Allison M Janda, MD
October 8, 2021
Multicenter Review of
Practice Patterns Regarding
Benzodiazepine Use in
Cardiac Surgery
Disclosures
2
Allison M Janda, M.D.
Clinical Lecturer in Anesthesiology
University of Michigan, Ann Arbor, Michigan, USA
– I have financial relationship(s) with:
• Grant / Research (current):
o PCORI – Co-investigator, “Trajectories of Recovery after Intravenous Propofol vs. Inhaled
Volatile Anesthesia (THRIVE)”
• Grant / Research (current):
o NIH R01 – Co-investigator, 1R01LM01389401 “A scalable service to improve health care
quality through precision audit and feedback”
• Grant / Research (past):
o NIH T32 Research Fellowship Grant – 5T32GM103730-07 (past)
• Grant / Research (past):
o Becton Dickinson and Company (past)
– My presentation does not include discussion of off-label or investigational use drugs or devices.
Introduction
There is little clarity on the impact of intraoperative benzodiazepines
- Benzodiazepine-sparing techniques are used due to the evidence in the ICU
population relating benzodiazepine use to delirium
1-13
- Others routinely administer benzodiazepines for their amnestic properties for
concern of intraoperative awareness in the higher risk cardiac surgery
population
1,4,14-16
Practice patterns are dogmatic and debated
Clinical trials are underway studying outcomes related to benzodiazepine use,
4
but little is
known about benzodiazepine use patterns beyond survey data
1
3
Introduction
Aims
- Describe benzodiazepine use during cardiac surgery across MPOG centers
- Identify patient factors associated with benzodiazepine use
- Describe the prevalence and variation of benzodiazepine use for cardiac surgeries
across patients, providers, and institutions
- Provide context for the future findings of clinical trials studying outcomes related to
benzodiazepine administration
Hypothesis
- Patient, provider, and institutional factors were independently associated with
benzodiazepine use during cardiac surgery, and patient factors are not the primary
driver of variation in use
4
Methods
Study Cohort
- Adults who underwent elective or urgent cardiac surgical procedures from January 1,
2014 until August 1, 2019 at MPOG institutions
Exclusions
- ASA 5 or 6
- Lung transplants, heart transplants, mechanical circulatory support, aortic procedures,
procedures requiring circulatory arrest or transcatheter procedures
- Case duration <120 minutes
5
Methods
Primary outcome: Exposure to benzodiazepines
- Defined as a bolus or infusion of midazolam, alprazolam, diazepam, clonazepam or
lorazepam given within two hours of anesthesia start and anesthesia end
6
Methods
Covariates
- Patient level
- Demographic data
- Surgery type and duration, whether bypass was used
- Comorbidities
- Year of surgery
- Provider level
- Case volume/year
- Institutional level
- University affiliation
- Case volume/year
7
Methods
Statistical Analyses
- Mixed effects and multilevel models to assess random versus fixed effects of
variation in benzodiazepine use
- Assessment of variance using variance estimates and median odds ratios (MORs)
- Goal is to inform us on the proportion of total variance in the outcome that is
attributable to that factor
8
Results
65,508 patients across 33 MPOG institutions were included
- 58,004 (88.5%) patients received a benzodiazepine
- Median midazolam-equivalent dose of 4.0mg (IQR 2.0-6.0mg)
- 29,824 (84.4%) patients over 65 years of age received benzodiazepines
9
Results
Preliminary unadjusted generalized linear mixed models showed:
- 30.5% of the variation was explained by patient factors
- 14.7% by the primary provider
- 54.7% by the institution
Over two-thirds of the variation was explained by provider and institution
10
Results
11
Results
Adjusted multilevel models showed that factors strongly associated with a decreased
likelihood of benzodiazepine administration included:
- Older age, >80 years versus ≤50 years, aOR 0.04, 95% CI 0.04-0.05, p<0.0001
- Recent year of surgery, 2019 versus 2014, aOR 0.42, 95% CI 0.37-0.49, p<0.0001
- University-affiliation, aOR 0.08, 95% CI 0.02-0.35, p=0.0007
- Low provider case-volume, aOR 0.44, 95% CI 0.25-0.75, p=0.002
Adjusted multilevel models showed that factors strongly associated with an increased
likelihood of benzodiazepine administration included:
- History of drug abuse, aOR 1.29, 95% CI 1.02-1.65, p=0.04
- Use of cardiopulmonary bypass, aOR 2.26, 95% CI 1.99-2.55, p<0.0001
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Results
Primary Analysis:
- Adjusted MORs for receiving a benzodiazepine:
- 2.7 between randomly selected providers
- 4.2 between randomly selected institutions
Low vs. High Dose Secondary Analysis:
- Adjusted MORs for receiving <0.05mg kg
-1
vs. ≥0.05mg kg
-1
- 3.1 between randomly selected providers
- 6.9 between randomly selected institutions
13
Results
Increased Risk of Hemodynamic Instability Cohort A Priori Sensitivity Analysis:
- Adjusted MORs for receiving a benzodiazepine:
- 2.1 between randomly selected providers
- 3.5 between randomly selected institutions
Starting Provider Post-hoc Sensitivity Analysis:
- Adjusted MORs for receiving a benzodiazepine:
- 2.9 between randomly selected providers
- 4.3 between randomly selected institutions
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Discussion
Conclusions
- Institution and provider as opposed to patient factors accounted for over
two-thirds of the variation of benzodiazepine administration
Limitations
- MPOG does not include ALL institutions providing cardiac surgical care
- Most institutions (27/33) were university-affiliated
Future Directions
- These data may serve as a model for understanding cardiac anesthesiology
practice variation provide context for the findings of randomized trials
evaluating intraoperative benzodiazepine administration and outcomes
15
References
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Thank You
Huge thanks to my co-authors:
- Jessica Spence, MD PhD
- Timur Dubovoy, MD
- Emilie Belley-Côté, MD PhD
- Graciela Mentz, PhD
- Sachin Kheterpal, MD MBA
- Michael R. Mathis, MD
Questions?
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