Opioid Overdose
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Etiology
- oxycodone & morphine account for most overdoses[10] (3.8 per 100,000)
- heroin (3.4 per 100,000)
- methadone (incidence declining due to diminished use)[12]
- fentanyl analogs detected in 14% of deaths[18]
- if multiple doses of naloxone required for resuscitation, suspect contamination with fentanyl[43]
- carfentanil, furanylfentanyl, acetylfentanyl most common
- > 50% also involve other drugs, such as heroin, cocaine
- 20% of deaths without injection drug use
- snorting & ingestion most common[18]
- metonitazene & para-fluorofentanyl associated with opioid overdoses in the U.S. often with fentanyl[42]
- synthetic opioid U-47700 found in 1% of deaths[18]
- concurrent use of opioids & benzodiazepines[16]
Epidemiology
- 90% of opioid overdose survivors continue to be prescribed opioids[11]
- policies discouraging use of methadone for treating pain have reduced opioid overdoses[12]
- annual incidence of opioid hospitalizations rose from 1.4 to 3.7 per 100,000 children from 1997-2012[13]
- 46% of opioid overdose death in U.S. 2016 due to synthetic opioids such as fentanyl[23]
- heroin-related deaths increase 21% from 2014-2015[14]
- people aged 45-54 with highest overdose mortality (30 per 100,000)
- 20% of deaths in U.S. adults 25-34 years related to opioid use[25]
- 18% of opioid-related deaths in U.S. among adults >=55 years[25]
- West Virginia (42 per 100,000), New Hampshire, Kentucky, & Ohio had the highest overdose mortality[15]
- non-Hispanic whites with highest overdose mortality (21 per 100,000)[15]
- fentanyl detected in ~ 2/3 of opioid overdose deaths in southeastern Massachusetts Oct 2014 - March 2015[17]
- 82% involved illicitly manufactured fentanyl.
- 90% without pulse when emergency medical services arrived
- 36% with evidence overdose within seconds or minutes
- 6% with evidence of naloxone administration by bystanders[17]
- high-potency fentanyl analog carfentanil involved in 11% of opioid related deaths[30]
- illicit fentanyl implicated in opioid-related deaths, even among people with current opioid prescriptions[31]
- largest increase of patients hospitalized for opioid overdose were whites, patients aged 50-64, Medicare recipients, & persons living in areas with low household income[20]
- 30% increase in opioid overdose seen in emergency department from 3rd quarter of 2016 to 3rd quarter of 2017[21]
- all regions of the country affected
- increases largest in the Midwest (70%)[21]
- overlapping prescriptions for opioids & benzodiazepines from multiple healthcare sources increase risk for overdose & death[31]
- more direct-to-physician opioid marketing associated with higher opioid-related mortality[33]
- opioid-related deaths are 10 times less common among cancer survivors than in the general population[37]
Clinical manifestations
- bradypnea, weak pulse, miosis, diminished bowel sounds
Adverse effects
- sedation, somnolence
- respiratory depression
- cardiac arrests occur largely via respiratory depression[40]
- results in anoxic perfusion with anoxic brain injury[40]
- hypotension
- bradycardia
- pupillary constriction
- increased risk for mortality[29]
Drug interactions
- 20% of opioid overdoses involve alcohol
- initiating oxycodone in patients taking paroxetine or fluoxetine associated with increased risk of opioid overdose (RR=1.23)
- effect attributed to CYP2D6 inhibition by paroxetine or fluoxetine[41]
Differential diagnosis
- heroin contaminated with fentanyl
- combination of opioid plus benzodiazepine
- usual dose of prescribed benzodiazepine & response to naloxone makes combination unlikely etiology[43]
Management
- supportive measures
- maintenance of airway
- ventilatory support
- rescue ventilation relatively more important in CPR[40]
- avoid gastric lavage
- limit whole body irrigation to 'body packers'
- body packers rarely require surgery, except with intestinal obstruction
- avoid endoscopic attempts at removal (danger of rupture)
- antidotes
- use judiciously, so as not to precipitate pain crisis
- naloxone
- start 0.4 mg
- escalate dose every few minutes as needed[3][4]
- user friendly naloxone FDA-approved for use by caregivers[6]
- naloxone 2 mg/mL intranasal as effective as 2 mg IM[19]
- not transporting patients to healthcare facilities after overdose reversal associated with low rates of mortality & serious adverse events[19]
- less likely to benefit pulseless victim[40]
- nalmefene
- larger doses associated with increased risk of overdose-related death[1]
- consider polysubstance abuse, especially benzodiazepines
- managing opioid overdose in a community setting[8]
- providing opioid overdose training & naloxone kits to laypersons who might witness an opioid overdose (close friends, partners, family members) can help reduce overdose mortality[9]
- first responders should concentrate on managing the person's airway, administering naloxone, & assisting ventilation
- people administering naloxone should choose the route of administration (intravenous, intramuscular, subcutaneous, or intranasal) based on the formulation available, how well they can administer it, the setting, & local context
- following successful naloxone administration & resuscitation, the person's level of consciousness & breathing should be closely monitored until he or she has fully recovered
- US Surgeon General urges more Americans to routinely carry naloxone[22]
- maintenance methadone & buprenorphine are associated with lower mortality risk following nonfatal opioid overdose[28]
- patient must bw assessed for interest & willingness to discontinue opioid use & adhere to addiction treatment prior to prescribing buprenorphine[3]
- when opioid misuse precipitates opioid overdose, discontinue opioids & start buprenorphine[44]
- preventive measures
- avoid coprescribing of opioids & benzodiazepines[16]
- prescription drug-monitoring programs of uncertain value[24]
- talk to patients about the risks with synthetic opioids[39]
- prescribe naloxone to those at risk for overdose, including those with a history of overdose & those with opioid use disorder & to patients receiving opioids & benzodiazepines.
- intranasal naloxone for use by friends & family members in the event of overdose
- educate patients that multiple naloxone doses may be needed for one overdose given the potency of fentanyl[39]
More general terms
Additional terms
References
- ↑ 1.0 1.1 Bohnert ASB et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 2011 Apr 6; 305:1315. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21467284
- ↑ Centers for Disease Control & prevention Vital Signs: Overdoses of Prescription Opioid Pain Relievers --- United States, 1999--2008 MMWR November 4, 2011 / 60(43);1487-1492 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm
- ↑ 3.0 3.1 3.2 Medical Knowledge Self Assessment Program (MKSAP) 16, 18, 19. American College of Physicians, Philadelphia 2012, 2018, 2022.
- ↑ 4.0 4.1 Dahan A, Aarts L, Smith TW. Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression. Anesthesiology. 2010 Jan;112(1):226-38 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20010421
- ↑ Centers for Disease Control and Prevention Vital Signs: Overdoses of Prescription Opioid Pain Relievers and Other Drugs Among Women - United States, 1999-2010 MMWR. July 5, 2013 / 62(26);537-542 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6226a3.htm
- ↑ 6.0 6.1 FDA News Release: April 3, 2014 FDA approves new hand-held auto-injector to reverse opioid overdose. First naloxone treatment specifically designed to be given by family members or caregivers. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm
- ↑ Jones CM et al Alcohol Involvement in Opioid Pain Reliever and Benzodiazepine Drug Abuse-Related Emergency Department Visits and Drug- Related Deaths - United States, 2010 MMWR. October 10, 2014 / 63(40);881-885 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6340a1.htm
- ↑ 8.0 8.1 World Health Organization. 2014 Community Management of opioid overdose http://apps.who.int/iris/bitstream/10665/137462/1/9789241548816_eng.pdf?ua=1
- ↑ 9.0 9.1 Wheeler E et al Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014 MMWR Weekly. June 19, 2015 / 64(23);631-635 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6423a2.htm
- ↑ 10.0 10.1 Rudd RA, Aleshire N, Zibbell JE, Gladden RM Increases in Drug and Opioid Overdose Deaths - United States, 2000-2014. MMWR. December 18, 2015 / 64(Early Release);1-5 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm64e1218a1.htm
CDC Press Release. Dec 18, 2015 Drug overdose deaths hit record numbers in 2014 http://www.cdc.gov/media/releases/2015/p1218-drug-overdose.html - ↑ 11.0 11.1 Larochelle MR et al Opioid Prescribing After Nonfatal Overdose and Association With Repeated Overdose: A Cohort Study. Ann Intern Med. Published online 29 December 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26720742 <Internet> http://annals.org/article.aspx?articleid=2479117
Gregg J Follow-up to Nonfatal Opioid Overdoses: More of the Same or an Opportunity for Change? Ann Intern Med. Published online 29 December 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26720852 <Internet> http://annals.org/article.aspx?articleid=2479118 - ↑ 12.0 12.1 12.2 Jones CM, Baldwin GT, Manocchio T, White JO, Mack KA Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths - United States, 2002-2014. MMWR Morb Mortal Wkly Rep 2016;65:667-671 https://www.cdc.gov/mmwr/volumes/65/wr/mm6526a2.htm
- ↑ 13.0 13.1 13.2 Gaither JR, Leventhal JM, Ryan SA et al National Trends in Hospitalizations for Opioid Poisonings Among Children and Adolescents, 1997 to 2012. JAMA Pediatr. Published online October 31, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27802492 <Internet> http://jamanetwork.com/journals/jamapediatrics/fullarticle/2571466
- ↑ 14.0 14.1 14.2 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. ePub: 16 December 2016. https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm
- ↑ 15.0 15.1 15.2 Hedegaard H, Warner M, Minino AM Drug Overdose Deaths in the United States, 1999-2015 NCHS Data Brief. No 273. Feb 2017 https://www.cdc.gov/nchs/data/databriefs/db273.pdf
- ↑ 16.0 16.1 16.2 Sun EC, Dixit A, Humphreys K et al Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ 2017;356:j760 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28292769 Free full text <Internet> http://www.bmj.com/content/356/bmj.j760
Karaca-Mandic P, Meara E, Morden NE. The growing problem of co-treatment with opioids and benzodiazepines. BMJ 2017;356:j1224 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28292825 Free full text <Internet> http://www.bmj.com/content/356/bmj.j1224 - ↑ 17.0 17.1 17.2 Somerville NJ, O'Donnell J, Gladden RM, et al. Characteristics of Fentanyl Overdose - Massachusetts, 2014-2016. MMWR Morb Mortal Wkly Rep 2017;66:382-386 https://www.cdc.gov/mmwr/volumes/66/wr/mm6614a2.htm
- ↑ 18.0 18.1 18.2 18.3 O'Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 - 10 States, July-December 2016. MMWR Morb Mortal Wkly Rep. ePub: 27 October 2017 https://www.cdc.gov/mmwr/volumes/66/wr/mm6643e1.htm
- ↑ 19.0 19.1 19.2 Chou R, Korthuis PT, McCarty D et al Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings: A Systematic Review. Ann Intern Med. 2017. Nov 28. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29181532 <Internet> http://annals.org/aim/fullarticle/2664376/management-suspected-opioid-overdose-naloxone-out-hospital-settings-systematic-review
Oliva EM, Bounthavong M. Emergency Medical Services Naloxone Administration: Many Unknowns and Opportunities. Ann Intern Med. 2017. Nov 28. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29181541 <Internet> http://annals.org/aim/article-abstract/2664377/emergency-medical-services-naloxone-administration-many-unknowns-opportunities - ↑ 20.0 20.1 Song Z Mortality Quadrupled Among Opioid-Driven Hospitalizations, Notably Within Lower-Income And Disabled White Population. Health Affairs. Dec 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29200349 https://www.healthaffairs.org/doi/10.1377/hlthaff.2017.0689
- ↑ 21.0 21.1 21.2 Vivolo-Kantor AM, Seth P, Gladden RM et al. Trends in Emergency Department Visits for Suspected Opioid Overdoses - United States, July 2016-September 2017. MMWR Morb Mortal Wkly Rep. ePub: 6 March 2018. https://www.cdc.gov/mmwr/volumes/67/wr/mm6709e1.htm
- ↑ 22.0 22.1 Brooks M Surgeon General Urges More Americans to Carry Overdose Antidote. Medscape - Apr 05, 2018. https://www.medscape.com/viewarticle/894837
Adams JM Increasing Naloxone Awareness and Use. The Role of Health Care Practitioners. JAMA. Published online April 5, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29621389 https://jamanetwork.com/journals/jama/fullarticle/2678206
U.S. Dept of Health & Human Services. Surgeon General's Advisory on Naloxone and Opioid Overdose. https://www.surgeongeneral.gov/priorities/opioid-overdose-prevention/naloxone-advisory.html - ↑ 23.0 23.1 23.2 Jones CM, Einstein EB, Compton WM et al Changes in Synthetic Opioid Involvement in Drug Overdose Deaths in the United States, 2010-2016. JAMA. 2018;319(17):1819-1821. May 1, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29715347 https://jamanetwork.com/journals/jama/fullarticle/2679931
- ↑ 24.0 24.1 Fink DS, Schleimer JP, Sarvet A et al. Association between prescription drug monitoring programs and nonfatal and fatal drug overdoses: A systematic review. Ann Intern Med 2018 May 8; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29801093 <Internet> http://annals.org/aim/article-abstract/2680723/association-between-prescription-drug-monitoring-programs-nonfatal-fatal-drug-overdoses
Compton WM, Wargo EM. Prescription drug monitoring programs: Promising practices in need of refinement. Ann Intern Med 2018 May 8 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29801101 <Internet> http://annals.org/aim/article-abstract/2680724/prescription-drug-monitoring-programs-promising-practices-need-refinement - ↑ 25.0 25.1 25.2 Gomes T, Tadrous M, Mamdani MM et al The Burden of Opioid-Related Mortality in the United States. JAMA Network Open. 2018;1(2):e180217. Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2682878
- ↑ NEJM Knowledge+ Question of the Week. June 5, 2018 https://knowledgeplus.nejm.org/question-of-week/1826/
- ↑ Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012 Jul 12; 367:146 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22784117 Free PMC Article https://www.nejm.org/doi/full/10.1056/NEJMra1202561
- ↑ 28.0 28.1 Larochelle MR, Bernson D, Land T et al Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study. Ann Intern Med. 2018. June 19. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29913516 <Internet> http://annals.org/aim/article-abstract/2684924/medication-opioid-use-disorder-after-nonfatal-opioid-overdose-association-mortality
Volkow ND, Wargo EM Overdose Prevention Through Medical Treatment of Opioid Use Disorders. Ann Intern Med. 2018. June 19 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29913514 <Internet> http://annals.org/aim/article-abstract/2684925/overdose-prevention-through-medical-treatment-opioid-use-disorders - ↑ 29.0 29.1 29.2 Olfson M, Crystal S, Wall M et al Causes of Death After Nonfatal Opioid Overdose. JAMA Psychiatry. Published online June 20, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29926090 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2685326
- ↑ 30.0 30.1 Centers for Disease Control & Prevention (CDC) Rising Numbers of Deaths Involving Fentanyl and Fentanyl Analogs, Including Carfentanil, and Increased Usage and Mixing with Non-opioids Emergency Preparedness and Response. July 11, 2018 https://emergency.cdc.gov/han/han00413.asp
O'Donnell J, Gladden RM, Mattson CL, Kariisa M. Notes from the Field: Overdose Deaths with Carfentanil and Other Fentanyl Analogs Detected - 10 States, July 2016 - June 2017. MMWR Morb Mortal Wkly Rep 2018;67:767-768 https://www.cdc.gov/mmwr/volumes/67/wr/mm6727a4.htm - ↑ 31.0 31.1 31.2 Carico R, Zhao X, Thorpe CT et al. Receipt of overlapping opioid and benzodiazepine prescriptions among veterans dually enrolled in Medicare Part D and the Department of Veterans Affairs: A cross-sectional study. Ann Intern Med 2018 Oct 9; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/30304353
- ↑ Gomes T et al. Contributions of prescribed and non-prescribed opioids to opioid related deaths: Population based cohort study in Ontario, Canada. BMJ 2018 Aug 29; 362:k3207. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30158106 Free PMC Article https://www.bmj.com/content/362/bmj.k3207
Hadland SE, Kertesz SG. Opioid deaths in Ontario, Canada: Curbs to prescribing must be part of a broader package of measures. BMJ 2018 Aug 29; 362:k3537 PMID: https://www.ncbi.nlm.nih.gov/pubmed/3015825 https://www.bmj.com/content/362/bmj.k3537 - ↑ 33.0 33.1 Hadland SE, Rivera-Aguirre A, Marshall BDL et al. Association of pharmaceutical industry marketing of opioid products with mortality from opioid-related overdoses. JAMA Netw Open 2019 Jan 18; 2:e186007. Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2720914
- ↑ Willman MW, Liss DB, Schwarz ES, Mullins ME. Do heroin overdose patients require observation after receiving naloxone? Clin Toxicol (Phila). 2017 Feb;55(2):81-87. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27849133
- ↑ Babu KM, Brent J, Juurlink DN. Prevention of opioid overdose. N Engl J Med 2019 Jun 6; 380:2246. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31167053 https://www.nejm.org/doi/full/10.1056/NEJMra1807054
- ↑ SAMHSA. Opioid Overdose Prevention Toolkit http://store.samhsa.gov/product/opioid-overdose-prevention-toolkit/all-new-products/sma13-4742
SAMHSA. Opioid Overdose Toolkit. Information for Prescribers. http://store.samhsa.gov/shin/content//SMA13-4742/Toolkit_Prescribers.pdf - ↑ 37.0 37.1 Chino F, Kamal A, Chino J et al Incidence of Opioid-Associated Deaths in Cancer Survivors in the United States, 2006-2016A Population Study of the Opioid Epidemic. JAMA Oncol. Published online May 7, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32379275 https://jamanetwork.com/journals/jamaoncology/fullarticle/2765326
Mehta AK, Smith TJ Palliative Care for Patients With Cancer in the COVID-19 Era. JAMA Oncol. Published online May 7, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32379855 https://jamanetwork.com/journals/jamaoncology/fullarticle/2765828 - ↑ Adewumi AD et al. Prescribed dose of opioids and overdose: a systematic review and meta-analysis of unintentional prescription opioid overdose. CNS Drugs 2018 Feb; 32:101. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29498021
- ↑ 39.0 39.1 39.2 Centers for Disease Control & Prevention (CDC) Increase in Fatal Drug Overdoses Across the United States Driven by Synthetic Opioids Before and During the COVID-19 Pandemic. CDC Health Alert Network. Dec 17, 2020 https://emergency.cdc.gov/han/2020/han00438.asp
- ↑ 40.0 40.1 40.2 40.3 40.4 Dezfulian C et al. Opioid-associated out-of-hospital cardiac arrest: Distinctive clinical features and implications for health care and public responses: A scientific statement from the American Heart Association. Circulation 2021 Mar 8; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/33682423 https://www.ahajournals.org/doi/10.1161/CIR.0000000000000958
- ↑ 41.0 41.1 Yunusa I, Gagne JJ, Yoshida K et al Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors. JAMA Netw Open. 2022;5(2):e220194 PMID: https://www.ncbi.nlm.nih.gov/pubmed/3520131 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789401
- ↑ 42.0 42.1 Stobbe M Two Powerful Drugs Now Adding to US Overdose Crisis Medscape. Jan 28, 2022 https://www.medscape.com/viewarticle/967484
- ↑ 43.0 43.1 43.2 43.3 NEJM Knowledge+ Psychiatry
- ↑ 44.0 44.1 NEJM Knowledge+ Pain Management and Opioids: Recharge