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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 5 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 5 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