17: 1390-1397
        • Vlavonou R.
        • Perreault M.
        • Barrière O.
        • et al.
        Pharmacokinetic characterization of baclofen in patients with chronic kidney disease: dose adjustment recommendations.
        J Clin Pharmacol. 2014; 54: 584-592
        • Centers for Medicare & Medicaid Services 2012
        Transition to Part D coverage of benzodiazepines and barbiturates beginning in 2013.