Association Between Baclofen and Respiratory Depression in Patients With Chronic Kidney Disease
2021; Wiley; Volume: 61; Issue: 6 Linguagem: Inglês
10.1002/jcph.1843
ISSN1552-4604
Autores Tópico(s)Healthcare Decision-Making and Restraints
ResumoThe Journal of Clinical PharmacologyVolume 61, Issue 6 p. 836-837 Letter to the EditorFree Access Association Between Baclofen and Respiratory Depression in Patients With Chronic Kidney Disease Satoru Mitsuboshi PhD, Corresponding Author Satoru Mitsuboshi PhD [email protected] orcid.org/0000-0002-6244-1253 Department of Pharmacy, Kaetsu Hospital, Niigata, Japan Corresponding Author: Satoru Mitsuboshi, PhD, 1459-1 Higashikanazawa, Akiha-ku, Niigata-shi, Niigata 956-0814, Japan Email: [email protected]Search for more papers by this author Satoru Mitsuboshi PhD, Corresponding Author Satoru Mitsuboshi PhD [email protected] orcid.org/0000-0002-6244-1253 Department of Pharmacy, Kaetsu Hospital, Niigata, Japan Corresponding Author: Satoru Mitsuboshi, PhD, 1459-1 Higashikanazawa, Akiha-ku, Niigata-shi, Niigata 956-0814, Japan Email: [email protected]Search for more papers by this author First published: 24 February 2021 https://doi.org/10.1002/jcph.1843Citations: 3AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Baclofen is used to manage spasticity and treat alcohol use disorder.1, 2 However, because baclofen is eliminated mainly via the kidneys,3 users with chronic kidney disease (CKD) have a high risk of adverse events, most notably encephalopathy.4 Respiratory depression is another serious adverse event caused by baclofen, and a case report suggested that baclofen caused respiratory depression in a patient with CKD.5-7 Although the risk of respiratory depression caused by baclofen has not been quantified, drug-induced respiratory depression is generally recognized as a serious adverse event that may even lead to death.8 In this study, data from the Japanese Adverse Drug Event Report (JADER) was used to evaluate whether baclofen increases the risk of respiratory depression in patients with CKD. This was an observational study using anonymized patient data recorded in JADER, and thus institutional review board review and approval was not required. Data recorded from April 2004 to May 2020 were downloaded from the Pharmaceuticals and Medical Devices Agency website (http://www.pmda.go.jp/) on November 3, 2020. Inclusion criteria were all oral baclofen and eperisone users regardless of whether the data reporter suspected a possible adverse event. Eperisone was set as the control because it is used to manage spasticity. Exclusion criteria were patients who used both baclofen and eperisone. Patients with missing data on sex, age, or body weight were also excluded. Respiratory depression was defined as reporting respiratory failure or respiratory depression. CKD was defined as reporting a comorbidity of CKD, kidney failure, and use of dialysis. Multiple logistic regression analysis was used to assess whether use of baclofen in patients with CKD is a risk factor for respiratory depression. Sex, age, body weight, and presence of CKD were considered in the analysis. Modeling was based on a complete-case analysis. Statistical analysis was performed using R version 3.4.1 (R Foundation for Statistical Computing, Vienna, Austria). In total, 351 baclofen users and 1241 eperisone users were identified. Baclofen users with CKD had a significantly increased risk of respiratory depression (odds ratio, 8.03; 95% confidence interval, 1.88-34.19; P = .02); no increased risk of respiratory depression was observed in eperisone users with CKD (Table S1). In baclofen users, respiratory depression was significantly associated with only the presence of CKD (odds ratio, 7.51; 95% confidence interval, 1.47-38.40; P = .02; Table 1). Table 1. Multivariate Logistic Analysis of Factors Associated With Respiratory Depression in Baclofen Users Odds Ratio (95% Confidence Interval) Fatal Events/Total, n (%) Crude Adjusted P * Female sex 1/147 (0.7) 1 [Reference] 1 [Reference] Male sex 6/204 (2.9) 4.32 (0.53-35.53) 5.11 (0.57-46.20) .15 Age 40 kg 2/201 (1.0) 1 [Reference] 1 [Reference] Body weight ≤40 kg 5/150 (3.3) 3.35 (0.66-17.03) 4.90 (0.83-28.80) .08 Without CKD 4/321 (1.2) 1 [Reference] 1 [Reference] With CKD 3/30 (10.0) 8.03 (1.88-34.19) 7.51 (1.47-38.40) .02 CKD, chronic kidney disease. * P values were calculated by multiple logistic regression analysis. To the author's knowledge, this is the first report to show increased risk of respiratory depression in baclofen users with CKD. Baclofen is eliminated mainly via the kidneys, and baclofen clearance is equal to creatinine clearance.9 Therefore, baclofen users with CKD may have an increased risk of respiratory depression due to the increased serum concentration of baclofen. A limitation of this study is potential reporting bias in JADER, and the results showed increased frequencies of only certain factors. Respiratory depression is a rare adverse event; therefore, a clinical trial with a large sample size would be needed to assess the risk factors. In conclusion, health care providers should recognize that baclofen users with CKD are at risk for potential respiratory depression. Conflicts of Interest The author declares no conflicts of interest. Funding No external funding was received to conduct this study. Supporting Information Filename Description jcph1843-sup-0001-TableS1.docx22.9 KB Supplementary information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Ertzgaard P, Campo C, Calabrese A. Efficacy and safety of oral baclofen in the management of spasticity: a rationale for intrathecal baclofen. J Rehabil Med. 2017; 49(3): 193- 203. 2Andrade C. Individualized, high-dose baclofen for reduction in alcohol intake in persons with high levels of consumption. J Clin Psychiatry. 2020; 81(4):20f13606. 3Vlavonou R, Perreault MM, Barrière O, et al. Pharmacokinetic characterization of baclofen in patients with chronic kidney disease: dose adjustment recommendations. J Clin Pharmacol. 2014; 54(5): 584- 592. 4Muanda FT, Weir MA, Bathini L, et al. Association of baclofen with encephalopathy in patients with chronic kidney disease. JAMA. 2019; 322(20): 1987- 1995. 5Chen KS, Bullard MJ, Chien YY, Lee SY. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother. 1997; 31(11): 1315- 1320. 6Aisen ML, Dietz M, McDowell F, Kutt H. Baclofen toxicity in a patient with subclinical renal insufficiency. Arch Phys Med Rehabil. 1994; 75(1): 109- 111. 7Roberts JK, Westphal S, Sparks MA. Iatrogenic baclofen neurotoxicity in ESRD: recognition and management. Semin Dial. 2015; 28(5): 525- 529. 8Ayad S, Khanna AK, Iqbal SU, Singla N. Characterisation and monitoring of postoperative respiratory depression: current approaches and future considerations. Br J Anaesth. 2019; 123(3): 378- 391. 9Wuis EW, Dirks MJM, Termond EFS, Vree TB, Van der Kleijn E. Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol. 1989; 37(2): 181- 184. 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