Anaphylactic Deaths

Most anaphylactic deaths seen by a medical examiner are caused by insect bites,
drugs, or foods
.
The symptoms of anaphylactic attack are faintness, itching of
the skin, urticaria, tightness in the chest, wheezing, respiratory difficulty, and
collapse. In anaphylactic deaths, the onset of symptoms is usually immediate
or within the first 15 to 20 min. Beyond that time, one would need a welldocumented
medical history of gradually developing symptoms to implicate
an anaphylactic reaction, e.g., the development of itching or wheals and flares.
Death usually occurs within 1 to 2 h. In some insects, e.g., fire ants, the venom
is directly toxic and death can occur without anaphylactic reaction if there were
a large number of bites.
13
In such cases, death typically occurs after 24 h.
A fatal anaphylactic reaction results in acute respiratory distress or circulatory
collapse
.
Obstruction of the upper airway can be caused by pharygeal
or laryngeal edema; of the lower airway, by bronchospasm with contraction
of the smooth muscle of the lungs, vasodilation, and increased capillary permeability.
14
Cardiac arrest may be caused by respiratory arrest; the direct
effects of the chemical mediators of anaphylaxsis on the heart or shock caused
by a combination of intravascular fluid loss from edema and vasodilatation.
Pumphrey and Roberts studied 56 anaphylactic deaths coming to autopsy.
15
They found that, in all 16 deaths that were caused by food allergy, there was
difficulty in breathing, with death in 13 of the cases caused by respiratory
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469
arrest. In contrast, shock without any difficulty in breathing occurred in eight
of 19 cases caused by insect venom and 12 of 21 caused by iatrogenic reactions.
At autopsy, the findings are often nonspecific. There is often laryngeal
edema, but rarely complete obstruction of the airway. Pumphrey and Roberts
reported larygeal or pharygeal edema in 8% and 49%, respectively, of individuals
who died immediately.
15
Emphysema caused by the bronchoconstriction
might be present. Visceral and pulmonary congestion, edema, and pulmonary
hemorrhage are present, but are nonspecific. In Pumphrey and Roberts’ study,
23 of 56 anaphylactic deaths had no macroscopic findings at autopsy.
To make a diagnosis of an anaphylactic reaction, one needs either a
history of an allergy or a witnessed collapse and death following an insect
bite, ingestion of food, or administration of a drug. Most deaths attributed
to therapeutic agents involve the administration of either penicillin or an
iodine-containing contrast agent used for diagnostic purposes. Death, however,
has been associated with a multitude of other therapeutic agents. The
introduction of low-osmolar contrast agents in radiology should reduce the
number of adverse and fatal reactions to iodinated contrast agents.
In death caused by an anaphylactic reaction to an insect bite, it is possible
to detect elevated levels of venom-specific IgE antibodies in postmortem
blood.
13,15,16
Elevated levels of a specific IgE antibody do not necessarily
indicate that an anaphylactic reaction took place, only that the individual is
sensitive to the venom
.
The presence of such an antibody would be confirmatory
evidence of an anaphylactic reaction caused by a sting from an insect.
One percent of normal blood donors have been found to have elevated
venom-specific IgE antibodies in their serum. Not all individuals dying of
an anaphylactic reaction demonstrate antibodies to the specific insect that
stung them. In such cases, a cross-reaction to antigens of another insect to
which the deceased is allergic is suspected.
When IgE interacts with specific antigens, mast cells are activated, releasing
a number of potent chemical mediators, including beta tryptase and
histamine, from secretory granules in the cells. The level of tryptase rises
rapidly, becoming detectible within 30 min, with peak concentrations
reached in the first 2–3 h
.
Half-life of tryptase is 2 h. Resting mast cells secrete
alpha tryptase. In mastocytosis, blood levels are raised. Anaphylaxis-like reactions
in individuals with mastocytosis might not require IgE antibodies. Both
IgE and tryptase can be measured in postmortem blood.
Injury of the Eye Caused by Acids and Alkalis
The degree of injury to the eye from either an acid or an alkaline compound
depends on the pH of the compound, its concentration, and the period of
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contact with the eye. The corneal epithelium is a barrier to injury from acid,
because acid produces a coagulative necrosis that limits penetration through
tissue. Alkali, on the other hand, produces a liquefaction necrosis enabling
greater penetration of tissue. Animal experiments have revealed that damage
to eyes is not always related to pH. The concept that acid solutions with a
pH below 2.5 produce severe damage to the cornea is not always correct.
Thus, hydrochloric acid with a pH of 1.28 produced no corneal opacity.
Phenol with a pH of 7.7 and acetic acid with a pH of 2.7 produced opacities.
17
Just as a pH below 2.5 was believed to always cause corneal damage to eyes,
it is generally felt that alkali, with a pH value of 11.45 or greater, will produce
severe ocular damage. This also is not absolutely correct. Sodium hydroxide
solutions with pH values of 12.8 and 12.3 did not produce corneal opacities.
If, however, the pH was elevated to 13.1, then opacities occurred. One must,
therefore, conclude that the degree of eye damage cannot be based on pH alone
and that pH values of 2.5 and 11. 5 can be used only as general guidelines for
the prediction of ocular injury. The concentration of the chemical and period
of contact with the eye prior to washing must be taken into account.
Death in the Dental Chair
Deaths associated with dentistry are extremely uncommon. Some deaths are
coincidental, caused by the stress, fear, and pain of dental procedures precipitating
a fatal heart attack. “Few men are heroes … at the moment of
visiting their dentist.”
18
In any death during a dental procedure, the forensic
pathologist must separate the natural coincidental deaths from those that are
non-natural. Most non-natural deaths are associated with general anesthesia.
One of the best study of deaths associated with dentistry appears to be
that of Coplans and Curson in England.
19
They examined 120 deaths over a
10-year period. One hundred were associated with general anesthesia, 10
with local anesthesia, 6 with neither of these, and, in 4 cases, there was
insufficient or inadequate information for classification. Coplans and Curson
used the term “general anesthesia” to include not only conventional general
anesthesia, but any sedation with analgesia where there was loss of consciousness
at some time during the procedure. Of the 100 deaths associated with
general anesthesia, in 54 of the cases the general anesthesia was directly
responsible for the death of a healthy individual; in 29 cases there was some
underlying disease that made a significant contribution to the death, but,
nonetheless, the general anesthesia provoked the fatal outcome, and, in 17
cases, the general anesthesia was incidental to the outcome.
Some deaths in the dental chair are attributed to allergic reactions to the
drugs given, principally local anesthetics. There is controversy as to the
validity of this etiology, however. True allergic reactions to a local anesthetic
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471
or a substance used as a preservative or stabilizer in the local anesthetic are
probably extremely rare.
20,21
Most so-called allergic reactions are probably
overdoses of the local anesthetic caused by an intravascular injection of the
drug, due to failure to aspirate after placement of the needle; injection of
large doses of a local anesthetic into a highly vascular area or unusually rapid
absorption
.
20,22
This last cause is aided by the fact that local anesthetics by
themselves are vasodilators that enhance absorption in vascular areas.
Naguib et al. produced an extensive review of adverse effects and drug
interactions associated with the use of local anesthetics.
20
They concluded,
as previously noted, that the adverse effects of local anaesthetics were usually
caused by excessive dosage, unusually rapid absorption, or inadvertent intravascular
injection, with the last cause the most common. Severe adverse
reactions were caused by either central nervous system or cardiovascular
toxicity. The amount ol local anesthetic necessary to produce cardiovascular
toxicity is 3.5 to 6.7 times higher than that needed to produce CNS toxicity.
High levels of local anesthetics produce direct depression of the myocardium,
with impairment of myocardial contractility, and decreased conduction
velocity. There is peripheral vasodilatation with hypotension and bradycardia.
This can progress to arrythmias and cardiac arrest. Bupivacaine and
etidocaine are apparently more cardiotoxic than other commonly used local
anesthetics, with bupivacaine arrhythmias more refractory to treatment. CNS
toxicity is first manifested by excitement (stimulation), followed by depression,
drowsiness, respiratory failure and coma.
Addition of epinephrine will reduce the systemic absorption of the anesthetic
injected in such areas and tends to reduce the probability of an overdose.
Unfortunately, epinephrine has the potential of being dangerous in itself. If too
much epinephrine is used in conjunction with the anesthetic, the epinephrine
might be absorbed and, in conjunction with the local anesthetic, cause cardiac
arrhythmias
.
This danger is more theoretical than actual.
23
One of the most common causes of death during general anesthesia in
a dental office is an overdose of drugs. This could be caused by an error in
dosage, ignorance of proper dosage, or carelessness. More common, however,
is the tendency to give multiple medications during induction and maintenance
of general anesthesia or deep sedation, with resultant synergestic action
of these drugs. The dentist often gives a barbiturate, a tranquilizer, and an
opiate (all central nervous system depressants) and then perhaps uses nitrous
oxide. The three central nervous system depressant drugs produce a synergistic
action, so that the combined effect of three different drugs is greater
than any one of their individual actions. Another common mistake is failure
to take a good medical history or, if it is taken, to appreciate its significance.
For example, one must realize that epileptics under general anesthesia may
have seizures. In addition, they may already be and, in fact, should be, on
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central nervous system depressant drugs such as barbiturates and phenytoin.
General anesthetics can also produce asthma-like attacks that are not as
apparent in an unconscious patient. Other problems involving anesthesia in
the dental office include failure to monitor the patient’s vital functions and
failure to have the proper drugs and equipment to resuscitate an individual
who is having difficulty.
Over one 5-year period, one of the authors saw four deaths involving
dentistry that were not coincidental — one in the operating room and three
in a private office.
24,25
The operating room fatality was a 36-year-old male
admitted to the hospital to have his teeth capped. It was decided to cap 21
teeth all at the same time. The patient received premedication of meperidine,
promethazine, and scopolamine 1 h prior to surgery. General anesthesia was
induced with an ultra-short-acting barbiturate, with general anesthesia
maintained by halothane and nitrous oxide. At 2 h and 45 min after induction
of the anesthesia, 10 min after the placement of a gingival retraction cord
around 21 teeth, the patient became cyanotic, with labored breathing. Ventricular
fibrillation was noted and cardiopulmonary resuscitation was unsuccessful.
The patient died of a cardiac arrhythmia caused by the combined
action of halothane and epinephrine.
24
The epinephrine was in the gingival
retraction cord. This cord, impregnated with 8% racemic epinephrine, is
used to provide hemostasis. The cord can contain as much as 1 mg of
epinephrine per inch. Absorption of epinephrine from the gingiva can produce
significant arrhythmias, especially in the presence of a halogenated
hydrocarbon anesthestic such as halothane. The epithelial lining of the gingival
sulcus is semipermeable, as well as being highly vascular. Thus, anywhere
from 24 to 92% of epinephrine applied to the gingival sulcus is
absorbed into the systemic circulation. The potential problem with using a
gingival retraction cord is recognized.
23
Within a 14-month period, the author also saw three other victims of
death in a dentist’s office.
25
The patients involved were a 7-year-old boy, a
38-year-old woman, and a 25-year-old woman. All three were given diazepam,
pentazocine, and methohexital intravenously. All died after the
administration of the presurgical anesthetic medication, during or immediately
after the procedure. Toxicological analysis for the drugs involved
and a review of the medical records confirmed that the three individuals
had all received potentially lethal doses of pentazocine, a narcotic analgesic,
along with unusually high and potentially lethal doses of diazepam. All had
also received anesthetic doses of methohexital, an ultra-short-acting barbiturate.
Doxapram, a respiratory stimulant, was given in all cases, without
beneficial effect; caffeine was administered in the first case. Narcotic antagonists
were not administered in any of the cases. All three deaths involved
the same oral surgeon.