CASE 2

On July 11 , 1 993, a 24-year-old male was sprayed with OC while resisting arrest for disorderly conduct. He was sprayed 10-15 times as he dodged away from law enforcement officers and repeatedly wiped his face with his shirt. Some of the spray attempts reportedly did not directly hit his face. He struggled with officers and subsequently was placed on the ground in the prone position while being handcuffed. Two pairs of linked handcuffs were required because of his large frame. He was then seated on the curb and reportedly complained of dyspnea at that time. After being placed in a prone position a second time, he stopped struggling. Two officers assisted him to the patrol car and he was placed in the rear seat, positioned on his side and facing forward. He exhibited labored breathing en route to the police station but became quiet just before arrival. He was left in the car, unattended, for several minutes while- one of the transporting officers, who had been hit by ''friendly fire" pepper spray, was decontaminated. They returned to find the subject unresponsive; aggressive resuscitation efforts were unsuccessful. This followed a time interval of 18 to 22 min from the initial exposure to OC spray.

Postmortem examination was remarkable for a 308-lb, 73-in.-tall male with a few scattered abrasions, but no evidence of significant traumatic injuries. The lungs showed a florid follicular bronchiolitis/bronchitis, edema, and acute aspiration of gastric contents without airway obstruction. Additional findings included mild edema of the arytenoid folds and a heart weight of 420 g. No other significant underlying natural disease was identified. The decedent had a vague clinical history of asthma, but no histologic changes of asthma were identified. A postmortem blood alcohol was 140 mg/dl, and stomach contents smelled strongly of alcoholic congeners. An extensive blood toxicologic screen was otherwise unrevealing except for a trace of caffeine.

Several factors warrant consideration in the determination of the cause of this man's death: repeated exposure to capsaicin, physical exertion and excitement during the course of a struggle with law enforcement officers, underlying pulmonary disease in the form of follicular bronchitis and bronchiolitis, acute alcohol intoxication, aspiration of stomach contents, and physical restraint during transport. The forensic pathologists investigating the death felt that the lack of symptoms prior to OC exposure, the rapid onset of dyspnea following exposure to the spray, the complaint of breathing difficulty by the decedent while in an upright seated position, and the underlying inflammatory process involving the airways suggested a direct contribution of pepper spray to the death, with the other factors mentioned above also playing a contributory role. Accordingly, the cause of death was listed as asphyxia due to bronchospasm precipitated by pepper spray, and the manner of death was certified as accidental.

Discussion

OC is the crude extract of hot peppers, named for the genus Capsicum, a group of tropical and subtropical herbs and shrubs in the nightshade family (Solonaceae). Capsaicin (8-methyl-N-vanillyl-6-nonenamide; (3) and four derivatives occur naturally in varying proportions and are collectively responsible for the hotness and bitterness of peppers (4). The relative ''heat" of tasted substances can be compared in terms of Scoville units, based, upon the greatest dilution of a pepper extract that can be detected by the human tongue.

Capsaicin applied to the ocular membranes causes stinging, lacrimation, and blepharospasm, which can range from involuntary blinking to sustained eyelid closure. Depending upon the complexion of the subject, the effect on facial skin ranges from slight skin discoloration to vivid redness, subjectively accompanied by slight tingling or intense burning pain. Exposure of respiratory membranes to aerosolized capsaicin causes tingling, coughing, and variable shortness of breath that parallels the intensity of the coughing. Some subjects are said to experience brief laryngeal paralysis and are acutely unable to speak. Visual acuity may return within 2-5 min after decontamination (saline ravage of eyes and face), and exposed subjects may return to nose breathing as early as 10 min after decontamination. Often subjects will hold their eyes closed tightly for 20-30 min after exposure. One of us (P.E.L.) was voluntarily sprayed with OC and can attest to the extreme but temporary discomfort induced by capsaicin.

Capsaicin has remarkable irritant potency; the minimum tolerated exposure of OC is less than that "chemical mace" agents such as chloroacetophenone (CN) and orthochlorobenzalmalonitrile (C S) . The recognized toxicity of capsaicin is, furthermore, much less than that of these agents. The lethal oral dose of capsaicin is estimated to be 0.5-5.0 g/kg, or a 35- to 350-g ingestion for a 70-kg adult (5).

The use of capsaicin by law enforcement authorities for control of uncooperative subjects is not new. Japanese police historically used the metsubishi, which consists of a lacquer or brass box with a wide mouthpiece on one end and a hole or pipe on the opposing end, to blow pepper dust into the eyes of a person they sought to apprehend. Modern OC spray canisters employ a liquid carrier as a solvent for capsaicin, a propellant to discharge the material, and an aerosol valve nozzle to create an effective spray pattern. The capsaicin concentration varies from 1% (civilian models) to 5 - 10% (primarily police models); a higher capsaicin concentration increases the time required to recover from exposure but does not significantly alter the initial magnitude of the irritant effect (1). The carriers employed by different products include water (in which the lipophilic capsaicin molecule has poor solubility), alcohols [which are flammable and have, in one reported case, ignited when used in association with a Taser electric weapon (1)], and nonflammable organic solvents (which present their own toxicity). Propellants include nitrogen, carbon dioxide (disfavored due to short shelf life), and halogenated hydrocarbons (disfavored due to potential toxicity and environmental considerations). Different nozzles provide a variety of spray patterns (stream, splatter-stream, mist, fog); the choice of a particular pattern depends upon the number of anticipated personnel targets (single individual, small group, crowd) and their expected distance from the officer. The range at which the spray canister is discharged is critical, in that the aerosol valve generates a mist that achieves effective particle size only several feet from the source (1).

Capsaicin stimulates chemonociceptors in primary afferent nerve endings (unmyelinated, type C slow-conducting fibers) to produce the sensation of pain, stimulate pain-associated behavioral reactions and reflexes, and cause peripheral release of neuropeptides that can effect neurogenic inflammation: vasodilation, extravasation of plasma proteins, and bronchoconstriction (7). Occupation of a plasma membrane protein binding site by capsaicin leads to opening of nonselective cation channels, which admit calcium and sodium into cytoplasm and thereby depolarize the cell. Capsaicin-sensitive afferent neurons are difficult to define as a group because they do not completely overlap with any population of afferent neurons that have been classified on morphological, neurochemical, or functional criteria (3). They are abundant in the conjunctive and mucosa of the upper aerodigestive tract; the afferent neurons in the human oral cavity and tongue have a threshold of 0.7 (mol/L for capsaicin, and subjects can taste capsaicin diluted to 1 part in I million (3).

The effects of supraphysiologic capsaicin exposure vary among species and among the specific tissues studied. Chemosis (conjunctival edema) is produced when capsaicin contacts ocular membranes, but no extravasation of plasma proteins has been noted upon intradermal application (3). After an initial stimulation of these neurons by capsaicin, substance P depletion incapacitates their ability to cause pain, and this effect has been employed in the pharmacotherapy of postherpetic neuralgia (8), painful diabetic neuropathy (9), osteoarthritis (10), postmastectomy pain (11), and pruritic dermatologic diseases such as lichen simplex chronicus, psoriasis, and hemodialysis-associated pruritis (12). Inhalation of a 2.0 (M aerosol of capsaicin can produce coughing in humans (3), probably by stimulation of capsaicin-sensitive afferents in the larynx (13,14), and this potent activity has been utilized in studies of cough suppressants (15).

Capsaicin-sensitive, substance P-releasing neurons are involved in initiating a number of protective mechanisms in the lung, including bronchoconstriction, mucus secretion, and cough ( 16), forming a local, non-cholinergic axon reflex that is less potent than mechanisms involving histamine and acetylcholine (7). Accordingly, capsaicin has been shown to cause subepithelial edema in the rat trachea and bronchial tree (17) and dose-dependent contraction of bronchial smooth muscle in isolated human bronchi (surgical specimens) at a concentration as low as 1 (M (7). An 11-year-old boy who deeply inhaled OC spray coughed for l h was asymptomatic until 4 h after exposure, when nonfatal pulmonary and laryngeal edema with stridor and respiratory arrest supervened (18). Given these findings, one might suspect that capsaicin would be capable of provoking significant pulmonary compromise. However, studies of in vivo human bronchial responses to capsaicin have not demonstrated profound or entirely consistent alterations in pulmonary physiology.

A transient (<1-min) increase in airways resistance following inhalation of capsaicin has been described (19), but the ability of capsaicin to provoke physiologically significant bronchoconstriction in vivo is not unequivocally established. Collier et al. (13) exposed human volunteers to nebulized capsaicin aerosols (between 2 and 65 (m; 0.14 to 2.6 ,(mol reached the airways) and found that capsaicin stimulated dose-dependent coughing, without dyspnea or a change in forced expiratory volume at 1 min. Fuller et al. (20) documented a dose-dependent fall in specific airways conductance after inhalation of 0.24 to 2.4 nmol of capsaicin, which was maximal within 20 s of exposure and lasted less than 60 s. Pretreatment with ipratropium significantly reduced the bronchoconstriction, indicating that it was dependent upon a cholinergic vagal reflex rather than upon local release of substance P from nerves in the airway. Lammers et al. (21) found a significant bronchoconstrictor response even after pretreatment with cholinergic and (-adrenergic blockade supplemented with the local anesthetic lignocaine. Conversely, the same group (22) delivered 2 nmol of nebulized capsaicin to the ipratropium-pretreated airways of asthmatic and nonasthmatic volunteers and found a short-lasting bronchodilation in both groups; however, the effect of capsaicin could not be dissociated from the bronchodilatory effects of deep inhalation alone or of the coughing that capsaicin stimulated.

Little experimental evidence supports the contention that individuals with hyperreactive airways are more susceptible to physiologically significant bronchoconstriction caused by capsaicin exposure. No difference in the duration or magnitude of the transient bronchoconstriction described previously was identified among normal, smoking, and asthmatic subjects (20). Asthmatics without a persistent cough do not have a hyperreactive cough reflex when stimulated by capsaicin (19), but increased sensitivity of the cough reflex to capsaicin has been observed in unstable asthmatics with a persistent cough, individuals with acute bronchitis, and possibly those with viral respiratory tract infections and other etiologies of nonproductive cough (23).

Granfield et al. (2) recently reviewed the findings in 30 cases of death-in-custody following OC exposure. All decedents were male, the majority were in their thirties, and a range of ethnicities were represented. All 30 decedents had exhibited violent or bizarre behavior, and 28 had offered a struggle; this may have prompted the use of OC. In only four instances was OC felt to be effective in subduing the individual. Drugs and/or ethanol were a significant factor in 23 cases, and 12 cases involved underlying natural disease. Sufficient information was available in 22 cases for review, and in no case was OC found by these reviewers to be the cause of death. Positional asphyxia was judged to be the cause in 18 of these 22 cases, with drugs and/or natural disease as contributing factors. The second case we describe was among these; Granfield et al. concluded in their review that OC was not causative of death. Among the remaining four cases, three were attributed to cocaine intoxication and one to cocaine-related disease (not otherwise specified).

The broader issue of deaths in custody has been reviewed by Lifschultz and Donaghue (24), who provide a very useful list of investigative considerations, and we emphasize elements most applicable to the investigation of OC-related deaths in. The most critical determinant of capsaicin's role in the death will be a reconstruction of the sequence of events following attempted arrest, with particular attention to the time interval between exposure and symptoms and the possibility of positional asphyxia during transport or incarceration. The consideration of positional asphyxia is particularly salient, since those arrested individuals who have offered sufficient resistance to warrant use of OC may also require extensive restraint or may frenetically place themselves in asphyxiaprone positions, and these individuals will also incur an increased oxygen demand as a result of the struggle. Autopsy and laboratory investigation will document the presence or absence of intoxicating substances and will document or exclude many natural disease processes capable of causing or contributing to death in the context of physical exertion. A reasonable goal for the investigating forensic pathologist is to reconstruct the time line of events leading to death, based upon interviews, objective premortem medical data, and police records of the arrest and surveillance while incarcerated. In phrasing all segments of the report, the pathologist must remember that the document will be scrutinized and perhaps quoted by members of the lay public-the media, the family of the decedent and their attorneys, police, and municipal officials. The findings must be carefully organized and should include terminology that can be understood by medically untrained individuals.

We have a new chemical agent on the streets, which has proven to be effective in most subject control applications and which has reduced the number of injuries to both officers and subjects in many municipalities. Based upon the small number of anecdotal reports of death in custody following OC exposure, compared to the large number of exposures that have occurred in police of finer training exercises and routine deployment in the field, OC spray appears to be relatively safe. We have insufficient physiologic data at this time, however, to conclude that capsaicin is incapable of causing or contributing to death. Whereas most deaths in custody following OC exposure will be purely coincidental, its use should serve as a red flag calling attention to individuals who face increased risk of sudden life-threatening events due to drug intoxication, the physical exertion of a struggle, a frenzied mental state, or other factors. As with any other in-custody death, a thorough autopsy and toxicologic analysis, coupled with evaluation of the premortem chain of events, postexposure symptomatology, and the extent of natural disease processes, will help to reveal the role of OC spray as unrelated, contributory, or causative.