DOT/FAA/AM-17/6

Office of Aerospace Medicine

Washington, DC 20591

Pilot-Reported Beta-Blockers 

Identified by Forensic 

Toxicology Analysis of 

Postmortem Specimens

Dennis V. Canfield

Kurt M. Dubowski

James E. Whinnery

Estrella M. Forster

Civil Aerospace Medical Institute 

Federal Aviation Administration 

Oklahoma City, OK 73125

January 2017

Final Report
NOTICE

This document is disseminated under the sponsorship of 

the U.S. Department of Transportation in the interest of 

information exchange. The United States Government 

assumes no liability for the contents thereof.

___________

This publication and all Office of Aerospace Medicine 

technical reports are available in full-text from the 

Civil Aerospace Medical Institute’s publications website: 

http://www.faa.gov/go/oamtechreports
i 

Technical Report Documentation Page 

1. Report No. 2. Government Accession No. 3. Recipient's Catalog No.

DOT/FAA/AM-17/6

4. Title and Subtitle 5. Report Date

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology 

Analysis of Postmortem Specimens

January 2017

6. Performing Organization Code

7. Author(s) 8. Performing Organization Report No.

Canfield DV, Dubowski KM, Whinnery JE, Forster EM

9. Performing Organization Name and Address 10. Work Unit No. (TRAIS)

FAA Civil Aerospace Medical Institute

P.O. Box 25082

Oklahoma City, OK 73125

11. Contract or Grant No.

12. Sponsoring Agency name and Address 13. Type of Report and Period Covered

Office of Aerospace Medicine

Federal Aviation Administration

800 Independence Ave., S.W.

Washington, DC 20591 14. Sponsoring Agency Code

15. Supplemental Notes

16. Abstract

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: (1) 

determine the capability of a toxicology laboratory to detect reported medications, and (2) 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. Metoprolol and Atenolol were the most commonly 

found beta-blockers (81%) in this study. Discussion: Time of death, therapeutic concentration, and 

specimen type were found to be factors in the ability of the laboratory to detect beta-blockers. Dose did not 

correlate with the ability of the toxicology laboratory to detect the beta-blocker. Conclusions: 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 taken from pilots that died in aviation accidents.

17. Key Words 18. Distribution Statement

Toxicology, medications, drugs, aviation, safety, fatal, 

pilots

Document is available to the public through 

the Internet:

http://www.faa.gov/go/oamtechreports/

19. Security Classif. (of this report) 20. Security Classif. (of this page) 21. No. of Pages 22. Price

Unclassified Unclassified 10

Form DOT F 1700.7 (8-72) Reproduction of completed page authorized 
ii

ACKNOWLEDGMENT

We acknowledge the Federal Aviation Administration Office of Aerospace Medicine and the Office of 

Aviation Accident Investigation & Prevention as the main sponsoring organizations for this research. 
iii

Contents

PILOT-REPORTED BETA-BLOCKERS IDENTIFIED BY 

FORENSIC TOXICOLOGY ANALYSIS OF POSTMORTEM SPECIMENS 

INTRODUCTION.........................................................................................................................................................1

MATERIALS AND METHODS ....................................................................................................................................1

Postmortem Biological Specimens ....................................................................................................................1

Toxicology Analysis.............................................................................................................................................1

Data Analysis.........................................................................................................................................................2

RESULTS......................................................................................................................................................................2

General Findings: .................................................................................................................................................2

Specimen Type:.....................................................................................................................................................4

Time of Death Findings: .....................................................................................................................................4

Dosage Findings: ..................................................................................................................................................4

DISCUSSION................................................................................................................................................................5

Time of Death.......................................................................................................................................................5

Dose .......................................................................................................................................................................5

Therapeutic Concentration .................................................................................................................................5

Specimen Analyzed ..............................................................................................................................................5

Route of Administration .....................................................................................................................................6

Missed Doses........................................................................................................................................................6

Conclusion.............................................................................................................................................................6

REFERENCES..............................................................................................................................................................6
1

PILOT-REPORTED BETA-BLOCKERS IDENTIFIED BY FORENSIC

TOXICOLOGY ANALYSIS OF POSTMORTEM SPECIMENS

INTRODUCTION

Several papers have been written over the years about a pilot’s failure to report medications found by 

postmortem toxicology analysis (1, 2), however, no one has published research findings on the ability of a 

postmortem toxicology laboratory to detect pilot-reported medications. This study looked at some of the 

factors that might affect the ability of a toxicology laboratory to detect beta-blockers in postmortem 

specimens.

This research intended to determine the ability of a forensic toxicology laboratory to identify betablockers reported in a pilot’s medical records and the factors that influence the detection of medications 

taken by pilots in postmortem specimens. Beta-blockers were selected for this study because they are one of 

the most commonly prescribed medications and should provide statistically significant numbers for analysis. 

In addition, the Aerospace Medical Certification Division of the Federal Aviation Administration (FAA) 

Civil Aerospace Medical Institute (CAMI) approves the use of these medications on a case by case basis, 

and we would expect to find these medications reported by pilots found by toxicology analysis. 

MATERIALS AND METHODS

Postmortem Biological Specimens

By law (3), the autopsied biological samples (blood, urine, liver, kidney, vitreous fluid, and other body 

specimens) collected from pilot fatalities in civil aircraft accidents are submitted to CAMI for toxicological 

testing. Not all of the pilots involved in these accidents are necessarily certified by the FAA to fly an aircraft. 

The specimens submitted for analysis are coordinated through the FAA’s Office of Accident Investigation 

and the National Transportation Safety Board (NTSB) (4). The collected samples are submitted in custombuilt FAA evidence containers (TOX-BOX) that provide all necessary instructions and materials for 

standardized toxicological collection and processing.

Toxicology Analysis

Postmortem specimens from pilots taking a beta-blocker with medical records on file with the FAA 

between 1999−2015 were included in this study. Biological specimens received for testing are routinely 

analyzed for the presence of combustion gases (carbon monoxide and hydrogen cyanide), a wide range of 

illicit, prescription, and nonprescription drugs, along with alcohol/volatiles. Specimens are screened, 

confirmed, and quantitated for the analytes mentioned above. All specimens are analyzed according to 

established standard procedures approved for use by the CAMI Laboratory. The methods used included gas 

chromatography, liquid chromatography, ultraviolet/visible spectrophotometry, immunoassay, gas 

chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS). 

Ethanol analysis is performed by headspace gas chromatography. Analytical procedures used are dependent 

upon their sensitivity and specificity, the nature of analytes, and the availability of sample types and 

amounts. An analyte might not necessarily be detected, or even analyzed in a particular case, because the 

specimen is unsuitable for analysis.

If urine is available in an aviation accident it is screened for drugs because the urine normally has high 

concentrations of drug relative to other biological specimens, and it is an easier biological matrix to recover 

drugs. In those cases where urine is not available, blood is screened for drugs. When there is no urine or 

blood, liver is screened for the presence of drugs. If all three of these biological matrixes are unavailable one 

of the other tissues will be selected for analysis based on the condition of the specimen and its availability.

Beta-blockers are screened by GC/MS, LC/MS, and LC/UV/FL. The confirmation of beta-blockers is 

based on a publication in the Journal of Analytical Toxicology (5). The laboratory can identify beta-blockers 
2

at concentrations below 20 ng/mL. The normal therapeutic concentrations are greater than 10 ng/mL for 

beta-blockers with the most commonly used beta-blockers above 50 ng/mL.

Data Analysis

All toxicology case results from civil aircraft accident fatalities that occurred between 1990 and the 

present are stored electronically in a SQL database maintained at CAMI, called the Toxicology Data Base 

(ToxDB). All trade Drug names, trade drug components, and doses were obtained from Rx Drugs Data 

(http://rxdrugdata.com/) a subscription web-based service. The ToxDB database was searched for pilots 

with reported and/or positive beta-blockers to identify the number of pilot fatalities taking beta-blockers 

during the period from 1999 to 2015 using the ToxFlo (Discoversoft Development, LLC), or Microsoft 

SQL Server Management Studio software packages. Information gathered from the ToxDB included cases 

with beta-blockers reported and/or found by toxicology analysis, drug, dose, time of accident, specimen, 

class of airman certificate, class of medical certificate, age, accident location, associated pathologies, and the 

type of flight certification of the associated accidents. Statistical analysis of data was performed using 

Microsoft Excel.

RESULTS

General Findings

The beta-blockers, in order of prevalence, found by postmortem toxicology analysis of specimens from 

pilot fatalities received by the CAMI toxicology laboratory, are listed in Table 1. A search of the ToxDB 

identified 319 pilots from fatal aviation accidents with reported or detected beta-blockers. The average age 

of the pilots taking beta-blockers was 64 (SD=10) years with a minimum age of 24 and a maximum age of 

89. Most of the pilots (95%) were flying private aircraft (general aviation). No pilots were flying Part 121 air 

transport aircraft in this study, and only 2.5% were flying air taxi or commercial aircraft. Fifty-three percent 

of the pilots were designated as private pilots, 28% were classified as commercial pilots, and 15% were 

classified as air transport pilots.

Metoprolol and Atenolol were the most common beta-blockers found (81%) by postmortem toxicology. 

Seventy-six percent of the pilots’ medical records reported the pilot was taking Metoprolol or Atenolol, the 

two most commonly prescribed beta-blockers (4). The majority (63.8%) of the beta-blockers reported in the 

medical records were identified by postmortem forensic toxicology analysis. More than 50% of the betablockers found by postmortem forensic toxicology analysis were not reported in the medical records (Table 1).

Carvedilol was found by postmortem toxicology analysis in 13 fatal aviation accidents, and only 3 of 

these pilots reported taking the medication. Six pilots reported taking Carvedilol but the toxicology 

laboratory only confirmed 3 of these pilots as taking carvedilol at the time of the accident.

Nadolol was detected in 3 pilots, and 2 of these were reported in the pilot’s medical record (Table 1). 

Four pilots reported taking the medication, and Nadolol was found in 2 of these pilots (Table 2). One of 

the pilots reporting Nadolol was actually found by postmortem toxicology analysis to be taking Amlodipine, 

a different antihypertensive medication.

Timolol was only detected in one pilot reporting the medication. Six pilots reported taking the 

medication. All 6 of the reported Timolol cases were eye drops used in the treatment of glaucoma.

Sotalol was detected in one pilot who did not report the medication. Three pilots reported taking the 

medication, but the drug was not found in specimens from the deceased pilots.

Alprenolol was included in this study because it has been detected in a non-aviation accident, and it is 

considered to be a beta-blocker. It is not approved for use by the FDA and can only be purchased from 

another country.
3

Table 1. Beta-blockers Identified by Postmortem Toxicology Analysis

Beta-Blocker Toxicology Found Not Reported % Not Reported

Metoprolol 124 65 52.4

Atenolol 87 45 51.7

Propranolol 18 11 61.1

Carvedilol 13 10 76.9

Bisoprolol 9 6 66.7

Labetalol 4 2 50.0

Nadolol 3 1 33.3

Timolol 1 0 0.0

Sotalol 1 1 100.0

Nebivolol 0 NA NA

Betaxolol 0 NA NA

Acebutolol 0 NA NA

Alprenolol 0 NA NA

Total 260 141 54.2

Table 2. Reported Beta-blockers Identified in Postmortem Specimens

Beta-Blocker Reported in Medical Tox Positive Tox Negative % Positive

Metoprolol 81 59 22 72.8

Atenolol 60 42 18 70.0

Propranolol 10 7 3 70.0

Carvedilol 5 3 2 60.0

Bisoprolol 6 2 4 33.3

Labetalol 2 2 0 100.0

Nadolol 4 2 2 50.0

Timolol 6 1 5 16.7

Sotalol 3 0 3 0.0

Nebivolol 5 0 5 0.0

Betaxolol 2 0 2 0.0

Acebutolol 1 0 1 0.0

Alprenolol 0 0 0 0.0

Total 185 118 67 63.8

Table 3. Reported Beta-Blockers Found in Postmortem Specimens

Specimen Positive Negative Count % Positive

Blood 88 32 120 73.3

Urine 69 10 79 87.3

Liver 44 13 57 77.2

Kidney 16 2 18 88.9

Heart 1 0 1 100.0

Lung 6 0 6 100.0

Muscle 8 4 12 66.7

Total 232 61 293 79.2
4

Specimen Type

All lung and heart specimens from cases where a beta-blocker was reported as being taken were found 

to be positive for the medication. Muscle was the least likely specimen to find reported beta-blockers.

Time of Death Findings

The percentage of reported beta-blockers identified by postmortem toxicology analysis decreased as a 

function of the time the accident occurred (Figure 1).

Figure 1. Percentage of Reported Beta-Blockers found by Postmortem Toxicology and time of death 

Time (Hours): 1 = (0601-1200), 2 = (1201-1800), 3 = (1801-2400), 4 = (0001-0600)

Dosage Findings

As found in this study, Metoprolol is the most commonly reported beta-blocker detected in postmortem 

toxicology specimens from fatal aviation accidents as found in this study. Metoprolol was, therefore, 

selected to determine the impact of dose on toxicology findings. Barely half (54%) of the pilot medical 

records reported the beta-blocker dose taken by the pilot. The medically reported Metoprolol dosage 

information was sorted by dose and toxicology results (Table 4).

Table 4. Detection of Metoprolol in Postmortem Toxicology Specimens Relative to Dose

Dosage Positive Negative Count % Detected

100 4 4 8 50.0

50 18 5 23 78.3

25 8 3 11 72.7

12.5 2 0 2 100.0

Total 32 12 44
5

DISCUSSION

Time of Death

The time of death, as might be expected, showed a decrease in the positive toxicology cases for deaths 

occurring between 1800 and 0600 hours (Figure 1). There was a steady decline in the ability of the CAMI 

toxicology laboratory to detect beta-blockers in postmortem specimens as a function of the time of death. 

The laboratory was able to detect 75% of the pilot-reported beta-blockers in pilots that died between 0601 

and 1200 and only able to identify 37% of the pilot-reported beta-blocker medications in pilots that died 

between 0001 and 0600 hours. Most patients take beta-blockers once a day in the morning, so we would 

expect to find the highest concentrations of the drug in the morning and the lowest concentrations in the 

evening and very early morning when the concentrations in the body should be at their lowest levels—the 

data supported this expectation. 

Dose

Although one might expect the dose taken by the pilot to be a major factor in detecting the reported 

beta-blocker, it was not found to be true in postmortem toxicology cases from fatal aviation accidents in this 

study (Table 4). Pilots taking a 100 mg dose were far less likely (50% positive) than pilots taking 12.5 mg 

doses (100% positive) to be positive by postmortem toxicology. Considering patients are dosed according to 

their weight and metabolism to achieve a therapeutic concentration in blood (6), we would not expect to see 

significant differences in concentration of the drug in blood based on dose, assuming the pilot was dosed 

(and executed such dose) correctly. 

The variability in the volume of distribution (VD) for the individual and the half-life of the drug for the 

individual taking the medication appear to be the most likely factors in the detection of the medication. The 

ability of the toxicology laboratory to detect the medication varied widely for some individuals of the same 

weight and who were taking a different dose of Metoprolol. The VD for Metoprolol, the beta-blocker used 

to evaluate the effect of dose on the detectability of the drug, varies from 2.5 to 5.6 L/Kg and a half-life that 

varies from 2.5 to 7.5 Hrs depending on the individual taking the medication.

Therapeutic Concentration

The therapeutic concentrations for beta-blockers vary from a low of 0.007 to a high of 3.0 ug/mL. 

When one only considers drugs with 5 or more cases and for which the medication was taken orally, there 

does appear to be a correlation between therapeutic concentration and the ability of the laboratory to detect 

the medication. Beta-blockers with a mean therapeutic concentration below 0.100 ug/mL were detected less 

often (33% positive) than beta-blockers having a mean therapeutic concentration above 0.50 ug/mL (70% 

positive).

Specimen Analyzed

A correlation found between the type of specimen screened and the ability of the toxicology laboratory 

to detect beta-blockers is shown in Table 3. In many postmortem toxicology laboratories, blood is the 

specimen of choice for screening drugs, but it may not be the best specimen for detecting trace levels of 

beta-blockers. It is the job of the CAMI forensic toxicology laboratory to detect drugs at sub-therapeutic 

concentrations to enable investigators to identify medical conditions that may have contributed to the cause 

of an accident. In this study, reported beta-blockers were identified 100% of the time when lung and heart 

were analyzed. The next best specimens for screening beta-blockers were urine and kidney, with an average 

positive rate of 88% for reported beta-blockers. In some aviation accidents, there are limited specimens 

available due to high speed impact and significant damage to the body. In some cases, the muscle is the only 

recoverable specimen. However, there is still a high probability (66.9% positive) that the medication will be 

detected even in a muscle specimen. 
6

Route of Administration

Medications can be taken by several different routes of administration including oral, sublingual, 

inhalation, topical, or injection. The route of administration does play a part in the ability of the laboratory 

to identify the medication. Timolol is an example of how the route of administration affects the ability of 

the laboratory to detect the medication. All of the reported Timolol cases were topically applied directly to 

the eye as an eye drop for the treatment of glaucoma. The dose applied to the eye is approximately 0.34 mg 

and not all of this dose would have actually been absorbed into the eye. This is a very small dose and is 

unlikely to be detected in most cases. The medication needs to be absorbed from the vitreous fluid into the 

blood stream prior to metabolism and excretion diluting the dose even more. There were 6 medically 

reported Timolol cases, and the laboratory only identified one of these cases. Recently, the laboratory did a 

technical refresh of all laboratory equipment and started using these new highly sensitive instruments in 

2014 that allow the laboratory to detect drugs at very low concentrations. One Timolol case was detected 

and reported in 2015. Timolol started to be reported in the medical records in 2003, but the laboratory did 

not detect the medication in these older cases. The one Timolol case reported in 2015 had approximately 

0.004 ug/mL in blood and 0.010 ug/g in liver. It is highly unlikely that this concentration would have been 

detected using the older instrumentation.

Missed Doses

One factor that could not be assessed using the data available in this study was missed doses by the 

pilot. However, studies have shown that approximately 30% of patients miss taking their medications (7-9). 

The “reasons for nonadherence were provided: 123 (73%) forgetfulness; 18 (11%) side effects; and 17 

(10%) the medication was not needed.(9)” These findings could account for the 70% of the reported betablockers being found in postmortem toxicology analysis and 30% where the medication was not found.

Conclusion

The majority of the pilots (70%) reporting commonly used beta-blockers were found to be taking the 

beta-blocker by postmortem forensic toxicology analysis. In those cases where the medication was not 

found, there does exist the possibility that the pilot missed taking the medication on the day of the accident. 

In some cases, pilots were found to be taking a different beta-blocker than was reported in their medical 

records. There are many other reasons why a postmortem forensic toxicology laboratory might not detect a 

beta-blocker in a postmortem specimen, such as the elapsed time from taking the medication resulting in the 

concentration of the beta-blocker dropping below therapeutic concentrations and detectable limit. 

Metoprolol and Atenolol were the most prevalent medication taken by pilots, which is consistent with 

the reported top 200 prescription drugs (10). Metoprolol, the most commonly found beta-blocker (48%) in 

postmortem forensic toxicology analysis of pilots, is ranked as the 16th most prescribed medication and 

Atenolol (33%) is ranked as the 82nd most prescribed medication.

Although one might assume the dose taken by the pilot would be a factor in the laboratory’s ability to 

detect a beta-blocker, there is no evidence that this is true based on the data considered in this study. If one 

assumes the pilot is taking a therapeutic dose consistent with weight and metabolism, one would expect the 

concentration to be in the normal therapeutic range of the medication. 

REFERENCES

1. Canfield, D.V., Salazar, G.J., Lewis, R.J., et al. (2006) Pilot medical history and medications found in 

post mortem specimens from aviation accidents. Aviat Space Environ Med 77:1171-1173.

2. Sen, A., Akin, A., Canfield, D.V., et al. (2007) Medical histories of 61 aviation accident pilots with 

postmortem SSRI antidepressant residues. Aviat Space Environ Med 78:1055-1059.

3. 49, H.R. 1758. 103 Congress. 1994

4. Aircraft Accident and Incident Notification, Investigation, and Reporting. Order 8020.11C, U.S. 

Department of Transportation Federal Aviation Administration, (2010)
7

5. Angier, M.K., Lewis, R.J., Chaturvedi, A.K., et al. (2005) Gas chromatographic-mass spectrometric 

differentiation of atenolol, metoprolol, propranolol, and an interfering metabolite product of 

metoprolol. J Anal Toxicol 29:517-521.

6. Canfield, D.V., Whinnery, J.E., Lewis, R.J., et al. (2014) A new equation for calculating the maximum 

wait time for pilots who use an impairing medication. Aviat Space Environ Med 85:668-671.

7. Cramer, J.A., Mattson, R.H., Prevey, M.L., et al. (1989) How often is medication taken as prescribed? A 

novel assessment technique. JAMA 261:3273-3277.

8. Alene, M., Wiese, M.D., Angamo, M.T., et al. (2012) Adherence to medication for the treatment of 

psychosis: rates and risk factors in an Ethiopian population. BMC Clin Pharmacol 12:10.

9. Carr-Lopez, S.M., Shek, A., Lastimosa, J., et al. (2014) Medication adherence behaviors of Medicare 

beneficiaries. Patient Prefer Adherence 8:1277-1284.

10. Bartholow, M. Top 200 Drugs of 2012. Pharmacy Times, 6/29/2016: Website 

http://www.pharmacytimes.com/publications/issue/2013/july2013/top-200-drugs-of-2012