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Educational Objectives:
After evaluating this article participants will be able to:
1. Discuss the issues regarding fentanyl abuse
2. Recognize the mortality risk associated with fentanyl abuse
3. Discuss various case presentations illustrating deaths associated with fentanyl


 
A 32-yr-old man was found in asystole after chewing and ingesting a fentanyl patch. Despite ACLS measures, naloxone administration, and intubation, the patient expired. Two men, ages 29 and 40, illegally purchased seven fentanyl patches. They smoked the drug together, returned to their respective homes and were found dead the following day.
 
A 38-year-old female injected the contents of one fentanyl patch, suffered an arrest en route to the ED and expired despite aggressive supportive care. A 41-year-old was found unresponsive by her family after she put 11 fentanyl patches on her skin. She was pronounced in the ED soon after arrival. A 4-year-old girl was found unresponsive at home by her grandmother. When EMS arrived they noted one fentanyl patch on the child and two additional patch marks. The grandmother had applied patches to relieve the child’s pain.
These tragic stories from the National Data System of the AAPCC (American Association of Poison Control Centers) highlight a deadly fentanyl epidemic that as been reported in major cities across the United States. Due to widespread availability, the potential exists for a continued high rate of abuse, associated with increased mortality. Fentanyl intoxication poses several challenges to emergency physicians. Signs and symptoms of toxicity are similar to that of other opioids (depressed mental status, miotic pupils, bradypnea); however, confirmation of fentanyl as the causative agent is difficult. Due to the high potency of fentanyl and the lack of a morphine derivative metabolite, most conventional urine drug screens are unable to detect the drug.

Fentanyl was first synthesized in Belgium by Jassen Pharmaceutica in 1959. In the 1960s, fentanyl was introduced as an intravenous anesthetic under the trade name of Sublimaze. In the mid-1990s, the Duragesic patch was introduced and reached one billion dollars in gross sales by 2004.

Initially, fentanyl abuse was most common among healthcare professionals. Illicit analogs have been manufactured in clandestine laboratories since the late 1970s. These analogs have been substituted for or combined with heroin resulting in other fatal epidemics. In 1979, the analog alpha-methylfentanyl, known on the street as “China White,” resulted in the death of 100 people in California. Epidemics related to fentanyl derivatives surfaced again in the 80s and 90s in Pennsylvania and Maryland.  3-methylfentanyl, a super potent fentanyl derivative, was detected in several of the Pennsylvania cases. Illicit use of fentanyl also occurs overseas and a cluster of fentanyl-related deaths occurred in Sweden in the mid 90s. In October 2002, the Russian military reportedly used a fentanyl derivative against terrorists holding hostages in a Moscow theater. Often, fentanyl derivatives are sold in clear plastic bags or “mini ziplocks” stamped with a skull and crossbones. Most users report a less euphoric high associated with the drug but stronger sedative and analgesic effects. Because the effects of fentanyl are brief and rapid in onset, it is even more addictive than heroin. Some heroin dealers mix fentanyl powder with larger amounts of heroin in order to increase potency or compensate for low-quality heroin.

Numerous recent fentanyl-related deaths have been reported in Chicago, Detroit, Milwaukee, Dallas, Pittsburgh, St. Louis, Philadelphia, and New Jersey. During 2006-07, the ME’s office in Chicago identified 348 fentanyl-related fatalities. In 2006, fentanyl was identified as the cause of death in 178 cases in Detroit. Reports indicate that fentanyl overdose was responsible for the hospitalization of 42 patients over one weekend in New Jersey. In Chicago, federal authorities arrested several members of a notorious street gang for preparing fentanyl for sale on the street. Since that time, a clandestine Mexican laboratory thought to be manufacturing and shipping illicit fentanyl to Chicago has been shut down by federal agents.

Available in intravenous, oral, and patch formulations, the routes of administration of this drug vary. Recently, fentanyl has been developed into an effervescent tab for buccal absorption much like the Actiq lollipop, along with an inhaler and nasal spray device for fast-acting pain relief.


Dermal Patch Toxicity
Mnemonic: FENCES
Fentanyl
Estrogen
Nicotine, NTG
Clonidine
Exelon (What is this drug used for?
See below for answer*)    
Scopolamine, Salicylates 


The most recent fentanyl epidemic has resulted in a re-evaluation of the management of opioid overdose patients. Opioids exert their effects by binding to a variety of receptors including mu, kappa, and delta. Management of opioid intoxication includes airway management and support, supportive care, and administration of opioid antagonists. Naloxone is an opioid receptor antagonist with a greater affinity for binding the opioid mu receptors than the opiates. Dosing recommendations vary based on the chronicity of opioid exposure, the potency of the opioid agonist, and the dose of the opioid. Due to fentanyl’s high potency, higher doses of naloxone may be required to reverse the opioid intoxication.

In May 2006, at the height of the fentanyl epidemic, our institution’s naloxone supply was depleted, and suspected opioid-related overdose patients were diverted to other institutions for several hours until our naloxone supply could be replenished (aka- Narcan bypass). Due to fentanyl’s widespread availability, the potential exists for a continued national epidemic associated with high mortality rates.

In the future, also watch out for other synthetic opioids much more potent and rapid in onset than fentanyl:
-Remifentanil: “Ultiva” (shortest acting opioid available- rapid onset/offset)
-Sufentanil: “Sufenta” (1000x more potent than morphine)
-Carfentanil: “Wildnil” (An elephant tranquilizer 10,000x more potent than morphine!)



The Word on the Street
Recent Street Names Used for Fentanyl in the United States
  • Lethal Injection, Killer Instinct
  • Flat Line, Tsunami
  • Undertaker, Drop Dead
  • Magic, The Bomb (fentanyl + heroin)
  • Jack Flash (fentanyl and oxycodone)
  • Bran Man (fentanyl and cannabis)
  • Tattered and Torn (fentanyl, morphine, oxycodone, midazolem) 
  • Cheese (fentanyl + Tylenol PM) – The new official toxin of Wisconsin?
 
 * Used for patients with Parkinson’s and Alzheimer’s Disease
 

 


REFERENCES
  • Schumann H, Erickson T, Thompson T, Zautke J, et al: Fentanyl epidemic in Chicago, Illinois and surrounding Cook County. Clin Toxicol 46(6): 501-506, 2008.
  • Center for Disease Control and Prevention (CDC): Nonpharmaceutical fentanyl-related deaths-multiple states, April 2005-March 2007. MMWR Morb Mortal Wkly Rep 25;57(29):793-6, 2008.
  • Boddiger D. Fentanyl-laced street drugs “kill hundreds.” Lancet. 2006;368:569-570.
  • Wax PM, Becker CE, Curry SC: Unexpected "gas" casualties in Moscow: a medical toxicology perspectie. Ann Emerg Med 42(2): 285, 2003.
  • www.DEA.gov: Fentanyl:  March, 2009
  • www.Erowid.org: Fentanyl: March 2009 
 

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