Intranasal versus Intramuscular/Intravenous Naloxone for Pre-hospital Opioid Overdose: A Systematic Review and Meta-analysis
Context: The present systematic review and meta-analysis aims to perform an extensive search in databases to compare the efficacy of the intranasal administration of naloxone with its intramuscular/intravenous administration in the pre-hospital management of opioid overdose. Evidence acquisition: This meta-analysis included controlled trials conducted on the efficacy of naloxone administration in the pre-hospital management of opioid overdose. A search was carried out in electronic databases on relevant articles published by the end of 2018. After data collection, analyses were performed in STATA 14.0 software and the efficacy and side-effects of the two administration routes of naloxone, i.e. intranasal and intramuscular/intravenous, were compared. An overall effect size with 95% confidence interval (95% CI) was provided for each section. Results: Eventually, data from six studies were included in this meta-analysis. The success rate of the intranasal and intramuscular/intravenous administration of naloxone in the management of opioid overdose in pre-hospital settings was 82.54% (95% CI: 57.97 to 97.89%) and 80.39% (95% CI: 57.38 to 96.04%), respectively. There was no difference between injectable (intramuscular/intravenous) naloxone and intranasal naloxone in the pre-hospital management of opioid overdose (Odds Ratio=1.01; 95% CI: 0.42 to 2.43; P=0.98). The onset of action of intranasal naloxone, however, was slightly longer than injectable naloxone (Standardized Mean Difference=0.63; 95% CI: 0.07 to 1.19; P=0.03). Additionally, the odds of needing a rescue dose was 2.17 times higher for intranasal naloxone than intramuscular/intravenous naloxone (OR=2.17; 95% CI: 1.53 to 3.09; P<0.0001). The prevalence of major side-effects was non-significant for both intranasal (0.00%) and intramuscular/intravenous (0.05%) routes of naloxone administration and there was no difference in the prevalence of major (OR=1.18; 95% CI: 0.38 to 3.69; P=0.777) and minor (OR=0.64; 95% CI: 0.17 to 2.34; P=0.497) side-effects between the two routes. Conclusion: The present meta-analysis demonstrated that intranasal naloxone is as effective as injectable naloxone in the pre-hospital management of opioid overdose complications. Consequently, intranasal naloxone may be an appropriate alternative to injectable naloxone.
2. Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-52.
3. Kelly AM, Kerr D, Dietze P, Patrick I, Walker T, Koutsogiannis Z. Randomised trial of intranasal versus intramuscular naloxone in prehospital treatment for suspected opioid overdose. Med J Aust. 2005;182(1):24-7.
4. Kerr D, Kelly AM, Dietze P, Jolley D, Barger B. Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose. Addiction. 2009;104(12):2067-74.
5. Chou R, Korthuis PT, McCarty D, Coffin PO, Griffin JC, Davis-O'Reilly C, et al. Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings: A Systematic Review. Ann Intern Med. 2017;167(12):867-75.
6. Yousefifard M, Movaghar VR, Baikpour M, Ghelichkhani P, Hosseini M, Jafari AM, et al. Early versus Late Decompression for Traumatic Spinal Cord Injuries; a Systematic Review and Meta-analysis. Emergency. 2017;5(1):e37.
7. Yousefifard M, Baikpour M, Ghelichkhani P, Asady H, Nia KS, Jafari AM, et al. Screening Performance Characteristic of Ultrasonography and Radiography in Detection of Pleural Effusion; a Meta-Analysis. Emergency. 2016;4(1):1-10.
8. Hosseini M, Yousefifard M, Aziznejad H, Nasirinezhad F. The Effect of Bone Marrow–Derived Mesenchymal Stem Cell Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review with Meta-Analysis. Biol Blood Marrow Transplant. 2015;21(9):1537-44.
9. Hosseini M, Ghelichkhani P, Baikpour M, Tafakhori A, Asady H, Ghanbari MJH, et al. Diagnostic Accuracy of Ultrasonography and Radiography in Detection of Pulmonary Contusion; a Systematic Review and Meta-Analysis. Emergency. 2015;3(4):127-36.
10. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: John Wiley & Sons; 2011.
11. Ghelichkhani P, Yousefifard M, Nazemi L, Safari S, Hosseini M, Baikpour M, et al. The value of serum β-subunit of human chorionic gonadotropin level in prediction of treatment response to methotrexate in management of ectopic pregnancy; a systematic review and meta-analysis. Int J Pediatr. 2016;4(9):3503-18.
12. Ebrahimi A, Yousefifard M, Kazemi HM, Rasouli HR, Asady H, Jafari AM, et al. Diagnostic accuracy of chest ultrasonography versus chest radiography for identification of pneumothorax: a systematic review and meta-analysis. Tanaffos. 2014;13(4):29-40.
13. Yousefifard M, Rahimi-Movaghar V, Nasirinezhad F, Baikpour M, Safari S, Saadat S, et al. Neural stem/progenitor cell transplantation for spinal cord injury treatment; A systematic review and meta-analysis. Neuroscience. 2016;322:377-97.
14. Rahimi-Movaghar V, Yousefifard M, Ghelichkhani P, Baikpour M, Tafakhori A, Asady H, et al. Application of Ultrasonography and Radiography in Detection of Hemothorax: a Systematic Review and Meta-Analysis. Emergency. 2016;4(3):116-26.
15. Rahimi-Movagha V, Yousefifard M, Ghelichkhani P, Baikpour M, Tafakhori A, Asady H, et al. Application of ultrasonography and radiography in detection of hemothorax: a systematic review and meta-analysis. Emergency. 2016;4(3):116–26.
16. Izadi A, Yousefifard M, Nakhjavan-Shahraki B, Baikpour M, Mirzay Razaz J, Hosseini M. Diagnostic value of Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) in detection of pediatric acute kidney injury; a systematic review and meta-analysis. Int J of Pediatr. 2016;4(11):3875-95.
17. Izadi A, Yousefifard M, Nakhjavan-Shahraki B, Baikpour M, Mirzay Razaz J, Ataei N, et al. Value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury; a systematic review and meta-analysis. Int J Pediatr. 2016;4(11):3815-36.
18. Hassanzadeh‐Rad A, Yousefifard M, Katal S, Asady H, Fard‐Esfahani A, Moghadas Jafari A, et al. The value of 18F‐fluorodeoxyglucose positron emission tomography for prediction of treatment response in gastrointestinal stromal tumors: a systematic review and meta‐analysis. J Gastroenterol Hepatol. 2016;31(5):929-35.
19. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-9.
20. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34.
21. Barton ED, Colwell CB, Wolfe T, Fosnocht D, Gravitz C, Bryan T, et al. Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting. J Emerg Med. 2005;29(3):265-71.
22. Kelly AM, Kerr D, Koutsogiannis Z, Dietze P, Patrick I, Walker T. Randomised trial of intranasal versus intramuscular naloxone in prehospital treatment for suspected opioid overdose. Med J Aust. 2005;182(1):24-7.
23. Merlin MA, Saybolt M, Kapitanyan R, Alter SM, Jeges J, Liu J, et al. Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses. Am J Emerg Med. 2010;28(3):296-303.
24. Robertson TM, Hendey GW, Stroh G, Shalit M. Intranasal naloxone is a viable alternative to intravenous naloxone for prehospital narcotic overdose. Prehosp Emerg Care. 2009;13(4):512-5.
25. Sabzghabaee AM, Eizadi-Mood N, Yaraghi A, Zandifar S. Naloxone therapy in opioid overdose patients: intranasal or intravenous? A randomized clinical trial. Arch Med Sci. 2014;10(2):309-14.
26. Weaver L, Palombi L, Bastianelli KMS. Naloxone Administration for Opioid Overdose Reversal in the Prehospital Setting: Implications for Pharmacists. J Pharm Pract. 2018;31(1):91-8.
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