The prevalence of nasal obstruction as a consideration in the treatment of opioid overdose

Scott G. Weiner, MD, MPH; Andrew R. Joyce, PhD; Heather N. Thomson, MS

doi:10.5055/jom.2017.0370

Authors

Scott G. Weiner, MD, MPH
Andrew R. Joyce, PhD
Heather N. Thomson, MS

DOI:

https://doi.org/10.5055/jom.2017.0370

Keywords:

nasal pathology, naloxone, opioid, respiratory depression

Abstract

Objectives: The intranasal route of administration for naloxone delivery is one treatment for opioid overdose, but treatment failures with this modality have been documented. This study determines the incidence of obstructive nasal pathology in patients who experienced serious opioid-induced respiratory depression (OIRD).

Design: Retrospective analysis of the IMS LifeLink: Health Plan Claims Database to detect patients with at least one opioid pharmacy claim from 2009 to 2013 and who experienced serious OIRD. Four controls were randomly assigned to each case.

Main Outcome Measures: A multivariable analysis determined the adjusted odds ratio of OIRD for patients with obstructive nasal pathology.

Results: A total of 7,234 patients experienced a serious OIRD event; 840 (11.6 percent) had obstructive nasal pathology: 20 (2.4 percent) had deviated nasal septum (International Classification of Disease, 9th revision [ICD-9] 470), 246 (29.3 percent) had polyp of the nasal cavity (ICD-9 470.1), 130 (15.5 percent) had hypertrophy of nasal turbinates (ICD-9 478.0), and 659 (78.5 percent) had other disease of the nasal cavity (ICD-9 478.19). The adjusted odds ratio for patients who experienced serious OIRD having concurrent obstructive nasal pathology was 1.28 (95% confidence interval 1.13-1.46).

Conclusions: Obstructive nasal pathology is relatively common in patients who experience serious OIRD, and in itself is associated with a higher risk of having OIRD.

Author Biographies

Scott G. Weiner, MD, MPH

Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Andrew R. Joyce, PhD

Venebio Group, LLC, Richmond, Virginia

Heather N. Thomson, MS

Medical Affairs, kaleo Inc., Richmond, Virginia

References

Chien YW, Chang SF: Intranasal drug delivery for systemic medications. Crit Rev Ther Drug Carrier Syst. 1987; 4(2): 67-194.

Arora P, Sharma S, Garg S: Permeability issues in nasal drug delivery. Drug Discov Today. 2002; 7(18): 967-975.

Watts P, Smith A, Perelman M: Nasal delivery of fentanyl. Drug Deliv Transl Res. 2013; 3(1): 75-83.

Robertson TM, Hendey GW, Stroh G, et al.: Intranasal naloxone is a viable alternative to intravenous naloxone for prehospital narcotic overdose. Prehosp Emerg Care. 2009; 13(4): 512-515.

Davis CS, Southwell JK, Niehaus VR, et al.: Emergency medical services naloxone access: A national systematic legal review. Acad Emerg Med. 2014; 21(10): 1173-1177.

Walley AY, Xuan Z, Hackman HH, et al.: Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: Interrupted time series analysis. BMJ. 2013; 346: f174.

Kelly AM, Kerr D, Dietze P, et al.: Randomised trial of intranasal versus intramuscular naloxone in prehospital treatment for suspected opioid overdose. Med J Aust. 2005; 182(1): 24-27.

Kerr D, Kelly AM, Dietze P, et al.: Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose. Addiction. 2009; 104(12): 2067-2074.

Zuckerman M, Weisberg SN, Boyer EW: Pitfalls of intranasal naloxone. Prehosp Emerg Care. 2014; 18(4): 550-554.

Weber R, Keerl R, Radziwill R, et al.: Videoendoscopic analysis of nasal steroid distribution. Rhinology. 1999; 37(2): 69-73.

Dowley AC, Homer JJ: The effect of inferior turbinate hypertrophy on nasal spray distribution to the middle meatus. Clin Otolaryngol Allied Sci. 2001; 26(6): 488-490.

Chen XB, Lee HP, Chong VF, et al.: Impact of inferior turbinate hypertrophy on the aerodynamic pattern and physiological functions of the turbulent airflow—A CFD simulation model. Rhinology. 2010; 48(2): 163-168.

Robinson A, Wermeling DP: Intranasal naloxone administration for treatment of opioid overdose. Am J Health Syst Pharm.

; 71: 2129-2135.

Zedler B, Xie L, Wang L, et al.: Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients. Pain Med. 2014; 15(11): 1911-1929.

Zedler B, Xie L, Wang L, et al.: Development of a risk index for serious prescription opioid-induced respiratory depression or overdose in Veterans' Health Administration patients. Pain Med. 2015; 16(8): 1566-1579.

U.S. National Center for Health Statistics: International Classification of Diseases, Ninth Revision, Clinical Modification

(ICD-9-CM). Available at https://www.cdc.gov/nchs/icd/icd9cm.htm. Accessed February 16, 2017.

Abraham M, Ahlman J, Boudreau A, et al.: Current Procedural Terminology—CPT®. Professional ed. Chicago, IL: American Medical Association, 2011.

Charlson ME, Charlson RE, Peterson JC, et al.: The Charlson comorbidity index is adapted to predict costs of chronic disease in primary care patients. J Clin Epidemiol. 2008; 61(12): 1234-1240.

Charlson ME, Pompei P, Ales KL, et al.: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis. 1987; 40(5): 373-383.

Deyo RA, Cherkin DC, Ciol MA: Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992; 45(6): 613-619.

Baser O, Xie L, Mardekian J, et al.: Prevalence of diagnosed opioid abuse and its economic burden in the Veterans Health Administration. Pain Pract. 2014; 14(5): 437-445.

Xie L, Joshi AV, Schaaf D, et al.: Differences in healthcare utilization and associated costs between patients prescribed vs. nonprescribed opioids during an inpatient or emergency department visit. Pain Pract. 2014; 14(5): 446-456.

R Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing. Available at http://www.R-project.org. Accessed January 16, 2017.

Garcia GJM, Rhee JS, Senior BA, et al.: Septal deviation and nasal resistance: An investigation using virtual surgery and computational fluid dynamics. Am J Rhinol Allergy. 2009; 24: e46–e53.

Costantino HR, Illum L, Brandt G, et al.: Intranasal delivery: Physicochemical and therapeutic aspects. Int J Pharm. 2007; 337(1-2): 1-24.

Wermeling DP: A response to the opioid overdose epidemic: Naloxone nasal spray. Drug Deliv Transl Res. 2013; 3(1): 63-74.

Illum L: Nasal clearance in health and disease. J Aerosol Med. 2006; 19(1): 92-99.

Grassin-Delyle S, Buenestado A, Naline E, et al.: Intranasal drug delivery: An efficient and non-invasive route for systemic administration: Focus on opioids. Pharmacol Ther. 2012; 134(3): 366-379.

Frank DO, Kimbell JS, Cannon D, et al.: Deviated nasal septum hinders intranasal sprays: A computer simulation study. Rhinology. 2012; 50(3): 311-318.

Merkus P, Ebbens FA, Muller B, et al.: Influence of anatomy and head position on intranasal drug deposition. Eur Arch Otorhinolaryngol. 2006; 263(9): 827-832.

Kreiter P, Chiang N, Gyaw S, et al.: Pharmacokinetic properties and human use characteristics of an FDA-approved intranasal naloxone product for the treatment of opioid overdose. J Clin Pharmacol. 2016; 56(10): 1243-1253.

Hiyari A: Naloxone nasal spray pharmacokinetic study. Mitovie Pharma Ltd. Available at https://clinicaltrials.gov/ct2/show/NCT01622504?term=naloxone%2C+nasal&rank=6. Accessed February 17, 2017.