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in adults is protective against respiratory depression, this effect is not observed in young children In the neonatal period, the neonatal abstinence syndrome may develop due to maternal use of illicit or prescription opioids or due to treatment of maternal opioid dependence with methadone or buprenorphine during pregnancy Symptom onset is generally within days of delivery and is characterized by irritability and high-pitched crying, and may progress to seizures if untreated Generally, the toxic opioid dose for a person who is not addicted depends on the particular drug For example, with morphine, clinical toxicity (excessive sedation) may appear with doses that exceed mg in the adolescent Individuals who are ultrarapid metabolizers of codeine through CYP2D6 may have increased morbidity and mortality Other toxicities of opiates include (neurogenic) pulmonary edema, mast cell degranulation (which leads to histamine release and an “anaphylactoid” reaction), cardiac disturbances (with propoxyphene or methadone intoxication), and neurotoxicity with seizures (with meperidine intoxication) Some opioids (i.e., methadone, buprenorphine) have particularly long half-lives Clinical Considerations Opioids invariably cause miosis, even after tolerance has developed Respiratory depression is another hallmark of opioid toxicity, due in part to decreased responsiveness of brainstem respiratory centers to increases in carbon dioxide tension This effect is often magnified during sleep The presence of coma, pinpoint pupils, and depressed respiration should suggest opioid poisoning in the absence of history Evidence of track marks may suggest IV drug use To confirm the diagnosis, toxicologic analysis of urine and/or serum should be considered Of note, however, several important synthetic or semisynthetic opioids, such as methadone, fentanyl, buprenorphine and oxycodone, may not be detected on routine urine drug screens The first management step with opioid intoxication is to ensure adequate ventilation and oxygenation Endotracheal intubation may be necessary if there is severe respiratory depression or pulmonary edema Consider GI decontamination if a large amount of oral opioids has been ingested The narcotic antagonist naloxone should be given by IV The dose of naloxone depends on the severity of the patient’s symptoms and whether there has been chronic use Naloxone can precipitate an abstinence syndrome in those who have developed physical dependence; in such patients, smaller initial doses of 0.2 to 0.4 mg, with upward titration as needed, are preferable A full reversal dose in a pediatric patient is 0.1
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