Quantifying a potential protective effect of buprenorphine on fatality risk during acute fentanyl exposures.

INTRODUCTION: Buprenorphine is an important therapy for opioid use disorder and may also reduce the risk of fatal overdoses in fentanyl exposures. However, the role of buprenorphine in reducing this risk has not been quantified. This cross-sectional study examined the association between buprenorphine presence, decedent characteristics, and other factors with the predicted fentanyl concentrations in overdose deaths. METHODS: The study identified unintentional fentanyl overdose decedents (n = 3036) from the West Virginia Forensic Drug Database, 2011 through mid-2020. The main outcome was fentanyl concentrations in overdose deaths in the presence and absence of buprenorphine. A multiple linear regression model examined the association of fentanyl concentrations with buprenorphine presence based on the concentrations of the parent drug buprenorphine (B) and its metabolite norbuprenorphine (N), adjusting for demographics, toxicological characteristics (presence of multiple opioids, benzodiazepines, stimulants, marijuana, and alcohol), and comorbidities. We used a B/N concentration ratio < 1 as an indirect indicator of longer-term buprenorphine exposure prior to drug overdose death. RESULTS: The median fentanyl concentration was 65 % higher when buprenorphine was present (N = 168) vs. absent (N = 2868) (0.028 vs. 0.017 µg/mL, p < 0.001). In the multivariable model, statistically significant associations occurred between buprenorphine presence and increased fentanyl concentrations (+28.7 %) with a B/N ratio < 1. Obesity, male sex, alcohol presence, and comorbid cardiovascular diseases were statistically significantly associated with lower (-11.3 % to -20.7 %) fentanyl concentrations, whereas marijuana presence and a history of substance use disorder were associated with statistically significant higher fentanyl concentrations (+8.8 % to +31.3 %). CONCLUSIONS: These findings suggest that sustained or longer-term buprenorphine intake might exert some protective effect on fatalities resulting from fentanyl exposure as documented by the association of higher fentanyl blood concentrations with buprenorphine presence among fatal drug overdoses. As fentanyl availability and overdose rates increase nationally, buprenorphine is a vital tool for effective opioid use disorder treatment that might also reduce the risk of fatality in an acute fentanyl exposure.

Oral Cavity Fluid as an Alternative Postmortem Matrix: Comparison to Simultaneously Collected Blood and Urine Specimens.

ABSTRACT: In postmortem toxicology analysis, a variety of specimens consisting of fluids and tissues are often collected, each with an intrinsic value. Oral cavity fluid (OCF) is emerging as an alternative matrix in forensic toxicology for contributing to a diagnosis in postmortem cases; especially when blood is limited or not available. The aim of this study was to assess the analytical results obtained from OCF and compare them with blood, urine, and other traditional matrices collected from the same postmortem subjects. Of the 62 decedents studied (including 1 stillborn, 1 charred, and 3 decomposed subjects), 56 had quantifiable drugs and metabolites data in the OCF, blood, and urine. Notable findings were benzoylecgonine (24 cases), ethyl sulfate (23 cases), acetaminophen (21 cases), morphine (21 cases), naloxone (21 cases), gabapentin (20 cases), fentanyl (17 cases), and 6-acetylmorphine (15 cases), which were detected more frequently in OCF than in blood (heart, femoral, or body cavity) or urine. This study suggests that OCF is a suitable matrix for detecting and quantifying analytes in postmortem subjects compared with traditional matrices, particularly when other matrices are limited or difficult to collect because of body condition or putrefaction.

Characterization of Unintentional Deaths Among Buprenorphine Users.

OBJECTIVE: Medications used to treat opioid use disorder (OUD) reduce drug overdose risk. Buprenorphine is often the preferred treatment for OUD because of its high safety profile. Given expanding buprenorphine use, this study sought to examine buprenorphine-involved deaths (BIDs) and compare them with other drug-related deaths. METHOD: West Virginia drug-related deaths from 2005 to early 2020 were identified. Study data included decedent demographics, toxicology, autopsy findings, and medical and prescription histories. Characteristics of BIDs compared with other drug-related deaths were statistically analyzed. RESULTS: Among 11,764 drug-related deaths, only 564 (4.8%) involved buprenorphine. Buprenorphine alone was present in 32 deaths, of which 20 were considered the direct cause of death (0.2% of all drug-related deaths). Significantly more BIDs involved five or more drugs (23%) compared with other opioid deaths (14.9%). Co-intoxicants found most frequently in BIDs were benzodiazepines (47.3%), methamphetamine (27.1%), and fentanyl (22.9%). Cardiovascular and pulmonary comorbidities were identified in 43% and 21% of BIDs, respectively. Of the 564 BIDs, a current buprenorphine prescription was present in 132 deaths (23.4%). CONCLUSIONS: Despite increasing buprenorphine use, BIDs comprised less than 5% of overall West Virginia drug-related deaths. Seldom was it the only drug found, and most decedents did not have current prescriptions for buprenorphine. Although buprenorphine is effective, with a wide safety margin, clinicians and patients should be aware that buprenorphine can be involved in overdose deaths, especially when buprenorphine is taken in combination with drugs such as benzodiazepines, methamphetamine, or fentanyl, and in persons with underlying cardiovascular or pulmonary comorbidities.

Characteristics of xylazine-related deaths in West Virginia-Xylazine-related deaths.

BACKGROUND AND OBJECTIVES: The involvement of xylazine, a veterinary drug, in West Virginia (WV) human drug-related deaths was examined. METHODS: WV drug deaths from 2019 (when xylazine was first identified) to mid-2021. Characteristics including toxicology findings were compared between xylazine and nonxylazine deaths. RESULTS: Of 3292 drug deaths, 117 involved xylazine, and the proportions of deaths with it have increased (1% [2019] to 5% [mid-2021)]. Xylazine decedents had more cointoxicants, with fentanyl (98%) predominant followed by methamphetamine. Xylazine decedents had a significantly greater history of drug or alcohol misuse and hepatic disease. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: In one of the largest analyses of xylazine-involved deaths in a predominantly rural state, identification of xylazine was increasing with multiple cointoxicants (especially fentanyl), and was present in a few deaths with only one other substance involved. Health professionals should be aware of possible enhanced toxicity from xylazine ingestion especially since naloxone does not reverse xylazine's adverse effects.

Quantitation and Validation of 34 Fentanyl Analogs from Liver Tissue Using a QuEChERS Extraction and LC-MS-MS Analysis.

Since 2013, drug overdose deaths involving synthetic opioids (including fentanyl and fentanyl analogs) have increased from 3,105 to 31,335 in 2018. Postmortem toxicological analysis in fentanyl-related overdose deaths is complicated by the high potency of the drug, often resulting in low analyte concentrations and associations with toxicity, multidrug use, novelty of emerging fentanyl analogs and postmortem redistribution. Objectives for this study include the development of a quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction and subsequent liquid chromatography-mass spectrometry--mass spectrometry analysis, validation of the method following the American Academy of Forensic Sciences Standards Board (ASB) standard 036 requirements and application to authentic liver specimens for 34 analytes including fentanyl, metabolites and fentanyl analogs. The bias for all 34 fentanyl analogs did not exceed ±10% for any of the low, medium or high concentrations and the %CV did not exceed 20%. No interferences were identified. All 34 analytes were within the criteria for acceptable percent ionization suppression or enhancement with the low concentration ranging from -10.2% to 23.7% and the high concentration ranging from -7.1% to 11.0%. Liver specimens from 22 authentic postmortem cases were extracted and analyzed with all samples being positive for at least one target analyte from the 34 compounds. Of the 22 samples, 17 contained fentanyl and metabolites plus at least one fentanyl analog. The highest concentration for a fentanyl analog was 541.4 µg/kg of para-fluoroisobutyryl fentanyl (FIBF). The concentrations for fentanyl (n = 20) ranged between 3.6 and 164.9 µg/kg with a mean of 54.7 µg/kg. The fentanyl analog that was most encountered was methoxyacetyl fentanyl (n = 11) with a range of 0.2-4.6 µg/kg and a mean of 1.3 µg/kg. The QuEChERS extraction was fully validated using the ASB Standard 036 requirements for fentanyl, metabolites and fentanyl analogs in liver tissue.

Fentanyl and other opioid involvement in methamphetamine-related deaths.

Background: Methamphetamine-related deaths have been rising along with those involving synthetic opioids, mostly fentanyl and fentanyl analogs (FAs). However, the extent to which methamphetamine involvement in deaths differs from those changes occurring in synthetic opioid involvement is unknown.Objectives: To determine the patterns and temporal changes in methamphetamine-related deaths with and without other drug involvement.Methods: Data from all methamphetamine-related deaths in West Virginia from 2013 to 2018 were analyzed. Quasi-Poisson regression analyses over time were conducted to compare the rates of change in death counts among methamphetamine and fentanyl//FA subgroups.Results: A total of 815 methamphetamine-related deaths were analyzed; 572 (70.2%) were male and 527 (64.7%) involved an opioid. The proportion of methamphetamine only deaths stayed relatively flat over time although the actual numbers of deaths increased. Combined fentanyl/FAs and methamphetamine were involved in 337 deaths (41.3%) and constituted the largest increase from 2013 to 2018. The modeling of monthly death counts in 2017-2018 found that the average number of deaths involving fentanyl without methamphetamine significantly declined (rate of change -0.025, p < .001), while concomitant fentanyl with methamphetamine and methamphetamine only death counts increased significantly (rate of change 0.056 and 0.057, respectively, p < .001).Conclusions: Fentanyl and FAs played an increasingly significant role in methamphetamine-related deaths. The accelerating number of deaths involving fentanyl/FAs and methamphetamine indicates the importance of stimulants and opioids in unintentional deaths. Comprehensive surveillance efforts should continue to track substance use patterns to ensure that appropriate prevention programs are undertaken.

Quantifying enhanced risk from alcohol and other factors in polysubstance-related deaths.

BACKGROUND: To quantify how alcohol, polysubstance use and other factors influence opioid concentrations in drug-related deaths in West Virginia (WV), United States. METHODS: Multiple linear regression models were employed to identify relationships among alcohol, other factors, and the concentrations of four commonly identified opioids (fentanyl, hydrocodone, oxycodone, methadone), accounting for demographic, toxicological and comorbid characteristics in WV drug-related deaths from 2005 to 2018. RESULTS: Alcohol concentrations of 0.08% or above were associated with significant reductions in blood concentrations of fentanyl (27.5%), hydrocodone (30.5%) and methadone (32.4%). Significantly lower predicted concentrations of all opioids studied were associated with multiple opioid vs. single opioid presence, with predicted concentration reductions ranging from 13.7% for fentanyl to 65-66% for hydrocodone and oxycodone. Benzodiazepine presence was associated with small, non-statistically significant changes in opioid concentrations, while stimulant presence was associated with statistically significant reductions in hydrocodone and oxycodone concentrations. CONCLUSIONS: Co-ingestion of alcohol, multiple opioids or stimulants were associated with significantly decreased predicted concentrations of commonly identified opioids in drug deaths. Further evidence is provided for enhanced risks from polysubstance use with opioids, which has important public health implications.

Fentanyl and fentanyl-analog involvement in drug-related deaths.

BACKGROUND: To describe and analyze the involvement of fentanyl and fentanyl analogs (FAs) in drug-related deaths in West Virginia (WV), United States. METHODS: Retrospective analyses of all WV drug-related deaths from 2005 to 2017 were performed, including comparisons of demographic and toxicological characteristics among total deaths, deaths in which fentanyl/FAs were present, deaths in which they were absent, heroin-related deaths, and prescription opioid-related deaths. RESULTS: Most of the 8813 drug-related deaths were overdoses, with about 11% resulting from transportation/other injuries in which drugs were contributors. Prescription opioid presence (without fentanyl) decreased by 75% from 2005-14 to 2015-17 (3545 deaths to 859 deaths, respectively), while fentanyl involvement in the deaths increased by 122% between these periods (487 to 1082 deaths). Ten FAs were identified (427 instances) after 2015. Alprazolam and ethanol were among the top five most frequently identified substances across years. Fentanyl, heroin and cocaine replaced oxycodone, diazepam and hydrocodone in the top five beginning in 2015. Few decedents had a prescription for fentanyl after 2015, with fewer prescriptions also present for other controlled substances identified. CONCLUSIONS: Fentanyl, rapidly emerging FAs, and other illicit drugs in recent years pose a serious health threat even though prescription opioid-related deaths decreased over the same time period.

The Importance of Melatonin Detection in Pediatric Deaths.

Melatonin is an endogenous hormone that regulates sleep patterns. It is available in varying formulations and dosages and is marketed as a natural substance that can alleviate insomnia. Recent news reports indicate that melatonin has been administered without appropriate authorization in daycare settings. Even though lethal outcomes have not been solely attributed to exogenous melatonin overdose, it has been relevant to select police and postmortem investigations. A quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the analysis of biological specimens. Results of 22 positive blood samples were evaluated based upon gender, age, and melatonin concentration from cases submitted by clinical, police, and death investigation agencies. Two cases are described. In Case 1, a 9-month-old was found unresponsive after cosleeping with a sibling. Allegations included exposure to an unspecified pesticide and dextromethorphan, and consumption of half a cigarette. There was admitted use of melatonin. Melatonin was quantified in blood and gastric fluid at concentrations of 13 ng/mL and 1200 ng/mL, respectively. In Case 2, a 13-month-old was found nonresponsive in a shared room. Melatonin was found within some of the sippy cups. The infant was extremely warm to the touch. Resuscitative efforts were unsuccessful and death was pronounce3d. Analysis showed a result of 210 ng/mL in blood. The presented quantitative LC-MS/MS method can successfully be applied to evaluate exposure to exogenous melatonin. Toxicology testing can assist in the investigation of these case types by substantiating the purposeful administration of melatonin.

Fatal Intoxication with Acetyl Fentanyl.

Among the new psychoactive substances encountered in forensic investigations is the opioid, acetyl fentanyl. The death of a 28-year-old man from recreational use of this compound is reported. The decedent was found in the bathroom of his residence with a tourniquet secured around his arm and a syringe nearby. Postmortem examination findings included marked pulmonary and cerebral edema and needle track marks. Toxicological analysis revealed acetyl fentanyl in subclavian blood, liver, vitreous fluid, and urine at concentrations of 235 ng/mL, 2400 ng/g, 131 ng/mL, and 234 ng/mL, respectively. Acetyl fentanyl was also detected in the accompanying syringe. Death was attributed to recreational acetyl fentanyl abuse, likely through intravenous administration. The blood acetyl fentanyl concentration is considerably higher than typically found in fatal fentanyl intoxications. Analysis of this case underscores the need for consideration of a wide range of compounds with potential opioid-agonist activity when investigating apparent recreational drug-related deaths.

Additive Effects of Cointoxicants in Single-Opioid Induced Deaths.

A forensic drug database (FDD) was used to capture comprehensive data from all drug-related deaths in West Virginia, with deaths also included from the northern New England states of Maine, Vermont, and New Hampshire. All four states serve predominantly rural populations under two million and all have similar state medical examiner systems that employ statewide uniform death certification policies and practices. This study focused on 1482 single opioid deaths (fentanyl, hydrocodone, methadone, and oxycodone) in the FDD from 2007-2011. We modeled relationships between the opioid concentrations and the presence or absence of the following commonly occurring non-opioid cointoxicants: benzodiazepines (alprazolam and diazepam), alcohol, tricyclic antidepressants, selective serotonin reuptake inhibitors, and diphenhydramine. Additional covariates of state, age, body mass index, and sex were included. Results showed that the presence of alcohol, benzodiazepines, and antidepressants were each associated with statistically significant lower concentrations of some but not all of the opioids studied, which may obscure the interpretation of postmortem toxicology results alone. Fentanyl concentrations appeared to be the least associated with the presence or absence of the variables studied, and cointoxicant alcohol appeared to be associated with lower concentrations in opioid concentrations than were most of the other factors in the model studied. These findings underscore the importance of documenting all potential cointoxicants in opioid-related deaths.

Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations.

Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored.

Fatal methadone toxicity: potential role of CYP3A4 genetic polymorphism.

Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype.

Validation of blood and liver oxymorphone analysis using LC-MS-MS: concentrations in 30 fatal overdoses.

A sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitation of oxymorphone (OM) in human whole blood and liver. Sample preparation was done by solid-phase extraction, using deuterated OM as the internal standard. Separation was achieved using a Waters Aquity UPLC HSS T3 column. Analysis utilized positive electrospray ionization and multiple reaction monitoring. As part of the validation, studies were conducted to determine potential interference, selectivity, ion suppression/enhancement and carryover. Calibration model, limit of detection (LOD), lower limit of quantitation (LLOQ), precision and accuracy were also established. The linear range of the method was 2-500 ng/mL in blood and 5-500 ng/g in the liver. The LOD and LLOQ were 2 ng/mL for blood and 5 ng/g for the liver. Blood and/or liver specimens from 30 cases were analyzed. OM concentrations ranged from 23 to 554 ng/mL ( , n = 26) in blood and 48 to 1740 ng/g ( , n = 30) in the liver.

Characteristics of alprazolam-related deaths compiled by a centralized state medical examiner.

BACKGROUND AND OBJECTIVE: Unintentional drug poisoning deaths represent a major health concern, particularly in rural areas. Although alprazolam is frequently detected in drug-related deaths, characterization of its involvement is limited. Our objective was to compare the characteristics of alprazolam-related deaths with nonalprazolam deaths in a predominantly rural state. METHODS: A comprehensive forensic drug database (FDD) was developed in 2005 to compile demographic, toxicology, and co-morbidity information from all West Virginia (WV) drug-related deaths. All FDD data from 2005 to mid-November 2007 were analyzed. RESULTS: Alprazolam contributed to 204 (17.0%) of the 1,199 drug-related deaths and was identified in 7.2% of the 363 deaths occurring during 2005 and in 27.5% of the 422 deaths entered in the database during 2007. At least one other drug, predominantly an opioid, was identified in 97.5% of the alprazolam cases, with concurrent benzodiazepines also found. Compared to nonalprazolam deaths, alprazolam decedents were significantly more likely to be obese and to have preexisting cardiovascular disease, but were less likely to have documented substance abuse. An alprazolam prescription existed in 52.5% of the alprazolam deaths, with 77.6% having a prescription for all drugs identified. CONCLUSIONS: Alprazolam was a contributing cause of death in a substantial and increasing number of drug-related deaths. Prescriptions for alprazolam and the other drugs detected were often present in these cases. SCIENTIFIC SIGNIFICANCE: Controlled substance monitoring programs should be routinely used as one mechanism to help prevent potential drug misuse/abuse. Our findings provide a baseline for ongoing alprazolam-related death surveillance.

Fatality involving the ingestion of phenazepam and poppy seed tea.

Phenazepam is a benzodiazepine derivative that has been in clinical use in Russia since 1978 and is not available by prescription in the United States; however, it is attainable through various internet websites, sold either as tablets or as a reference grade crystalline powder. Presented here is the case of a 42-year old Caucasian male who died as the result of combined phenazepam, morphine, codeine, and thebaine intoxication. A vial of white powder labeled "Phenazepam, Purity 99%, CAS No. 51753-57-2, Research Sample", a short straw, and several poppy seed pods were found on the scene. Investigation revealed that the decedent had a history of ordering medications over the internet and that he had consumed poppy seed tea prior to his death. Phenazepam, morphine, codeine, and thebaine were present in the blood at 386, 116, 85, and 72 ng/mL, respectively.

Potential biomarkers of smoked fentanyl utilizing pyrolysis gas chromatography-mass spectrometry.

Fentanyl is a potent opioid analgesic that is increasingly becoming a choice drug of abuse. Fentanyl transdermal patches (FTPs) are easily obtained and consumed by smoking the reservoir gel and/or the whole patch. This allows for an increased bioavailability when inhaled. A method using analytical pyrolysis was developed to identify possible biomarkers associated with smoked fentanyl and FTPs. Pyrolysis was carried out under anaerobic and aerobic conditions using helium and air coupled to a gas chromatograph-mass spectrometer. The presence of a trap enhanced recovery and afforded a positive identification of pyrolytic products. Anaerobic and aerobic pyrolysis of fentanyl and FTPs consistently yielded propionanilide as the major pyrolytic product along with pyridine and previously reported metabolites (norfentanyl and despropionyl fentanyl). Analysis of fentanyl resulted in chlorine-containing compounds, presumably formed from the HCl salt of fentanyl. Analysis of FTPs showed significant polymeric and hydrocarbon compounds and products likely derived from the gel matrix. Fentanyl in the FTPs was in the citrate salt form; therefore, the chlorine-containing pyrolytic products obtained with the neat drug were not observed. Based on this application, it may be possible to identify what salt form of the drug was smoked based on pyrolytic products and to target distinguishing metabolic products for future research.

Comparison of oxycodone in vitreous humor and blood using EMIT screening and gas chromatographic-mass spectrometric quantitation.

Vitreous humor may serve as a useful alternative specimen for oxycodone analysis in death investigations where blood samples are not available or are of poor quality or limited quantity. The purpose of this study was to investigate the relationship between immunoassay results and gas chromatography-mass spectrometry (GC-MS) quantitation of oxycodone in postmortem vitreous humor and blood. When used with vitreous humor calibrators, the Microgenics DRI Oxycodone (EMIT) Assay was found to be linear from 25 to 500 ng/mL with an limit of detection of 25 ng/mL. Vitreous humor and postmortem blood precipitate immunoassay responses in 57 oxycodone-positive cases were found to be correlated (r(2) = 0.69, p < 0.01). Confirmation and quantitation of oxycodone in vitreous humor by GC-MS was linear from 50 to 1000 ng/mL with a limit of detection of 10 ng/mL and a limit of quantitation of 50 ng/mL. In 30 cases, oxycodone vitreous humor concentrations ranged from less than 50 to 945 ng/mL, and blood concentrations ranged from 103 to 768 ng/mL. The average vitreous humor/blood ratio was 1.16 and ranged from 0.12 to 3.26. Disparities between vitreous fluid and blood oxycodone concentrations were seen in a few cases.

Cocaine detection in postmortem samples following therapeutic administration.

Cocaine is one of the most widely abused drugs and one that is frequently encountered in forensic toxicology laboratories. Most often, the detection of cocaine would lead toxicologists and forensic pathologists to believe that the drug was used illicitly; however, cocaine is an effective local anesthetic and vasoconstrictor and is used clinically in surgeries of the eye, ear, nose, and throat. Therefore, it is important to note that the presence of cocaine and its metabolites in forensic samples cannot always be attributed to abuse and that a thorough investigation and review of medical records is warranted before an informed conclusion can be made. In this case report, a 54-year-old male died three days after an altercation in which he suffered multiple injuries. In addition to natural disease and injuries documented at autopsy, cocaine and its metabolites were detected in the decedent's urine, and a review of surgical records showed that earlier on the day of death, he was administered cocaine clinically during a procedure to repair nasal bone fractures. If not for this comprehensive investigation and review of surgical records, the assumption of cocaine abuse might have otherwise been made and the cause and manner of death incorrectly established.