Four Cases Involving Extraction of Fentanyl From
Transdermal Patches
Amy M. Tharp, MD, Ruth E. Winecker, PhD, and David C. Winston, MD, PhD
Abstract: The transdermal fentanyl system delivers a specific dose
at a constant rate. Even after the prescribed application time has
elapsed, enough fentanyl remains within a patch to provide a
potentially lethal dose. Death due to the intravenous injection of
fentanyl extracted from transdermal patches has not been previously
reported. We present 4 cases in which the source of fentanyl was
transdermal patches and was injected. In all of these cases, the
victim was a white male who died at home. Case 1 was a 35-year-old
with no known history of drug use, who was found by his wife on
the floor of his workshop. Police recovered a fentanyl patch, needle,
and syringe at the scene. Case 2 was a 38-year-old with a known
history of drug use whose family claimed that he was in a treatment
program that used fentanyl patches for unknown reasons. His
brother found him dead in bed, and law enforcement officers found
a hypodermic needle beside the body; a ligature around his left hand,
and apparent needle marks between his first and second digits were
also noted. Case 3 was a 42-year-old with a recent attempted suicide
via overdose who was found dead at his home. An empty box of
fentanyl patches, Valium, Ritalin, and 2 syringes were found at the
scene. Case 4 was a 39-year-old found by his mother, who admitted
to removing a needle with attached syringe from the decedent’s arm.
Medications at the scene included hydrocodone, alprazolam, zolpidem,
and fentanyl patches. All reported deaths were attributed to
fentanyl intoxication, with blood concentrations ranging from 5 to
27 g/L.
From the Department of Pathology, Wake Forest University School of
Medicine, Winston-Salem, North Carolina (A.M.T.); Office of the Chief
Medical Examiner, Chapel Hill, North Carolina (R.E.W.); Forensic
Science Center, Tucson, Arizona (D.C.W.); and Department of Pathology,
University of Arizona College of Medicine (D.C.W.).
entanyl overdose is classically associated with intravenous
use of -methyl-fentanyl (“China White”),1 a powder
form that is chemically different from therapeutic fentanyl.
However, fentanyl overdose has also been reported in
cases of excessive transdermal application2 and ingestion3,4
or inhalation5 of transdermal patches. Fentanyl is a narcotic
analgesic, which primarily binds to opioid -receptors, producing
not only the analgesia for which it is primarily used
but also sedation, euphoria, and at high doses, respiratory
depression and death.6 Transdermal fentanyl therapy (Duragesic;
Janssen Pharmaceutica, Beerse, Belgium) has been used
successfully to treat postoperative pain, as well as pain
associated with malignancies, but as with all opioid agents,
the potential for abuse exists. The transdermal fentanyl system
is designed to deliver a specific dose at a constant rate
based on the initial concentration present in the patch. This
delivery system effectively limits the peak versus trough
concentration, which is a common problem associated with
other routes of administration. Following 3 days of continuous
therapeutic use, enough fentanyl remains within a patch
to provide a potentially lethal dose.7 We present 4 cases
occurring in North Carolina between January 1997 and July
2001 in which the fatal dose of fentanyl was extracted from
transdermal patches and injected intravenously.
MATERIALS AND METHODS
Case Selection
The case files of the Office of the Chief Medical
Examiner (Chapel Hill, NC) were searched from 1991 to
2001 for deaths related to fentanyl. An initial search identified
53 cases,8 of which only 4 involved intravenous abuse of
a transdermal fentanyl patch. Case histories are listed below.
Toxicologic Analysis
All toxicologic analyses were performed at the Office
of the Chief Medical Examiner (Chapel Hill, NC). All cases
were screened for volatiles, common drugs of abuse (eg,
cocaine and morphine), and other basic drugs. Other tests (eg,
fentanyl) were performed as needed.
Fentanyl Screen
The specimens were screened by enzyme linked immunoassay,
with a 1 g/L cutoff concentration (Orasure Technologies,
Bethlehem, PA) utilizing a Biochem Personal Laboratory
Autoanalyzer (Allentown, PA). The assays were performed in
accordance with the manufacturers instructions and as validated
for use in the Office of the Chief Medical Examiner Toxicology
Laboratory.9
Fentanyl Confirmation and Quantification
Quantification and confirmation analyses were performed
by first isolating fentanyl by basic extraction6 of a 1to
5-mL (g) specimen. Underivatized specimens were analyzed
on an Agilent Technologies (Wilmington, DE) gas
chromatograph/mass spectrometer (GC/MS). The GC/MS
system was composed of an Agilent 6890 gas chromatograph,
a 5973 mass selective detector (MSD) and a 7683 liquid
auto-sampler. The GC/MS was fitted with a HP-1MS capillary
column (30 m .
0.25 mm inside diameter .
0.25-m
film thickness). A 13.19-minute run time occurred after 1-L
splitless injection into a 275°C injection port equipped with
0.4-mm gooseneck liner with base-deactivated fused silica
wool. Oven temperature programming began at 125°C, holding
for 1.00 minute, then ramping at 3 intervals: 35°C/minute
to 195°C, 7°C/minute to 230°C and 32°C/minute to a final
temperature of 300°C, holding for 3 minutes. Helium was
used as the carrier gas at a linear velocity 61 cm/s; flows
included a septum purge of 15.0 mL/minute at 2.0 minutes
and a constant column flow of 2.6 mL/minute. The MSD was
operated in selective ion mode, with a transfer line temperature
of 280°C.
CASE PRESENTATIONS
Case 1
A 35-year-old Caucasian man with no known history of
drug use was working in his workshop at home one evening.
His wife reported that at approximately 12:30 AM, she asked
him to come into the house, but that he stated that he would
probably continue building porch swings through the night.
His father, who stated that he “appeared OK,” last saw him
alive at 2:30 AM. At approximately 5:00 AM, the decedent’s
wife found him lying on the floor of his workshop. Paramedics
were unable to resuscitate him. Police investigating the
scene found a fentanyl patch, a needle, and syringe in the
workshop. External examination of the body revealed no
evidence of trauma, except for a 3/4-inch recent contusion
with some yellow discoloration at its margins in the left
antecubital fossa and a faint petechial-like contusion along a
vein on the right forearm. Pulmonary congestion and edema,
with a combined lung weight of 920 g, were the only other
significant autopsy findings. Toxicological analysis of aortic
blood was remarkable for a fentanyl concentration of 5 g/L,
as well as a concentration of 0.8 mg/L of propoxyphene
(generally considered to be a nontoxic concentration), and
therapeutic concentrations of amitriptyline (0.08 mg/L) and
its metabolite nortriptyline (0.33 mg/L). No other organic
bases were detected, and testing for norpropoxyphene was
not performed. The cause of death was attributed to “fentanyl
poisoning,” with the manner of death listed as accident.
Case 2
A 38-year-old Caucasian man with a history of drug use
was living with his relatives. His family claimed that he had
begun a treatment of his drug use in a program that used
“morphine patches” for unknown therapeutic purposes. He
was last seen alive at 10:00 PM, at which time he complained
of nausea. His brother found him dead in bed the following
morning at 8:15 AM. Resuscitative efforts were attempted but
were unsuccessful. Law officers found a hypodermic needle
in the bed beside the body and a ligature on his left hand, with
apparent needle marks between the thumb and forefinger. On
external examination at the time of autopsy, scars were noted
in the right antecubital fossa as well as over each wrist,
including a relatively recent puncture site over the dorsum of
the left hand, between the thumb and second digit. Internal
examination revealed pulmonary congestion and edema, with
a combined lung weight of 1500 g, and cardiomegaly (450 g).
A focus of granulomatous inflammation was present within
the left lung with caseous necrosis, which was found to be
due to Coccidioides immitis on silver stains. Focal chronic
hepatitis and moderate coronary atherosclerosis were also
identified. Toxicologic studies of aortic blood were positive
fora27 g/L concentration of fentanyl, with no other
substances identified. The cause of death was listed as “fentanyl
poisoning” with the manner of death as accident.
Case 3
A 42-year-old Caucasian man was found dead in his
home, lying prone in the hallway, with his eyeglasses broken
and hanging from his face. He had last been known to be
alive on the previous day at 10:30 PM, when he had answered
a phone call. At the scene, a bottle of diazepam with 11 pills
missing from the prescribed number, a methylphenidate tablet,
and 2 syringes (1 empty and 1 filled with a clear liquid),
as well as an empty box of fentanyl patches were recovered.
He had a history of ethanol and multisubstance abuse and was
seen in his local emergency room the week prior to his death
for treatment of an attempted suicide by Percocet and Restoril
overdose, as well as self-inflicted abrasions and lacerations,
and ethanol intoxication. Following a work-up, gastric decontamination,
and observation, he was sent to a psychiatric
hospital for involuntary commitment. It was not determined
how he came to be at his home on the day of his death.
External examination was unremarkable, with the exception
of abundant healed apparently self-inflicted incised wounds
© 2004 Lippincott Williams & Wilkins
on the wrists, abdomen, and forearms. No fentanyl patches
were found on the body. Pulmonary congestion and edema,
with a combined lung weight of 1920 g, cardiomegaly (450
g), with mild coronary atherosclerosis, and mild hepatic
steatosis were found at autopsy. Aortic blood was sent for
toxicologic analyses and was positive for 17 g/L of fentanyl,
0.49 mg/L of paroxetine, low concentrations of cocaine
(0.061 mg/L) and its metabolite, benzoylecgonine (0.36 mg/
L), and diazepam (0.15 mg/L). Fentanyl overdose was listed
as the cause of death and the manner of death was classified
as suicide.
Case 4
A 39-year-old Caucasian man complained of a fever,
sore throat, and malaise. He was seen in his local urgent care
facility and given hydrocodone cough syrup. Two weeks
later, he was found unresponsive in the bathroom of his home
by his mother, who admitted removing a needle with attached
syringe from his arm. Also found at the scene were 2 empty
bottles of hydrocodone, a one-third full bottle of hydrocodone
syrup, empty bottles of alprazolam and zolpidem, 2 additional
syringes, and 2 empty wrappers from fentanyl patches. He
was taken to the local emergency room, where he was
pronounced dead. Further investigation revealed a history of
drug use, asthma, depression, and psychosis. At the time of
autopsy, old needle puncture sites were found within bilateral
antecubital fossae, with a relatively recent needle puncture in
the left antecubital fossa. Microscopic examination of these
sites revealed dermal foreign body giant cells with polarizable
material. Internal findings included cardiomegaly (510
g) with left ventricular hypertrophy and hepatosplenomegaly.
Numerous foreign body giant cells with polarizable material
were present within the lungs, surrounding the pulmonary
blood vessels. Toxicologic analysis of femoral blood was
positive for 13 g/L of fentanyl, 0.083 mg/L of hydrocodone,
and 0.076 mg/L of oxycodone. Testing of the syringe found
at the scene was positive for fentanyl. The cause of death was
determined to be fentanyl toxicity, with hydrocodone and
oxycodone listed as significant contributing factors. The manner
of death was determined to be accident.
DISCUSSION
Fentanyl, developed by Janssen Pharmaceutica, was
originally introduced in the United States in 1968 for use as
an intravenous analgesic-anesthetic drug. The abuse of fentanyl
has classically been by health care professionals who
had access to the controlled drug. In the 1980s, a street
version began to appear, resulting in many deaths. “China
White,” or -methyl-fentanyl, was found to be up to 1000
times more potent than heroin1 and with demographics similar
to those of heroin abuse.10 In particular, Caucasian men
with an average age of 32 years old and a prior history of
intravenous drug use were most likely to abuse China White
usually in combination with other drugs (alcohol, cocaine,
other opiates). The FDA approved Duragesic (Janssen Pharmaceutica,
Beerse, Belgium), the first transdermal fentanyl
system, in 1990 for use in the control of chronic and postsurgical
pain.
Since their introduction in 1990, transdermal fentanyl
patches have been abused in a number of ways. Edinboro et
al2 reported a case of an 83-year-old female with terminal
cancer who was found to have fatal levels of fentanyl in her
blood (25 g/L) after applying 3 patches to her chest. Arvanitis
and Satonik3 described a case of a 38-year-old man who
was found unresponsive on 3 separate occasions after chewing
transdermal fentanyl patches. He was treated successfully
with naloxone the first 2 times, but the final time, he was
found dead with a fentanyl patch in his oropharynx. Complete
postmortem evaluation and toxicologic analyses were not
complete at the time of publication. Another case of intentional
oral ingestion of fentanyl patches was reported by
Purucker and Swann,4 who described a 24-year-old woman
who reported to her local emergency room complaining of
pain due to miscarriage, as well as chronic pain and muscle
spasms. She received an intramuscular injection of meperidine
and a fentanyl patch was applied for continued pain
relief. She was found shortly thereafter in the lavatory,
unresponsive and apneic. She was successfully resuscitated,
and an empty Duragesic (Janssen Pharmaceutica) patch was
found in her wallet, with bite marks found on the polyester
backing and none of the fentanyl gel remaining in the patch.
Neither a urine drug screen nor serum fentanyl level was
obtained. Marquardt and Tharratt5 reported a case of a 36year-
old man who became apneic, hypotensive, and tachycardic
following heating of a fentanyl patch with subsequent
inhalation of the evolving vapors, which was witnessed by his
girlfriend. Naloxone was administered and he was able to be
resuscitated; urine or serum drug screens were not performed
at that time. This man subsequently died as a result of further
inhalation abuse of fentanyl patches, and (according to Marquardt
and Tharratt5) he was found at autopsy to have the
following fentanyl concentrations: femoral blood, 2.66 ng/
mL; urine, 41 ng/mL; and liver, 122 ng/mL.
Transdermal fentanyl therapy consists of a patch composed
of 4 layers with an outer protective liner. The 4 layers
include a polyester film backing; the drug reservoir, which
contains a mixture of fentanyl, alcohol, and hydroxyethyl
cellulose; a membrane that controls the rate of fentanyl
delivery; and a silicone adhesive, which also contains fentanyl.
The rate-limiting step in absorption is through the lipophilic,
keratinous stratum corneum by passive diffusion.11
Extraction of the contents of the drug reservoir followed by
intravenous injection of the fentanyl effectively bypasses this
rate-limiting step and provides a bolus dose. This unique
method of abuse, therefore, increases a person’s risk of fatal
overdose by rapidly administering larger than the usual in
© 2004 Lippincott Williams & Wilkins
The American Journal of Forensic Medicine and Pathology • Volume 25, Number 2, June 2004 Fatal Intravenous Fentanyl Abuse
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