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The United States is in the midst of an opioid epidemic. The crisis consists of two separate threats. One is the increased presence of powerful illicit street drugs such as fentanyl. The second threat is the increasing use of oral prescription painkillers like Oxycontin, Percocet, and Vicodin. This column addresses fentanyl—its medical aspects and the on-the-street abuses of this powerful narcotic.
MEDICAL USE OF FENTANYL
I’ve administered fentanyl to over 20,000 patients in my career, and can vouch for the medical utility and import of this drug. Fentanyl is the most commonly administered narcotic during surgery in the United States. If you’ve had a surgical anesthetic, or even a colonoscopy, you’ve likely received fentanyl with few ill effects. Fentanyl is an essential ingredient in the pharmaceutical armamentarium of acute care medicine in hospitals, surgery centers, intensive care units, and emergency rooms throughout the United States. On the streets, fentanyl is killing people. In our hospitals and surgery centers, fentanyl is a useful adjunct as omnipresent as Tylenol.
Fentanyl was first synthesized by Dr. Paul Janssen of Janssen Pharmaceuticals in the 1960s, and was then introduced into anesthetic practice under the brand name Sublimaze.1 Fentanyl is a rapid-onset narcotic drug usually administered by intravenous injection. Compared to morphine, fentanyl is more lipid (fat) soluble, which means the drug crosses into the central nervous system more quickly and works faster than morphine. The termination of the effect of low doses of fentanyl results from decreased concentration, as the drug redistributes from the bloodstream to other organ tissues.
The elimination of higher doses of fentanyl from the body depends on elimination by the liver. Morphine, Demerol, and Dilaudid are other common intravenous medical narcotics, which have slower onset and longer duration of action. When injected into an intravenous line, fentanyl reaches its peak analgesic effect in minutes, significantly faster than morphine. This quicker onset makes fentanyl an easier drug for anesthesiologists to titrate to a desired effect., which makes fentanyl superior when timing for a patient’s awakening from anesthesia. As outpatient and ambulatory surgery blossomed, a short-acting narcotic such as fentanyl, which wore off promptly, became the narcotic of choice.
The most daunting feature of fentanyl is its potency. Most drugs used by anesthesiologists are in doses of milligrams (mgs) or grams (gms). Fentanyl is approximately 100 times more potent than morphine, so a typical 5 mg (5 mg = 5000 microgram) dose of morphine is equivalent to a mere 50 microgram dose of fentanyl. A typical intravenous incremental dose of fentanyl to an adult patient is a mere 50-100 micrograms. The drug is marketed as one milliliter = 50 micrograms for this reason, so 1 – 2 milliliters is an appropriate dose. This potency and the need to be packaged in micrograms is unique to fentanyl and its analogues sufentanil and remifentanil, and requires medical personnel to become comfortable with the low ranges of the appropriate microgram doses.2
Medical fentanyl can be administered in several ways:
- Intravenous fentanyl, as described above, is the most common medical usage of the drug.
- Rarely, fentanyl is added to the spinal fluid as part of a spinal anesthetic block prior to surgery, or to the epidural space as part of an epidural block prior to surgery or prior to labor for childbirth.
- Transdermal drug delivery of fentanyl via an adhesive skin patch is also possible, because of the drug’s high solubility in both water and oil, low molecular weight, high potency, and its lack of skin irritation. Fentanyl transdermal patches (Durogesic or Duragesic) are useful in chronic pain management. The patches work by slowly releasing fentanyl through the skin into the bloodstream over 48 to 72 hours, allowing for long-lasting pain management. Dosage is based on the size of the patch.
- Oral transmucosal fentanyl citrate (OTFC) is a solid dosage form of fentanyl that consists of fentanyl incorporated into a sweetened lozenge on a stick. A commercially available fentanyl product for oral administration, the fentanyl lollipop Actiq, is an application of this technology. The lollipop provides a means by which the drug can dissolve slowly in the mouth. The lollipop is only FDA approved for providing analgesia to patients with chronic pain or cancer pain, and the fentanyl lollipop is not FDA-approved for analgesia after surgery.
Narcotics suppress pain by their action in the brain and spinal cord, but they cause their adverse side effects in multiple organ systems, including the respiratory and cardiovascular systems. The principal danger from narcotics is respiratory depression. The respiratory rate is usually markedly slowed in narcotic overdose, as excessive doses of narcotics make people stop breathing. If there’s an anesthesiologist present to support a person’s breathing, respiratory depression is not a problem. On the streets, with no medical personnel present, respiratory depression from a narcotic overdose can be fatal.
The anesthesia world is well aware of the risks of fentanyl addiction. Narcotic addiction has struck down many anesthesia providers who found themselves vulnerable to sampling the potent euphoria-inducing fentanyl doses they were administering to their patients. Stanford authors described fentanyl addiction in anesthesiologists in 1980.3 More than a dozen of my personal friends and colleagues died anesthetic drug-related addiction deaths in the 1980s and 1990s.
For some of these physicians the first sign of their addiction was death by overdose. In others the addiction was uncovered, they were sent to rehabilitation programs, and they are still alive today. Anesthesiologists graduating from narcotic rehab programs are still known to have a risk to relapse. The relapse rate for anesthesiologists after drug abuse treatment is greatest in the first 5 years and decreases as time in recovery increases. The positive news is that 89% of anesthesiologists who complete treatment and commit to aftercare remain abstinent for longer than 2 years. However, death is still the primary presenting sign of relapse in opiate-addicted anesthesiologists.
FENTANYL AS A STREET DRUG
The current battle against fentanyl as a street drug has little or nothing to do with American medical practice. Most of the fentanyl found on the streets is not diverted from hospitals, but rather is sourced from China and Mexico. Dealers sought a narcotic product cheaper and even stronger than heroin, and that product is fentanyl. In 2016 there were more than 60,000 fatal overdoses in America. More than half were due to opioids, and the newest and most potent street narcotic was fentanyl.
Fentanyl-related overdose deaths increased nearly 600 percent from 2014 to 2016. “If anything can be likened to a weapon of mass destruction in what it can do to a community, it’s fentanyl,” said Michael Ferguson, a special agent in charge of the Drug Enforcement Administration’s New England division. “It’s manufactured death.” Illicit fentanyl is imported directly from China or Mexico, where the drug is manufactured. Dealers then mix the powder into other drugs, making for imprecise potency in sometimes-lethal doses.4 The IV street drug fentanyl is believed to be manufactured in China or Mexico, and is smuggled across the borders. Highly organized drug cartels are spreading the drug throughout the country. Its street nickname is “China White” or “China Girl,” referring at where most of the drug is thought to be coming from. The DEA estimates that drug traffickers can buy a kilogram of fentanyl powder for $3,300 and sell it on the streets for more than 300 times that, generating nearly a million dollars.5
As a street drug, fentanyl can be injected intravenously, taken orally, or snorted nasally. Each of these routes poses a threat:
- Intravenous fentanyl as a street drug – Prior to fentanyl, heroin was the injectable street drug of choice. Because of the extremely high strength and potency of pure fentanyl powder, it’s difficult to dilute appropriately. The diluted mixture may be far too strong and, may cause respiratory depression and death. Some heroin dealers mix fentanyl powder with heroin to increase potency or compensate for low-quality heroin. Because fentanyl is more potent than heroin, the presence of even small quantities of fentanyl in injected heroin can result in respiratory depression. The fentanyl sold on the streets is likely made in a non-pharmaceutical lab, and is less pure than the medical version anesthesiologists administer. Its effect on the body can be hard to predict. Heroin and fentanyl look identical, and with drugs purchased on the street, addicts don’t know what they’re taking. An intravenous fentanyl overdose can cause a person to cease in breathing within minutes of injection, and result in death. Narcan, or naloxone, is a specific antagonist of narcotic overdose. Administration of Narcan as a fentanyl overdose antidote is a potential acute rescue remedy.
- Oral fentanyl as a street drug – Fentanyl is also sold as an oral street drug. Ten people died in just twelve days from fentanyl-laced pills in Sacramento County, California in March of 2016. In San Francisco, fentanyl showed up in pills labeled as Xanax, which turned out to be pure fentanyl. After 26 years in a Orange County crime lab south of Los Angeles, forensic scientist Terry Baisz said, “I was shocked the first time I tested this stuff and it came back as fentanyl. We hadn’t seen it before 2015.” Dealers were describing their pills as Xanax or Oxycodone. The tablets looked nearly identical to products manufactured by commercial pharmaceutical companies, although the pills sold on the streets contained fentanyl.6 The singer Prince’s death in 2016 was due in part to an overdose of fentanyl, likely in a pill form of counterfeit hydrocodone-acetaminophen (Vicodin) tablets.7
- Intranasal fentanyl as a street drug – If fentanyl is supplied to the addict in powder form, and the powder is confused with cocaine and is snorted intranasallly, the addict may die. A hospital in New Haven, Connecticut treated twelve overdoses, three of them fatal, in just an eight-hour period in June 2016 among addicts who were snorting a white powder they purchased on the city’s streets. 8The powder they believed was cocaine turned out to be fentanyl. The absorption of a nasal dose of fentanyl can lead to immediate respiratory depression and death.
U.S. Surgeon General Jerome Adams, an anesthesiologist, has suggested distributing the narcotic antagonist Narcan freely, so that onlookers can quickly treat fentanyl-overdosed individuals.9 I respect Dr. Adams at the highest level, but I’m skeptical of this approach. An addict injecting fentanyl while he or she is alone is still at high risk of dying, and I’m not aware of any statistics documenting whether addicts reliably have company present while they are injecting themselves.
First response Emergency Medical Technicians should carry Narcan. Treatment of patients who are discovered comatose for unknown reasons has long included an empiric injection of Narcan to reverse possible narcotic overdose. The public needs to be aware of the existence of fentanyl powder, its ultra-high potency, and the danger of a fatal overdose immediately after the intravenous injection, oral ingestion, or intranasal inhalation of any street drug. There’s a real threat that any dose of street fentanyl can be lethal.
In our operating rooms, hospitals, surgery centers, and intensive care units, fentanyl is used safely. On the streets, fentanyl poses nothing but problems. Education, prevention, and DEA enforcement will have key roles in addressing the crisis of fentanyl in non-medical settings.
- Fentanyl, Chemical and Engineering News, https://pubs.acs.org/cen/coverstory/83/8325/8325fentanyl.html
- Kazuhiko F, Opioid Analgesics, Miller’s Anesthesia, 8th Edition, Chapter 31, 864-914.
- Spiegelman WG, Saunders L, Mazze Ri, Addiction and anesthesiology, Anesthesiology 1984 Apr;60(4):335-41.
- Lewis N et al. Fentanyl linked to thousands of urban overdose deaths, Washington Post, August 15, 2017.
- https://www.washingtonpost.com/graphics/2017/national/fentanyl-overdoses/?utm_term=.8c722ada39be Nazarenus C. The opioid fentanyl: the new heroin, but deadlier. Medical Marijuana 411, May 11, 2016.
- https://medicalmarijuana411.com/opiod-fentanyl-new-heroin-deadlier/Sidner S. The opioid fentanyl: the new heroin, but deadlier. ClickonDetroit.com, May 10, 2016. https://www.clickondetroit.com/health/fentanyl-the-new-heroin-but-deadlier
- Kroll D, Prince’s Death From Fentanyl May Have Been Due To Counterfeit Generic Drugs, Pharma and Healthcare, Aug 22, 2016. https://www.forbes.com/sites/davidkroll/2016/08/22/princes-death-from-fentanyl-may-have-been-due-to-counterfeit-generic-drugs/#52096f902b17
- Bebinger M, Fentanyl-laced cocaine becoming a deadly problem among drug users, Health News from NPR, March 29, 2018. https://www.npr.org/sections/health-shots/2018/03/29/597717402/fentanyl-laced-cocaine-becoming-a-deadly-problem-among-drug-users
- Surgeon General Urges More Americans To Carry Opioid Antidote, NPR Public Health, April 5, 2018. https://www.npr.org/sections/health-shots/2018/04/05/599538089/surgeon-general-urges-more-americans-to-carry-opioid-antidote
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