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.

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.

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.

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.

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.

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.

Utilizing the urinary 5-HTOL/5-HIAA ratio to determine ethanol origin in civil aviation accident victims.

Specimens from fatal aviation accident victims are submitted to the FAA Civil Aerospace Medical Institute for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Care must be taken when interpreting a positive ethanol result due to the potential for postmortem ethanol formation. Several indicators of postmortem ethanol formation exist; however, none are completely reliable. The consumption of ethanol has been shown to alter the concentration of two major serotonin metabolites, 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindole-3-acetic acid (5-HIAA). While the 5-HTOL/5-HIAA ratio is normally very low, previous studies using living subjects have demonstrated that the urinary 5-HTOL/5-HIAA ratio is significantly elevated for 11-19 h after acute ethanol ingestion. Recently, our laboratory developed and validated an analytical method for the simultaneous determination of both 5-HTOL and 5-HIAA in forensic urine samples using a simple liquid/liquid extraction and LC/MS/MS and LC/MS/MS/MS. In this previous work a 15 pmol/nmol serotonin metabolite ratio cutoff was established in postmortem urine, below which it could be conclusively determined that no recent antemortem ethanol consumption had occurred. In the current study this newly validated analytical method was applied to five ethanol-positive aviation fatalities where the origin of the ethanol present could not previously be conclusively determined. In four of the five cases examined the detected ethanol was demonstrated to be present due to postmortem microbial formation, and not consumption, even though some indication of ethanol consumption may have been present.

Storage stability of simulator ethanol solutions for vapor-alcohol control tests in breath-alcohol analysis.

We conducted a one-year stability study on aqueous alcohol simulator solution, stored in sealed polyethylene bottles at 4 degrees C and at room temperature. Thirty-nine aliquots of simulator solution with a VAC target value of 0.079 +/- 0.010 g/210 L were stored and analyzed independently monthly at two locations: The University of Oklahoma HSC Toxicology Laboratories (OUHSC) and Oklahoma Department of Public Safety Alcohol and Drugs Countermeasures Unit (DPS/ADCU). Paired Intoxilyzer 5000 Evidential Breath-Alcohol Analyzers + Guth Breath Test Simulators were used to measure 20 consecutive VACs generated at 34 degrees C with individual simulator solution aliquots, followed by VAC control tests in triplicate. Control tests at OUHSC were carried out with a NIST-traceable compressed ethanol/nitrogen gas mixture with a validated label ethanol concentration of 0.085 g/210 L +/- 2% at 760 torr. Control tests at DPS/ADCU were carried out with simulator-generated vapor-alcohol samples with a validated VAC of 0.10 +/- 0.01 g/210 L. The measurement results were analyzed by standard statistical methods with a STATGRAPHICS Plus for Windows Version 6.0 microcomputer statistics program. No significant changes occurred during the one-year study period in the concentration of the aqueous simulator alcohol solution, as reflected by close agreement of the mean results of each set of 20 consecutive VAC analyses. The summary descriptive statistics for the VAC measurements were OUHSC (4 degrees C) mean +/- SD = 0.077 +/- 0.0004 g/210 L, median = 0.077, mode = 0.077, span = 0.075-0.079; DPS/ADCU (4 degrees C) mean +/- SD = 0.079 +/- 0.0013 g/210 L, median 0.079, mode = 0.078, span = 0.077-0.081; DPS/ADCU (Room Temp.) mean +/- SD = 0.078 +/- 0.0011 g/210 L, median = 0.078, mode = 0.078, span = 0.076-0.080. All OUHSC and DPS/ADCU VAC control tests were within acceptable target value ranges. The least squares linear regression model equations for y (= VAC, g/210) upon x (= time in months) were OUHSC (4 degrees C) y = 0.077 - 0.000021x; DPS/ADCU (4 degrees C) y = 0.079 + 0.000032x; and DPS/ADCU (Room Temp.) y = 0.078 + 0.000038x. The essentially zero slopes for all 3 models signify that no significant change occurred in the alcohol concentrations of all 39 simulator solutions aliquots measured over the 1-year study period, for either 4 degrees C or room temperature storage. The Pearson correlation coefficients for the above three regression models were R = -0.20, 0.10, and 0.13, respectively; each value is close to zero, confirming the absence of significant statistical relationship between VACs and passage of time. The coefficients of determination for the above three regression models were 4.3%, 1.0%, and 1.7%, respectively. These statistics indicate that the fitted models explain only 1 to 4% of the small total variability in the VAC as a function of time. ANOVA statistics for each of the three sets of VAC test results yield a P-value greater than 0.10, indicating that there is not a statistically significant relationship between VAC and the passage of time, at a 90% or higher confidence level. We conclude that the ethanol concentration of simulator alcohol solutions stored in sealed polyethylene bottles, at either 4 degrees C or normal room temperature, does not change significantly for at least one year after preparation, and that a correct initial VAC target value will remain valid during that time period.