National opioid shortage is associated with increased use of ketamine infusion for analgosedation in the medical intensive care unit

Gregory Eisinger, MD, MSSW; Matthew Huang, MD; Michael S. Cardone, MD; Jessica L. Elefritz, PharmD, BCCP; Bruce Doepker, PharmD, BCPS; Matthew Exline, MD, MPH; Jennifer McCallister, MD

doi:10.5055/jom.2022.0749

Authors

Gregory Eisinger, MD, MSSW https://orcid.org/0000-0003-2748-9603
Matthew Huang, MD
Michael S. Cardone, MD
Jessica L. Elefritz, PharmD, BCCP
Bruce Doepker, PharmD, BCPS
Matthew Exline, MD, MPH
Jennifer McCallister, MD

DOI:

https://doi.org/10.5055/jom.2022.0749

Keywords:

ketamine infusion, opioid shortage, analgosedation, ICU, mechanical ventilation

Abstract

Objective: To assess the impact of the national shortage of injectable opioids during the winter of 2017-2018 on the use of ketamine infusion for analgosedation in the medical intensive care unit (MICU).

Design: A retrospective cohort study.

Setting: Single-center tertiary care MICU at The Ohio State University Wexner Medical Center.

Patients: All patients who received continuous infusion of ketamine to facilitate mechanical ventilation between May 1, 2015 and September 1, 2018.

Measurements and main results: Seventy-seven patients were identified during the study time frame: 43 before and 19 during the opioid shortage. During the peak of the shortage, there was a sevenfold increase in orders for ketamine infusion (2.2 patients/week vs 0.32 patients/week; p < 0.001). Median time from the start of mechanical ventilation to initiation of ketamine infusion was significantly shorter during the shortage (14.1 hours) versus before (51.2 hours; p = 0.03). There was a trend toward adding ketamine into the sedation regimen earlier during the shortage (mean number of drips added prior to ketamine was 2.74 during the shortage vs 3.3 before; p = 0.06). There was also a trend toward increased use of ketamine infusion as monotherapy during (21.1 percent of patients) versus before the shortage (7 percent), though this did not reach statistical significance (p = 0.19).

Conclusion: The national opioid shortage may have led to earlier and more frequent use of ketamine infusion for anaglosedation in mechanically ventilated MICU patients.

Author Biographies

Gregory Eisinger, MD, MSSW

Fellow in Pulmonary and Critical Care Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio

Matthew Huang, MD

Fellow in Pulmonary and Critical Care Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio

Michael S. Cardone, MD

Resident in Emergency and Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Jessica L. Elefritz, PharmD, BCCP

Assistant Professor of Pharmacy, Residency Program Director, Critical Care Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio

Bruce Doepker, PharmD, BCPS

Assistant Professor of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio

Matthew Exline, MD, MPH

Professor of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, ICU Medical Director, The Ohio State University Wexner Medical Center, Columbus, Ohio

Jennifer McCallister, MD

Professor of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Associate Dean of Medical Education, The Ohio State University Wexner Medical Center, Columbus, Ohio

References

US Drug Enforcement Administration: DEA reduces amount of opioid controlled substances to be manufactured in 2017. 2016. Available at https://www.dea.gov/press-releases/2016/10/04/dea-reduces-amount-opioid-controlled-substances-be-manufactured-2017. Accessed May 10, 2019.

Hernandez M, Bigham C: FDA warning letter to Pfizer pharmaceuticals. 2017. Available at https://www.fda.gov/inspectionscompliance-enforcement-and-criminal-investigations/warningletters/hospira-inc-506761-02142017. Accessed May 10, 2019.

Wang B, Downing N: A crisis within an epidemic: Critical opioid shortage in US hospitals. Postgrad Med J. 2019; 95: 515-516. DOI: 10.1136/postgradmedj-2018-136058.

Malacos K: Drug shortages: Contributing factors, mitigating the impact. Pharm Times. 2019. Available at https://www.pharmacytimes.com/news/drug-shortages-continue-to-be-achallenge.

American Society of Health Systems Pharmacists: Injectable opioid survey report. 2018. Available at https://www.ashp.org/Drug-Shortages/Shortage-Resources/Injectable-Opioid-Survey-Report. Accessed May 10, 2019.

Hemmings HC, Egan TD: Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application. Amsterdam, The Netherlands: Elsevier Health Sciences, 2013. DOI: 10.1016/C2009-0-41712-4.

Li L, Vlisides PE: Ketamine: 50 years of modulating the mind. Front Hum Neurosci. 2016; 10: 612. DOI: 10.3389/fnhum.2016.00612.

Niesters M, Aarts L, Sarton E, et al.: Influence of ketamine and morphine on descending pain modulation in chronic pain patients: A randomized placebo-controlled cross-over proof-of-concept study. Br J Anaesth. 2013; 110(6): 1010-1016. DOI: 10.1093/bja/aes578.

Peltoniemi MA, Hagelberg NM, Olkkola KT, et al.: Ketamine: A review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clin Pharmacokinet. 2016; 55(9): 1059-1077. DOI: 10.1007/s40262-016-0383-6.

Devabhakthuni S, Armahizer MJ, Dasta JF, et al.: Analgosedation: A paradigm shift in intensive care unit sedation practice. Ann Pharmacother. 2012; 46(4): 530-540. DOI: 10.1345/aph.1Q525.

Barr J, Fraser GL, Puntillo K, et al.: Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013; 41(1): 263-306. DOI: 10.1097/CCM.0b013e3182783b72.

Miller AC, Jamin CT, Elamin EM: Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011; 77(8): 812-820.

Kolenda H, Gremmelt A, Rading S, et al.: Ketamine for analgosedative therapy in intensive care treatment of head-injured patients. Acta Neurochir. 1996; 138(10): 1193-1199. DOI:

1007/BF01809750.

McGhee LL, Maani CV, Garza TH, et al.: The correlation between ketamine and posttraumatic stress disorder in burned service members. J Trauma Acute Care Surg. 2008; 64(Suppl): S195-S199. DOI: 10.1097/TA.0b013e318160ba1d.

Pizon AF, Lynch MJ, Benedict NJ, et al.: Adjunct ketamine use in the management of severe ethanol withdrawal. Crit Care Med. 2018; 46(8): e768-e771. DOI: 10.1097/CCM.0000000000003204.

Goyal S, Agrawal A: Ketamine in status asthmaticus: A review. Indian J Crit Care Med. 2013; 17(3): 154-161. DOI: 10.4103/0972-5229.117048.

Fang Y, Wang X: Ketamine for the treatment of refractory status epilepticus. Seizure. 2015; 30: 14-20. DOI: 10.1016/j.seizure.2015.05.010.

Lange M, Bröking K, Van Aken H, et al.: Role of ketamine in sepsis and systemic inflammatory response syndrome. Anaesthesist. 2006; 55: 883-891. DOI: 10.1007/s00101-006-1048-x.

Li K, Yang J, Han X: Ketamine attenuates sepsis-induced acute lung injury via regulation of HMGB1-RAGE pathways. Int Immunopharmacol. 2016; 34: 114-128. DOI: 10.1016/j.intimp.2016.01.021.

Strayer RJ, Nelson LS: Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008; 26(9): 985-1028. DOI: 10.1016/j.ajem.2007.12.005.

Wang X, Ding X, Tong Y, et al.: Ketamine does not increase intracranial pressure compared with opioids: Meta-analysis of randomized controlled trials. J Anesth. 2014; 28(6): 821-827. DOI: 10.1007/s00540-014-1845-3.

Drayna PC, Estrada C, Wang W, et al.: Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. Am J Emerg Med. 2012; 30(7): 1215-1218. DOI: 10.1016/j.ajem.2011.06.001.

Premier Inc.: More than 96 percent of health systems report moderate to severe shortages of injectable narcotics. Available at https://www.premierinc.com/newsroom/press-releases/morethan-96-percent-of-health-systems-report-moderate-to-severeshortages-of-injectable-narcotics. Accessed June 26, 2019.

Haider A, Qian Y, Lu Z, et al.: Implications of the parenteral opioid shortage for prescription patterns and pain control among hospitalized patients with cancer referred to palliative care. JAMA Oncol. 2019; 5: 841-846. DOI: 10.1001/jamaoncol.2019.0062.

Bruera E: Parenteral opioid shortage—Treating pain during the opioid-overdose epidemic. N Engl J Med. 2018; 379: 601-603. DOI: 10.1056/nejmp1807117.

Klaus DA, De Bettignies AM, Seemann R, et al.: Impact of a remifentanil supply shortage on mechanical ventilation in a tertiary care hospital: A retrospective comparison. Crit Care. 2018; 22(1): 1-8. DOI: 10.1186/s13054-018-2198-3.

Soumerai TE, Kamdar MMC: The other opioid crisis: Just another drug shortage? Oncologist. 2019; 24(5): 574-575.