Patient Care

Fentanyl Presents Need for New Strategies for Combatting Opioid Abuse

Issue 11 and Volume 41.

In 2014, more Americans died of drug overdoses than any other year on record. There were more than 47,000 deaths, with roughly two-thirds of those deaths linked to opioids. This opioid epidemic includes synthetic opioids, such as fentanyl, which are responsible for the rise in death rates. Fentanyl analogs and carfentanil potent opioid receptor agonists can cause a toxidrome characterized by significant central nervous system and respiratory depression. Fentanyl has been implicated in multiple outbreak of poisonings.1 (See Figure 1, below.)

Acetyl fentanyl, an analog similar to the Schedule II (i.e., a classification of drugs that means potential for abuse is high) opioid fentanyl, is a potent opioid analgesic. Acetyl fentanyl hasn’t been approved for medical use in the United States and there are no published studies on safety for human use. According to the Drug Enforcement Administration’s National Forensic Laboratory Information System (NFLIS), federal, state and local forensic laboratories reported 10 exhibits identified as acetyl fentanyl in 2013 and 40 exhibits identified as acetyl fentanyl in 2014.2

EMS strategy for fentanyl overdose
Fentanyl can be laced into counterfeit pills meant to resemble prescription opioids. Photo courtesy DEA

Although pharmaceutical fentanyl can be diverted for misuse, most cases of fentanyl-related morbidity and mortality have been linked to illicitly manufactured fentanyl and fentanyl analogs, collectively referred to as non-pharmaceutical fentanyl (NPF)-related compounds. (Drug analogs are, according to the DEA, “a substance which is intended for human consumption and is structurally or pharmacologically substantially similar to or is represented as being similar to a Schedule I or Schedule II substance and is not an approved medication in the United States.”) These are sold via illicit drug markets for their heroin-like effect. Drug dealers have found NPF to be less expensive and easier to manufacture than heroin. Counterfeit street drugs are produced of pharmaceuticals such as hydrocodone-acetaminophen or alprazolam. Pills produced in this manner may have widely varying potentially lethal amounts of NPF.3–5

Prehospital naloxone (Narcan) usage in the management of opioid overdoses is increasing. The Obama Administration signed the Comprehensive Addiction and Recovery Act (CARA) in July to help states fight heroin and opiate addiction, support the expansion of diversion programs, and include expanded use of naloxone by first responders.

Although these efforts are increasing public awareness and the availability of naloxone, they typically focus on the abuse of morphine, hydrocodone, oxycodone and illicit heroin rather than more highly potent opioids. The naloxone role for professional first responders to these highly potent opioid overdoses characterized by profound respiratory depression needs to be revised. Respiratory depression caused by illicitly manufactured NPF can be treated with naloxone, although multiple doses of naloxone are needed to counteract NPF’s much greater potency. It may take six times the customary naloxone dose to reverse otherwise lethal NPF-induced respiratory depression.

Figure 1: Drug overdose deaths involving opioids, by type of opioid, United States, 2000–2014
EMS strategy for fentanyl overdose

Poisoning Outbreaks

In March 2015, the DEA issued a nationwide alert identifying fentanyl as a threat to public health and safety.1 This was followed by the June 2016 DEA National Heroin Threat Assessment Summary, which noted that “beginning in late 2013 and throughout 2014, several states have reported spikes in overdose deaths due to fentanyl and its analog acetyl-fentanyl. Most of the more than 700 fentanyl-related overdose deaths reported to DEA during this time were attributable to illicitly-manufactured fentanyl—not diverted pharmaceutical fentanyl—and either mixed with heroin or other diluents. The DEA report noted that the “true number is most likely higher” because “many coroners’ offices and state crime laboratories do not test for fentanyl or its analogs unless given a specific reason to do so.”3,4

The DEA confirmed 52 fatalities involving acetyl fentanyl in the United States in 2013–2015. These fatalities have been confirmed in California, Louisiana, Maryland, North Carolina, Oregon, Pennsylvania, Rhode Island and Wisconsin.

From August 2013 through the end of 2015, U.S. law enforcement agencies seized at least 239 kilograms of illicitly produced NPF. Although the total quantity of NPF seized may appear small relative to other illicit drugs, NPF is more dangerous to potential users than other illicit drugs due to its extremely small lethal dose (approximately 2 mgs). In addition to being deadly to users, NPF poses a grave threat to law enforcement officials and first responders, as a lethal dose of fentanyl can be accidentally inhaled or absorbed through the skin.4

Carfentanil is a powerful synthetic opioid analgesic 10,000 times stronger than morphine and 100 times more potent than fentanyl. It’s used by veterinarians for large animals. Carfentanil has been discovered in Ohio and Florida’s supplies of heroin.6,7 In July 2016, there was a cluster of NPF toxidromes in Ohio. Within three days, 25 cases with four deaths were reported in Akron.

The danger of NPF is prompting advocates to push for more availability of naloxone to counter overdoses. Education about NPF could reduce mortality among illicit-drug users. Improving naloxone availability to emergency response personnel and those in contact with at-risk persons might prevent deaths.

Naloxone & Fentanyl Toxidromes

A spike in opioid overdoses in Florida’s Manatee County and the emergence of carfentanil cut into heroin led medical personnel, paramedics and law enforcement to discuss changing naloxone protocols.7

These NPF toxidrome outbreaks stress EMS, public health agencies, hospitals and first responders. Toxicologic confirmation of the presence of NPF is often not immediately available, requiring responders to identify it by clinical observation of profound respiratory depression requiring multiple naloxone doses for reversal. Because fentanyl can be absorbed through the skin or inhaled if it becomes airborne, first responders need precautions in order to keep personnel safe. Fentanyl’s high potency can cause rapid and profound respiratory depression and death; if injected intravenously, maximum respiratory depression is reached in two minutes.8

Because of this, DEA agents in St. Louis are trained in how to give themselves the anti-overdose naloxone in case of accidental exposure to fentanyl.9 Other recommendations by the DEA include undercover officers being told to accept drugs in baggies or aluminum foil, not directly by hand. Officers should wear protective gloves and masks to protect their skin and lungs. Law enforcement can aassume that the methamphetamine or heroin may be mixed with fentanyl. Naloxone should be kept ready for police dogs as they’re trained to sniff heroin.9

A March 2016 outbreak of toxidromes caused by fentanyl-adulterated counterfeit tablets purchased on the street as hydrocodone/acetaminophen in California resulted in 18 patients presenting to a single Sacramento hospital over eight days.10,11 These patients required higher dosing and prolonged naloxone infusions. Observation periods off naloxone were extended due to recurrent toxicity.

In August 2016 the city of Huntington, W.V. reported 27 overdoses within four hours in one evening. The Cabell County EMS Director Gordon Merry noted that it sometimes took more than one dose of naloxone to revive the victims; one victim was given naloxone three times.12

Counterfeit street NPF drugs have serious ramifications for public health, law enforcement, and healthcare facilities. Repeated doses of naloxone over several hours may be needed to adequately treat NPF toxidromes. EDs must have adequate naloxone available as well as contingency plans for additional supplies, services and personnel. During the Cabell County outbreak, Merry stated, “Seven ambulances were tied up within minutes due to overdose calls and still needed more, which we had to get from other parts of the county. It was basically like a mass casualty event.”12

The current lack of guidelines for NPF outbreaks adds to the strain on EMS services. In short, the current epidemic requires “A far more aggressive and strategic expansion of evidence-based interventions in geographic areas heavily affected by heroin and fentanyl … to reduce demand and stop deaths.”8

In August, the Obama Administration announced it will spend $17 million to help law enforcement agencies disrupt fentanyl heroin trafficking, train medical providers in safe prescribing practices, and increase the use of naloxone to reverse overdoses.13 It called for $1.1 billion in new funding to address the current prescription opioid and heroin epidemic; however, funding hasn’t been provided.

Education & Social Media

One approach to reducing fatalities is expanding overdose response education to broader audiences. One study suggests that web-based online training—with its widespread reach and accessibility—may be a promising approach to basic overdose education.14 Another approach is to utilize social media, as it provides timely interaction facilitating community engagement for time-pressed providers.

Twitter is a social media platform that promotes concise information sharing in a peer-to-peer format, which may make professional educational materials more readily accessible and acceptable. Professional first responder tweets that mention naloxone use problems as well as potential solutions can help guide EMS administrators towards an overdose reversal educational needs assessment.15 Competency in naloxone usage can be assessed with feedback by tweets.

Updated guidelines in the use of prehospital naloxone for fentanyl overdoses can be presented as tweets. Twitter, with its wide reach and brevity, can alert EMS agencies of NPF outbreaks. It can help coordinate public health agencies with EMS stressed by coping with NPF toxidromes. The Twitter profile @BroochOpioidEMS (in which “Brooch” stands for “basic response to opioid overdose by community help”) promotes timely dialog in management of opioid overdose for professional first responders.16


Collaborative efforts among public health, medical and law enforcement officials are essential for a rapid and effective response for EMS stressed by coping with the emerging threat of NPF toxidromes. EMS personnel can lead the initiative by educating the public about the dangers of opioid overdoses in their communities and collaborating with other agencies to establish an opiate action plan.17 Outbreaks of NPF poisonings may be treated as a mass casualty event. Communities can prepare with EMS personnel working alongside social agencies and family members of drug users in educating them on naloxone usage for opioid overdoses.


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2. Acetyl fentanyl. (July 2015.) Drug Enforcement Administration. Retrieved July 20, 2016, from

3. Carter D. CDC advisory warns of possible nationwide increase in fentanyl deaths. Am J Nurs. 2016;116(2):15.

4. Counterfeit prescription pills containing fentanyls: A global threat. (July 2016.) Drug Enforcement Administration. Retrieved Aug. 1, 2016, from

5. National heroin threat assessment summary—updated. (June 2016.) Drug Enforcement Administration. In DEA Intelligence Brief. Retrieved July 20, 2016, from

6. Heroin adulterant creating deadly combination: Synthetic opioid carfentanil found in local drugs. (July 15, 2106.) Hamilton County Heroin Coalition. Retrieved Aug. 2, 2016, from

7. De Leon J. (July 19, 2016.) Protocols changing as heroin overdoses spike, stronger opioid being cut into supply. Bradenton Herald. Retrieved July 29, 2016, from

8. Green TC, Gilbert M. Counterfeit medications and fentanyl. JAMA Intern Med. Aug. 8, 2016. [e-pub ahead of print.]

9. Danger of fentanyl alters way police officers operate. (June 29, 2016.) Houston Herald. Retrieved June 30, 2016, from

10. Sutter ME, Gerona R, Davis M, et al. Fatal fentanyl: One pill can kill. Acad Emerg Med. June 20, 2016. [e-pub ahead of print.]

11. Counterfeit Norco poisoning outbreak—San Francisco Bay Area, California, March 25-April 5, 2016. (April 29, 2016.) Centers for Disease Control and Prevention. Retrieved June 15, 2016, from

12. Marco T. (Aug. 18, 2016.) West Virginia city has 27 heroin overdoses in 4 hours. CNN. Retrieved Aug. 19, 2016, from

13. Obama administration funds new projects to disrupt prescription opioid fentanyl and heroin trafficking. (Aug, 17, 2016.) The White House. Retrieved Aug. 19, 2016, from

14. Roe SS, Banta-Green CJ. An initial evaluation of web-based opioid overdose education. Subst Use Misuse. 2016;51(2):268–275.

15. Bielenberg J, Haug NA, Linder SH, et al. Assessment of provider attitudes towards #naloxone on Twitter. Subst Abus. 2016;37(1):35–41.

16. Muquit LS, Krasner S, Bielenberg J, et al. (March 2016.) Naloxone and opioid overdose education on Twitter: Facilitating community engagement. [Poster presented at the annual meeting of the Society of Addiction Psychology (Division 50 of the American Psychological Association).] San Diego. 

17. Clary M. (Aug. 22, 2016.) Rise in heroin overdoses draws response plan in Broward. SunSentinel. Retrieved Aug. 22, 2016, from