Boys at Risk: Fatal Accidental Fentanyl Ingestions in Children

Abstract

We analyze 25 accidental childhood fentanyl exposures reported to FDA, 2004–2013. These exposures had a case-fatality rate = 48%; male:female ratio = 7.3; 76% were within the 2–4 age range. The ability of fentanyl to kill children so quickly is explained by fentanyl’s ability to suppress respiration—as quantified by the antinociceptive potency per milligram, fentanyl far and away leads all narcotics. FDA recommends for fentanyl disposal: flush all forms of fentanyl down the toilet.

Introduction: Fentanyl Ingestion

We first heard of the dangers of an ingested fentanyl patch through the ‘grapevine’ in Rolla, Missouri. The tragedy as we heard it was confirmed with our county coroner. The story began when a parent called her child’s day care center and nobody answered the telephone. After several calls went unanswered, the concerned parent went to the day care center and found the babysitter lying unresponsive on the bed with the unsupervised children wandering around. Postmortem investigation revealed a chewed fentanyl patch in her mouth; the coroner ruled the death an accidental fentanyl overdose. A second case was related by a patient who reported that they were going to a funeral for a toddler who had retrieved a fentanyl patch from a wastebasket and had eaten the patch—again with fatal results. We were unable to reach the devastated family to find out more about this accident. We still wanted to know—what are the circumstances surrounding these tragic accidents? Can case reports give details that help us know more about avoiding these incidents and tell us who is at greatest risk? We first performed a literature search and found three recent cases of fatal fentanyl accidents in children.

Case Study

Three cases of fatal accidental fentanyl patch exposure in children: fentanyl as a Band-Aid, fentanyl pulled off a toy truck, fentanyl picked up off the floor.

Case 1

Fentanyl used as a Band-Aid

A two-year-old girl was found dead in her bed by her grandmother. The previous evening, the child had fallen and abraded her knee. The grandmother had placed a fentanyl patch on the largest abrasion to stop the bleeding sometime after 6:30 p.m. The child fell asleep at 9:00 p.m. By 1:00 a.m, the grandmother heard the child breathing harder, wheezing, and snoring. By 7:00 am, the child was found unresponsive and declared dead. At autopsy, the 12 kg. child had multiple abrasions from minor trauma sustained the previous evening. The largest abrasion, 2×2 cm, was covered by a transdermal fentanyl patch. Drug analysis detected high systemic fentanyl in the child’s urine.¹

Case 2

Fentanyl patch pulled off a toy truck

A two-year-old boy was found unresponsive in his home and could not be resuscitated. A used transdermal fentanyl patch was found lodged in the child’s mouth. Two days earlier, he had visited his great-grandmother in a nursing home. Detectives and the state health department determined that the child likely acquired the patch from the nursing home, where used patches were found stuck to bed rails and bedside tables. Analysis by the Institute for Safe Medical Practices (ISMP) determined that the most likely scenario was that the child rolled over the patch with a toy truck, and ingested it later, as the mother recalled seeing “what looked like a Band-Aid” on one of the truck wheels.” ²

Case 3

Fentanyl patch picked up off the floor and ingested

A1-year-old baby girl was put to bed and two hours later was found dead. Autopsy revealed a transdermal fentanyl patch in the girl’s stomach. Investigation established that the child has unintentionally swallowed the patch, which had been lying on the floor. Drug analysis detected high systemic fentanyl in the child’s heart and peripheral blood.³

Our small medical informatics research group of two pre-medical students, one computer science student and a dermatologist used the FDA adverse drug reaction database MedWatch (AERS) and the CDC Wonder data to learn more about these narcotic casualties.^4,5 We confined our study to children, who are most vulnerable to the powerful respiratory depression of fentanyl. We would try to answer these questions: Which children are primarily at risk for accidental fentanyl ingestion? What recommendations can we make that could reduce the number of these terrible events? The remaining sections of this report include methods, results, discussion, conclusions and recommendations, and limitations.

Methods

Data-mining techniques were applied to study childhood accidental fentanyl overdoses. All AERS reports of accidental childhood ingestions of fentanyl received by FDA and reported on MedWatch January 2004–June 2013 were analyzed. Cases were limited to children, ages 0–18, those where fentanyl was primary suspect, and those with the entry “accidental exposure” within the MedWatch field patient indication (INDI_PT). No cases had any indication such as pain, pain management, neuralgia, or any indication of chronic disease. Downloaded data was imported in SQLite, a public-domain relational database management system able to store very large databases and answer complex queries. Our analysis included totals for gender, age, and fatal vs. nonfatal outcome.

Results

A. FDA Data

Twenty-five cases met study criteria: 22 male and 3 female; 76% of these cases were within the two to four age range. Twelve of these 25 cases were fatal, corresponding to a case-fatality rate of 48%. Of the fatal cases, five involved ingestion of oral fentanyl citrate, in the form of lollipops and lozenges; five involved fentanyl patches, and two fatalities were by oral route from unknown type of fentanyl. Females represented only one of twelve fatalities; the male:female ratio for all cases was 7.3. (See Figure 1).

Figure 1.

B. CDC Wonder Data

The CDC Wonder database was examined to see if CDC data confirmed the age ranges for narcotic poisonings found in the FDA data. The CDC Wonder data tracks narcotic overdoses generally, without specifying specific drugs. CDC Wonder data shows that most pre-adolescent narcotic poisonings occur in the zero to four age range. Selecting the ICD-10 code “accidental poisoning by and exposure to narcotics and psychodysleptics (hallucinogens)” and deaths for individual ages shows that 160 deaths occurred during 1999–2013 for the zero to four age group and only 69 deaths occurred in the five to twelve age group. By twelve years of age, total narcotic deaths begin to approach the high levels observed in adolescent children.

Discussion

Fentanyl: A popular, powerful narcotic that kills quickly

Fentanyl is widely prescribed, ranking fourth (behind acetominophen-oxycodone, buprenorphine-naloxone, and acetaminopvhen-hydrocodone) among narcotics prescribed in the U.S.⁶ It is not widely appreciated that fentanyl is the strongest μ-opioid agonist. In antinociceptive potency per milligram, fentanyl is the most powerful narcotic-ten times as powerful as heroin. As measured by antinociceptive potential in rats, assigning codeine a potency =1, the order of potency is: fentanyl 774.2, heroin 77.4, oxycodone 28.7, methadone 28.2, hydrocodone 18.8, morphine 11.3, and codeine 1.⁷ This potency is increased for children, so that even low doses of fentanyl patches, 25 mg in two of the cases above, can lead to a fatal outcome. The package insert for fentanyl patches states that fentanyl “should ONLY be used in patients who are already receiving opioid therapy,” and “who have demonstrated opioid tolerance.”⁸ Opioid tolerance is defined explicitly in the package insert: “those who have been taking, for a week or longer, at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily.”

The bioavailability of fentanyl varies according the route of administration. Putting the patch in the mouth and chewing or sucking the patch increases the bioavailable dose significantly beyond that which is obtained from application of the patch to the skin or even eating the patch: “If the entire contents of a 50 mg fentanyl patch were removed and administered transbuccally, this systemic level would be approximately three times that achieved with gastrointestinal absorption (i.e., approximately 5,000 micrograms of fentanyl or 375 milligrams of intravenous morphine.”⁹ Therefore, an adult sucking on a fentanyl patch, even an adult with opioid tolerance, is at risk for fatal overdose, as in the fatal case of the Rolla babysitter. A baby or toddler lacking opioid tolerance is at higher risk, and may die quickly sucking on a fentanyl patch, lozenge or lollipop. The one-year-old girl in Case 3 was found dead only two hours after ingestion of a 25 microg/hr patch.³

The FDA recommends disposal of fentanyl patches by “folding them in half with the sticky sides together, and then flushing them down a toilet.”¹⁰ The FDA reported 32 cases of accidental exposure to fentanyl ingestion, with 12 deaths, from 1997–April, 2012, mostly “involving children younger than 2 years old.”¹⁰ One more year of AERS data ending in April 2013 in our analysis yielded seven new cases of accidental fentanyl ingestion: six cases in two-year-olds, and one in a 10-year-old child.

Our report shows that fentanyl accidents continue unabated, with most childhood cases occurring in boys, with most childhood victims either two or four years of age. All of the accidental patch exposures occurred in four-year-old boys. All fatal accidental ingestions of oral lollipop or lozenge forms occurred in one- or two-year-old children, all but one of whom were boys.

Why are two-to-four-year-old boys at risk?

Two-year-olds are particularly predisposed to putting things in their mouths. Greater abilities possessed by four-year-olds, who can better observe where adults put things that are of potential interest and are agile enough to successfully access trash containers and storage areas, may account for patch ingestion in the older children. Data presented here suggest that males, 22 of 25 reported cases, are particularly susceptible to accidental ingestion of improperly disposed fentanyl. The reason for this male preponderance is unknown. Greater risk-taking by males could account for this gender disparity.¹¹

Our study of fentanyl primary suspects in accidental exposures reported to the FDA 2004–2013 showed that nearly 50% (12 of 25) cases were fatal. We also examined reports where fentanyl was a secondary suspect. For this situation, 28% (112 of 375) cases were fatal. In contrast, only 0.4% exposures of methadone involving children reported to the FDA were fatal.⁴ The high potency of fentanyl, the high levels of absorption from mucosal surfaces, and the power of fentanyl to depress respiration completely and rapidly can explain this high case-fatality rate. For all these reasons, accidental exposures of fentanyl in children remains an important public health problem, with highest risk for boy toddlers and preschoolers exploring and putting objects in their mouths .

Conclusion and Recommendations

Tragically, accidental ingestions of fentanyl by children continue. Users of fentanyl should protect children and pets by following FDA recommendations to flush all forms of fentanyl down the toilet. The FDA specifies that “Fentanyl patches should be folded “in half with the sticky sides together.”¹² Those persons using fentanyl patches and caregivers for those using fentanyl patches should always dispose of patches immediately in the recommended manner. Any other method of disposal places any child in the area at risk for a fatal accident.

Limitations

AERS cases are submitted voluntarily; therefore data provide only a subset of all exposures. AERS “route of administration” distinguishes transdermal patches from oral forms of fentanyl. We have inferred final exposure by ingestion in most cases, as ingestion was the circumstance for most of the case reports with fatal outcome.

Biography

William V. Stoecker, MD, MS, MSMA member since 1984, is with S&A Technologies, Rolla, Missouri, and the Department of Dermatology, University of Missouri Health Sciences Center, Columbia, Missouri. Justin G. Cole, BS, is in Indianapolis, Indiana. David E. Madsen, BS, and Zachary Woolsey are with S&A Technologies, Rolla, Missouri.

Contact: wvs@mst.edu