TY - JOUR
AU - Tiscione, Nicholas B
AB - Abstract The incidence of fentanyl in forensic toxicology analyses in the USA has dramatically increased over the past several years. The increase in death cases has been well studied; however, little has been reported on the impact to drug impaired driving. Fentanyl driving while under the influence of drugs (DUID) case data from 2014 to 2019 is presented. The data were obtained from three toxicology laboratories in the Northeast, Southeast, and Midwest regions of the USA. Fentanyl whole blood concentrations ranged from 0.1 to 157 ng/mL in living drivers with a 466% to 524% increase in fentanyl-positive DUID cases from 2014 to 2019, depending on the US region. The vast majority of fentanyl cases involved poly-drug use. Twenty case histories are presented where fentanyl was the only drug identified. The mean (standard deviation) fentanyl concentration for these cases was 5.2 ± 3.8 ng/mL with a median of 3.7 ng/mL, and the concentrations ranged from 2.0 to 16 ng/mL. Naloxone administration was documented in exactly half of these cases similar to another study involving carfentanil-impaired driving. The case histories also demonstrate that some recreational opioid users may display limited signs of impairment either due to tolerance or naloxone administration. The top three observations in common among the cases were the driver was found unresponsive behind the wheel, the vehicle left the travel lane or roadway, and the driver was involved in a crash. The increase in fentanyl use not only poses a risk for overdose and death, but is also a significant concern for traffic safety. This study supports the movement of fentanyl from a Tier II drug to Tier I due to its significant potential for impairment and increase in prevalence in impaired driving cases. Introduction Driving while under the influence of drugs (DUID) is a public safety threat to roadways in the USA as well as worldwide. In 2017, 12.8 million people in the USA aged 16 and older admitted to driving while under the influence of illicit drugs (i.e., cannabis, cocaine/crack, heroin, hallucinogens or methamphetamine), which was a 9% increase from 2016 (1). The prevalence of drugs in drivers has been examined using several methods to include a review of the available scientific literature and roadside testing studies (2–4), as well as from the results of surveys completed by forensic toxicology laboratories across the nation (5, 6). The National Safety Council’s (NSC) Alcohol, Drugs and Impairment Division (ADID) has been working toward standardizing forensic toxicology laboratory testing practices for casework involving DUID. Over the years, the NSC-ADID has sent surveys to forensic toxicology laboratories across the USA asking them to respond to questions about the most frequently encountered drugs found in the blood, urine and oral fluid collected from drivers suspected of DUID. The results from several surveys have been reported since this project began in 2004. Results from the 2012 (October 2011–October 2012) survey reported that fentanyl was among the 20 most prevalent drugs identified by 15% of the responding laboratories (5). A follow-up survey in 2016 showed a significant increase in the prevalence of fentanyl in drivers as 26% of the surveyed laboratories responded that fentanyl was one of their 10 most frequently encountered drugs. Therefore, the NSC-ADID categorized Fentanyl as a Tier I drug due to its prevalence in the driving population and strong evidence of impairment. Tier I is a list of drugs recommended as the minimum scope of routine tests performed by analytical toxicology laboratories supporting DUID investigations (6). In October 2017, the US federal government declared a national public health emergency due to the unprecedented number of opioid overdose deaths related largely to illicitly produced fentanyl (7, 8). A recent meta-analysis concluded that there was a significant increased risk of crash involvement and crash culpability when prescription opioids were used by drivers (9). The interpretation of fentanyl concentrations in the blood of suspected impaired drivers is challenging, and there has been little reported in the literature on this topic. This is the first publication to our knowledge that reports on blood fentanyl concentrations from living drivers suspected of DUID. Forensic Toxicology laboratories from New Hampshire, Florida and Kansas worked collaboratively to present their methodology, data and case histories, which are summarized in this report. Pharmacodynamic and Pharmacokinetic Characteristics of Fentanyl Fentanyl is a potent synthetic opioid, introduced in 1960 by Janssen Pharmaceutica. In a clinical setting, fentanyl may be administered via multiple routes to include intranasal, intravenous, transmucosal, buccal and transdermal. Illicit routes of administration are similar to clinical routes and also include oral and inhalation/smoking. Fentanyl is used as an analgesic in low doses and an anesthetic in large doses. Fentanyl is approximately 75 to 100 times more potent than morphine. The significant lipophilicity of the drug, allowing for easy penetration across the blood-brain barrier, and high receptor affinity are reasons for increased potency. Similar to other opioids (e.g., hydrocodone, morphine and oxycodone), it will also cause euphoria, pain relief, sedation, confusion, drowsiness, dizziness, headache, nausea, vomiting, urinary retention, pupillary constriction and respiratory depression. The dose-dependent central nervous system (CNS) and respiratory depression activity is mediated through the mu-opioid receptor. It can also bind to the delta and kappa opioid receptors but with a lower affinity. Fentanyl has a rapid onset and short duration of action when administered intravenously due to its biphasic distribution. The drug is rapidly redistributed from plasma to highly vascular tissue depots (heart, lung and brain), with over 90% eliminated from the plasma within 5 min (10). The second phase eliminates the drug from the vascular tissues and redistributes it into muscle and fat. Fentanyl is released from these sites at a much slower rate back into plasma, which accounts for its long elimination half-life. Authors have reported a terminal fentanyl half-life ranging from 3 to 12 h (11). McClain and Hug reported that intravenous fentanyl plasma concentration fell by 98% within 60 min, and a terminal half-life of 3.65 h (12). Fentanyl’s long half-life allows for the drug to accumulate when a single large or multiple small intravenous doses are administered, rendering redistribution from the brain less effective and prolonging the duration of action (13). Fentanyl is primarily metabolized in the liver to the major inactive metabolite norfentanyl. A small amount of parent drug (8–10%) is cleared by the kidneys in urine and intestines in feces (10, 12). Fung and Eisele (14) dosed 4 volunteers intravenously with 2 µg/kg of fentanyl. The authors reported an initial mean serum fentanyl concentration of 11 ng/mL, rapidly declining within the first 10 min, then decreasing to 1 ng/mL at approximately 60 min. Bovill and Sebel (15) gave a high-dose intravenous injection of fentanyl (60 µg/kg) to 5 patients undergoing cardiac surgery. After 5 min on cardiac by-pass, the fentanyl concentration had an average decrease of 53%; at 1 h, the concentration declined to approximately 10 ng/mL. Opioids and Driving Several authors have investigated the effects of chronic/stable opioid use on driving performance. Byas-Smith et al. (16) evaluated 21 patients who reported chronic daily pain for at least 3 months and were maintained on a stable dose of opioids and compared them against matched control subjects. They were evaluated for errors in the operation of their own automobile while driving during daylight hours through a specific route in the community and performance through a 5-station obstacle course. Computerized tests to assess reaction time, errors of omission and commission, along with a digital substitution test were also administered. The authors concluded that patients maintained on a stable dose of opioids were capable of operating a motor vehicle during daylight hours. Stevenson et al. (17) studied nine opioid-naïve volunteers who were given 100 mcg of fentanyl intravenously. Skills related to driving, such as reaction time and motor coordination were assessed on a tracometer (‘stressalyser’), a steering task device developed by the National Research Council (18). Baseline measurements and 30 min post-injection and 120 min post-injection were evaluated. Significant deficits to include increased reaction time and psychomotor impairment were still observed at the 120 min time point. Nine healthy volunteers had fentanyl infused, with target concentrations of 1.0, 1.5 and 2.5 ng/mL (19). Prior to the study day, the volunteers were instructed on and practiced the various psychomotor tests utilized in the study. The measured plasma concentrations were generally higher than the target concentration; 1.0 target ranged from 0.5 to 1.3 ng/mL, 1.5 target ranged from 1.5 to 2.3 ng/mL and 2.5 target ranged from 2.5 to 3.5 ng/mL. The subject’s performances on the psychomotor tests were then assessed. Fentanyl at concentrations >2.5 ng/mL had significant detrimental effects on the psychomotor tests administered and the decrement was 15% to 30% lower than baseline performance. A few studies have evaluated the driving performance of patients who are maintained on long-term stable fentanyl therapy. Sabatowski et al. (20) conducted a prospective trial in 21 patients who received stable doses of transdermal fentanyl for at least 2 weeks and compared them to matched control patients. The subjects completed a series of tests designed to assess their attention, reaction time, visual orientation, motor coordination and vigilance. The authors found no significant difference in the fentanyl patients as compared to the control group. Meneffe et al. (21) evaluated driving performance, cognition and balance in patients who were on low dose oxycodone and were switched and stabilized on transdermal fentanyl. The median dose of fentanyl was 50 µg/h. After 1 month of stabilization, the subjects were re-assessed in the driving, cognitive and balance tests. The authors found no difference in pretreatment and post treatment periods for driving simulation tests and balance. No decrements in cognitive performance were observed, whereas they did note improvements in visual motor tracking, visual memory and attention with pain reduction in the subjects over the study timeframe. A study on the fentanyl analog carfentanil involved in impaired driving reported data on 61 cases (22). Although other CNS active drugs were identified in the majority of the cases (93%), the impairment observed was characteristic of the effect of opioids. The observed symptoms included agonal breathing, blue/purple skin discoloration, miosis, slurred speech, droopy eyelids, lethargy, difficulty with balance and slow response to questions. In at least 49% of the cases, the driver was found unconscious and 56% specified the administration of naloxone. At least 54% of the impaired driving cases involved some type of crash. Three out of the four cases in which carfentanil was the only drug identified involved a crash and similar symptoms to the other reported cases were observed. Individuals who are opioid tolerant may not have performance decrements relating to driving ability. However, individuals who are opioid naïve, have upward changes in opioid dose, use in combination with other CNS active drugs, and/or abuse opioids, are a risk for poor driving performance and traffic crashes (23). Our study assesses the impact of fentanyl in 20 drivers who were investigated by law enforcement for impaired driving. The drivers were from three different areas of the country supporting the fact that fentanyl impaired driving is not a regional phenomenon, although prevalence is. Toxicological Analyses New Hampshire State Police Forensic Laboratory Blood samples were screened for volatile compounds (ethyl alcohol, methanol, isopropanol and acetone) using headspace gas chromatography (HS-GC) with a flame ionization detector (FID) when requested. All the blood samples were qualitatively screened for drugs using a protein precipitation extraction method. The extract was then analyzed using a liquid chromatograph equipped with a mass spectrometer time-of-flight detector (LC–MS-TOF). The drug screen method targeted the following drugs: amphetamines (amphetamine, methamphetamine, 3,4-Methylenedioxyamphetamine, 3,4-Methylenedioxymethamphetamine, 3,4-Methylenedioxy-N-ethylamphetamine), barbiturates (butalbital, phenobarbital), benzodiazepines (alprazolam, clonazepam, 7-aminoclonazepam, diazepam, lorazepam, nordiazepam, oxazepam and temazepam), cannabinoids (delta-9-THC, delta-9-carboxy-THC), cocaine (cocaethylene, benzoylecgonine), carisoprodol (meprobamate), fentanyls (fentanyl, norfentanyl, acetyl fentanyl, furanyl fentanyl, carfentanil), opioids (6-acetylmorphine, buprenorphine, codeine, hydrocodone, methadone, oxycodone, morphine), ketamine (norketamine) and zolpidem. The limit of detection (LOD) for the fentanyls was initially 1.0 ng/mL but revalidated in 2016 to 0.25 ng/mL. Samples that screened positive for any of the fentanyls were confirmed using solid-phase extraction techniques for blood and then analyzed using a gas chromatography–mass spectrometer (GC–MS) with a limit of quantitation (LOQ) of 1.0 ng/mL. Since 2016, a liquid chromatograph–mass spectrometer equipped with a triple quadrupole (LC–MS-QQQ) was used to confirm samples that tested positive for the fentanyls with a LOQ of 0.1 ng/mL. Norfentanyl was included in the LC–MS-QQQ confirmation method. Palm Beach County Sheriff’s Office Volatile analysis was performed in duplicate as described previously with HS-GC–FID-MS on all blood specimens (24, 25). The blood drug screen (BDS) consisted of an 11 panel enzyme linked immunosorbent assay (ELISA) utilizing kits (amphetamine, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, cannabinoids, carisoprodol, fentanyl, methamphetamine, opiates and oxycodone/oxymorphone) from Neogen (Lexington, KY). The ELISA cutoffs used were the same as described previously (26). The cutoff for fentanyl was 1.0 ng/mL prior to 2018 and lowered to 0.5 ng/mL in 2018. The ELISA was supplemented by a liquid/liquid extraction (LLE) followed by analysis on GC–MS using scan MS detection for determination of basic drugs not covered in the ELISA. Drug history and observations of impairment provided by the officer on a laboratory analysis request form required for evidence submission to the laboratory were also reviewed. Further testing was performed based on specific drugs that were suspected. The scope of this testing was reported previously (26). The validated LOD and LOQ for fentanyl confirmation/quantitation by LC–MS-QQQ was 1.0 ng/mL (27). The method did not include testing for norfentanyl. Sedgwick County Regional Forensic Science Center Blood was screened for volatile compounds (ethyl alcohol, methanol, isopropanol, acetone, difluoroethane and toluene) by HS-GC–FID. Blood was screened using a 12 panel (amphetamine, barbiturates, benzodiazepines, benzoylecgonine, cannabinoids, carisoprodol, fentanyl, methamphetamine, methadone, opiates, phencyclidine and zolpidem) ELISA (Immunalysis Corporation, Pomona, CA, USA). The cutoff for the blood fentanyl immunoassay was 1.0 ng/mL. Fentanyl confirmation and quantitation was performed by GC–MS with an LOD and LOQ of 1.0 ng/mL. The method did not include testing for norfentanyl. Case Histories The case histories reported below represent drivers that were investigated for impaired driving in which fentanyl was the only drug identified by toxicological analysis. New Hampshire drivers Case # 1:fentanyl at 2.7 ng/mL, norfentanyl at 0.78 ng/mL A 29-year-old male was reported to be passed out behind the wheel of his running vehicle that was stopped in an intersection. He was not breathing and unresponsive and was revived with Narcan® (naloxone) by emergency responders. A small baggie of what appeared to be heroin was observed clutched in his hand, however it was not tested. A blood specimen was collected ∼ 1.0 h after the incident. Case # 2:fentanyl at 3.4 ng/mL, norfentanyl at 1.3 ng/mL A 58-year-old male was reported to law enforcement (LE) for erratic operation of his vehicle resulting in driving off the roadway onto a residential lawn. When LE arrived on scene the male was ‘snoring’ heavily and was difficult to arouse. He attempted Standardized Field Sobriety Tests (SFSTs) but was unable to complete them. He was extremely unsteady and unbalanced. Miotic pupils were observed. He stated he just left an alcohol and drug treatment program. A blood specimen was collected ∼ 1.5 h after the incident. Case # 3:fentanyl at 3.6 ng/mL, norfentanyl at 1.3 ng/mL A 27-year-old male was witnessed swerving all over the road, crossing the center line and eventually drove off the road into the woods. The driver was uninjured but a witness described him as ‘hammered’. His pupils were very constricted. SFSTs revealed the following indicators: horizontal gaze nystagmus (HGN), 6/6 indicators; walk and turn (WAT), 3/8 indicators; one leg stand (OLS), 3/4 indicators. Several hypodermic needles and small plastic baggies were found in the vehicle. He stated he last used drugs ∼ 13.5 h before the incident and ‘shoots up’ between his fingers or on his hand. He indicated he just completed a drug rehab program 2 weeks before crash. A blood specimen was collected ∼ 1.25 h after the incident. Case # 4:fentanyl at 3.6 ng/mL, norfentanyl at 1.4 ng/mL A 48-year-old male was reported to LE for erratic operation of his vehicle resulting in driving off the roadway into a large field. The male was able to be aroused but was extremely lethargic and slow to follow simple instructions. He was unsteady on his feet and had pinpoint constricted pupils that did not react to light. ‘Track marks’ were also observed on his arm. A blood specimen was collected ∼ 1.75 h after the incident. Case # 5:fentanyl at 3.6 ng/mL, norfentanyl at 0.89 ng/mL A 48-year-old male was reported to LE for erratic operation of his vehicle nearly striking several other vehicles. He ran off the road several times and crossed into the opposite lane of travel. LE noted his left nostril was almost completely blocked with a white substance. His pupils were pinpoint. The driver was arrested less than 2 weeks prior for DUI-impairment (same driver as in Case # 4). SFSTs were performed and yielded the following results: HGN 2/6 indicators; WAT 4/8 indicators; OLS 3/4 indicators. A rolled up $10 bill was located on his person as well as a corner of a baggie that contained a white substance later identified as fentanyl. The driver advised he had ‘snorted heroin’ about 45 min before he was stopped. A blood specimen was collected ∼ 0.75 h after the incident. Case # 6:fentanyl at 7.2 ng/mL, norfentanyl at 0.79 ng/mL A 51-year-old female was found unresponsive in her vehicle. She was revived with Narcan® (naloxone) by emergency responders. She admitted that she had ‘snorted heroin’ before driving to a local convenience store. She was parked waiting to give a family member a ride home. She had been in the parking lot for ∼ 20 min before a family member, who was an employee of the store, discovered her passed out in the vehicle. A small plastic baggie that had been twisted closed containing a small amount of white powder (not tested) along with a small cut plastic straw with white powder residue inside (not tested) were discovered in the woman’s purse. She claimed she had not used ‘heroin’ in a long time and had purchased some and snorted it prior to driving to the store. She stated she felt fine while driving but did not remember anything after arriving at the parking lot of the store. A blood specimen was collected ∼ 0.5 h after the incident. Case # 7:fentanyl at 6.4 ng/mL A 24-year-old male was involved in a crash resulting in serious bodily injury to him and the female driver of another vehicle. The male crossed the center line and hit the other oncoming vehicle head on causing life threatening injuries to the other driver. Prior to the crash, the young man had stopped at a local gas station and went inside to the bathroom. A store video confirms he was in the bathroom for approximately 20 min. The crash occurred less than 5 min after he drove away from the store. Emergency responders arrived on scene and administered 0.5 mg Ativan® (lorazepam) to the male driver who appeared ill and anxious. Lorazepam was identified in the blood specimen at a concentration of 19 ng/mL. The male suffered a C2 fracture and lacerated spleen. Approximately half an hour after the crash, he arrived at the hospital, and his pulse, blood pressure, respiratory rate and O2 levels began to significantly decline. He was eventually put on a non-rebreathing (NRB) mask when his O2 saturation dropped to 78%. The emergency department made note that he experienced an episode of apnea transiently but with stimulation he ‘came back’. His blood was collected before any other medications were administered. The male subject later admitted that he ‘nodded off’ while driving due to being ‘dope sick’ and stated he last used ‘heroin’ 2 days before the crash. He went on to describe that when he was ‘dope sick’ that he could not think straight, had a foggy head, felt nauseous and could not sleep. A fresh injection mark was noted on his arm. He stated he had been using ‘heroin’ for the last 4 months but was a previous Percocet® user since he was 17 years old. The blood specimen was collected ∼ 0.75 h after the incident. Case # 8:fentanyl at 4.6 ng/mL, norfentanyl at 1.9 ng/mL A 49-year-old male was reported to be operating his vehicle erratically; weaving within his lane and leaving the road several times. He was stopped and had glassy eyes, was especially nervous, had unsteady hands and did not make eye contact. SFSTs were performed: HGN 0/6 indicators, miotic pupils observed, no reaction to light; WAT 7/8 indicators, OLS could not complete due to poor balance. At the police department he drank several glasses of water. He said that he had an opioid addiction to prescription medications that started after a work related injury. He admitted that he had stopped at a friend’s house after work and ‘shot up’ a dose of fentanyl. A drug recognition expert (DRE) evaluation was done at ∼ 1.25 h after the stop. The subject stated he had a stroke several years ago. During the DRE evaluation the following were observed: Modified Romberg-Balance Test, swaying front to back, side to side and circular motion, estimated 30 seconds in 21 seconds; WAT 4/8 indicators; OLS unable to complete the test; finger to nose on five attempts, he brought his finger up to ∼ 3 to 4″ from his nose and stopped for several seconds, then would slowly bring his finger towards his nose, pause and bring his hand back down to his side; lack of convergence, present; HGN 0/6 indicators; vertical gaze nystagmus was negative; pupil sizes were 2.0 mm in room light, 2.5 mm in near total darkness, 1.5mm in direct light; reaction to light slow and little to none; rebound dilation negative; pulse 100 bpm (19:45 h), 105 bpm (19:57 h), 106 bpm (20:07 h); blood pressure 150/100 mmHg; body temperature 97.3 °F. A blood specimen was collected ∼ 4.0 h after the incident. Palm Beach County, FL drivers Case # 9:fentanyl at 3.4 ng/mL A 29-year-old male driver was passed out behind the wheel and unresponsive. He also had miosis. Naloxone was administered and the driver regained consciousness. A blood specimen was collected ∼ 1.5 h after the incident. Case #10:fentanyl at 2.1 ng/mL A 31-year-old male driver was involved in a single vehicle accident. The driver was unresponsive after the crash and transported to the hospital. A needle and baggie with a powder substance were located in the vehicle. The powder was not submitted for analysis. At the hospital the driver was observed to be confused and had slow dexterity. Miosis was also observed. A blood specimen was collected ∼ 1.75 h after the incident. Case #11:fentanyl at 16 ng/mL A 29-year-old male was traveling at a high rate of speed on a multi-lane interstate. He passed other cars and then rear-ended a vehicle traveling ahead of him. Witnesses stated that the driver did not attempt to brake or take evasive action to avoid the crash. After crashing into the vehicle ahead of him the car crossed a travel lane and the inside median and struck the median wall. When officers arrived the driver was in an ambulance and seemed normal with the exception of speech that was a little sluggish. The driver refused transport to the hospital. A short time later the driver was sitting near the median wall and leaning against it. He appeared to be in and out of consciousness and was sweating profusely. Paramedics requested that the officer speak to the driver about seeking additional medical attention. When the officer spoke to the driver he appeared incoherent and was not aware of his location. His pupils were miotic, and at times, he would close his eyes as if he had fallen asleep and then suddenly awaken. A blood specimen was collected ∼ 2 h after the incident. Case #12:fentanyl at 3.7 ng/mL A 31-year-old male was involved in a single vehicle crash in which the vehicle jumped a curb and crashed into a palm tree. The driver advised that he had not used drugs for 6 months prior. On the day of the crash he purchased what he thought was heroin and snorted a small amount prior to driving home (~ 15 min prior to the crash). The driver stated that he lost consciousness while driving. Naloxone (2 mg) was administered after the crash by paramedics and the driver regained consciousness. After naloxone administration, the officer observed slightly slurred speech. A blood specimen was collected∼ 1 h after the crash. Case #13:fentanyl at 9.3 ng/mL A 29-year-old male was found slumped over the steering wheel in a running vehicle improperly stopped on the side of the road. He was gurgling/gasping for air and unconscious. The driver did not respond to sternum rubs. Naloxone was administered and the driver regained consciousness within ∼ 2 min. A blood specimen was collected∼ 1 h later. Case #14:fentanyl at 3.7 ng/mL A 24-year-old male with a history of heroin use was found unconscious with agonal breathing behind the wheel of a motor vehicle. The subject was given 0.4-mg naloxone. Two capsules containing a white powdery substance were located inside the vehicle (not submitted for analysis). The subject admitted to snorting half a capsule of heroin. The driver was sweating, had pin-point pupils, thick and slurred speech and a flushed face. The blood sample was collected about 80 min later. Case #15:fentanyl at 3.3 ng/mL A 35-year-old female rear-ended another vehicle stopped at a red light. The subject made no attempt to stop. Capsules containing tan powder (not submitted for analysis) were located in the car. Needles and other drug paraphernalia were observed on the lap of the driver. At the scene, the driver asked witnesses to hide her drugs before police arrived. Subject had slow speech, constricted pupils, droopy eyelids, pale skin and a flushed face. She admitted to using heroin 4 h prior to the accident. She stated she also took other medications (tramadol and lorazepam) approximately 8 h prior to the crash. Neither was identified in the blood specimen. The driver advised that she reached down to scratch an itch on her leg and was not watching the road when she crashed. The blood specimen was collected about 1 h after the accident. Case #16:fentanyl at 2.0 ng/mL A 26-year-old female driver was found unconscious behind the wheel after a crash. Officers had to break a window to extricate her. She did not regain consciousness until she was administered 1.2 mg of naloxone. A syringe and two capsules, one empty, were found in the vehicle and the driver, who had a history of heroin use, admitted to using before the crash. The remaining capsule tested positive for fentanyl. A blood specimen was collected ∼ 1.5 h after the incident. The sample was sent to a reference lab for fentanyl analog testing with negative results. Case #17:fentanyl at 5.2 ng/mL A 26-year-old female driver was found unresponsive behind the wheel at a major intersection. Her two small children were in the backseat. First responders observed the subject’s lips were blue and administered naloxone. The driver regained consciousness and was taken to the hospital. She stated she took three Percocet® tablets prior to driving and had no memory of recent events. She also stated the Percocet® tablets were prescribed to her due to a Cesarean delivery 6 weeks prior. Officers did not observe any impairment at the hospital. A blood specimen was collected ∼ 1 h after the incident. Sedgwick County, KS drivers Case #18:fentanyl at 3.0 ng/mL A 37-year-old male was witnessed driving against the center divider on the highway before swerving across lane lines, striking another driver, then eventually driving off the road and striking a fence and legally parked truck. Emergency medical services (EMS) found the driver in the vehicle unresponsive. Naloxone was administered and the subject regained consciousness. Blood was drawn ∼ 4.25 h after the incident. Case #19:fentanyl at 14 ng/mL A 43-year-old male was involved in a single vehicle injury collision when he struck the center divider on the interstate. Officers found the driver unconscious in the vehicle. EMS arrived shortly after, noted that the subject’s pupils appeared constricted and administered naloxone. The subject quickly regained consciousness, had no memory of the crash, and admitted to taking prescription narcotic medicine shortly before. Blood was drawn ∼ 1 h after the incident. Case #20:fentanyl at 3.7 ng/mL A 26-year-old male driver was stopped by officers after weaving across lane lines and driving into oncoming traffic. The officer noted the driver had slurred speech, exhibited balance problems, and was slow to respond with appropriate answers to the officer’s questions. Blood was drawn ∼ 1.25 h after contact with law enforcement. Results This case study involves 20 drivers that were suspected of driving while under the influence, with fentanyl as the only CNS active drug identified. The fentanyl blood concentrations are reflected in Table I. There was no correlation of blood concentration of fentanyl to time of the blood draw. Cases 1 to 8, 9 and 12 were tested for fentanyl analogs, and none was detected. The sample for case 16 was sent to a reference lab for fentanyl analog testing with negative results. Table I. Fentanyl-Only Intoxicated Drivers Case No. . Fentanyl [ng/mL] . Norfentanyl [ng/mL] . 1 2.7 0.78 2 3.4 1.3 3 3.6 1.3 4 3.6 1.4 5 3.6 0.89 6 7.2 0.79 7 6.4 NT 8 4.6 1.9 9 3.4 NT 10 2.1 NT 11 16 NT 12 3.7 NT 13 9.3 NT 14 3.7 NT 15 3.3 NT 16 2.0 NT 17 5.2 NT 18 3.0 NT 19 14 NT 20 3.7 NT Mean 5.2 1.2 Median 3.7 1.3 Range 2.0–16 0.78–1.9 Case No. . Fentanyl [ng/mL] . Norfentanyl [ng/mL] . 1 2.7 0.78 2 3.4 1.3 3 3.6 1.3 4 3.6 1.4 5 3.6 0.89 6 7.2 0.79 7 6.4 NT 8 4.6 1.9 9 3.4 NT 10 2.1 NT 11 16 NT 12 3.7 NT 13 9.3 NT 14 3.7 NT 15 3.3 NT 16 2.0 NT 17 5.2 NT 18 3.0 NT 19 14 NT 20 3.7 NT Mean 5.2 1.2 Median 3.7 1.3 Range 2.0–16 0.78–1.9 NT, not included in testing. Open in new tab Table I. Fentanyl-Only Intoxicated Drivers Case No. . Fentanyl [ng/mL] . Norfentanyl [ng/mL] . 1 2.7 0.78 2 3.4 1.3 3 3.6 1.3 4 3.6 1.4 5 3.6 0.89 6 7.2 0.79 7 6.4 NT 8 4.6 1.9 9 3.4 NT 10 2.1 NT 11 16 NT 12 3.7 NT 13 9.3 NT 14 3.7 NT 15 3.3 NT 16 2.0 NT 17 5.2 NT 18 3.0 NT 19 14 NT 20 3.7 NT Mean 5.2 1.2 Median 3.7 1.3 Range 2.0–16 0.78–1.9 Case No. . Fentanyl [ng/mL] . Norfentanyl [ng/mL] . 1 2.7 0.78 2 3.4 1.3 3 3.6 1.3 4 3.6 1.4 5 3.6 0.89 6 7.2 0.79 7 6.4 NT 8 4.6 1.9 9 3.4 NT 10 2.1 NT 11 16 NT 12 3.7 NT 13 9.3 NT 14 3.7 NT 15 3.3 NT 16 2.0 NT 17 5.2 NT 18 3.0 NT 19 14 NT 20 3.7 NT Mean 5.2 1.2 Median 3.7 1.3 Range 2.0–16 0.78–1.9 NT, not included in testing. Open in new tab Law enforcement and/or lay witnesses reported some common observations in the case study drivers as reflected in Table II. In 11 out of 20 cases (55%) the driver was found unresponsive in the vehicle. Leaving the roadway or lane of travel was also observed in 55% of the cases and 8 out of 20 (40%) involved a crash. Table II. Common Observations in Case Study Drivers Passed out or unresponsive behind wheel of vehicle Leaving the roadway or travel lane while driving Traffic crash In and out of consciousness during contact with law enforcement Difficult to arouse Erratic driving behavior Thought to have ingested heroin or oxycodone Drug paraphernalia found in vehicle Passed out or unresponsive behind wheel of vehicle Leaving the roadway or travel lane while driving Traffic crash In and out of consciousness during contact with law enforcement Difficult to arouse Erratic driving behavior Thought to have ingested heroin or oxycodone Drug paraphernalia found in vehicle Open in new tab Table II. Common Observations in Case Study Drivers Passed out or unresponsive behind wheel of vehicle Leaving the roadway or travel lane while driving Traffic crash In and out of consciousness during contact with law enforcement Difficult to arouse Erratic driving behavior Thought to have ingested heroin or oxycodone Drug paraphernalia found in vehicle Passed out or unresponsive behind wheel of vehicle Leaving the roadway or travel lane while driving Traffic crash In and out of consciousness during contact with law enforcement Difficult to arouse Erratic driving behavior Thought to have ingested heroin or oxycodone Drug paraphernalia found in vehicle Open in new tab Table III reflects the incidence of fentanyl, either by itself or with other CNS impairing drugs from the three jurisdictions. The prevalence of fentanyl in impaired drivers is increasing in all three jurisdictions, with Sedgwick County, KS lagging behind Palm Beach County, FL and the state of New Hampshire. However, in all three jurisdictions the prevalence of fentanyl in the driving population sampled significantly higher than the 0.3% of drivers that was found in the 2013 to 2014 National Highway Traffic Safety study (3). An interesting anomaly in the Palm Beach data was that in 2017 there were no fentanyl-only cases; however, 48% of the positive DUID cases contained carfentanil, often in combination with fentanyl (22). Table III. Fentanyl Prevalence in DUID Drivers (2014–2019) Year . Positive DUID Cases . All Fentanyl-Positive Casesa . Fentanyl-Only Casesa . AFPb Mean (ng/mL) . AFPb Median (ng/mL) . AFPb Range (ng/mL) . New Hampshire 2014 767 29 (4%) 11 (1%) 9.3 6.2 1.9–26 2015 824 125 (15%) 17 (2%) 6.5 4.0 1.0–157 2016 839 138 (16%) 34 (4%) 6.4 3.9 1.0–58 2017 882 176 (20%) 34 (4%) 5.9 3.9 0.1–38 2018 935 197 (21%) 47 (5%) 5.2 3.1 0.1–53 2019 837 181 (22%) 28 (3%) 6.1 3.7 0.1–65 Palm Beach County, FL 2014 85 6 (7%) 0 2.7 2.9 1.2–4.1 2015 104 10 (10%) 0 2.6 2.3 1.0–6.7 2016 118 35 (30%) 3 (3%) 4.3 3.6 1.3–8.3 2017 114 39 (34%) 0 7.3 5.6 1.4–25 2018 75 34 (45%) 2 (3%) 5.5 4.6 1.1–23 2019 84 34 (40%) 3 (4%) 5.0 4.3 1.2–16 Sedgwick County, KS 2014 NA 1 (NA) 0 3.4 3.4 3.4 2015 143 1 (1%) 0 2.7 2.7 2.7 2016 126 0 0 – – – 2017 135 0 0 – – – 2018 134 1 (1%) 0 1.0 1.0 1.0 2019 133 6 (5%) 2 (2%) 5.0 3.0 2.4–14 Year . Positive DUID Cases . All Fentanyl-Positive Casesa . Fentanyl-Only Casesa . AFPb Mean (ng/mL) . AFPb Median (ng/mL) . AFPb Range (ng/mL) . New Hampshire 2014 767 29 (4%) 11 (1%) 9.3 6.2 1.9–26 2015 824 125 (15%) 17 (2%) 6.5 4.0 1.0–157 2016 839 138 (16%) 34 (4%) 6.4 3.9 1.0–58 2017 882 176 (20%) 34 (4%) 5.9 3.9 0.1–38 2018 935 197 (21%) 47 (5%) 5.2 3.1 0.1–53 2019 837 181 (22%) 28 (3%) 6.1 3.7 0.1–65 Palm Beach County, FL 2014 85 6 (7%) 0 2.7 2.9 1.2–4.1 2015 104 10 (10%) 0 2.6 2.3 1.0–6.7 2016 118 35 (30%) 3 (3%) 4.3 3.6 1.3–8.3 2017 114 39 (34%) 0 7.3 5.6 1.4–25 2018 75 34 (45%) 2 (3%) 5.5 4.6 1.1–23 2019 84 34 (40%) 3 (4%) 5.0 4.3 1.2–16 Sedgwick County, KS 2014 NA 1 (NA) 0 3.4 3.4 3.4 2015 143 1 (1%) 0 2.7 2.7 2.7 2016 126 0 0 – – – 2017 135 0 0 – – – 2018 134 1 (1%) 0 1.0 1.0 1.0 2019 133 6 (5%) 2 (2%) 5.0 3.0 2.4–14 a Percentage of cases in parentheses (rounded to whole number). b AFP—all fentanyl-positive cases include fentanyl-only + fentanyl poly-drug. NA, not available. Data only available in KS for November and December of 2014. Open in new tab Table III. Fentanyl Prevalence in DUID Drivers (2014–2019) Year . Positive DUID Cases . All Fentanyl-Positive Casesa . Fentanyl-Only Casesa . AFPb Mean (ng/mL) . AFPb Median (ng/mL) . AFPb Range (ng/mL) . New Hampshire 2014 767 29 (4%) 11 (1%) 9.3 6.2 1.9–26 2015 824 125 (15%) 17 (2%) 6.5 4.0 1.0–157 2016 839 138 (16%) 34 (4%) 6.4 3.9 1.0–58 2017 882 176 (20%) 34 (4%) 5.9 3.9 0.1–38 2018 935 197 (21%) 47 (5%) 5.2 3.1 0.1–53 2019 837 181 (22%) 28 (3%) 6.1 3.7 0.1–65 Palm Beach County, FL 2014 85 6 (7%) 0 2.7 2.9 1.2–4.1 2015 104 10 (10%) 0 2.6 2.3 1.0–6.7 2016 118 35 (30%) 3 (3%) 4.3 3.6 1.3–8.3 2017 114 39 (34%) 0 7.3 5.6 1.4–25 2018 75 34 (45%) 2 (3%) 5.5 4.6 1.1–23 2019 84 34 (40%) 3 (4%) 5.0 4.3 1.2–16 Sedgwick County, KS 2014 NA 1 (NA) 0 3.4 3.4 3.4 2015 143 1 (1%) 0 2.7 2.7 2.7 2016 126 0 0 – – – 2017 135 0 0 – – – 2018 134 1 (1%) 0 1.0 1.0 1.0 2019 133 6 (5%) 2 (2%) 5.0 3.0 2.4–14 Year . Positive DUID Cases . All Fentanyl-Positive Casesa . Fentanyl-Only Casesa . AFPb Mean (ng/mL) . AFPb Median (ng/mL) . AFPb Range (ng/mL) . New Hampshire 2014 767 29 (4%) 11 (1%) 9.3 6.2 1.9–26 2015 824 125 (15%) 17 (2%) 6.5 4.0 1.0–157 2016 839 138 (16%) 34 (4%) 6.4 3.9 1.0–58 2017 882 176 (20%) 34 (4%) 5.9 3.9 0.1–38 2018 935 197 (21%) 47 (5%) 5.2 3.1 0.1–53 2019 837 181 (22%) 28 (3%) 6.1 3.7 0.1–65 Palm Beach County, FL 2014 85 6 (7%) 0 2.7 2.9 1.2–4.1 2015 104 10 (10%) 0 2.6 2.3 1.0–6.7 2016 118 35 (30%) 3 (3%) 4.3 3.6 1.3–8.3 2017 114 39 (34%) 0 7.3 5.6 1.4–25 2018 75 34 (45%) 2 (3%) 5.5 4.6 1.1–23 2019 84 34 (40%) 3 (4%) 5.0 4.3 1.2–16 Sedgwick County, KS 2014 NA 1 (NA) 0 3.4 3.4 3.4 2015 143 1 (1%) 0 2.7 2.7 2.7 2016 126 0 0 – – – 2017 135 0 0 – – – 2018 134 1 (1%) 0 1.0 1.0 1.0 2019 133 6 (5%) 2 (2%) 5.0 3.0 2.4–14 a Percentage of cases in parentheses (rounded to whole number). b AFP—all fentanyl-positive cases include fentanyl-only + fentanyl poly-drug. NA, not available. Data only available in KS for November and December of 2014. Open in new tab The state of New Hampshire saw a steady rise in the number of positive fentanyl DUID cases increasing from 4% in 2014 to ∼ 20% in 2017, 2018 and 2019. Palm Beach County, FL, had a dramatic increase in fentanyl driving cases; with it jumping from 7% of the suspected impaired drivers in 2014 to 45% and 40% in 2018 and 2019, respectively. Sedgwick County, KS, was still somewhat immune to fentanyl intoxicated drivers in the study years; with only 6% of the drivers having fentanyl in 2019. The percent increase from 2014 to 2019 in the incidence of fentanyl in impaired driving cases for New Hampshire, Palm Beach County, FL, and Sedgwick County, KS, was 524%, 466% and 500%, respectively. The mean and median blood concentrations found in all fentanyl-positive driving cases were comparable to those reported in the fentanyl alone drivers presented herein. The 20 case histories from the three states had a mean (standard deviation) fentanyl concentration of 5.2 ± 3.8 ng/mL with a median of 3.7 ng/mL and range of 2.0 to 16 ng/mL. In New Hampshire the mean (standard deviation), median, and range for all fentanyl-positive driving cases from 2014 to 2019 were 6.2 ± 1.4, 4.1 and 0.1 to 157 ng/mL, respectively. In Palm Beach County, FL the mean, median, and range were 5.1 ± 4.0, 4.1 and 1.0 to 25 ng/mL, respectively. In Sedgwick County, KS the mean, median, and range were 4.1 ± 3.8, 3.0 and 1.0 to 14 ng/mL, respectively. Statistics for the concentrations observed by region over the time period are included in Table III. Discussion This case study demonstrates that the incidence of fentanyl in impaired driving cases is on the rise. There is an exceptionally wide concentration range found in these drivers. This apparent interindividual variation in blood concentrations may be explained by: (i) routine use of naloxone, (ii) tolerance to the drug itself, (iii) cross-tolerance with other opioids used/abused and (iv) the time difference between the observed impairment, traffic stop or crash and the blood draw. The measured blood concentrations found in these drivers would potentially be lethal in an opioid-naïve individual. Surgical analgesia and respiratory depression are associated with plasma concentrations of 2 to 5 ng/mL (10), and the blood to plasma ratio for fentanyl has been estimated to be from 0.8 to 1.0 (12). Deaths in health care providers have been reported in the range from 0.1 to 5 ng/mL (10). In our case study, it can be assumed that the drivers had developed some tolerance to opioids, especially in the driver who had 16 ng/mL of fentanyl in his blood around the time of the crash. The NH case from 2015 with the extremely high blood fentanyl concentration of 157 ng/mL involved a driver who overdosed and was administered naloxone at the scene. Evidence suggested that this individual used fentanyl again at the hospital minutes before the blood sample was collected. Tolerance to opioids can be significant, but it does not negate all potential for impairment. The majority of studies conducted on patients stabilized on long-term opioid therapy, including fentanyl, have demonstrated little to no adverse effects on human performance (16, 20, 21, 23). Therefore, these patients may be able to operate a motor vehicle safely after developing a tolerance to the impairing effects of the drug. However, some research has indicated that even in stabilized patients cognitive deficits, including delayed reaction time and information processing, may remain (28). Changes to dosage, frequency, or type of opioid will also impact tolerance and may lead to impairing effects (23). This may be particularly relevant when illicit preparations of opioids are used since the drug composition and dosage may vary substantially. Illicit use was admitted to and/or indicated in 12/20 (60%) of the fentanyl cases in this study. Five of the drivers indicated that they had recently been in a drug treatment program. Both of these factors would likely impact the individual’s tolerance and contribute to the significant impairment that was observed. Poly-pharmacy accounts for the vast majority of the fentanyl-positive findings during the study period. Other CNS active compounds were detected in ∼ 80% of the cases, with positive findings for fentanyl in New Hampshire and Sedgwick County, KS, whereas the detection rate was 95% in Palm Beach County, FL. Interestingly, many of the highest concentrations observed were in cases in which other CNS active drugs were detected in combination with fentanyl. A number of the drivers in the cases presented herein believed they were using either heroin or oxycodone; not realizing the drug being ingested was fentanyl. Unbeknownst to the user fentanyl is sometimes mixed with or substituted for heroin. Fentanyl has also been detected in counterfeit hydrocodone, oxycodone or alprazolam tablets (29, 30). As with other opioids, fentanyl can cause significant sedation, confusion/mental clouding and dizziness in the user. Limited studies have demonstrated an increase in reaction time and impairment of motor coordination (17, 19, 28). The common observations in this study were that the drivers were in/out of consciousness, difficult to arouse or passed out in the vehicle; exhibited erratic operation of the vehicle, which included leaving their travel lane and/or the roadway; and involved a traffic crash. Thus, as demonstrated in the cases presented herein, fentanyl may cause serious impairment of driving skills. Conclusion The incidence of fentanyl in impaired driving cases has increased dramatically in two regions of the eastern USA, with some cases also observed in one region of the Midwest. The concentrations detected in these living drivers ranged from 0.1 to 157 ng/mL with mean and median concentrations that may cause death in an opioid-naïve individual. Differences in tolerance between individuals and other uncontrolled variables (e.g., time to specimen collection) preclude definitive statements regarding a degree of impairment based on fentanyl concentration alone. However, in this series of cases in which fentanyl was the only CNS active drug identified, significant impairment was observed with blood concentrations of 2.0 ng/mL and higher. In several cases, the drivers required administration of naloxone to reverse severe respiratory depression and loss of consciousness. 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Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2020. Published by Oxford University Press on behalf of Society of Forensic Toxicologists, Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Fentanyl and Driving Impairment
JF - Journal of Analytical Toxicology
DO - 10.1093/jat/bkaa105
DA - 2020-08-14
UR - https://www.deepdyve.com/lp/oxford-university-press/fentanyl-and-driving-impairment-cRqIlo83pm
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -