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Abstract
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In the United States from 2013 to 2019, the nonmethadone synthetic opioid-involved death rate increased 1040%, from 1.0 to 11.4 per 100 000 (age adjusted), with 51.5% of all 2019 drug overdose deaths linked to synthetic opioids such as fentanyl.1 Opioid-involved poisoning deaths overall contributed a loss of 0.21 years in life expectancy from 2000 to 20152 and undoubtedly contributed to the 2- to 3.5-fold increase in excess mortality in American teenagers and young adults from 2000 to 2017.3 Emerging data during the coronavirus disease 2019 pandemic suggest further worsening of the opioid crisis.4
Medical uses of opioids have come under increased scrutiny among physicians; anesthesiologists in particular have sought to minimize their administration.5 Nonetheless, opioids in limited amount and over limited duration have benefitted countless patients. Fentanyl requirements are variable and depend on procedure and individual patient sensitivity, the latter a consequence of interacting environmental and genetic factors that set different pain thresholds and alter fentanyl pharmacokinetics and pharmacodynamics. The variability in fentanyl pharmacokinetics is well established,6,7 but genetic associations gauging fentanyl response sensitivity are only in initial discovery stages and are focused largely on analgesic phenotypes.8,9
Central to our story, opioid response phenotypes of respiratory depression and airway compromise are multifactorial, uncommon in children, and most certainly underreported.10 Fentanyl may be especially dangerous because of its potency, rate of onset, and other ligand-specific factors.11 Although low-dose intraoperative fentanyl has been associated with lower odds of postoperative respiratory complications than a high dose or none altogether,12 as little as 0.5 μg/kg intravenous fentanyl has been associated with respiratory arrest.13 Secondary drug exposure and comorbidities such as obstructive sleep apnea may exaggerate respiratory sensitivity to fentanyl.10,13,14 Novel quantitative trait loci have been associated with morphine-induced respiratory depression in mice,15 but pharmacogenetic understanding of fentanyl-induced respiratory depression and overdose death in humans is limited.16,17
With this article, we offer 4 recollections of the experience of a 17-year-old male patient who had no history of drug use or obstructive sleep apnea but who displayed heightened sensitivity to fentanyl after a routine medical procedure. These overlapping perspectives strive to convey the lived experience of opioid-induced respiratory depression and its life-threatening potential outside of medical supervision. Clinicians must be vigilant in identifying opioid outliers, namely, those who may be at high risk for abuse, addiction, respiratory compromise, and death, taking every opportunity to educate and prevent such events.
Language: en |