Pediatric Naloxone Use Out of Hospital Confirmed Safe

ORLANDO, Fla. — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented on September 29 at the American Academy of Pediatrics (AAP) 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, an assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” Taylor Nichols, MD, an assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician, told Medscape Medical News. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

Nichols, who was not involved in either study, added that all 50 states have some version of Good Samaritan laws that offer protection to individuals who attempt to aid in emergency assistance in good faith, and all except Kansas and Wyoming have laws specifically protecting people trying to help with overdose prevention.

“I tell people that everyone should carry naloxone and have naloxone available to be able to reverse an overdose, whether they personally use opioids or know people who use opioids because if they happen to come into a situation in which someone is passed out and unresponsive, that timely administration of naloxone may save their life,” Nichols said.

He added that primary care physicians, “particularly in family medicine and pediatrics, should be asking about any opioids in the home prescribed to anyone else and ensure that those patients also are prescribed or have access to naloxone to keep at home. Just as with asking about any other potential safety hazards, making sure they have naloxone available is crucial.”

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration.

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 47% afterward, and their correct identification of an overdose increased from 68% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.

Tara Haelle is a Dallas-based science journalist.