FORENSIC TOXICOLOGY - Bio Medical Forensics

Facts of the case: RB was a 60-year-old female in good general
health who underwent facial cosmetic surgery and subsequently died
from cardiorespiratory collapse. She had been diagnosed with
depression and was taking Fluoxetine (Prozac ® ) and no other medications.
The medical examiner’s report stated the following: The intubation
went smoothly and she was initially stable from a cardiovascular
point of view. About five minutes into the anesthesia a local anesthetic
consisting of lidocaine, bupivacaine and epinephrine was injected
beneath the skin of the face and scalp. She began to demonstrate cardiovascular
instability …. Heart rate decreased to the 30s and CPR was
begun with return of pulse and blood pressure. She again deteriorated
and was transferred by paramedics to the ER…. Her condition gradually
deteriorated to anoxic encephalopathy and she was pronounced dead
approximately seven hours after the initial cardiovascular collapse.
Toxicology ante- and postmortem lidocaine® and bupivacaine blood
levels were:
Time Ante-Mortem Post-Mortem Blood
Blood Concentrations (mcg/ml) Concentrations (mcg/ml)
Lidocaine® Bupivacaine Lidocaine® Bupivacaine
9:50 a.m. 3.1 0.9
10:34 a.m. 4.5 2.0
4:27 p.m. DEATH
At autopsy: (46 hours after death) 5.3 3.3
Injection sites were identified as follows: “On the midline upper
forehead just below the hairline is a punctuate mark representing a
needle puncture. A second punctuate mark is present on the left lower
forehead just above the lateral end of the left eyebrow. A third punctuate
mark is noted on the left upper lateral cheek just lateral to the lateral
angle of the left eye. Fourth and fifth punctures are noted on the lateral
aspect of the right eye…. A ½ inch area of subcutaneous hemorrhage is
present about the lower of the two puncture marks near the lateral angle
of the right eye.” The Medical Examiner also offered the following interpretation
in his report, “Lidocaine® and bupivacaine levels are within
the range previously documented following clinical administration. The
actual mechanism of her cardiorespiratory collapse is unknown.”
Benjamin G. Covino, MD, PhD, was Professor of Anesthesiology at
Harvard Medical School and Vice-President of Astra Pharmaceuticals, (a
company that marketed lidocaine® and bupivacaine) from the mid-
1960s through the 1980s and was an internationally-respected expert in
local anesthesia pharmacology and toxicology. Dr. Covino recognized
that bupivacaine was four times as potent as lidocaine® and that toxic
blood levels of lidocaine® ranged from 6-10 mcg/ml while those of
bupivacaine ranged from 1.5-2.5 mcg/ml. Dr. Covino was also the first
investigator to convert blood levels of bupivacaine to “lidocaine® equivalents”
by multiplying the bupivacaine blood level by four and adding
that number to the blood level of lidocaine® to obtain the combined
blood level of both local anesthetic agents in “lidocaine® equivalents”.
Applying the “Covino Algorithm” to the above data, at 9:50 am, a lidocaine®
equivalent level of 6.7 and at 10:34 am, a lidocaine® equivalent
level of 12.5, well into the toxic cardiodepressant level, and rising. The
rapid appearance of bradycardia most likely indicated an initial unintended
intravascular administration followed by continuous absorption
from the infiltrated region resulting in an additive toxic cardiovascular
effect that was further compromised by poor management and
hypoxemia, and resulted in the death of a patient.
Lidocaine®, Bupivacaine, Additive Toxicity
K8 Distribution and Optical Purity of
Methamphetamine Found in Toxic
Concentration in a Civil Aviation
Accident Pilot Fatality
Patrick S. Cardona, BA*, Arvind K. Chaturvedi, PhD, John W. Soper,
PhD, and Dennis V. Canfield, PhD, Bioaeronautical Sciences Research
Laboratory (AAM-610), FAA Civil Aerospace Medical Institute, PO
Box 25082, Oklahoma City, OK 73125-5066
The authors will present toxicological findings of a pilot fatality
involved in a unique methamphetamine-related civil aviation accident to
aid investigations of such accidents.
This presentation will provide information on the distribution of
methamphetamine present in toxic concentration and the stereoselective
analysis of this amine in biological samples.
The Federal Aviation Administration’s Civil Aerospace Medical
Institute conducts toxicological evaluation of postmortem biological
samples collected from pilots involved in fatal civil aircraft accidents.
The submitted samples are primarily analyzed for the presence of
primary combustion gases, alcohol/volatiles, and drugs. Related to such
an evaluation, findings of a unique aircraft accident are described in this
report. Upon colliding with terrain in weather conditions of poor visibility,
a 1-occupant airplane was substantially damaged with no evidence
of fire. Remains of the pilot were found outside the crashed aircraft.
Pathological examination of the pilot’s body revealed multiple blunt
force injuries and vascular congestion, including subdural hemorrhage
of the cerebral cortex. Autopsied samples—blood, brain, gastric contents,
heart, liver, muscle, spleen, urine, and vitreous fluid—were submitted
for toxicological analysis. The fluorescence polarization
immunoassay disclosed the presence of 8.0 μg/mL amphetamines in
urine. Subsequent gas chromatographic/mass spectrometric confirmatory
analysis determined the presence of methamphetamine (1.134
μg/mL in blood and 59.171 μg/mL in urine) and amphetamine (0.022
μg/mL in blood and 1.495 μg/mL in urine). Both amines were present in
all the submitted sample types, except for amphetamine, which was
detected neither in vitreous fluid nor in muscle. The amount of methamphetamine
found in gastric contents was 575-fold higher than that of
amphetamine. Stereochemical analyses of gastric contents, blood, and
urine using a chiral probe, (S)-(–)-N-(trifluoroacetyl)prolyl chloride,
indicated that methamphetamine detected in the sample types was not
optically pure. In gastric contents and urine, this secondary amine’s
optical isomers were present in equal proportions. The enantiomeric
excess of (+)-methamphetamine over its (–)-form was about 32% in
blood. Both optical forms of amphetamine were present in the ratio of
1.2–1.5:1.0 in the 3 sample types. The blood methamphetamine concentration
found was in the range sufficient to produce toxic effects,
including performance impairment. The observed variation in the ratios
of amine isomer concentrations in the sample types would have been
attributed to stereoselective metabolic and other pharmacokinetic
processes. Findings of this study supported the conclusion of the
National Transportation Safety Board that, in addition to the visibilityassociated
adverse meteorological conditions, the use of the controlled
substance played a contributory role in the causation of the aircraft
accident.
Forensic Toxicology, Methamphetamine, Stereochemical Analyses
205 * Presenting Author