Fentanyl-related deaths: demographics, circumstances, and toxicology of 112 cases

Since 1979, the potent narcotic analgesic fentanyl and its analogs have been synthesized in clandestine laboratories and sold as heroin substitutes. At least 112 overdose deaths have been associated with their use. In this study, toxicology data, autopsy findings, and coroners' investigative reports were reviewed in order to construct a profile of the typical fentanyl overdose victim and to identify any factors that might heighten the risk of death from fentanyl use. The "typical" fentanyl overdose victim was 32.5 +/- 6.7 years of age (range, 19 to 57 years), male (78%, compared with 22% female), and Caucasian (50%, compared with 29% Hispanic, 20% Black, and 0.9% Asian). With the exception of his or her age, the typical fentanyl overdose victim is quite similar to the typical heroin user. Nearly all the deaths (94%) occurred in California, yet within the state they were widely distributed throughout 17 counties and 44 cities. Pulmonary edema and congestion and needle puncture sites were consistent postmortem findings. No preexisting medical conditions were identified as possible risk factors. Although most of the fentanyl victims had a prior history of intravenous drug use, morphine or codeine were not commonly found, which suggests that the victims had little or no opiate tolerance. Ethanol was present in 38% of the cases and is thought to be a significant risk factor. Mean fentanyl concentrations in the body fluids were quite low: 3.0 +/- 3.1 ng/mL (0.3 +/- 0.31 micrograms/dL) in blood and 3.9 +/- 4.3 ng/mL (0.39 +/- 0.43 micrograms/dL) in urine, measured by radioimmunoassay. Although the potency of the analogs and the purity of street samples varies considerably, it is probably the general availability of the drug rather than the potency of a particular analog that determines the incidence of overdose deaths.     

Trends and pattern of drug abuse deaths in Maryland teenagers

The Office of the Chief Medical Examiner of Maryland recorded a total of 149 drug abuse deaths of teenagers aged 13-19 years between 1991 and 2006. Of these deaths, 96 (64.4%) were caused by the use of narcotic drugs only, 29 (19.5%) by both narcotics and cocaine, four (2.7%) by both narcotics and methylenedioxymethamphetamine, six (4.0%) by cocaine only, and 14 (9.4%) by volatile substances (e.g., butane, Freon, nitrous oxide, and propane). The annual death rate from drug abuse for teenagers increased from 1.4 deaths per 100,000 population in 1991 to 2.7 deaths per 100,000 population in 2006 (chi-square test for time trend, p<0.01). The increase in teenager drug abuse deaths occurred in 1999 and since has remained at a higher rate. Further analysis revealed that the increase in drug abuse deaths was attributable to a large degree to narcotic drugs, particularly heroin/morphine and methadone, and was confined to teenagers residing in the suburban and rural areas.     

Heroin maintenance in Britain and heroin for the relief of pain in the United States of America

SUMMARY

The British themselves have recognized that heroin may not be the safest and most appropriate form of treatment for heroin addicts. The percentage of narcotic addicts in Britain being treated with methadone alone has risen steadily from 58% (of 1,549 addicts) in 1971 to 67% (of 2,588 addicts) in 1981. Also, the percentage of narcotic addicts receiving heroin alone has dropped from 7.1% (of 1,549 addicts) in 1971 to 2.6% (of 3,844 addicts) in 1981. The amount of heroin prescribed to addicts also fell from 22,778 grams in 1969 to 8,501 grams in 1978.

Further increases in the use of oral methadone and sterile injectable methadone, and resulting decreases in unsterile injections of heroin, would no doubt greatly diminish the incidence of death and severe disability in the treatment of British addicts.

On the issue of heroin's use for intractable pain, there is no evidence that heroin has unique advantages over other drugs. When given in equivalent doses, morphine has been proven to be as effective as heroin, orally or subcutaneously, for the relief of pain. In fact, heroin is rapidly converted into morphine in the body. Given the fact that heroin is the drug most narcotic addicts prefer, legally stocking the drugs in pharmacies, hospitals, and hospices would pose serious security and personal safety risks at these facilities. It is possible, in fact, that most pharmacies would refuse to stock the drug.     

An epidemic of intravenous narcoticism deaths associated with the resurgence of black tar heroin

In the latter part of 1985, a dramatic rise in the number of illicit narcotic (heroin) related deaths in the State of New Mexico became apparent, and this increase persisted through the majority of the following year. A careful inspection of samples of narcotics found at the scenes of death, coupled with changes in the illicit drug traffic detected by local and state law enforcement agencies, revealed that the rising death rate corresponded with the distinctively increased availability of a form of heroin that is produced in Mexico, commonly termed "black tar" heroin. An analysis of heroin deaths, comparing characteristics of cumulative deaths in the six years before the increase with those deaths associated with the apparent epidemic, revealed several significant observations. These factors, along with the distinctive physical features of black tar heroin, suggest that the rise in the narcotic abuse death rate may be related to both unfamiliarity with this type of heroin on the part of the user and the inherent difficulty of diluting nonpowdered forms of the drug to sublethal levels.     

Forensic-biochemical indices of serum amilase and cholinesterase activity in lethal poisoning with heroin

The examination of the activity of serum amilase and cholinesterase in the blood from subjects who had died of heroin poisoning showed significant elevation of such activity. These findings allow experts to use the activity of the above enzymes as effective markers in detection of narcotic drugs in cadaveric blood, opiate narcotics, in particular.     

Opiate poisoning (an analysis of section material)

Section specimens from subjects dead from narcotic poisoning in 1998-1999 are analyzed. The results indicate that narcotic poisonings were primarily due to opiates or their combinations with other drugs (primarily ethanol). The ratio of male to female mortality was 3:1. Death after narcotic poisoning occurs at home in the majority of cases. The concentration of morphine/heroin in the blood and urine of victims varied within a very wide range. Acute renal failure, myoglobulinuremic nephrosis, and compression syndrome are not typical of acute narcotic poisoning. Use of immunotest for urinary morphine-heroin deserves further investigation.     

Heroin body packing: three fatal cases of intestinal perforation

Death from heroin body packing has been well described in the forensic literature. Most fatalities are due to drug leakage and consequent acute heroin toxicity. Recently, drug traffickers have become more sophisticated in their packaging, and the risk of rupture of drug packets is more remote. Though intestinal obstruction is a recognized risk of body packing, rarely has this resulted in death. We describe four cases of heroin body packing presenting to the Regional Medical Examiner Office in New Jersey. Death in three of these cases was due to intestinal obstruction, with resultant intestinal rupture and peritonitis. Toxicologic evaluation in these three cases was negative for opiates or other drugs of abuse. In one case, death was due to acute heroin toxicity, validated by toxicologic analysis. We briefly discuss the differing drug packaging found in these four cases and the ramifications of packaging as it relates to intestinal obstruction.     

Narcotics and Drug Abuse

Fifty years ago, the U.S. President's Commission on Law Enforcement and Administration of Justice saw drugs as a modest but growing problem for the criminal justice system. The reemergence of heroin occupied the Commission's attention. Many recommendations are admirable, such as a focus on public health interventions and a concern about the appropriateness of criminal prohibitions on marijuana use. Throughout the past 50 years, the problem has both massively expanded and changed in many ways; the principal drug of abuse has shifted multiple times, as has the populations most affected by them. Policy, largely stuck on tough enforcement for 30 years, is now moving in a direction more consistent with the Commission's views. Researchers have made only modest advances in understanding what enforcement can do to reduce drug use and related problems, but society has made some progress in developing interventions that have both a sound theoretical base and the promise of avoiding the unintended negative consequences of the highly punitive system of the 1980s and 1990s. A Commission in 2018 would face a much different and larger problem that has transformed many aspects of criminal justice. Investing in more data collection and evaluation research would be among its major recommendations, as would an admission of considerable uncertainty about what to do with the latest twist in the U.S. drug problem, the addition of the much more dangerous fentanyls.     

Evaluating the Potential for Unintentional Occupational Exposure to Fentanyl and Fentanyl Analogues Among Medicolegal Death Investigators and Autopsy Technicians

Recent increases in deaths in the United States from synthetic opioids such as fentanyl and fentanyl analogues (fentanyls) have raised concerns about possible occupational exposures to these potent agents. Medicolegal death investigators and autopsy suite staff might perform job tasks involving exposure to fentanyls. The potential for exposure to fentanyls among medicolegal death investigators and autopsy technicians at a state medical examiner's office was evaluated through review of caseload characteristics, injury and illness logs, and procedures and policies and discussions with management and employee representatives. The evaluation showed that this medical examiner's office had low potential for work-related exposure to fentanyls; its standard operating procedures and personal protective equipment requirements should reduce the potential for occupational exposure. Medicolegal death investigation agencies can develop and implement guidance to control exposures and provide workforce education and training to reduce the potential for work-related exposure to fentanyls.     

Heroin impurity profiling: trends throughout a decade of experimenting.

Heroin is still one of the most frequently abused drugs of today. All over the world, law enforcement agencies try to eradicate the illicit production and trafficking of this potent and highly addictive narcotic. To this aim, important information is provided by physical and chemical toxicological analysis of confiscated samples, with special attention for the identification and the quantification of minor components, such as the impurities related to the origin and manufacturing. By combining these data complex characterisations, i.e. impurity profiles, chemical signatures or fingerprints, can be obtained and used for comparative analysis. This review focuses on heroin impurity profiling during the 1990s, proclaimed by the United Nations as the 'Decade for Eradicating Drug Abuse'. Special attention will be given to the new trends in analytical techniques as well as in data handling strategies, so called chemometrics, to produce these profiles. The latter can be used in comparative analysis of seized heroin samples for tactical (batch-to-batch comparison) and strategic (origin determination) intelligence purposes.     

Review of analytical methods for screening and quantification of fentanyl analogs and novel synthetic opioids in biological specimens

Fentanyl, fentanyl analogs, and other novel synthetic opioids (NSO), including nitazene analogs, prevail in forensic toxicology casework. Analytical methods for identifying these drugs in biological specimens need to be robust, sensitive, and specific. Isomers, new analogs, and slight differences in structural modifications necessitate the use of high-resolution mass spectrometry (HRMS), especially as a non-targeted screening method designed to detect newly emerging drugs. Traditional forensic toxicology workflows, such as immunoassay and gas chromatography mass spectrometry (GC–MS), are generally not sensitive enough for detection of NSOs due to observed low (sub-μg/L) concentrations. For this review, the authors tabulated, reviewed, and summarized analytical methods from 2010–2022 for screening and quantification of fentanyl analogs and other NSOs in biological specimens using a variety of different instruments and sample preparation approaches. Limits of detection or quantification for 105 methods were included and compared to published standards and guidelines for suggested scope and sensitivity in forensic toxicology casework. Methods were summarized by instrument for screening and quantitative methods for fentanyl analogs and for nitazenes and other NSO. Toxicological testing for fentanyl analogs and NSOs is increasingly and most commonly being conducted using a variety of liquid chromatography mass spectrometry (LC–MS)-based techniques. Most of the recent analytical methods reviewed exhibited limits of detection well below 1 μg/L to detect low concentrations of increasingly potent drugs. In addition, it was observed that most newly developed methods are now using smaller sample volumes which is achievable due to the sensitivity increase gained by new technology and new instrumentation.     

One hundred seventy two deaths involving the use of oxycodone in Palm Beach County

Oxycodone is a potent semi-synthetic narcotic prescribed for the management of pain. Previous investigators have reported that the abuse of oxycodone is most frequently seen in conjunction with the abuse of other drugs, although fatalities have been reported with oxycodone alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of oxycodone. A total of 172 consecutive cases were studied, including 18 in which death was attributed to oxycodone toxicity, 117 to combined drug toxicity, 23 to trauma, 9 to natural causes and 5 to another drug or drugs. The postmortem blood concentrations of oxycodone overlapped among the groups. The mean blood oxycodone concentration among the cases of oxycodone toxicity was 0.69 mg/L, combined drug toxicity 0.72 mg/L and trauma 0.62 mg/L. Concentrations were lower in cases of deaths attributed to natural causes and to another drug or drugs (mean each 0.087 mg/L). Benzodiazepines, detected in 96 cases, were the most common co-intoxicants in the cases of combined drug toxicity, followed by cocaine, which was found in 41. The most frequently encountered benzodiazepine was alprazolam. This study confirms that deaths in which oxycodone is a factor are most commonly cases of combined drug toxicity. The high incidence of alprazolam as a co-intoxicant has not been previously recognized.     

Dynamics of the Soviet illicit drug market

The demise of communism, Westernization, internal economic reform and the disintegration of the Soviet state create fertile soil for the growth of drug abuse and drug trafficking in (the former) USSR. Rates of drug abuse have soared since the mid-1980s, especially in the European parts of the (former) Union; also, organized interregional drug mafias have emerged to serve this rapidly expanding market. The (former) USSR does not now participate significantly in the international narcotics market as a consumer or supplier of illicit substances; however, this pattern of relative self-sufficiency could change dramatically in the 1990s. Convertibility of the ruble could result in a large flow of Western hard drugs such as cocaine, heroin or crack into European Russia. A rapid expansion of trade, travel and economic ties with Western countries will widen the pipeline for the movement of drugs. Finally, Moscow's weakening hold over the (former) Soviet Central Asian republics and Central Asia's generally bleak economic prospects correlate with an apparent massive expansion of drug crop cultivation in that region; if current trends continue, (former) Soviet Central Asia could well become a significant world supplier of hashish and opium products, during the 1990s.Research for this study was completed prior to the transformation of the USSR into the Commonwealth of Independent States.This paper was published as an occasional paper by the Kennan Institute of Advanced Soviet studies and has been updated since then.This paper was prepared for the Department of State as part of its external research program. Views or conclusions contained herein should not be interpreted as representing the official opinion or policy of the Department of State.     

Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner's Office

Recreational drugs, such as cocaine and heroin, are often adulterated with other pharmacological agents to either enhance or diminish the drug effects. Between April 21, 2006 and August 8, 2006, the Philadelphia Medical Examiner's Office detected xylazine (a veterinary sedative) and fentanyl (a synthetic opioid) in specimens taken from seven cases. Initial immunoassay screening was performed on urine and blood for fentanyl, opiate, cocaine, phencyclidine (PCP), and benzodiazepines. All tests reported positive were confirmed by gas chromatography-mass spectrometry. All seven xylazine positive cases tested positive for fentanyl and six cases tested positive for 6-acetylmorphine (a metabolite and definitive marker for heroin). The seventh case was positive for morphine and had a history of heroin abuse. Xylazine was present in urine in all seven cases and blood levels were detected in three cases. The blood concentrations ranged from trace to 130 ng/mL. Fentanyl was present in the blood and urine in each case and blood concentrations ranged from 4.7 to 47 ng/mL. Adulteration of illicit drugs has become an epidemic health concern for drug users. Healthcare professionals need to be aware of this issue, so the patients can be treated in an effective, timely manner.     

Fatal Intoxications in a Forensic Autopsy Material from Epirus,Greece, During the Period 1998‐2010

In this retrospective study, we report the epidemiological characteristics of all poisoning deaths in Epirus, Greece, from 1998 to 2010; we present the toxicological findings and the statistical evaluation of the results. This is the first detailed scientific report on all the officially certified poisoning deaths concerning part of the Greek population. A total of 126 poisoning fatalities were recorded, 67 of them being mono‐intoxications (53.2%). The cause of poisoning was as follows: drugs of abuse (60%); carbon monoxide (19.8%); pesticides (9.5%); corrosives (4.8%); pharmaceuticals (4.8%); and spider bite (0.8%). The most frequently detected poisonous substances were as follows: heroin (65 cases), ethanol (55), benzodiazepines (42), carbon monoxide (25), cocaine (17), cannabinoids (17) and pesticides (12). Increasing tendency in poisoning death rates was recorded, due to an increase in accidental poisoning deaths attributed mainly to drugs of abuse (total, accidental, and drugs‐of‐abuse poisoning death rates per 100,000 inhabitants per year were 1.87, 1.19, and 0.79, respectively, in the period 1998–2002 and 3.97, 3.41, and 2.55, respectively, in the period 2007–2010).     

Drug use in India: Historical traditions and current problems

By all accounts, drug abuse in India — as elsewhere around the world — is reaching near epidemic proportions. Although India has been a world producer of legal drugs for pharmaceutical markets, it also has an ancient tradition of using drugs in daily activities and ceremonial rituals. Only in recent years has this historically drug‐rich country developed a drug abuse problem. Because of its history of tolerance of drug use in culturally sanctioned activities, India offers a rich site for investigating the conditions that foster responsible and irresponsible use of drugs. Global efforts at crop reduction, interdiction, and criminal sanctions continue to be disappointing at best. A more realistic approach may be to identify factors that make drugs particularly alluring to some segments of the population and not to others. This approach emphasized responsible conduct in drug‐rich environments rather than depending on the increasingly unlikely eradication of the supply.     

Blood levels of 3-methylfentanyl in 3 fatal poisoning cases

Three fatal poisoning cases due to 3-methylfentanyl are described. In each case, the death was accidental and occurred after injection of the opioid combined with amphetamine, heroin, or other drugs. The victims' ages, ranging from 30 to 41 years, were higher than those typically found in heroin poisonings in Finland. The blood concentrations of cis-3-methylfentanyl, measured here for the first time by a specific tandem mass spectrometric method, ranged from 0.3 to 0.9 microg/L (mean 0.5 microg/L). These values are significantly lower than the levels reported for alpha-methylfentanyl and fentanyl in fatal poisonings. Repeated seizures of fentanyl and its analogs have been reported in Europe close to the Russian border.     

Identification of synthetic cannabinoids in herbal incense blends in the United States

Abstract: Synthetic cannabinoid agonists are chemically diverse with multiple analogs gaining popularity as drugs of abuse. We report on the use of thin layer chromatography, gas chromatography mass spectrometry, high‐performance liquid chromatography, and liquid chromatography time of flight mass spectrometry for the identification and quantitation of these pharmacologically active chemicals in street drug dosage forms. Using these approaches, we have identified the synthetic cannabinoids JWH‐018, JWH‐019, JWH‐073, JWH‐081, JWH‐200, JWH‐210, JWH‐250, CP47,497 (C=8) (cannabicyclohexanol), RCS‐4, RCS‐8, AM‐2201, and AM‐694 in various commercially available products. Other noncannabinoid drugs including mitragynine have also been detected. Typical concentrations of drug in the materials are in the range 5–20 mg/g, or 0.5–2% by weight for each compound, although many products contained more than one drug.     

Designer drugs in herbal aphrodisiacs

In the presented case three herbal aphrodisiacs (Libidfit, Satibo and Viamax) were investigated for the presence of regular pharmaceuticals against erectile dysfunction. However, high-performance liquid chromatography with diode array detection and mass spectrometry (HPLC-DAD-MS) and nuclear magnetic resonance (NMR) analyses revealed the presence of ingredients, having a molecular structure strongly resembling those of sildenafil (Viagra) and vardenafil (Levitra). The health risk posed by these analogous substances is high because they were found to be potent phosphodiesterase 5 (PDE5) inhibitors used in pharmacologically relevant quantities having no known safety profile. Based on structural and functional analogy these analogs represent a new class of designer drugs and should be taken off the market for being unapproved drug substances. In the Libidfit court case this was done successfully, setting a precedent.     

Alprazolam-related deaths in Palm Beach County

Alprazolam is a commonly prescribed benzodiazepine. The abuse of benzodiazepines is most frequently seen in conjunction with the abuse of other drugs. Only rare fatalities have been attributed to alprazolam alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of alprazolam, to further study the pattern of alprazolam abuse. Our review consisted of 178 cases, including 87 in which death was attributed to combined drug toxicity, 2 to alprazolam toxicity alone, 44 to trauma, 12 to natural causes, and 33 to another drug or drugs. Cocaine and methadone were the most common cointoxicants in the cases of combined drug toxicity, while heroin was less frequently detected. There was considerable overlap in the postmortem blood alprazolam concentrations among the groups. The overlapping ranges of concentrations of alprazolam detected indicate that it may be difficult to define a lethal alprazolam range, and that it may not be possible to determine the actual role of alprazolam as a causal factor in cases of combined drug toxicity. This study confirms that alprazolam alone is rarely a cause of death, and that alprazolam abuse usually occurs within a polydrug use pattern. The high incidence of cocaine as a cointoxicant has not been previously reported.