Breath/Blood Alcohol Concentration as an Indicator of Alcohol Use Problems.

INTRODUCTION: The Federal Aviation Administration Office of Aerospace Medicine (AAM) is required by law to identify pilots who have driving under the influence (DUI) convictions. It is the responsibility of AAM to determine, based on the DUI, if the pilot has a drinking problem and needs follow-up treatment. Pilots with alcohol problems are at risk to themselves and the public and need to have treatment to reduce the extent of the risk. It has been suggested by some that a blood alcohol concentration (BAC) of 0.15 g · dL-1 is evidence of tolerance and the pilot should be placed in an alcohol treatment program.METHOD: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) Clinician's Guide considers a person at risk for a drinking problem when a man drinks 5 or more drinks or a woman drinks 4 or more drinks in a day and reaches a 0.08 g · dL-1 of ethanol in the blood. It is possible to estimate from a BAC or breath alcohol concentration (BrAC) the number of drinks consumed using the volume of distribution for ethanol and the weight of the individual. A spread sheet tool was developed to estimate the number of drinks consumed.RESULTS: It was determined that DUI/DWI concentrations could be used to determine the minimum number of drinks consumed. Overweight people reach binge drinking levels and higher Hingson levels at lower DUI/DWI concentrations than people with an average weight or lower.DISCUSSION: Using this tool there is a high probability (99.7%) of identifying a true binge drinker.Canfield DV, Forster EM, Cheong Z-I, Cowan JM. Breath/blood alcohol concentration as an indicator of alcohol use problems. Aerosp Med Hum Perform. 2019; 90(5):488-491.

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens.

INTRODUCTION: This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approach: Compare the drug found by toxicology analysis with the drug reported by the pilot. This study uniquely examined first the pilot-reported medication and then compared it to that detected by toxicology analysis. This study will serve two purposes: (i) to determine the capability of a toxicology laboratory to detect reported medications, and (ii) to identify pilots with medications below detectable limits. METHOD: All information required for this study was extracted from the Toxicology Data Base system and was searched using ToxFlo or SQL Server Management Studio. The following information was collected and analyzed: pilot-reported trade and/or generic drug, date specimens received, time of accident, type of aviation operations (CFR), state, pilot level, age, class of medical, specimen type, specimen concentration, dose reported, frequency reported associated with the accident, quantity reported, National Transportation Safety Board (NTSB) accident event number, and all NTSB reports. RESULTS: There were 319 pilots that either reported taking a beta-blocker or were found to be taking a beta-blocker by postmortem toxicology analysis. DISCUSSION: Time of death, therapeutic concentration and specimen type were found to be factors in the ability of the laboratory to detect beta-blockers. Beta-blockers taken by pilots will, in most cases, be found by a competent postmortem forensic toxicology laboratory at therapeutic concentrations. The dose taken by the pilot was not found to be a factor in the ability of the laboratory to identify beta-blockers. Time of dose, route of administration, specimen tested and therapeutic concentration of the drug were found to be factors in the ability of the laboratory to identify beta-blockers in postmortem specimens.

Ethanol and Drugs Found in Civil Aviation Accident Pilot Fatalities, 1989-2013.

BACKGROUND: Biological specimens from pilots fatally injured in civil aviation accidents are analyzed for ethanol and drugs at the Civil Aerospace Medical Institute (CAMI). Prevalence of these substances in the pilots has been evaluated at 5-yr intervals since 1989. In continuation, a fifth 5-yr study (2009-2013) was conducted. METHODS: The CAMI toxicology/medical certification and National Transportation Safety Board (NTSB) aviation accident databases were searched. RESULTS: During 2009-2013, samples from 1169 pilots were analyzed. Aircraft involved in the accidents were primarily operating under general aviation. Most airmen were private pilots and held third-class medical certificates. In relation to the first 5-yr (1989-1993) period, the pilot fatality cases decreased by 37% and the presence of ethanol and/or drugs in the pilots increased by 239% in the fifth 5-yr period. The ethanol usage was unchanged, but increases were 267% and 583% with illicit and prescription drugs, respectively. The use of ethanol and/or drugs by aviators, along with underlying medical conditions, was determined by the NTSB to be cause/factors in 5% of the accidents. CONCLUSION: The observed decrease in the fatality cases does not necessarily suggest the decrease in aviation accidents, as active airmen numbers also declined. The increase in the drug positive cases is primarily attributed to the continuous rise in the use of prescription drugs. Although prevalence of ethanol and drugs has been evaluated in fatally injured aviators, such evaluation has not been performed in active pilots not involved in accidents. This type of comparative study would be crucial in assessing aviation safety.

A new equation for calculating the maximum wait time for pilots who use an impairing medication.

INTRODUCTION: Pilots who use an impairing medication to treat a medical condition are required to wait an appropriate amount of time after completing the treatment before returning to duty. However, toxicology findings from fatal aviation accidents indicate not all pilots wait a sufficient period of time. Methods used today do not take into consideration the time required for the drug to reach subtherapeutic concentrations. METHODS: An equation was developed based on the therapeutic range and the maximum expected half-life of the medication to objectively calculate a safe return-to-duty time for pilots. The new equation assumes the treating physician will not dose the patient beyond the upper therapeutic range of the medication and the person taking the medication has the maximum half-life reported in the literature. The equation N ln(0.5*Cmin/Cmax)/ln(0.5) was developed to determine the number of half-lives (n) required to reach one-half of Cmin, where Cmin = lower therapeutic concentration and Cmax = upper therapeutic concentration. Anonymous subjects were recruited under an approved IRB protocol. Blood and plasma were collected at approximately Cmax (2-3 h) and again after waiting approximately another 5 h. Toxicological analysis was performed on the specimens collected. RESULTS: One subject taking a 25-mg dose had a 0.033 ug x ml(-1) blood concentration after waiting 8 h, well above the 0.025 ug x ml(-1) reported as impairing concentration. The new equation estimated a mean wait time for the 18 medications composed of 4 half-lives. DISCUSSION: The new CAMI equation takes into consideration safety without grossly over estimating pilot wait times.

In vitro absorption of atmospheric carbon monoxide and hydrogen cyanide in undisturbed pooled blood.

Blood samples from aircraft accident victims are analyzed for carboxyhemoglobin (COHb) and cyanide ion (CN(-)). Such victims often suffer open wounds near the autopsy blood collection sites. Many aircraft crashes result in fires that fill the victim's atmosphere with smoke that is rich in carbon monoxide (CO) and hydrogen cyanide (HCN). It is important to determine whether pooled blood in those wounds may have absorbed these gases after death, which could lead one to erroneously conclude that the presence of COHb and CN(-) in blood was the result of breathing in these gases. A laboratory desiccator was used as a chamber to establish whether CO or HCN may be absorbed in undisturbed, pooled blood. COHb levels were 4.3-11.0% after exposure to CO (5,532, 8,298, 11,064, 22,129 and 33,193 ppm) for 30 and 60 min. Blood CN(-) concentrations (1.43-5.01 µg/mL) increased with exposure to HCN at 100 and 200 ppm, each at 15, 30, 45 and 60 min. The observed COHb increases do not exclude the possibility for higher COHb levels in blood exposed to highly CO-rich atmospheres, but there is a strong potential for CN(-) levels to increase by the absorption of atmospheric HCN. Thus, postmortem COHb and CN(-) levels should be carefully interpreted.

Effects of fluid load on human urine characteristics related to workplace drug testing.

During workplace drug testing, urine is tested for dilution, substitution and adulteration. Donors argue that these findings are due to medical, health or working conditions or diet and genetic differences. There is a paucity of data correlating changes in urine characteristics after a fluid load to various body parameters. Therefore, five urine specimens (one in the morning, one prior to drinking 800 mL of a beverage, and three time intervals thereafter) from 12 males and 12 females were tested for four different beverages on separate occasions. Of the 480 samples, 376 were in sufficient amounts. Of these 376, 36 (10%) had creatinine <20 mg/dL but ≥2 mg/dL; 27 (75%) of 36 had specific gravity <1.0030 but >1.0010. Thus, these 27 samples can be considered to be dilute; 20 (74%) of 27 were from females. For males with at least one dilute sample, body fat was 11% less and resting metabolic rate (RMR) was 29% more than males with no dilute samples (p > 0.05); for females with at least one dilute sample, height was 8% less and weight 20% less than females with no dilute samples (p > 0.05). Individuals with a higher RMR appear to have a greater potential for producing dilute urine specimens than those with a lower RMR. Thus, a dilute sample does not necessarily indicate that it was intentionally diluted. Such samples must be carefully evaluated in consideration with recent consumption of liquid by donors to avoid false accusations.

Postmortem ethanol in the setting of ethanol-containing automotive fuel.

The pilot of a light aircraft that crashed after a loss of power was found to have ethanol in the vitreous and the blood, but almost none in the urine. The globes of the eyes were intact, and the body was refrigerated after recovery until the autopsy was performed the following morning. The pilot was described as a "nondrinker," and additional specialized toxicology testing results were inconsistent with ethanol ingestion. The pilot's body was extensively exposed to fuel during the prolonged extraction. Investigation determined that the aircraft had been fueled with gasoline that contained 10% ethanol. Although exposure to automotive fuel has not been previously described as a source of ethanol in postmortem specimens, it may represent a source for the ethanol detected during postmortem toxicology testing in this case, and this finding may be relevant to other cases with similar exposure.

Drugs and alcohol found in civil aviation accident pilot fatalities from 2004-2008.

INTRODUCTION: The Federal Aviation Administration (FAA) Office of Aerospace Medicine sets medical standards needed to protect the public and pilots from death or injury due to incapacitation of the pilot. As a part of this process, toxicology testing is performed by the FAA on almost every pilot who is fatally injured in an aviation accident to determine the medical condition of the pilot, medications used by the pilot at the time of the accident, and the extent of impairment, if any. METHOD: The data were extracted from the FAA toxicology database for all pilots who died from 2004 to 2008 in aviation accidents. RESULTS: The laboratory received and tested specimens from 1353 pilots who died in aviation accidents between 2004 and 2008; 507 of these pilots were found to be taking drugs and 92 had ethanol in excess of 0.04 g x dl(-1). DISCUSSION: This study was conducted to determine the extent of drug use in pilots who have died in aviation accidents from 2004 to 2008 and to determine the types of drugs most commonly found. A comparison of previously published reports with this study's report was made to determine trends in drug use by pilots who have died in aviation accidents over the past 20 yr. Factors were discussed that could influence drug trends. Diphenhydramine, an H1 antihistamine with impairing properties, is the most commonly found drug in pilots who died in an aviation accident.

Resolution of aviation forensic toxicology findings with the aid of DNA profiling.

Body components of aviation accident fatalities are often scattered, disintegrated, commingled, contaminated, and/or putrefied at accident scenes. These situations may impose difficulties in victim identification/tissue matching. The prevalence of misidentification in relation to aviation accident forensic toxicology has not been well established. Therefore, the Civil Aerospace Medical Institute (CAMI) toxicology database was searched for the 1998-2008 period for those cases wherein DNA profiling was performed to resolve identity issue of the samples submitted to CAMI for toxicological evaluation. During this period, biological samples from the casualties of a total of 3523 accidents were submitted to CAMI. The submitted samples were primarily from pilots. Out of the 3523 accidents, at least, one fatality had occurred in 3366 (≈ 96%) accidents; thus, these accidents were considered fatal accidents. Accordingly, biological samples from 3319 pilots (3319 of the 3366 accidents) were received at CAMI for toxicological testing. Of these 3319 pilots, 3275 (≈ 99%) were fatally injured. DNA profiling was performed in 15 (≈ 0.5%) of the 3319 accidents. The profiling was conducted upon the requests of families in two accidents, accident investigators in three, and pathologists in four. In six accidents, contradictory toxicological findings led CAMI to initiate DNA profiling. The requests made by families and investigators were primarily triggered by inconsistency between the toxicological results and the history of drug use of the victims, while by pathologists because of commingling of samples. In three (20%) of the 15 accidents, at least one submitted sample was misidentified or mislabeled. The present study demonstrated that the number of aviation accident cases requiring DNA profiling was small and this DNA approach was effectively applied in resolving aviation toxicology findings associated with those accidents.

Increased cannabinoids concentrations found in specimens from fatal aviation accidents between 1997 and 2006.

The National Institute on Drug Abuse (NIDA) and the Office of National Drug Control Policy (ONDCP) reported a 1.5-fold increase in the delta-9-tetrahydrocannabinol (THC) content of street cannabis seizures from 1997 to 2001 versus 2002 to 2006. This study was conducted to compare the changes, over those years, in blood and urine cannabinoid concentrations with the potency of THC reported in the cannabis plant. Cannabinoids were screened using radioimmunoassay (RIA) for blood and fluorescence polarization immunoassay (FPIA) for urine and confirmed using GC/MS. A total of 95 individuals were found to be using cannabis from a total number of 2769 (3.4%) individuals tested over the period 1997 through 2006. Other impairing drugs were found in 38% of the cannabinoids-positive individuals. The mean concentration of THC in blood for 1997-2001 was 2.7 ng/mL; for 2002-2006, it was 7.2 ng/mL, a 2.7-fold increase in the mean THC concentration of specimens from aviation fatalities, compared to a 1.5-fold increase in cannabis potency reported by the NIDA and ONDCP. The mean age for cannabis users was 40 years (range 18-72) for aviation fatalities. For all blood and urine specimens testing negative for cannabinoids from aviation fatalities, the mean age of the individuals was 50 years (range 14-92). More than half of the fatalities tested were 50 years or older, whereas, 80% of the positive cannabis users were under 50. As indicated by these findings, members of the transportation industry, government regulators, and the general public should be made aware of the increased potential for impairment from the use of high-potency cannabis currently available and being used.

The FAA's postmortem forensic toxicology self-evaluated proficiency test program: the second seven years.

During toxicological evaluations of samples from fatally injured pilots involved in civil aviation accidents, a high degree of quality control/quality assurance (QC/QA) is maintained. Under this philosophy, the Federal Aviation Administration (FAA) started a forensic toxicology proficiency-testing (PT) program in July 1991. In continuation of the first seven years of the PT findings reported earlier, PT findings of the next seven years are summarized herein. Twenty-eight survey samples (12 urine, 9 blood, and 7 tissue homogenate) with/without alcohols/volatiles, drugs, and/or putrefactive amine(s) were submitted to an average of 31 laboratories, of which an average of 25 participants returned their results. Analytes in survey samples were correctly identified and quantitated by a large number of participants, but some false positives of concern were reported. It is anticipated that the FAA's PT program will continue to serve the forensic toxicology community through this important part of the QC/QA for laboratory accreditations.

Vitreous fluid and/or urine glucose concentrations in 1335 civil aviation accident pilot fatalities.

During aviation accident investigations, vitreous fluid and urine samples from pilot fatalities are analyzed for glucose and blood for hemoglobin A(1c) (HbA(1c)) to monitor diabetic pilots and to discover other pilots with undiagnosed/unreported diabetes. The prevalence of elevated glucose concentrations in fatally injured pilots was evaluated by searching the Civil Aerospace Medical Institute's Toxicology Database for the period 1998-2005. Out of 1335 pilots involving 363 vitreous fluid, 365 urine, and 607 vitreous fluid and urine analyses, 43 pilots had elevated glucose in vitreous fluid (>125 mg/dL) and/or in urine (>100 mg/dL). Of the 20 pilots whose blood samples were analyzed, nine had >6% HbA(1c)--four were known diabetics, and five were unknown diabetics. Urinary glucose levels were elevated in all 13 known hyperglycemic pilots. A considerable number of pilots (30 of 43) had elevated glucose and HbA(1c) (5 of 20), suggesting undiagnosed/unreported diabetic conditions.

Intensity of the internal standard response as the basis for reporting a test specimen as negative or inconclusive.

Under normal circumstances, a test specimen is reported as "negative" when the response of the analyte is absent. However, if the intensity of the internal standard (IS) is low, indicating interference factors, the test could be considered "inconclusive." A quantitative hypothesis, A=(R x I x S)/L, serves as the "cutoff" for the acceptable signal-to-noise (S/N) ratio for the IS in making "negative/inconclusive" decisions, where A is the acceptable S/N ratio for internal standard; R is the relative response of the IS and the analyte (same concentration); I is the concentration of the IS; S is the (minimal S/N ratio); and L is the limit of detection. The hypothesis was empirically tested using the 9-carboxy-11-nor-Delta(9)-tetrahydrocannabinol (THC-COOH) analyte, THC-COOH-d(3) IS, with ibuprofen and hydrogen peroxide (H2O2) as interference factors. Urine specimens containing 0-5 ng/mL of THC-COOH were spiked with various quantities of ibuprofen or H(2)O(2), followed by liquid-liquid extraction, derivatization, and gas chromatography-mass spectrometry (GC-MS) analysis under selected-ion-monitoring mode. Among the "adulterated" test specimens evaluated (those with an S/N for the internal standard below the acceptable IS S/N "A") the quantitative criterion was indeed found to provide a useful guide for making negative/inconclusive decisions. This equation could be programmed into the instrument software to flag results as being inconclusive when they do not meet the criteria described in this paper.

Medical histories of 61 aviation accident pilots with postmortem SSRI antidepressant residues.

INTRODUCTION: Selective serotonin reuptake inhibitor (SSRI) antidepressants are popularly prescribed, but these drugs are not currently approved for use by U.S. civilian aviators. In a 2003 study, the presence of 4 SSRIs--citalopram, fluoxetine, paroxetine, and sertraline-was reported in 61 pilot fatalities of civil aviation accidents that occurred during 1990-2001. However, it was not known whether these pilots had disqualifying psychological conditions, including depression, and had properly reported the use of the antidepressants. METHODS: The aeromedical history of the pilots was retrieved from the Federal Aviation Administration's (FAA's) Aerospace Medical Certification Database; additional pilot medical information and the cause/factor of the accidents were obtained from the National Transportation Safety Board's (NTSB's) Aviation Accident Database. RESULTS: There were 59 pilots who had medical records in the FAA's Certification Database. Disqualifying psychological conditions were self-reported in the past examinations of only 7 (12%) of the 59 pilots, and the use of an SSRI was reported by 3 of the 7 pilots. In later examinations, 6 of the 7 indicated that they were free from the conditions and not taking SSRIs; thus, they were reissued medical certificates. Such conditions and/or drug use were not self-reported in the aeromedical records of the remaining 52 (88%) pilots. Nevertheless, the NTSB investigations revealed that 12 (20%) of the 61 pilots had a history of a psychological condition and/or an SSRI use, as suggested by their personal medical records. CONCLUSIONS: These findings reconfirm that SSRIs were used by the aviators but were not reported in their last aeromedical examinations.

First-generation H1 antihistamines found in pilot fatalities of civil aviation accidents, 1990-2005.

INTRODUCTION: First-generation H1-receptor antagonists are popularly used for alleviating allergy and cold symptoms, but these antihistaminics cause drowsiness and sedation. Such side effects could impair performance and, thus, could be the cause or a factor in accidents. Therefore, the prevalence of these antagonists was evaluated in aviation accident pilot fatalities. METHODS: The Civil Aerospace Medical Institute's (CAMI's) Toxicology Database was examined for the presence of the first-generation antihistamines in pilot fatalities of civil aircraft accidents that occurred during a 16-yr (1990-2005) period. RESULTS: Of 5383 fatal aviation accidents from which CAMI received specimens, there were 338 accidents wherein pilot fatalities (cases) were found to contain brompheniramine, chlorpheniramine, diphenhydramine, doxylamine, pheniramine, phenyltoloxamine, promethazine, and triprolidine. Of the 338 accidents, 304 were general aviation accidents, and 175 of the 338 pilots held private pilot airman certificates. Antihistamines were detected alone in 103 fatalities (1 antihistamine in 94 and 2 antihistamines in 9), while other drug(s) and/or ethanol were also present in an additional 235 fatalities. The antihistamines were found in approximately 4 and 11% of the fatalities/accidents in 1990 and in 2004, respectively. The use of antihistamine(s) was determined by the National Transportation Safety Board to be the cause of 13 and a factor in 50 of the 338 accidents. CONCLUSIONS: There was an overall increasing trend in the use of antihistamines by aviators during the 16-yr span. Blood levels of the antihistaminics were in the sub-therapeutic to toxic range. Findings from this study will be useful in investigating future accidents involving antihistamines.

Pilot medical history and medications found in post mortem specimens from aviation accidents.

INTRODUCTION: Federal Aviation Administration (FAA) regulations require pilots to report all medications and medical conditions for review and consideration as to the overall suitability of the pilot for flight activities. METHODS: Specimens were collected by local pathologists from aviation accidents and sent to the Bioaeronautical Sciences Research Laboratory for analysis. The results of such tests were entered into the Forensic Case Management System. This database was searched to identify all pilots found positive for medications used to treat cardiovascular, psychological, or neurological conditions over the period January 1, 1993, through December 31, 2003. RESULTS: Toxicological evaluations were performed on 4143 pilots. Psychotropic drugs were found in 223 pilots. Cardiovascular medications were found in 149 pilots. Neurological medications were found in 15 pilots. Pilots reported psychological conditions in 14 of the 223 pilots found positive for psychotropic drugs. Only 1 of the 14 pilots reporting a psychological condition to the FAA reported the psychotropic medication found after the accident. Cardiovascular disease was reported by 69 of the pilots found with cardiovascular drugs in their system. Cardiovascular medications found in the pilots were reported by 29 of the 69 pilots reporting a cardiovascular condition. Only 1 of the 15 pilots reported having a neurological condition to the FAA; none of the pilots found with neurological medications reported the medication. CONCLUSIONS: Toxicology successfully identified 93% of the medications reported by the pilots. Pilots involved in fatal accidents taking psychotropic or neurological medications rarely reported the medication or their underlying medical condition to the FAA.

Simultaneous analyses of cocaine, cocaethylene, and their possible metabolic and pyrolytic products.

A method was developed for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), norbenzoylecgonine (BNE), norcocaine (NCOC), ecgonine (ECG), ecgonine methyl ester (EME), m-hydroxybenzoylecgonine (HBZE), anhydroecgonine methyl ester (AEME), cocaethylene (CE), norcocaethylene (NCE), and ecgonine ethyl ester (EEE) in blood, urine, and muscle. Available deuterated analogs of these analytes were used as internal standards. Proteins from blood and muscle homogenate were precipitated with cold acetonitrile. After the removal of acetonitrile by evaporation, the supernatants and urine were subjected to solid-phase extraction. The eluted analytes were converted to their hydrochloride salts and derivatized with pentafluoropropionic anhydride and 2,2,3,3,3-pentafluoro-1-propanol. The derivatized products were analyzed by a gas chromatograph (GC)/mass spectrometer by selected ion monitoring. The limit of detection (LOD) for COC, BZE, NCOC, EME, CE, NCE, and EEE was 2ng/ml, while the LODs for BNE, ECG, HBZE, and AEME were 25, 640, 50, and 13 ng/ml, respectively. This method was successfully applied in analyzing 13 case samples from aviation accident pilot fatalities and motor vehicle operators. AEME concentrations found in the 13 samples were consistent with those produced solely by the GC inlet pyrolysis of COC controls in blood. Anhydroecgonine cannot be used as a marker for the abuse of COC by smoking because it is also pyrolytically produced from COC metabolites on the GC inlet. The developed method can be effectively adopted for analyzing COC and related compounds in urine, blood, and muscle by a single extraction with increased sensitivity through formation of hydrochloride salts and using a one-step derivatization.

Toxicological findings from 1587 civil aviation accident pilot fatalities, 1999-2003.

INTRODUCTION: The prevalence of drug and ethanol use in aviation is monitored by the Federal Aviation Administration (FAA). Under such monitoring, toxicological studies for the 1989-1993 and 1994-1998 periods indicated lower percentages of the presence of controlled substances (illegal drugs) than that of prescription and nonprescription (over-the-counter) drugs in aviation accident pilot fatalities. In continuation, a toxicological assessment was made for an additional period of 5 yr. METHODS: Biosamples from aviation accident pilot fatalities submitted to the FAA Civil Aerospace Medical Institute (CAMI) are analyzed, and those findings are stored in a database. This database was examined for the 1999-2003 period for the presence of controlled substances (Schedules I-V), prescription/nonprescription drugs, and ethanol in the fatalities. RESULTS: Out of 1629 fatal aviation accidents from which CAMI received biosamples, pilots were fatally injured in 1587 accidents. Drugs and/or ethanol were found in 830 (52%) of the 1587 fatalities. Controlled substances from Schedules I-II (SI-II) and Schedules III-V (SIII-V) were detected in 113 and 42 pilots, respectively. Prescription drugs were present in 315 pilots, nonprescription drugs in 259, and ethanol in 101. SI-II substances were detected in 5 of 122 first-class medical certificate-holding airline transport pilots. In addition to the controlled substances, many of the prescription/nonprescription drugs found in the fatalities have the potential for impairing performance. CONCLUSIONS: Findings from this study were consistent with those of two previous toxicological studies and support the FAA's programs aimed at reducing the usage of performance-impairing substances.

Carboxyhemoglobin and blood cyanide concentrations in relation to aviation accidents.

INTRODUCTION: It is important in aviation accident investigations to determine if a fire occurred during flight or after the crash and to establish the source(s) of the toxic gases. METHODS: Bio-specimens from aviation accident fatalities are submitted to CAMI for analyses. In blood, CO is analyzed as carboxyhemoglobin (COHb) and hydrogen cyanide as cyanide (CN-). Analytical data were stored in a database, and this database was searched for the period of 1990-2002 for the presence of COHb and CN in the submitted cases. RESULTS: Out of 5945 cases, there were 223 (4%) cases wherein COHb was > or = 10%. Of the 223 cases, fire was reported with 201, no fire with 21, and undetermined fire status with 1. CN concentrations were at or above 0.25 microg x ml(-1) in 103 of the 201 fire-related cases. None of the 21 non-fire cases had CN-, but nicotine was detected in 9 of the cases. All non-fire cases with COHb > 30% (four cases) were associated with exhaust leaks. Of the 223 cases, COHb-CN- fractional toxic concentration (FTC) was lethal only in 31 cases with elevated CN levels. CONCLUSIONS: The presence of COHb and CN in elevated concentrations in the blood of victims found by autopsy to have died on impact would indicate an in-flight fire. In the absence of fire and CN-, the elevated COHb concentrations would suggest an exhaust leak, particularly at COHb > 30%. The findings of this study also suggest that, in addition to COHb, CN plays a detrimental role in fire-associated aviation accident fatalities.

Gas chromatographic-mass spectrometric differentiation of atenolol, metoprolol, propranolol, and an interfering metabolite product of metoprolol.

Over a 10-year period, 1993-2002, Federal Aviation Administration identified 50 pilot fatalities involving atenolol, metoprolol, and propranolol, which is consistent with the fact that these drugs have been in the lists of the top 200 drugs prescribed in the U.S. In a few of the 50 pilot fatality cases, initial analysis suggested the presence of atenolol and metoprolol. However, there was no medical history with these cases supporting the use of both drugs. Therefore, atenolol, metoprolol, and/or propranolol, with their possible metabolite(s), were re-extracted from the selected case specimens, derivatized with pentafluoropropionic anhydride (PFPA), and analyzed by gas chromatography-mass spectrometry (GC-MS). The MS spectra of these three antihypertensives and a metoprolol metabolite are nearly identical. All of the PFPA derivatives had baseline GC separation, with the exception of a metoprolol metabolite product, which co-eluted with atenolol. There were four primary mass fragments (m/z 408, 366, 202, and 176) found with all of the PFPA-beta-blockers and with the interfering metabolite product. However, atenolol has three unique fragments (m/z 244, 172, and 132), metoprolol has two unique fragments (m/z 559 and 107), propranolol has four unique fragments (m/z 551, 183, 144, and 127), and the metoprolol metabolite product has two unique fragments (m/z 557 and 149). These distinctive fragments were further validated by using a computer program that predicts logical mass fragments and performing GC-MS of deuterated PFPA-atenolol and PFPA-propranolol and of the PFPA-alpha-hydroxy metabolite of metoprolol. By using the unique mass fragments, none of the pilot fatality cases were found to contain more than one beta-blocker. Therefore, these mass ions can be used for differentiating and simultaneously analyzing these structurally similar beta-blockers in biological samples.