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Opioid Overdose

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] - annual incidence increase among adolescents age 15-19 years increased from 3.7 to 10.2 per 100,000 (from 1997-2012) [13] - prescription opiates most commonly implicated - heroin overdose significant among adolescents age 15-19 years - 46% of opioid overdose death in U.S. 2016 due to synthetic opioids such as fentanyl [23] - 72% increase in deaths from synthetic opioids 2014-2015 [14] - 80% of overdose deaths in 2016 also involved alcohol or another drug [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] - substance-abuse, drug overdose (25% of deaths) - circulatory system diseases - cancer - HIV1 infection - chronic respiratory disease - viral hepatitis - suicide [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 - response to naloxone [43] - combination of opioid plus benzodiazepine - usual dose of prescribed benzodiazepine & response to naloxone makes combination unlikely etiology [43] Management: 1) supportive measures a) maintenance of airway b) ventilatory support - rescue ventilation relatively more important in CPR [40] c) avoid gastric lavage d) limit whole body irrigation to 'body packers' 1] body packers rarely require surgery, except with intestinal obstruction 2] avoid endoscopic attempts at removal (danger of rupture) 2) antidotes a) use judiciously, so as not to precipitate pain crisis b) 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] c) nalmefene 3) larger doses associated with increased risk of overdose-related death [1] 4) consider polysubstance abuse, especially benzodiazepines 5) managing opioid overdose in a community setting [8] a) 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] b) first responders should concentrate on managing the person's airway, administering naloxone, & assisting ventilation c) 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 d) following successful naloxone administration & resuscitation, the person's level of consciousness & breathing should be closely monitored until he or she has fully recovered e) US Surgeon General urges more Americans to routinely carry naloxone [22] f) a community-based intervention did not prevent opioid overdose [45] 6) 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] 7) 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]

Related

opioid receptor agonist (narcotic)

General

toxicity; poisoning; overdose

References

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