Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • ASN Meeting Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
    • Reprint Information
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Reprint Information
    • Subscriptions
    • Feedback
  • ASN Kidney News
  • Other
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • ASN Meeting Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
    • Reprint Information
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Reprint Information
    • Subscriptions
    • Feedback
  • ASN Kidney News
  • Visit ASN on Facebook
  • Follow CJASN on Twitter
  • CJASN RSS
  • Community Forum
Original ArticlesMaintenance Dialysis
Open Access

Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis

Abimereki D. Muzaale, Matthew Daubresse, Sunjae Bae, Nadia M. Chu, Krista L. Lentine, Dorry L. Segev and Mara McAdams-DeMarco
CJASN June 2020, 15 (6) 794-804; DOI: https://doi.org/10.2215/CJN.13341019
Abimereki D. Muzaale
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew Daubresse
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sunjae Bae
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nadia M. Chu
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Krista L. Lentine
3Department of Medicine, St. Louis University School of Medicine, St. Louis, Missouri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dorry L. Segev
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dorry L. Segev
Mara McAdams-DeMarco
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mara McAdams-DeMarco
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • Figure1
    • Download figure
    • Open in new tab
    • Download powerpoint
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    Sixty-nine thousand, three hundred sixty-eight adults initiating hemodialysis between 2013 and 2014 were selected to be in the study sample. The dialysis initiation cohort was restricted to United States citizens aged 18 years old and older. MPAB, medicare part A and B; MPO, mediare primary, other.

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2.

    Benzodiazepine dispensing differed by geographic region among patients inititiating hemodialysis (n=69,368) between 2013 and 2014.

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3.

    Benzodiazepine dispensing barely changed over time among patients inititiating hemodialysis (n=69,368) between 2013 and 2014. Rates by quarter (Q) are presented as lorazepam milligram equivalent (LME) per 100 person-days.

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4.

    The cumulative incidence of time to first short-acting benzodiazepine prescription dispensed among patients initiating hemodialysis (n=69,368) between 2013 and 2014 differed by race and sex. (A) Cumulative incidence of short-acting benzodiazepine. Approximately 18.1% of white women, 12.5% of white men, 9.5% of nonwhite women, and 6.1% of nonwhite men had used a short-acting benzodiazepine within 6 months of initiating dialysis. (B) Cumulative incidence of long-acting benzodiazepine. Approximately 5.1% of white women, 3.4% of white men, 2.3% of nonwhite women, and 1.8% of nonwhite men had used a long-acting benzodiazepine within 6 months of initiating dialysis.

Tables

  • Figures
  • Additional Files
    • View popup
    Table 1.

    Characteristics of patients who initiated dialysis (n=69,368) between January 2013 and December 2014 by benzodiazepine dispensing within 6 months of initiation

    CharacteristicBenzodiazepine within 6 mo, n=11,289No Benzodiazepine within 6 mo, n=58,079
    Age, yr, median [IQR]68 [59–77]67 [56–76]
    BMI, kg/m2, median [IQR]28 [24–34]28 [24–34]
    Women, %5444
    White, %8065
    Dialysis initiation in 2013, %5957
    Opioids, %7656
    Neuropathic pain medication, %
     Any6849
     Gabapentin2618
    Antidepressant, %5629
    CNS depressant, %3718
    Comorbidity, %
     Diabetes5860
     Cardiovascular disease5752
     Peripheral vascular disease1411
     Hypertension8889
     COPD1610
     Tobacco use86
     Cancer87
     Drug use32
     Inability to ambulate2016
     Institutionalized139
     No comorbidity12
    Cause of kidney failure, %
     Diabetes4749
     Hypertensive kidney disease3132
     GN66
     Other1613
    Dual eligible, %4746
    Employment status, %
     Unemployed1926
     Full time12
     Part time12
     Retired4642
     Disabled2924
     Other34
    • Medications were ascertained at any point during follow-up. IQR, interquartile range; BMI, body mass index; CNS, central nervous system; COPD, chronic obstructive pulmonary disease.

    • View popup
    Table 2.

    Factors associated with short-acting and long-acting benzodiazepines among adults initiating hemodialysis (n=69,368) between 2013 and 2014

    FactorBenzodiazepine
    Short ActingLong Acting
    aHR (95% CI)P ValueaHR (95% CI)P Value
    Age, per 10-yr older1.05 (1.03 to 1.07)<0.0010.90 (0.87 to 0.93)<0.001
    Women1.32 (1.27 to 1.37)<0.0011.35 (1.26 to 1.45)<0.001
    White1.73 (1.65 to 1.82)<0.0011.74 (1.59 to 1.89)<0.001
    Opioids1.66 (1.59 to 1.74)<0.0011.11 (1.03 to 1.20)0.01
    Antidepressant1.89 (1.81 to 1.96)<0.0011.59 (1.47 to 1.71)<0.001
    CNS depressant1.73 (1.66 to 1.80)<0.0011.69 (1.56 to 1.82)<0.001
    Year of dialysis initiation
     2013 versus 20141.11 (1.07 to 1.16)<0.0011.30 (1.21 to 1.40)<0.001
    BMI, per 10-kg/m2 higher0.95 (0.92 to 0.97)<0.0010.97 (0.93 to 1.02)0.24
    Comorbidity
     Diabetes0.92 (0.88 to 0.97)0.0030.99 (0.90 to 1.08)0.76
     Cardiovascular disease1.06 (1.02 to 1.10)0.0090.95 (0.88 to 1.03)0.22
     Peripheral vascular disease1.03 (0.98 to 1.09)0.251.09 (0.98 to 1.21)0.13
     Hypertension0.97 (0.91 to 1.03)0.270.99 (0.88 to 1.12)0.90
     COPD1.20 (1.13 to 1.27)<0.0011.28 (1.16 to 1.43)<0.001
     Tobacco use1.09 (1.01 to 1.17)0.021.19 (1.05 to 1.35)0.01
     Cancer1.10 (1.02 to 1.18)0.011.02 (0.88 to 1.17)0.80
     Drug use1.10 (0.97 to 1.24)0.141.03 (0.83 to 1.28)0.75
     Inability to ambulate1.09 (1.04 to 1.15)0.0021.11 (1.00 to 1.23)0.06
     Institutionalized1.08 (1.01 to 1.15)0.030.90 (0.79 to 1.02)0.11
     No comorbidity0.87 (0.73 to 1.04)0.130.91 (0.68 to 1.23)0.56
    Cause of kidney failure
     DiabetesReferenceReference
     Hypertensive kidney disease1.04 (0.99 to 1.09)0.151.03 (0.93 to 1.14)0.53
     GN1.01 (0.93 to 1.10)0.781.22 (1.05 to 1.42)0.01
     Other1.06 (0.99 to 1.13)0.081.20 (1.06 to 1.35)0.005
    Employment status
     Full timeReferenceReference
     Part time0.95 (0.76 to 1.18)0.641.24 (0.84 to 1.84)0.28
     Unemployed0.98 (0.84 to 1.14)0.761.31 (0.98 to 1.75)0.07
     Retired1.05 (0.90 to 1.23)0.521.38 (1.02 to 1.85)0.04
     Disabled1.13 (0.97 to 1.32)0.131.67 (1.25 to 2.24)0.001
     Other0.90 (0.75 to 1.08)0.261.22 (0.88 to 1.71)0.24
    Bureau of economic analysis regions
     Midwest0.89 (0.80 to 0.99)0.030.73 (0.60 to 0.88)0.003
     Great Lakes0.96 (0.86 to 1.06)0.400.93 (0.77 to 1.11)0.41
     Plains0.78 (0.69 to 0.88)<0.0010.77 (0.62 to 0.96)0.02
     Southeast1.03 (0.93 to 1.13)0.590.93 (0.78 to 1.11)0.42
     Southwest0.93 (0.84 to 1.04)0.200.74 (0.61 to 0.89)0.004
     Rocky0.73 (0.61 to 0.88)0.0020.76 (0.55 to 1.04)0.09
     Far West0.98 (0.88 to 1.09)0.690.70 (0.58 to 0.85)0.001
    • All factors were included in a single Cox proportional hazards model with time from hemodialysis initiation to the first dispensed prescription for a short-acting or long-acting benzodiazepines as the outcome. aHR, adjusted hazard ratio; 95% CI, 95% confidence interval.

    • View popup
    Table 3.

    Association between benzodiazepines and mortality in patients initiating hemodialysis (n=69,368) between 2013 and 2014

    ExposureNo. of DeathsAny, aHR (95% CI)Short Acting, aHR (95% CI)Long Acting, aHR (95% CI)
    Benzodiazepine16,981
     Unadjusted1.52 (1.41 to 1.64)1.73 (1.60 to 1.88)0.83 (0.67 to 1.02)
     Adjusted1.31 (1.23 to 1.40)1.45 (1.35 to 1.56)0.84 (0.72 to 0.99)
    LME per milligram higher1.05 (1.03 to 1.07)0.98 (0.91 to 1.05)
    Alprazolam (0.5 LME)1.33 (1.17 to 1.51)
    Lorazepam (1.0 LME)2.06 (1.82 to 2.34)
    Temazepam (10 LME)1.48 (1.23 to 1.80)
    Clonazepam (0.25 LME)0.73 (0.56 to 0.94)
    Diazepam (5 LME)1.00 (0.69 to 1.44)
    • Use of benzodiazepines was treated as time varying, and all models were adjusted. The results below are from three separate models; all models were adjusted for age, sex, race, prescription (antidepressants and CNS depressants), and comorbidities. CNS depressants included sedatives, muscle relaxants, and antipsychotics. Comorbidities included diabetes mellitus, cardiovascular disease, peripheral vascular disease, hypertension, COPD, smoking history, cancer, drug abuse, inability to ambulate, institutionalized, and obesity. In the short-acting benzodiazepine model, those taking long-acting benzodiazepines were treated as unexposed. Similarly, in the long-acting benzodiazepine model, those taking short-acting benzodiazepines were treated as unexposed. LME, lorazepam milligram equivalent.

    • View popup
    Table 4.

    Association between benzodiazepines and mortality in patients initiating hemodialysis (n=69,368) between 2013 and 2014 stratified by age, sex, race, and opioid codispensing

    ExposureNo. of DeathsFollow-Up Time, person-yrUnadjusted aHR (95% CI)Adjusted aHR (95% CI)P Value for Interaction
    Any benzodiazepine0.001
     No opioid/no benzodiazepine2556182,800ReferenceReference
     No opioid/benzodiazepine48541,2731.32 (1.20 to 1.44)1.22 (1.13 to 1.32)
     Opioid/no benzodiazepine2071141,526ReferenceReference
     Opioid/benzodiazepine19081052.35 (2.04 to 2.71)1.66 (1.46 to 1.90)
    Short-acting benzodiazepine<0.001
     No opioid/no benzodiazepine2514174,636ReferenceReference
     No opioid/benzodiazepine42031,1861.50 (1.36 to 1.65)1.34 (1.23 to 1.45)
     Opioid/no benzodiazepine2094143,450ReferenceReference
     Opioid/benzodiazepine16761812.74 (2.35 to 3.19)1.90 (1.65 to 2.18)
    Long-acting benzodiazepine0.72
     No opioid/no benzodiazepine2305157,870ReferenceReference
     No opioid/benzodiazepine6710,2800.74 (0.58 to 0.94)0.83 (0.69 to 1.00)
     Opioid/no benzodiazepine2238147,590ReferenceReference
     Opioid/benzodiazepine2320411.11 (0.74 to 1.67)0.89 (0.64 to 1.24)
    • Use of benzodiazepines and other medications was treated as time varying, and all models were adjusted. The results below are from three separate models; all models were adjusted for age, sex, race, prescription (antidepressants and CNS depressants), and comorbidities. CNS depressants included sedatives, muscle relaxants, and antipsychotics. Comorbidities included diabetes mellitus, cardiovascular disease, peripheral vascular disease, hypertension, COPD, smoking history, cancer, drug abuse, inability to ambulate, institutionalized, and obesity.

Additional Files

  • Figures
  • Tables
  • Supplemental Data

    • Supplemental Data
PreviousNext
Back to top

In this issue

Clinical Journal of the American Society of Nephrology: 15 (6)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 6
June 08, 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in CJASN.
Enter multiple addresses on separate lines or separate them with commas.
Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis
Abimereki D. Muzaale, Matthew Daubresse, Sunjae Bae, Nadia M. Chu, Krista L. Lentine, Dorry L. Segev, Mara McAdams-DeMarco
CJASN Jun 2020, 15 (6) 794-804; DOI: 10.2215/CJN.13341019

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis
Abimereki D. Muzaale, Matthew Daubresse, Sunjae Bae, Nadia M. Chu, Krista L. Lentine, Dorry L. Segev, Mara McAdams-DeMarco
CJASN Jun 2020, 15 (6) 794-804; DOI: 10.2215/CJN.13341019
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Funding
    • Acknowledgments
    • Supplemental Material
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

Original Articles

  • Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States
  • Availability, Accessibility, and Quality of Conservative Kidney Management Worldwide
  • Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance Hemodialysis
Show more Original Articles

Maintenance Dialysis

  • The Mobile Health Readiness of People Receiving In-Center Hemodialysis and Home Dialysis
  • Effect of Phosphate-Specific Diet Therapy on Phosphate Levels in Adults Undergoing Maintenance Hemodialysis
  • Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance Hemodialysis
Show more Maintenance Dialysis

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • A Patient’s Perspective on Benzodiazepines, Co-Dispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis
  • PubMed
  • Google Scholar

Keywords

  • Benzodiazepines
  • Analgesics
  • Opioid
  • Medicare
  • Proportional Hazards Models
  • Opioid Epidemic
  • Follow-Up Studies
  • renal dialysis
  • dialysis
  • Cohort Studies
  • Prescriptions
  • Records

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Trainee of the Year
  • Author Resources
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • CJASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About CJASN
  • CJASN Email Alerts
  • CJASN Key Impact Information
  • CJASN Podcasts
  • CJASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1555-9041 Online ISSN - 1555-905X

Powered by HighWire