WEBB FELLOW: Respiratory Depression Risk with Co-administered Parenteral Olanzapine and Benzodiazepines: A Retrospective Study

Background/Significance: In 2008, post-marketing data on olanzapine administration showed correlation in risk of cardiorespiratory depression with co-administration of parenteral benzodiazepines with parenteral olanzapine (Marder 2008) which lead to a package insert warning of the combination. Since that time, two prospective trials (Chan 2013, Taylor 2016) utilizing parenteral olanzapine with parenteral benzodiazepines have not shown an increased risk. Physicians commonly avoid the combination despite the improved efficacy for agitation often obtained from multi-modal treatment.

Methods: We retrospectively examined 712 patients receiving the combination of parenteral olanzapine and benzodiazepines within two hours of each other at a tertiary care academic center. We excluded all patients who were ventilated prior to the first intervention, patients < 18 years old, or patients on continuous infusion benzodiazepines. Primary outcomes were respiratory depression as defined by new oxygen saturation < 92%, the need for supplemental oxygen, CPAP, BiPAP, or mechanical ventilation within four hours of administration of the second agent. Secondary outcomes include episodes of hypotension, bradycardia, initiation of or need for additional vasopressors, co-administered opioid exposure, co-administered non-benzodiazepine sedative-hypnotic exposure, QTc prolongation, resolution of agitation, need for additional chemical sedation or restraints, and RASS score change. Nominal data will be assessed using Chi square analysis and categorical data will be assessed using Mann-Whitney U Tests or ANOVA as appropriate. This was presented to the Brigham and Women’s IRB and received approval.

Results: We are still in the data-collection stage but will report on the frequency of cardiorespiratory depression and any risk factors that become statistically significant. We anticipate being finished with data collection and analysis by July 2021.

Discussion: In this retrospective trial, we examined all patients receiving the combination of parenterally administered olanzapine and benzodiazepines. Discussion to follow data.

Conclusion/Implications: Conclusion to follow data. We hope to comment on the safety of this combination.

References:
1. Marder SR, Sorsaburu S, Dunayevich E, Karagianis JL, Dawe IC, Falk DM, Dellva MA, Carlson JL, Cavazzoni PA, Baker RW. Case reports of postmarketing adverse event experiences with olanzapine intramuscular treatment in patients with agitation. J Clin Psychiatry. 2010 Apr;71(4):433-41. doi: 10.4088/JCP.08m04411gry. Epub 2010 Feb 9. PMID: 20156413.
2. Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013 Jan;61(1):72-81. doi: 10.1016/j.annemergmed.2012.07.118. Epub 2012 Sep 13. PMID: 22981685.
3. Taylor DM, Yap CYL, Knott JC, Taylor SE, Phillips GA, Karro J, Chan EW, Kong DCM, Castle DJ. Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A Randomized Clinical Trial. Ann Emerg Med. 2017 Mar;69(3):318-326.e1. doi: 10.1016/j.annemergmed.2016.07.033. Epub 2016 Oct 10. PMID: 27745766.