FORENSIC TOXICOLOGY - Bio Medical Forensics

This presentation will impact the forensic community and/or
humanity by emphasizing the need for extreme caution when administering
a local anesthetic to a patient with a low body mass, such as a child.
Severe toxicity from local anesthetics used in dental procedures is
often due to accidental intravascular injection. To lessen the likelihood of
such an occurrence, aspiration is performed before the anesthetic solution
is injected. In the event that blood is aspirated, the needle is repositioned
until no blood is observed upon aspiration. Nevertheless, rigorous
adherence to such a precautionary measure, although fairly preemptive,
does not definitively abolish inadvertent intravascular injection.
Among the local anesthetics commonly used in dental procedures is
prilocaine or Citanest® (AstraZeneca Pharmaceuticals, Wilmington, DE).
As with other local anesthetics, the pharmacological activity of prilocaine
is mediated by blockage of voltage gated sodium channels. Administration
of local anesthetics involves injection into the region of the nerve fibers to
be blocked. The onset of anesthesia occurs an average of two minutes following
prilocaine injection and lasts for approximately two hours.
Prilocaine has a volume of distribution of 0.7-4.4 L/kg with 30% of the
plasma concentration bound to proteins (1) .
In preparation for a dental extraction procedure, a healthy 2-year-old
male was administered nitrous oxide for sedation. This was followed by
injection of four 1.8 mL ampules of the local anesthetic, prilocaine, with
another ampule applied topically. Shortly thereafter, the child became quiet,
exhibited seizure-like activity and became cyanotic. The child’s condition
improved following administration of 100% oxygen. However, upon
arrival at the hospital, he went into cardiopulmonary arrest and was pronounced
dead approximately 85 minutes after conclusion of prilocaine
delivery. Routine toxicology screening analysis of blood and urine revealed
the presence of only prilocaine and lidocaine. Anaphylactic reactions to
amide-type local anesthetics are rare and measurement of serum tryptase,
an indicator of anaphylaxis, was negative. Prilocaine concentration was
measured by GC-MS with SKF-525A as internal standard. Blood obtained
from the subclavian vein and the heart contained prilocaine at 14.6 and 13.0
mg/L, respectively. Concentrations of prilocaine in additional samples
obtained at autopsy are indicated in Table 1. The cause of death was determined
to be prilocaine toxicity resulting from excessive administration by
injection. Prilocaine was measured in several other samples obtained at
autopsy with the results reported herein. Kaliciak and Chan reported the
death of an elderly patient undergoing a dental procedure with the blood
prilocaine concentration of 13.4 mg/L, very similar to that found in the
present fatality (2) .
Table 1
Heart blood 13.0 mg/L
Peripheral blood 14.6 mg/L
Liver 14.0 mg/kg
Lung 26.1 mg/kg
Bile 31.1 mg/L
Vitreous fluid 14.7 mg/L
Urine 12.4 mg/L
Gastric contents 76.4 mg/L
As with all drug administration in the pediatric age group, the
maximum dosage of prilocaine that may be safely delivered is governed by
the weight of the child. Based on the manufacturer’s recommendation of a
maximum dose of 8 mg per kilogram, the total administered dose of prilocaine
to this child, who weighed slightly less than 15 kilograms, would be
limited to 120 mg of prilocaine (15 kg x 8 mg/kg). Delivery of such a dose
corresponds to a total of 3 mL of prilocaine solution; available only as a 4%
solution. As such, a maximum of one and two-thirds dental cartridges of
prilocaine should be administered simultaneously to a child of this weight.
* Presenting Author
This indicates that the significantly elevated concentration of prilocaine in
this child is the result of excessive administration of this local anesthetic
rather than a complication of direct intravascular bolus administration; a
conclusion that is further supported by the dentist’s account of the delivery
of the prilocaine injections.
References:
1. R.C. Baselt. Disposition of Toxic Drugs and Chemicals in Man, 7th ed.,
Biomedical Publications, Foster City, CA, 2004, pp 929-930.
2. H.A. Kaliciak and S. C. Chan. Distribution of prilocaine in body fluids
and tissues in lethal overdose. J. Anal. Toxicol. 10: 75-6 (1986).
Prilocaine, Fatality, Anesthetic
K13 Case Report: Death Due to Snorting
of Crushed Sustained-Release
Morphine Tablets
James W. Rajotte, MSc*, Centre of Forensic Sciences, Northern
Regional Laboratory, Suite 500, 70 Foster Drive, Sault Ste. Marie,
Ontario P6A 6V3, Canada
After attending this presentation, attendees will learn about potentially
fatal low blood morphine concentrations that are not heroin-related can
exist, especially if the route of administration and drug formulation administered
are unusual.
This presentation will impact the forensic community and/or
humanity by providing a case report of a death due to snorting of a sustained-release
morphine formulation, especially one where heroin is not a
potential confound. This case report will therefore address this specific
absence in the literature.
MS-Contin® is a sustained-release morphine formulation that is
administered orally to treat moderate to severe pain. MS-Contin® is
available in tablets containing 15, 30, 60, 100 and 200 mg of morphine
sulfate. Within four hours of the administration of 30 or 60 mg tablets of
MS-Contin®, the reported peak plasma morphine concentrations are 10
and 30 ng/mL, respectively. Therapeutic plasma morphine concentrations
persist for about 12 hours thereafter.
This report documents a morphine-related death in a male prisoner
known to be an intravenous drug user who reportedly snorted three crushed
100 mg tablets of MS-Contin® in his jail cell. The prisoner died 8 hours
later. Prior to death this individual exhibited symptoms of profound
sedation and laboured breathing that progressed to apnea. At autopsy the
pathologist observed pulmonary edema. In addition, two condoms were
found in his rectum, one containing three 100 mg tablets of MS-Contin®,
the other containing plant material suspected of being marijuana.
Absorption of morphine from the condom was ruled out based on a visual
assessment of condom integrity and the condition of the tablets.
Toxicological examinations of post-mortem blood and urine samples were
conducted to determine whether death was related to the presence of illicit
substances or pharmaceutical preparations often encountered in death
investigations. Analysis for heroin was not performed as there was no
investigative information to suggest its use. The analytical procedures consisted
of immunoassays and gas chromatographic methods, utilizing flame
ionization, nitrogen-phosphorus, and mass spectrometric detection. A concentration
of 103 ng/mL of free morphine was detected in the femoral
blood, and cannabinoid metabolites were indicated by an immunoassay in
heart blood. No alcohol, or other substances of toxicological significance
were detected.
The reported symptoms, autopsy findings, and the results of the toxicology
examination point to a fatal morphine overdose. In the experience
of this laboratory, this is the first known death associated with the snorting
of a crushed sustained-release morphine tablet.
Morphine, Snorting, Fatal
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