FORENSIC TOXICOLOGY - Bio Medical Forensics

presumptive pneumonia, and administered Propofol for sedation. His
arterial blood gases after intubation showed a pH 7.38, PCO2 38, PO2 143 and his measured CO2 26 was mmol/L. Over the following 4 days,
his measured CO2 progressively decreased to 8 mmol/L with an anion
gap of 419, negative ketones, and normal serum lactate with no corresponding
significant changes in his arterial blood gases. On the 7th day
of hospitalization, he received lipid infusion with total parentral
nutrition. A grossly lipemic serum specimen showed a CO2 level of 3
mmol/L. Propofol was discontinued. Four hours later, a 2nd lipemic
specimen showed, after ultracentrifugation to remove the chylous
material, a CO2 level of 21 mmol/L. A lipid panel showed a triglyceride
level of 4426 mgldL. The patient’s condition continued to deteriorate
and he died later on the 7th day. At autopsy, the cause of death was
poorly differentiated small cell carcinoma in the right upper and middle
lung lobes with liver and lymph node metastasis.
Propofol ® is a short-acting anesthetic agent. It is a hydrophobic
compound, which is formulated in a lipid emulsion (Intralipid) to facilitate
intravenous use. Several cases have been reported in which an
association between the use of Propofol and a clinical presentation of
metabolic acidosis, cardiac dysrhythmias, and lipemia has been
suggested. Some of these cases were complicated by fatality. Most of
these fatal cases involved children who were ventilated for laryngotracheobronchitis.
The cause of metabolic acidosis in these cases was not
determined. It was also suggested that the Intralipid in the Propofol
preparation might interfere with lactate metabolism in the liver causing
accumulation of lactate and acidosis.
In this case, there was a consistent, progressive decrease in the measured
serum bicarbonate level during Propofol infusion. However, the
patient acid-base status, as simultaneously measured by arterial blood
gases did not show a corresponding change that would match the very
low level of serum bicarbonate. There was also a marked hypertriglyceridemia
that may be related to both Propofol infusion and lipid infusion
for nutritional support. After ultracentrifugation of the serum, the
measured bicarbonate level in the supernatant returned to the patient’s
baseline value prior to Propofol and lipid administration. That bicarbonate
value was consistent with the patient’s acid-base status measured
by arterial blood gases. Ultracentrifugation removes the chylous
material from serum. It may also remove Propofol from serum since it’s
a hydrophobic compound. Neither Propofol nor hypertriglyceridemia
have been reported as a potential interfering substance with serum bicarbonate
assays. In most of the previously reported cases, metabolic acidosis,
dysrhythmias, cardiac failure, and death have been related to
Propofol by exclusion of all other causes. No conclusive evidence has
been reported to prove or disprove this association. This is the first report
suggesting that low bicarbonate level associated with Propofol infusion
may be largely due to an interfering substance or substances with the
bicarbonate assay. Further studies are needed to determine the role of
Propofol and hypertriglyceridemia in serum bicarbonate measurement.
Propofol, Fetal Metabolic Acidosis, Bicarbonate
K5 Death Attributed to Intravenous Oxycodone
Loralie J. Langman, PhD*, Henry A. Kaliciak, BSc, and Asa Louis, BSc,
Provincial Toxicology Centre, Riverview Hospital, North Lawn, Port
Coquitlam, British Columbia, Canada
The authors will present the first case of death caused by intravenous
oxycodone at the Provincial Toxicology Centre.
Oxycodone is a semisynthetic narcotic analgesic derived by
chemical modification from codeine. It produces potent euphoria,
analgesic and sedative effects, and has a dependence liability similar to
morphine.
* Presenting Author
A 34-year-old Caucasian male was pronounced dead in hospital. A
full autopsy was performed approximately 24 hours after death.
Autopsy findings included acute bronchitis and bronchiolotis, and recent
puncture sites in left arm, pulmonary edema, mucous plugging of small
airways, and cerebral edema. Specimens were collected for toxicological
analysis.
Blood (central) and urine specimens were initially subjected to a
thorough qualitative analysis. Screening was performed for illicit drugs
including morphine and cocaine by radioimmunoassay. Basic drugs
were screened for by liquid-liquid extraction followed by GC-NPD and
GC-MS electron impact detection. Acidic and neutral drugs were
screened for by liquid-liquid extraction followed by HPLC-DAD.
Volatiles were assayed by GC-FID. Qualitative analysis identified
methadone, cocaine/benzoylecoginine (BE), and oxycodone. The
methadone concentration was quantitated by GC-NPD and found to be
0.034 mg/L (0.11 umol/L) in blood. Quantitation of cocaine/BE was
performed by GC-MS. Neither cocaine or BE were detected in blood,
and no cocaine was detected in urine; however, BE was detected in urine
at 0.11 mg/L (0.38 umol/L). This suggests remote cocaine useage. The
methadone level was considered to be insufficient as the cause of death.
Oxycodone was assayed in biological specimens as follows: briefly,
to 1 mL of specimen standards and controls 100 uL of prazepam solution
(internal standard, 1.0 ug/L) and 1 mL of saturated sodium carbonate
solution was added, and extracted into 5 mL n-butyl chloride. The
extract was concentrated under nitrogen, reconstituted with 100 uL of
methanol, and 1 µL was injected into an Agilent model 6890 gas chromatograph
coupled to a NP Detector using a 30 m HP-5 capillary
column (Agilent). Separation was achieved isothermally at 250°C. The
concentration was measured by comparison of peak height ratio of the
drug to that of prazepam against a standard curve. Since prazepam is not
used therapeutically in Canada and extracts efficiently under the above
conditions, it was chosen as the internal standard. Linearity was
observed from 0.010 mg/L up to 0.50 mg/L. Samples with concentrations
exceeding the linearity were diluted.
Elevated concentrations of oxycodone were found in blood 0.27
mg/L (0.86 mmol/L). The usual adult oral dose is 2.5-5 mg as the
hydrochloride salt every 6 hours, although patients with moderately
severe pain may take 10-30 mg every 4 hours. Published pharmacokinetic
studies involving oxycodone show that plasma concentrations are
generally less than 0.100 mg/L. For example, the peak plasma concentrations
in 12 patients receiving a 10 mg oral dose averaged 0.030 mg/L.
There is little reported on the lethal levels of oxycodone in blood when
administered intravenously. For oral oxycodone alone, a minimum
lethal level of 5.0 mg/L has been suggested, and fatal concentrations
involving oxycodone and at least one other depressant drug have been
reported at 0.60 mg/L. Although the concentration of oxycodone in this
case was lower, it is well known that for other opiates the minimum
lethal level can be considerably lower when administered intravenously
than when orally administered. The cause of death in this case was
ascribed to oxycodone administered by intravenous route.
Oxycodone, Intravenous, Fatality
K6 Validation and Application of the
PE TMX 110 Autosystem for Packed
Column Analysis of the Confirmation
of Volatiles in Death Investigation
Bradford R. Hepler, PhD*, Daniel S. Isenschmid, PhD, and Sawait
Kanluen, MD, Wayne County Medical Examiner’s Office, Detroit MI
After attending this presentation, the attendee will be
knowledgeable in method validation for volatiles by headspace gas
chromatography. Documentation of linear dynamic range, precision, and
carryover of volatile headspace methods on two instrumental systems
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