Editor’s note: This is an updated submission written by Simon Taxel in 2019. He will be presenting on this topic at JEMS Con. Click here to register for the class.
Fentanyl, a potent synthetic opioid, was first synthesized in December 1960 by Dr. Paul Jansen in Belgium. It was developed as an intravenous analgesic and its first clinical use was recorded in 1963. Fentanyl was brought to the United States in 1968 and today, is one of the most frequently used intraoperative analgesics across the world.1 Additionally, it is available in a variety of forms including transdermal patches as well as nasal, buccal, sublingual, and transmucosal preparations used to treat a variety of acute, chronic, cancerous, and palliative pain conditions. In prehospital emergency care, fentanyl is now a common medication for the relief of severe pain associated with acute injuries and illnesses. Its popularity stems from its minimal cardiovascular effects, lack of increases in plasma histamine, rapid onset of action, relatively short half-life, and low cost resulting from its ease to synthesize and produce.
Fentanyl functions in the same manner as other opioids, binding with neurochemical transmitters in the central nervous system, providing analgesia and sedation. It blocks the transmission of pain signals and activates the parasympathetic nervous system. Fentanyl also binds to the same brain receptors as naturally produced endorphins – such as dopamine, serotonin and oxytocin – causing feelings of euphoria and pleasure at levels similar to those experienced during sexual intercourse. With repeated exposures, the human body quickly adapts to this increased endorphin production and when endorphin levels drop, feelings of depression, pain, and physical craving occur. These neurochemical changes are a primary physiological agent of opioid dependence. In the respiratory system, fentanyl causes decreased respirations, cough suppression, and smooth muscle relaxation. In the gastric system it decreases oral secretions, slows gastric motility, and causes constipation. Signs and symptoms of fentanyl ingestion as well as opioid toxicity and overdose in general, include respiratory depression and apnea, altered mental status, confusion, hypoxia, diaphoresis, miosis (constricted pupils), and slurred speech.
Fentanyl – and its analogs, such as acetyl, butyryl, carfentanil, or furanyl fentanyl – are relatively simple and cheap to produce. They are also incredibly potent at lower concentrations compared to other opioids such as oxycodone (Oxycontin®), morphine, and heroin. Aggressive supply-side drug interdiction stemming from prohibition and U.S. drug-war policy puts incredible pressure on illicit drug markets to produce products with increased concentration and potency at lower volumes. This is a phenomenon that is known as the iron law of prohibition. The term, first coined in 1986, by renowned drug policy activist Richard Cowan, points out that increased pressure from law enforcement on illicit substances inevitably leads to increased potency.2 There are a multitude of examples of this dating back to America’s failed alcohol prohibition experiment which lasted from 1920 until 1933. During prohibition, bootleggers preferred smuggling high proof distilled spirits rather than lower proof fermented beverages such as beer and wine due to the decreased volume and higher profit margin associated with the stronger liquors.3 In the 1980s, the pressure from Ronald Reagan’s international anti-cannabis enforcement caused farmers in central America and Southeast Asia to switch from the cultivation of marijuana to cocoa and poppies. This led to substantial increases in the production of heroin and cocaine, which are much more potent and profitable at lower volumes than marijuana.4 Synthetic, lab-produced cannabinoids (also known as spice or K2) flooded the United States in the mid-2000s as the result of ongoing domestic cannabis prohibition. In November 2021, nitazenes, a class of opioids even more potent than fentanyl, were detected on used syringes in Washington, DC, and may be linked to the substantial increase in overdose deaths in the area.5
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Much of the fentanyl that makes it to the streets of the United States is manufactured in China, sold on the dark web, and shipped through legal channels such as the United States Postal Service, the United Parcel Service, or Federal Express. It is also produced and distributed by transnational drug cartels based in South and Central American and then smuggled, along the same routes used to traffic heroin and cocaine, through Mexico, the Caribbean, and West Africa. In some cases, it is also now being manufactured in clandestine drug labs in the United States. In 2018, Drug Enforcement Agency (DEA) special agents raided what they thought was a methamphetamine lab in a western Pennsylvania hotel room; it turned out that the room’s occupant had been trying to make fentanyl.6 Fentanyl has been found to be packaged and distributed as a standalone product. More often, however, it is used as a cutting agent to increase the profitability of heroin and other illicit drugs.
According to the DEA in Philadelphia, a kilogram of heroin sells for $50,000 to $80,000, and a drug trafficker can make about $500,000 in profit. A kilogram of fentanyl sells for $53,000 to $55,000, is 50 times stronger than heroin and can render profits in excess of $5 million.7 The addition of fentanyl to heroin, as well as other illicit drugs, is a primary cause of the recent explosion of opioid-related deaths (that despite the ongoing multibillion dollar war on drugs) have continued to rise with tragic speed. In 2017, approximately 72,000 Americans died of drug overdose.8 The Centers for Disease Control notes that in the 12-month period between April 2020 and April 2021, more than 100,000 Americans died from drug overdoses. This represents a 28.5% increase from the previous year and the overwhelming majority of all of deaths involved opioids like fentanyl.9
Fentanyl is not just being mixed with heroin. In some tests, a majority of all illicit pills and powder, including cocaine, crack, methamphetamine, PCP, and ecstasy (MDMA) now contains fentanyl or one of its analogues. In August, of 2019 multiple people overdosed and three people died after ingesting what they believed to be cocaine at an afterhours party in Pittsburgh. Law enforcement testing later determined that the substance was at least in part fentanyl.10 In August of 2021, six people died and many others overdosed in separate incidents over the course of three-days in a small community in Suffolk County, New York. Local law enforcement stated that all of the victims ingested cocaine that was contaminated with fentanyl.11 Anyone who injects, inhales, or ingests illicit pills and powders should be encouraged to test their drugs with fentanyl test strips prior to use. EMS providers must remain vigilant and be prepared to treat patients presenting with symptoms consistent with the opioid toxidrome who did not knowingly use opioids.
Fentanyl-laced cannabis products are a malevolent myth that has appeared multiple times in law enforcement press releases and subsequent media reports.12 These rumors began as early as 2017 when a county coroner in Ohio erroneously stated that he had seen evidence of marijuana laced with fentanyl. It was later determined that his remarks were unsubstantiated and were based on third-hand hearsay. To-date, there are no scientifically verified reports fentanyl contamination of cannabis products.13 Writer and drug researcher Claire Zagorski notes that in addition to the paucity of evidence associated with the rumors, fentanyl is destroyed and rendered inert when it is burned. Meaning that even if it made its way onto cannabis flower, it would not have any effect on the individuals who inhaled it when smoking.14 Additionally, fentanyl is not well absorbed through the gastrointestinal tract, which is why there are no oral preparations of the medication which minimizes the risk of its impact if it were to end up in edible products. Finally, it is worth noting that it is possible that fentanyl could be vaporized (heated to its boiling point as opposed to burning). However, it requires much higher temperatures than are found in vaping devices that are used to consume tobacco and cannabis products.
According to producers, the maximum temperature of most commercially produced vape devices is approximately 428 degrees Fahrenheit, and it would require temperatures close to 900 degrees Fahrenheit to vaporize fentanyl.15 The maximum temperature of the devices is limited because the higher temperatures would destroy and render inert the tobacco and cannabis products that they are intended for. There are a multitude of postmortem toxicology reports that note the presence of both cannabinoids and opioids in the bodies of overdose victims. This is believed to be coincidental and the result of the ingestion of different substances at different times. It may also be related to the extended half-life of cannabis in human body compared to the relatively rapid excretion of opioids.16 While the risk of fentanyl contamination in illicit pills and powder cannot be overstated, the risk of being exposed to it when ingesting cannabis products is essentially non-existent.
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Over the course of the last few years, there have been numerous reports where police officers, firefighters, EMS providers, and other emergency responders have described acute illnesses after being in close proximity to illicit powder believed to contain fentanyl. There is a growing concern that merely being near fentanyl can lead to passive exposure, presenting a life-threatening hazard. In many of these case reports, the responders believe that inert powdered product is being aerosolized and inhaled or transdermally absorbed through the skin , even when little to no visible skin contact has occurred. The victims complain of a variety of nonspecific symptoms including dizziness, anxiety, fatigue, dyspnea, nausea, vomiting, and syncope. In some cases, they self-administer naloxone (Narcan®). In others, they are treated and transported to the hospital by EMS. All of the supposed victims recovered quickly without any significant complications.
In August of 2021, the San Diego County Sheriff’s Department released a video that quickly went viral. It purportedly showed a deputy overdose and become unresponsive after simply being near fentanyl powder during a traffic stop. The officer was given multiple doses of naloxone and was transported to the hospital where he was evaluated and then discharged. Interestingly, none of the other officers present on scene or the occupants of the car who were arrested experienced any ill effects. When the video is viewed, there does not seem to be clinical evidence of opioid toxicity. While the officer does appear to suddenly pass out, he does not experience drowsiness, hypoventilation, apnea, cyanosis, or diaphoresis. After the video’s release, it was uncritically reported on by both local and national media outlets. A large public outcry ensued, and some news agencies amended their reporting and included the testimony of medical experts who stated that it was not possible that deputy inadvertently overdosed, but the sheriff’s department has refused to release the toxicological evidence that would confirm or refute their story.17
In November of 2021, two officers and a school nurse experienced non-specific symptom, were given naloxone, and were transported to the hospital after carfentanil was found on a high school student in Tennessee. The initial reports stated the carfentanil was in a cannabis vape pen but were later changed to say that it was in a paper packet next to the vape pen. All three of the reported victims were evaluated at the emergency department and then discharged. After the incident, the school was evacuated, a hazardous materials team responded, and the building was closed for days for “deep” cleaning. The student who was carrying the illicit substance did not require medical attention and neither did any of his teachers or classmates.
Cases like continue to be widespread and there is a growing public hysteria. Some are seeking to profit from the perceived crisis, advertising personal protective equipment manufactured specifically to protect first responders from the supposed threat of passive exposure to fentanyl. They are hawking specialized gloves, respirator masks, and protective suits.18 This profiteering only serves to increase stigma, as well as provide unsubstantiated validation to individual and organizational bias and fear. To date, there has been no toxicological evidence presented in any of the cases to support the conclusion that these individuals actually experienced opioid toxicity. There is unanimous agreement among physicians and toxicologists that toxicity and overdose from passive exposure to fentanyl is not possible. If there was a real hazard, it stands to reason that the people who produce fentanyl, distribute, or use it would suffer similar exposures. This is simply not happening.
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Some of the victims may have suffered legitimate medical problems that coincidently occurred after the perceived exposure while others appear to be suffering from psychosomatic symptoms related to fear and anxiety. The pervasive anxiety surrounding passive exposure to opioids is only serving to increase the stigma associated with people who use drugs. This at-risk population already struggles to get the vital medical care needed for them to survive and recover, and this misconception is only serving to make access more difficult. There have been reported incidents of overdose patients not being provided appropriate medical care; hazardous materials response teams are being activated erroneously; or criminal charges being leveled against individuals based upon the belief that their actions endangered responders. A 2020 study in International Journal on Drug Policy found law enforcement and government agencies continue to amplify rumors and push inaccurate information which harms both first responders and members of the community who use drugs.19 This must stop. It is our duty as healthcare professionals and patient advocates to ensure that all stake holders receive the necessary education to dispel these myths and that clear, evidence-based safety guidelines are provided.
In December 2017, the American College of Medical Toxicology (ACMT) and the American Academy of Clinical Toxicology (AACT), the two preeminent organizations representing medical toxicologists across the country, published a joint position statement discussing occupational fentanyl and fentanyl analog exposure to emergency responders. In the document, they stated unequivocally that the risk of clinically significant exposure to fentanyl and its analogs to emergency responders is extremely low.20 Additionally, the report states that the transdermal absorption of fentanyl powder is extremely unlikely to occur. It is further noted that inert fentanyl powder is not aerosolized, and it would be exceptionally rare for drug droplets or particles to be suspended in the air.21
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Safety Guidelines for operating at emergency scenes where suspected fentanyl powder is present.
1. Standard nitrile medical gloves and duty uniforms provide adequate dermal protection. If suspected fentanyl powder is found on skin or clothing, the dry powder should be brushed away and then the area should be cleansed with soap and water. Contact with intact skin or clothing is not considered a hazardous exposure.
2. In the extremely unlikely event that it is suspected that drug droplets or particles are suspended in the air, standard disposable N95 Masks will provide sufficient respiratory protection. Respiratory protection is not required for routine operations.
3. Naloxone should be available and all responders should be trained in its use and administration. Naloxone should only be administered to individuals who present with objective signs of opioid toxicity such as , altered mental status with hypoventilation, unconsciousness, and respiratory depression. Naloxone is not indicated for individuals who experience vague sub-clinical symptoms like nausea, vomiting, fatigue, dyspnea, dizziness, and anxiety.22 In the unlikely event that an exposure to fentanyl occurs, in the absence of extended hypoxia, there is no long-term risk to responders.
4. Despite anecdotal reports to the contrary, there is no evidence to support the claim that overdoses caused by fentanyl and its analogs require increased doses of naloxone to reverse. If a patient’s altered mental status and respiratory depression are persistent after the administration of standard doses of naloxone along with oxygenation and positive pressure ventilation, then medical providers should have a high index of suspicion for additional complicating sequalae such as polysubstance ingestion, hyperkalemia, hypothermia, rhabdomyolysis, and or anoxic brain injury.23
Conclusion
The use of psychoactive substances to alter human consciousness for both recreational and ceremonial purpose has been a part of human culture as long as history has been recorded. Our desire to chemically change our state of minds has only increased in modern times. As long as drug policy centers on prohibition, and the war on drugs continues, it is reasonable to assume novel and increasingly potent substances will continue to poison people who use drugs. Fentanyl is endemic in illicit drug markets across the country, and despite the efforts of law enforcement agencies, there is no indication its illicit production, distribution, and use is going to be stopped.
Resuscitation Airway and Internal Dynamics
Additionally, fentanyl has a multitude of necessary medical uses and its value to pain patients is significant. The public hysteria and misconceptions about fentanyl cannot be allowed to jeopardize its legitimate use. Law enforcement officers, EMS providers, firefighters, and other first responders must be properly trained to safely respond to incidents where illicit fentanyl is present without unnecessary anxiety. The guidelines presented here represent the best evidence that is currently available and can serve as a standard for all stake holders. The public at large looks to public safety professionals for guidance, and it is imperative that we adopt recognized best practices to reduce their fear.
References
1. Stanley, Theodore H. The Fentanyl Story. The Journal of Pain, Vol 15, No 12 (December), 2014: pp 1215-1226.
2. Mosher, Clayton J.; Akins, Scott (2007). Drugs and Drug Policy: The Control of Consciousness Alteration. SAGE. pp. 308–09.
3. Burns, Trevor. How Drug Prohibition Created the Fentanyl Crisis. Cato Institute Website. Available at: https://www.cato.org/commentary/how-drug-prohibition-created-fentanyl-crisis#. Accessed December 17, 2021.
4. Loewenstein, Antony. The United States. In: Pills, Powder, and Smoke. Scribe Publications. Minneapolis, Minnesota. 2019; 141-188.
5. Jamison, Peter. New opioids, more powerful than fentanyl, are discovered in D.C. amid deadly wave of overdoses. Washington Post Website. Available at: https://www.washingtonpost.com/local/dc-politics/new-opioids-more-powerful-than-fentanyl-are-discovered-in-dc-amid-deadly-wave-of-overdoses/2021/11/29/680afb2c-4d43-11ec-94ad-bd85017d58dc_story.html. Accessed December 17, 2021.
6. Whelan, Aubrey. How Fentanyl, the deadly synthetic opioid, took over Pennsylvania. The Philadelphia Inquirer website. Available at: http://www2.philly.com/philly/health/fentanyl-synthetic-opioid-drug-overdoses-philadelphia-pennsylvania-20181024.html.
7. Whelan, Aubrey. How Fentanyl, the deadly synthetic opioid, took over Pennsylvania. The Philadelphia Inquirer website. Available at: http://www2.philly.com/philly/health/fentanyl-synthetic-opioid-drug-overdoses-philadelphia-pennsylvania-20181024.html.
8. Sanger-Katz, Margot. Bleak New Estimates in Drug Epidemic: A Record 72,000 Overdose Deaths in 2017. The New York Times Website. First Published August 15, 2018. Available at https://www.nytimes.com/2018/08/15/upshot/opioids-overdose-deaths-rising-fentanyl.html.
9. Drug Overdose Deaths in the U.S. Top 100,000 Annually. CDC Website. Available at: https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm. Accessed December 17, 2021.
10. Man indicted in deadly mass overdose at Pittsburgh party. ABC News Website. Available at: https://abcnews.go.com/US/wireStory/man-indicted-deadly-mass-overdose-pittsburgh-party-65874083. Accessed December 17, 2021.
11. Nir, Sara Maslin. The Cocaine Was Laced With Fentanyl. Now Six Are Dead From Overdoses. New York Times Website. Available at: https://www.nytimes.com/2021/08/31/nyregion/fentanyl-cocaine.html. Accessed December 17, 2021.
12. Hilton, Jazmine. Rosenzweig-Ziff, Dan. Fatal opioid overdoses are up by the hundreds, devastating families and worrying officials. The Washington Post Website. Available at: https://www.washingtonpost.com/local/public-safety/fatal-opioid-overdoses-dc/2021/07/08/0c50d298-db51-11eb-9bbb-37c30dcf9363_story.html. Accessed December 17, 2021.
13. Zagorski, Claire. The Pernicious Myth of Fentanyl-Laced Cannabis. Filter Magazine Website. Available at: https://filtermag.org/fentanyl-marijuana-myth/. Accessed December 17, 2021.
14. Ibid
15. Ibid
16. Ibid
17. Paz, Isabella, Grullon. Video of Officer’s Collapse After Handling Powder Draws Skepticism. The New York Times Website. Available at: https://www.nytimes.com/2021/08/07/us/san-diego-police-overdose-fentanyl.html. Accessed December 17, 2021.
18. Fentanyl Protection Solutions. Ansel Website. Available at: https://www.ansell.com/eu/en/campaigns/fentanyl. Accessed December 17, 2021.
19. Beletsky, Leo. Marino, Ryan. Seymour, Sarah. Et al. Fentanyl panic goes viral: The spread of misinformation about overdose risk from casual contact with fentanyl in mainstream and social media. The International Journal on Drug Policy. Published online 2020 Sep 16. doi: 10.1016/j.drugpo.2020.102951.
20. Moss MJ, Warrick BJ, Nelson LS, et al. ACMT and AACT Position Statement: Preventing Occupational Fentanyl and Fentanyl Analog Exposure to Emergency Responders. J Med Toxicology. 2017;13(4):347–351. doi:10.1007/s13181-017-0628-2
21. Ibid
22. Ibid
23. Taxel, Simon. High Dose Naloxone: Is it evidence based? Critical Care Now. Available at: https://criticalcarenow.com/high-dose-naloxone-is-it-evidence-based/. Accessed December 17, 2021.
