a) SUMMARY: The increasing use of fentanyl patches for pain control has resulted in more cases of fentanyl misuse and diversion (Firestone et al, 2009; Sutlovic & Definis-Gojanovic, 2007; Flannagan et al, 1996).
b) INGESTION: Numerous reports of fatal opioid intoxication have occurred following the intentional ingestion (ie, chewing or sucking on the content of patches) of fentanyl patches by adults (Woodall et al, 2008; Kramer & Tawney, 1998; Marquardt & Tharratt, 1994).
c) INADVERTENT INGESTION: There have been reports of acute poisoning in toddlers and young children following the inadvertent ingestion of transdermal fentanyl patches. Fatalities have occurred (Teske et al, 2007; Sachdeva & Stadnyk, 2005).
d) INTRAVENOUS: Two adults developed opioid poisoning following the intravenous injection of the contents of a 5 mg transdermal fentanyl patch. One patient recovered at the scene after 1.2 mg naloxone, and the other patient died the following day after the withdrawal of care after developing hemodynamic instability and multi-organ failure (Reeves & Ginifer, 2002). In another case series, 4 individuals died after intravenous exposure to fentanyl following extraction from a transdermal patch. All of the deaths were attributed to fentanyl toxicity (Tharp et al, 2004).
e) INHALATION: A man was observed emptying the contents of a fentanyl patch onto aluminum foil and heating the contents; he collapsed after taking one inhalation. Paramedics gave naloxone in the field and the patient was alert and oriented with 30 minutes. He was discharged with no residual effects (Marquardt & Tharratt, 1994).
f) RECTAL: Opioid intoxication occurred in an adult after placing 3 fentanyl (100 mcg/hour) patches into his rectum. The patient recovered completely once the patches were removed (Coon et al, 2005).
g) DIVERTED PRESCRIPTION PRODUCT: A fatal fentanyl overdose occurred in an adult employed at a funeral center after removing a fentanyl patch from the body of an elderly woman. Postmortem blood concentrations were positive for fentanyl only; the toxicology screen was negative for other drugs of abuse (Flannagan et al, 1996).

a) Transdermal fentanyl has been available by prescription since 1990. In 2005, the manufacturers reformulated the transdermal system so that the active drug was contained in a polymer matrix rather than a gel filled reservoir. This resulted in a thinner and smaller patch to minimize adverse events and intentional diversion of the product. However, one study suggested that the drug could easily be extracted from the revised patch by adding vinegar and water, and then soaking, heating or microwaving the patch and collecting the liquid. The extracted liquid could then be placed in a syringe for injection, which might be shared by several individuals. The findings suggest that reformulation had limited effect on preventing illicit drug use (Firestone et al, 2009).

a) PHARMACEUTICAL: Intentional misuse of pharmaceutical fentanyl has been well recognized among health professionals including physicians, anesthesiologists, nurses and pharmacists (Firestone et al, 2009; Sutlovic & Definis-Gojanovic, 2007). It has also been misused by individuals with a history of heroin use (Henderson, 1991).

a) Clandestine laboratories have synthesized alpha-methylfentanyl and distributed it as a heroin substitute referred to as "China White". Numerous other illicit fentanyl analogs have also been identified. Deaths have been related to overdose of these products. It has been suggested that the most toxic of these agents is 3-methylfentanyl, which has a potency of 6000 times that of morphine. Although studies in humans have not been conducted, it appears that these analogs have similar pharmacologic action as fentanyl (Poklis, 1995).
b) ACETYL FENTANYL: Between March and May 2013, Rhode Island public health officials and the Centers for Disease Control identified 14 acetyl fentanyl-related deaths. Acetyl fentanyl, a synthetic opioid, is an illicit agent. Based on animal studies, it is up to 5 times more potent than heroin. One death was attributed to acetyl fentanyl alone (Centers for Disease Control and Prevention (CDC), 2013a).

1) VOLATILIZATION: A respiratory rate of 6 breaths per minute was reported in a 36-year-old man following the volatilization and inhalation of the contents of a fentanyl patch (Marquardt & Tharratt, 1994). In another case, a 37-year-old woman was found apneic, unresponsive (Glasgow coma score of 3) with miosis after the volatilization and inhalation of the contents of a fentanyl patch (Souders et al, 2000).
2) BUCCAL/DERMAL EXPOSURE: An adult was admitted to the Emergency Department in respiratory arrest unresponsive with fixed and dilated pupils. He was immediately intubated; a transdermal patch (75 mcg/hr) found in the buccal cavity and second patch found (75 mcg/hr) on the inner thigh. Resuscitation efforts were unsuccessful (Kramer & Tawney, 1998).
3) INGESTION: Apnea developed shortly after ingestion of a 5 mg transdermal patch. Symptoms resolved with intravenous naloxone (Purucker & Swann, 2000).
4) CASE SERIES: In a case series involving 76 cases of intentional ingestion of fentanyl transdermal patches, 13 patients (17%) developed respiratory depression and 6 patients (7.9%) developed respiratory arrest (Mrvos et al, 2011).
5) FENTANYL ANALOGS: The Swedish STRIDA project was started in 2010 to identify and monitor the occurrence of emerging drugs of abuse in Sweden. Approximately 350 cases were enrolled in the STRIDA project from April 2015 to November 2015. Of these 350 cases, 14 cases of fentanyl analog intoxications were analytically confirmed, involving acetylfentanyl (n=9), 4-methoxybutyrfentanyl (n=3), furanylfentanyl (n=1), and 4-methoxybutyrfentanyl in combination with furanylfentanyl (n=1). In addition, other drugs were also detected in these patients (eg, benzodiazepines, other opioids, pregabalin). Apnea was reported in 5 patients with either acetylfentanyl (n=3) or 4-methoxybutyrfentanyl (n=2) intoxications (Helander et al, 2016).

1) TRANSDERMAL: PEDIATRIC: Respiratory depression, with decreased respirations and decreased oxygen saturation (pulse oximetry 88% on room air), occurred in a 2-year-old boy who was inadvertently exposed to a transdermal fentanyl patch (Hardwick et al, 1997).

1) CASE SERIES: INGESTION: In a case series, 4 patients ages 22 to 38 years intentionally ingested the gel reservoirs of 50 mcg to 100 mcg/hour fentanyl transdermal patches resulting in recurrent respiratory depression. In one case, the patient ingested the gel from a 100 mcg/hour patch and applied another 100 mcg/hour patch to his buccal mucosa. In each case, the patient was found unconscious or severely impaired and was treated with, and responded to, prehospital IV naloxone. However, within 2 hours of arrival at the emergency department, each patient developed a recurrence of symptoms including oxygen desaturation (88% on room air to 93% on 100% oxygenation) and a decreased respiratory rate (8 to 11 breaths/minute). All cases were treated with additional doses of IV naloxone followed by continuous infusions for 5 to 12 hours. Three patients recovered and were discharged 24 to 27 hours after presentation. One patient was hospitalized for psychiatric evaluation and discharged 50 hours after presentation (D'Orazio & Fischel, 2012).
2) CASE REPORT/PEDIATRIC: TRANSDERMAL: A 15-year-old girl was found apneic with pinpoint pupils 12 hours after intentionally applying 5 fentanyl dermal patches to her body. The strength of each patch was 100 mcg/hour for a total dose of 6 mg or 120 mcg/kg. She responded to IM naloxone prehospital with improved respirations and normal level of consciousness. However, a second dose of naloxone was required for recurrence of symptoms. Upon arrival at the emergency department, she was tachycardic, diaphoretic, her respiratory rate dropped from 6 to 2 breaths/minute, and her Glasgow Coma Scale score was 14. She was treated with 2 IV doses of naloxone over 30 minutes. She recovered after each naloxone administration but then deteriorated back into respiratory depression and a decreased level of consciousness. A naloxone IV infusion at 6 mcg/kg/hour was initiated and then increased to 12 mcg/kg/hour for 24 hours. She was weaned off the naloxone infusion over 12 hours with no recurrence of symptoms. She was discharged 9 days after admission with no residual effects (Lyttle et al, 2012).

1) The first patient, a 24-year-old man, recovering from respiratory arrest suspected to be secondary to heroin abuse, became cyanotic and collapsed, requiring cardiopulmonary resuscitation, and was subsequently comatose with a Reaction Level Scale (RLS) between 4 and 8. The patient was also hypothermic (35.8 degrees Celsius) and his pupils were miotic. With supportive care for 24 hours, the patient completely recovered. Laboratory analysis of a white powder that was found on the patient, and labeled as butyrfentanyl, determined the active ingredients to be fentanyl and butyrfentanyl at a molar ratio of approximately 7.5:1. Both substances were detected in the patient's serum and urine at a fentanyl:butyrfentanyl ratio of approximately 5:1 and approximately 16:1, respectively (Backberg et al, 2015).
2) The second patient, a 19-year-old man, presented to emergency personnel comatose (RLS of 6), with respiratory depression approximately 8 hours after using a butyrfentanyl nasal spray. Following administration of naloxone, the patient presented to the ED completely awake (RLS 1) and anxious. Vital signs indicated tachycardia (109 beats/min), a blood pressure of 140/80 mmHg, a respiratory rate of 14 breaths/min, and a body temperature of 38.7 degrees Celsius, and the patient had metabolic acidosis. Following supportive care and observation in the ICU, the patient remained stable and was discharged within 24 hours. Analysis of the nasal spray determined that it contained fentanyl and butyrfentanyl as the active ingredients in a molar ratio of approximately 10:1. A serum sample from the patient, obtained approximately 6 hours post-presentation, was negative for butyrfentanyl but revealed a fentanyl level of 1.5 ng/mL (Backberg et al, 2015).

1) HEAT-INDUCED RAPID ABSORPTION: Heat (eg, heating blankets, hot water bottles, saunas) applied to a fentanyl patch found on the skin may induce overdose effects, due to rapid absorption from the cutaneous site (None Listed, 2010; Newshan, 1998; Rose et al, 1993). An increase in body temperature may also increase the risk of developing fentanyl toxicity (None Listed, 2010).

1) CASE REPORT: A 22-year-old man presented with rhabdomyolysis, swelling, paresthesia, and dermal erythema of the dorsal thigh muscles. Prior to presentation, he had been unconscious for several hours. Laboratory data at admission revealed a plasma myoglobin of 70,033 mcg/L, serum creatinine level of 561 mcmol/L, and a serum potassium level of 7.1 mmol/L. Treatment included dialysis for 3 days. Toxicologic analysis revealed exposure to acetylfentanyl in combination with clonazepam and ethanol (Helander et al, 2016).

1) Narcan(R) nasal spray is supplied as a single 4 mg dose of naloxone hydrochloride in a 0.1 mL intranasal spray (Prod Info NARCAN(R) nasal spray, 2015).
2) FDA DOSING: Initial dose: 1 spray (4 mg) intranasally into 1 nostril. Subsequent doses: Use a new Narcan(R) nasal spray and administer into alternating nostrils. May repeat dose every 2 to 3 minutes. Requirement for repeat dosing is dependent on the amount, type, and route of administration of the opioid being antagonized. Higher or repeat doses may be required for partial agonists or mixed agonist/antagonists (Prod Info NARCAN(R) nasal spray, 2015).
3) AMERICAN HEART ASSOCIATION GUIDELINE DOSING: Usual dose: 2 mg intranasally as soon as possible; may repeat after 4 minutes (Lavonas et al, 2015). Higher doses may be required with atypical opioids (VandenHoek et al, 2010).
4) ABSORPTION: Based on limited data, the absorption rate of intranasal administration is comparable to intravenous administration. The peak plasma concentration of intranasal administration is estimated to be 3 minutes which is similar to the intravenous route (Kerr et al, 2009). In rare cases, nasal absorption may be inhibited by injury, prior use of intranasal drugs, or excessive secretions (Kerr et al, 2009).

1) This dose can also be given intramuscularly or subcutaneously in the absence of intravenous access (Howland & Nelson, 2011; Prod Info naloxone HCl IV, IM, subcutaneous injection solution, 2008; Maio et al, 1987; Wanger et al, 1998).

1) Single doses of up to 24 milligrams have been given without adverse effect (Evans et al, 1973).

1) OPIOID DEPENDENT PATIENTS: The goal of naloxone therapy is to reverse respiratory depression without precipitating significant withdrawal. Starting doses of naloxone 0.04 mg IV, or 0.001 mg/kg, have been suggested as appropriate for opioid-dependent patients without severe respiratory depression (Howland & Nelson, 2011). If necessary the dose may be repeated or increased gradually until the desired response is achieved (adequate respirations, ability to protect airway, responds to stimulation but no evidence of withdrawal) (Howland & Nelson, 2011). In the presence of opioid dependence, withdrawal symptoms typically appear within minutes of naloxone administration and subside in about 2 hours. The severity and duration of the withdrawal syndrome are dependant upon the naloxone dose and the degree and type of dependence.(Prod Info naloxone HCl IV, IM, subcutaneous injection solution, 2008)
2) PRECAUTION should be taken in the presence of a mixed overdose of a sympathomimetic with an opioid. Administration of naloxone may provoke serious sympathomimetic toxicity by removing the protective opioid-mediated CNS depressant effects. Arrhythmogenic effects of naloxone may also be potentiated in the presence of severe hyperkalemia (McCann et al, 2002).

1) LESS THAN 5 YEARS OF AGE OR LESS THAN 20 KG: 0.1 mg/kg IV/intraosseous/IM/subcutaneously maximum dose 2 mg; may repeat dose every 2 to 5 minutes until symptoms improve (Kleinman et al, 2010; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008)
2) 5 YEARS OF AGE OR OLDER OR GREATER THAN 20 KG: 2 mg IV/intraosseous/IM/subcutaneouslymay repeat dose every 2 to 5 minutes until symptoms improve (Kleinman et al, 2010; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Krauss & Green, 2006). Although naloxone may be given via the endotracheal tube for pediatric resuscitation, optimal doses are unknown. Some experts have recommended using 2 to 3 times the IV dose (Kleinman et al, 2010)
3) AVOIDANCE OF OPIOID WITHDRAWAL: In cases of known or suspected chronic opioid therapy, a lower dose of 0.01 mg/kg may be considered and titrated to effect to avoid withdrawal: INITIAL DOSE: 0.01 mg/kg body weight given IV. If this does not result in clinical improvement, an additional dose of 0.1 mg/kg body weight may be given. It may be given by the IM or subQ route if the IV route is not available (Prod Info naloxone HCl IV, IM, subcutaneous injection solution, 2008)

1) The American Academy of Pediatrics recommends a neonatal dose of 0.1 mg/kg IV or intratracheally from birth until age 5 years or 20 kilograms of body weight (AAP, 1989; Kleinman et al, 2010).
2) Smaller doses (10 to 30 mcg/kg IV) have been successful in the setting of exposure via maternal administration of narcotics or administration to neonates in therapeutic doses for anesthesia (Wiener et al, 1977; Welles et al, 1984; Fischer & Cook, 1974; Brice et al, 1979).
3) POTENTIAL OF WITHDRAWAL: The risk of precipitating withdrawal in an addicted neonate should be considered. Withdrawal seizures have been provoked in infants from opioid-abusing mothers when the infants were given naloxone at birth to stimulate breathing (Gibbs et al, 1989).
4) In cases of inadvertent administration of an opioid overdose to a neonate, larger doses may be required. In one case of oral morphine intoxication, 0.16 milligram/kilogram/hour was required for 5 days (Tenenbein, 1984).

1) If intravenous access cannot be rapidly established, naloxone can be administered via subcutaneous or intramuscular injection, intranasally, or via inhaled nebulization in patients with spontaneous respirations.
2) INTRAMUSCULAR/SUBCUTANEOUS ROUTES: If an intravenous line cannot be secured due to hypoperfusion or lack of adequate veins then naloxone can be administered by other routes.
3) The intramuscular or subcutaneous routes are effective if hypoperfusion is not present (Prod Info naloxone HCl IV, IM, subcutaneous injection solution, 2008). The delay required to establish an IV, offsets the slower rate of subcutaneous absorption (Wanger et al, 1998).
4) Naloxone Evzio(TM) is a hand-held autoinjector intended for the emergency treatment of known or suspected opioid overdose. The autoinjector is equipped with an electronic voice instruction system to assist caregivers with administration. It is available as 0.4 mg/0.4 mL solution for injection in a pre-filled auto-injector (Prod Info EVZIO(TM) injection solution, 2014).
5) INTRANASAL ROUTE: Intranasal naloxone has been shown to be effective in opioid overdose; bioavailability appears similar to the intravenous route (Kelly & Koutsogiannis, 2002). Based on several case series of patients with suspected opiate overdose, the average response time of 3.4 minutes was observed using a formulation of 1 mg/mL/nostril by a mucosal atomization device (Kerr et al, 2009; Kelly & Koutsogiannis, 2002). However, a young adult who intentionally masticated two 25 mcg fentanyl patches and developed agonal respirations (6 breaths per minute), decreased mental status and mitotic pupils did not respond to intranasal naloxone (1 mg in each nostril) administered by paramedics. After 11 minutes, paramedics placed an IV and administered 1 mg of IV naloxone; respirations normalized and mental status improved. Upon admission, 2 additional doses of naloxone 0.4 mg IV were needed. The patient was monitored overnight and discharged the following day without sequelae. Its suggested that intranasal administration can lead to unpredictable absorption (Zuckerman et al, 2014).
6) NEBULIZED ROUTE: DOSE: A suggested dose is 2 mg naloxone with 3 mL of normal saline for suspected opioid overdose in patients with some spontaneous respirations (Weber et al, 2012).
7) ENDOTRACHEAL ROUTE: Endotracheal administration of naloxone can be effective(Tandberg & Abercrombie, 1982), optimum dose unknown but 2 to 3 times the intravenous dose had been recommended by some (Kleinman et al, 2010).

1) A continuous infusion of naloxone may be employed in circumstances of opioid overdose with long acting opioids (Howland & Nelson, 2011; Redfern, 1983).
2) The patient is given an initial dose of IV naloxone to achieve reversal of opioid effects and is then started on a continuous infusion to maintain this state of antagonism.
3) DOSE: Utilize two-thirds of the initial naloxone bolus on an hourly basis (Howland & Nelson, 2011; Mofenson & Caraccio, 1987). For an adult, prepare the dose by multiplying the effective bolus dose by 6.6, and add that amount to 1000 mL and administer at an IV infusion rate of 100 mL/hour (Howland & Nelson, 2011).
4) Dose and duration of action of naloxone therapy varies based on several factors; continuous monitoring should be used to prevent withdrawal induction (Howland & Nelson, 2011).
5) Observe patients for evidence of CNS or respiratory depression for at least 2 hours after discontinuing the infusion (Howland & Nelson, 2011).

1) In general, the smallest dose of naloxone required to reverse life threatening opioid effects should be used in pregnant women. Naloxone detoxification of opioid addicts during pregnancy may result in fetal distress, meconium staining and fetal death (Zuspan et al, 1975). When naloxone is used during pregnancy, opioid abstinence may be provoked in utero (Umans & Szeto, 1985).

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

1) LOW DOSE: 2 mcg/kg (0.002 mg/kg; 0.04 mL/kg) (Prod Info SUBLIMAZE(R) intravenous injection, intramuscular injection, 2012)
2) MODERATE DOSE: 2 to 20 mcg/kg (0.002 to 0.02 mg/kg; 0.04 to 0.4 mL/kg) (Prod Info SUBLIMAZE(R) intravenous injection, intramuscular injection, 2012).
3) HIGH DOSE (eg, cardiac bypass, neurosurgery): 20 to 50 mcg/kg (0.02 to 0.05 mg/kg; 0.4 to 1 mL/kg) (Prod Info SUBLIMAZE(R) intravenous injection, intramuscular injection, 2012).

1) TRANSDERMAL PATCH: A 12-month-old girl (weight 11 kg) was found unresponsive 2 hours after being put to bed and resuscitation efforts were unsuccessful. Upon autopsy, a transdermal fentanyl patch 25 mcg/hr (4.2 mg) was found in the stomach, which was prescribed for an adult in the household. Distribution of fentanyl was as follows (Teske et al, 2007):

1) SUMMARY/CASE SERIES: In one study, fentanyl concentrations were obtained in 23 postmortem cases, the findings suggest that significant overlap may occur between therapeutic concentrations of fentanyl and lethal concentrations. Serum concentrations should be interpreted cautiously, and the patient's medical history and autopsy findings should be taken in consideration in determining the cause of death. Tolerance appears to develop in some patients that are receiving chronic fentanyl therapy. Of the 19 cases that were found to be drug overdoses, fentanyl alone was responsible for 8 deaths, with mean and median fentanyl concentrations of 36 (SD 38) mcg/L and 22 mcg/L, respectively. The remaining 11 cases were due to a mixed drug overdose with mean fentanyl concentration of 31 (SD 46) mcg/L (range: 5 to 152 mcg/L). As a comparison, 11 inpatients receiving fentanyl for chronic pain had serum levels drawn. Nine patients had concentrations of less than 4 mcg/L, and 2 had concentrations of 8.5 mcg/L and 9.9 mcg/L , respectively after receiving fentanyl for 3 months for chronic pain (Thompson et al, 2007).
2) INTRAVENOUS: An adult man who injected an unknown amount of fentanyl intravenously was found dead. Postmortem levels included: serum, 17.7 mcg/L; blood, 27.5 mcg/L; urine, 92.7 mcg/L; liver, 77.5 mcg/kg; and brain, 30.2 mcg/kg (Chaturvedi et al, 1990). In another case, a woman was found dead after injecting an unknown amount of fentanyl, and had a postmortem blood concentration of 540 mcg/L, urine 95 mcg/g, and stomach tissue mixed with blood of 40 mcg/g (Sutlovic & Definis-Gojanovic, 2007).
3) TRANSDERMAL/INGESTION: Postmortem serum, taken from femoral blood, revealed fentanyl and norfentanyl levels of 2.5 and 4.4 ng/mL, respectively, in a 43-year-old man who ate the contents of a 7.5 mg fentanyl transdermal patch (Gaultieri et al, 2000).
4) TRANSDERMAL/INTRAVENOUS: In a series of 4 fatal cases of intravenous exposure to fentanyl following extraction from a transdermal patch, the postmortem blood concentrations ranged from 5 to 27 mcg/L. All of the deaths were attributed to fentanyl toxicity (Tharp et al, 2004).
5) TRANSDERMAL/CASE SERIES: Seven adults died following oral abuse or potential abuse of fentanyl patches. Of the 7 cases, 2 deaths were related to fentanyl alone overdose, 3 were caused by a fentanyl and alcohol overdose, one was a mixed ingestion, and the last case was due to fentanyl and an underlying medical condition. Postmortem blood concentrations for all cases ranged from 7 to 97 ng/mL. Of the 2 cases that were due to fentanyl alone, the blood fentanyl concentrations were 13 and 22 ng/mL, respectively (Woodall et al, 2008).
6) TRANSDERMAL/INHALATION: Postmortem fentanyl concentrations were as follows: femoral blood 2.66 ng/mL, heart blood 6.05 ng/mL, urine 41 ng/mL, vitreous 41 ng/mL and liver 122 ng/g in an adult who had heated the contents of a fentanyl transdermal patch and inhaled the fumes (Marquardt & Tharratt, 1994).
7) TRANSDERMAL/EXCESSIVE APPLICATION: An 83-year-old woman with terminal cancer was found dead with three 100 mcg/hr fentanyl patches on her chest. The postmortem blood concentration was 25 ng/mL. It was estimated that 3 patches of 100 mcg/hr should produce a blood fentanyl concentration of 10 ng/mL with a 24 hr application. It was suggested that fentanyl metabolism may have been decreased based on age or reduced metabolism (Edinboro et al, 1997).
8) CASE REPORT: Blood fentanyl concentration in a man found dead of an overdose was 4.9 ng/mL; liver concentration was 5.9 ng/g (Levine et al, 1990).
9) CASE SERIES: In a series of 23 autopsy cases of fentanyl misuse and abuse, the average fentanyl concentrations were as follows: blood, 18 mcg/L ({n=23} range 2 to 48 mcg/L); liver, 399 mcg/L ({n=8} range 64 to 1465 mcg/L); bile, 56 mcg/L ({n=8} range 9 to 205 mcg/L); and urine, 195 mcg/L ({n=7} range 34 to 674 mcg/L), respectively (Kuhlman et al, 2003).
10) CASE REPORT: A 42-year-old man, with a history of non-Hodgkin's lymphoma, received two 75-mcg/hour fentanyl patches for pain management. Approximately 5 hours after initiation of therapy, one of the patches could not be found and was replaced. Approximately 16 hours after beginning therapy, the patient was found apneic, pulseless, and cyanotic. A fentanyl patch was removed from the patient's oropharynx; however, despite resuscitative efforts, the patient died. Femoral blood fentanyl concentrations, obtained 0.5 hours and 2 hours post-mortem were 1.6 ng/mL and 14 ng/mL, respectively. It is suspected that the increased fentanyl concentration post-mortem may be due to either decreasing plasma pH associated with a decrease in protein binding and a subsequent increase in water solubility, redistribution, or collection or laboratory error (Moore et al, 2015).