Acute Organophosphate Poisoning Case Review With Consideration of Off-Gassing During Postmortem Examination

Abstract

Although self-harm via ingestion of organophosphorus compounds is relatively common in the developing world, it is rare in the United States. This article reviews the signs and symptoms associated with acute organophosphate poisoning and highlights the effects of organophosphate off-gassing during postmortem examinations to increase awareness of this potentially dangerous workplace exposure.

Paramedics responded to a 42-year-old man with pulseless electrical activity. Spontaneous circulation was restored after aggressive resuscitation. Before loss of consciousness, the patient exhibited diaphoresis, vomiting, and diarrhea. Upon admission, the patient had a Glasgow Coma Scale score of 3. Significant laboratory values included a pH of 6.8, pco₂ of 72 mm Hg, and lactic acid of 21.8 mmol/L. Electrocardiography suggested inferior ST-elevation myocardial infarction. Electroencephalogram revealed severe cerebral dysfunction. The patient died shortly thereafter.

Scene investigation revealed suicidal ideations, which included a snapshot of a bottle containing granular sediment associated with statements that he had imbibed fertilizer. During the postmortem examination, the decedent exuded a petroleum-like odor. In addition, autopsy personnel developed symptoms consistent with organophosphate exposure.

A reported history of suspected organophosphate exposure in a decedent should prompt increased safety practices to avoid potential harm to autopsy personnel.

Organophosphates are commonly used in pesticides (generic name for insecticides, anthelmintics, fungicides, and herbicides); therefore, most cases of organophosphate (OP) toxicity occur in agricultural environments.¹ Pesticide use is more common in developing countries, with approximately 3 million people (about the population of Arkansas) globally being exposed to OPs every year, 10% of which are fatal.² However, the use of OPs is not limited to pesticides. The widespread use of OPs in standard household products, such as cleaning agents, germicides, fire retardants, and rodent poisons, makes OP-containing products easily accessible at a low cost.³ Pesticides are one of the most frequently used suicide methods in the Western Pacific region.⁴ Worldwide, OP pesticide self-poisoning contributes to approximately 110,000 deaths annually and is the culprit of 1 of every 6 suicides.⁵

Organophosphates can enter the body via absorption through the skin, the gastrointestinal tract, or inhalation. Once absorbed into the body, these substances inhibit acetylcholinesterase (AChE) by phosphorylation, resulting in several acute cholinergic symptoms.¹ Acetylcholinesterase inhibition results in acetylcholine accumulation in synapses at neuromuscular junctions, contributing to nicotinic (tachycardia, weakness, hypertension, mydriasis, and fasciculations), muscarinic (diarrhea, miosis, bronchospasm, bradycardia, nausea, emesis, lacrimation, salivation, and diaphoresis), and central nervous system (confusion, headache, convulsions/seizures) signs and symptoms. Ultimately, in severe cases, the cardiorespiratory effects can lead to coma and/or death.

Although self-harm via ingestion of organophosphorus compounds is relatively common in rural communities in the developing world, it is not a standard method of suicide in the United States. Here, we present a case of OP self-poisoning in the United States and discuss the effects of off-gassing on autopsy personnel.

CASE PRESENTATION

Paramedics responded to the residence of a 42-year-old man with pulseless electrical activity after notification from the patient's wife that she witnessed him become unresponsive.

Subsequent scene investigation revealed that on the day of his terminal event, the patient sent both verbal and text-based suicidal ideations to his wife via phone. Text-based communications included a snapshot of a soda bottle containing material with granular sediment in addition to statements indicating that he had imbibed fertilizer (Fig. 1). After receiving these messages and upon being alerted to her husband's location by another family member, the decedent's wife came to the location and confronted him about the reported self-harm. However, at that time, the decedent denied the ingestion of any injurious substances and his wife accompanied him back to their residence. Shortly after returning to the residence, the decedent exhibited diaphoresis, vomiting, and diarrhea, called for assistance from the bathroom, and subsequently became unresponsive.

FIGURE 1.

Image of text message photograph illustrating the soda bottle containing material with granular sediment.

Upon arrival by first responders, the patient was intubated and an electrocardiogram demonstrated pulseless electrical activity. While en route via helicopter to a nearby regional medical center, return of spontaneous circulation was achieved after approximately 48 minutes of aggressive cardiopulmonary resuscitation (11 rounds of epinephrine, 1 mg of atropine). Upon admission to the intensive care unit, the patient had a Glasgow Coma Scale score of 3. Physical examination revealed “nonreactive pinpoint pupils” and diaphoresis with fundoscopic examination demonstrating bilateral papilledema with right flame hemorrhage. The most significant laboratory values were a pH of 6.8, pco₂ of 72 mm Hg, and lactic acid of 21.8 mmol/L. As the patient's presentation was consistent with cholinergic toxidrome, atropine and pralidoxime were initiated. Of note, neither butyrylcholinesterase nor acetylcholinesterase activity was measured during the patient's short clinical course. An electrocardiogram demonstrated QT prolongation in addition to ST segment changes, suggestive of an inferior ST-segment elevation myocardial infarction; however, an emergent coronary angiogram was unremarkable. After cardiac imaging, myocardial instability was evidenced by periodic ventricular fibrillation and ventricular tachycardia. Over the next 24 hours, the patient's renal function gradually deteriorated and ever-increasing ventilator support was required to maintain adequate oxygenation. Despite a lack of sedation, the patient continued to lack corneal reflex and withdrawal to pain. An electroencephalogram revealed severe cerebral dysfunction consistent with anoxic brain injury arising from prolonged resuscitative efforts. Upon confirming the patient's poor prognosis via neurology consultation, family members elected to place the patient on comfort care with death occurring shortly thereafter.

During the postmortem examination, the decedent exuded a strong, pervasive petroleum-like odor upon opening the remains pouch, which increased in intensity throughout the autopsy. Gastric examination revealed widespread mucosal erythema accompanied by a large amount of black-green granular material analogous in appearance to the granular sediment within the soda bottle depicted in antemortem scene photographs. Also of particular significance were renal acute tubular necrosis, marked pulmonary congestion and edema, and copious tracheobronchial mucinous secretions. Significant underlying natural pathology included hypertensive cardiovascular disease. Additional autopsy findings are demonstrated in Table 1 and Figures 2A to C. Toxicological analysis of the decedent's urine revealed a total dialkyl phosphate concentration of 200,000 nmol/L (creatinine corrected: 180,000 nmol/g creatinine); additional toxicology results are noted in Table 2. Because of the autopsy and toxicologic findings, the cause of death was determined to be acute OP toxicity, with the manner of death as suicide.

TABLE 1.

Autopsy Findings

Organ System	Specific Findings
General	Strong petroleum odor exuded by blood and gastric contents
Respiratory	Pulmonary congestion and edema, marked (right: 900 g; left: 900 g)
	Copious serosanguineous fluid within the tracheobronchial tree
	Aspiration pneumonitis, lower lobe
	Glottal edema, marked
	Copious serous secretions from nares
Gastrointestinal	Copious black-green granular material within the gastric contents
	Acute gastritis
	Status postappendectomy, remote
Renal	Renal acute tubular necrosis, bilateral
Cardiovascular	Hypertensive cardiomegaly (500 g) with left ventricular hypertrophy (1.7 cm)
Miscellaneous	Edematous gallbladder, marked
	Congestive splenomegaly (220 g)
	Fibrous atrophic thyroid

FIGURE 2.

Findings present at autopsy included granular material present within the gastric contents (A), gastric mucosal erythema (B), and glottal erythema and edema (C).

TABLE 2.

Postmortem Urine—Toxicology Results

Analyte	Result
Total DAP	200,000 nmol/L
Total DAP (creatinine corrected)	180,000 nmol/g creatinine
DEP	15,000 μg/L
DETP	11,000 μg/L
DEDTP	7500 μg/L
Sum of DEAP	200,000 mg/dL
Sum of DEAP (creatinine corrected)	180,000 nmol/g creatinine
Creatinine	1108 mg/L

DAP, dialkyl phosphate; DEAP, diethyl alkyl phosphates; DEDTP, diethyldithiophosphate; DEP, diethylphosphate; DETP, diethylthiophosphate.

As a complication of this postmortem procedure, the forensic pathologist and autopsy technicians developed signs and symptoms of varying durations (12–24 hours) consistent with OP exposure, including severe headache, confusion, salivation, increased bowel motility, and miosis. As technician and pathologist staffing varies each day, the cholinergic spectrum of symptoms and their linkage to off-gassing exposure was retrospectively identified over the subsequent few days. Consequently, neither acetylcholinesterase nor butyrylcholinesterase activity was assessed.

DISCUSSION

Globally, organophosphorus poisoning is one of the leading causes of self-poisoning, with higher incidences in developing countries with agriculturally dependent economies.⁵ A lack of regulation on pesticide use, easy accessibility, low-cost products, and local knowledge of its effects may explain the predominance of OPs in self-poisoning in these regions. Although OP self-poisoning may be expected in developing countries, it is uncommon in the United States, making this case unique.

Mechanism of Action

Organophosphates (OP) are extremely potent compounds; therefore, minimal exposure or ingestion is needed to cause rapid clinical deterioration.⁶ Several factors, including the structure of the compound, amount and concentration of OPs, pre-exposure patient health status, and timing of diagnosis, all play a role in patient outcomes after OP toxicity.⁶ The primary mechanism of acute OP toxicity is the inhibition of AChE via phosphylation (denotes phosphorylation and phosphonylation) of the active site serine.⁷ The potency often depends on the agent's structural elements, such as varying residues bound to the central phosphorus and differing leaving groups, which give the agent specific inhibitory properties.⁸ Acetylcholinesterase inhibition prevents the degradation of acetylcholine, leading to overstimulation of cholinergic receptors and affecting the central, peripheral, and autonomic nervous systems.⁵ If left untreated, OPs form an irreversible bond with AChE, a process called aging.⁹ Spontaneous dealkylation (aging) is one of several postinhibitory reactions of OP-inhibited AChE. Other postinhibitory reactions of OP-inhibited AChE include spontaneous reactivation (spontaneous dephosphorylation) via an endogenous hydrolysis reaction and reactivation via a strong nucleophile, often by oxime and nonoxime reactivators.¹⁰ Oxime and nonoxime reactivators, such as pralidoxime, have been developed to restore AChE function via a strong nucleophilic attack, thus reducing the symptoms of OP toxicity.⁸ While atropine, a muscarinic antagonist, is often used to treat symptoms of toxicity, oximes restore enzyme function.⁷

Pharmacokinetics

Spontaneous dealkylation and reactivation rates are heavily dependent on the chemical structure and concentration of the agent that causes OP toxicity.^7,11 In addition, several pharmacokinetic properties contribute to the onset and duration of toxicity, including volatility, lipophilicity, chemical/biological stability, volume of distribution, elimination, and route of exposure.^8,11

The route of exposure can be used to determine the rapidity of the onset of symptoms. The 3 main routes of exposure are inhalation, oral ingestion, and contact with the skin. Organophosphate inhalation generally exerts its effects within a few minutes of exposure and has the most rapid onset of symptoms.⁸ Skin exposure varies depending on the volume of exposure, chemical solubility, and skin integrity and can cause immediate local effects (local diaphoresis and fasciculation) in addition to delayed systemic effects.^8,11 Oral ingestion toxicity, which is commonly observed in self-harm cases, is dependent on the following:

1. cytochrome P450 transformation (into active oxon form),

2. agent-specific chemical structures affecting potency toward AChE,

3. detoxification via endogenous enzymes,

4. and lipophilicity (the main factor in the persistence of specific agents).⁸

Muscarinic symptoms are observed more frequently than nicotinic symptoms in acute poisoning.¹² Overstimulation of muscarinic and nicotinic cholinergic receptors gives rise to several clinical features collectively known as acute cholinergic syndrome or acute cholinergic crisis. Signs and symptoms of OP toxicity appear within 24 hours of ingestion. Severe cases typically result in respiratory failure and death. Respiratory failure occurs either within the first 24 hours of ingestion (manifesting as cholinergic crisis, as presented in this case) or after 24 hours (intermediate syndrome, which is often without cholinergic features).⁵ Evolving literature also suggests that there are additional targets for OPs that lead to oxidative stress, neuroinflammation, axonal transport deficits, and autoimmunity, thus leading to long-term health effects in cases of survival from the initial toxic insult.³

Although OP poisoning in the current case was suspected before death via clinical presentation in the context of alleged fertilizer ingestion, OP poisoning may be confirmed via assessment of either acetylcholinesterase activity (whole blood) or butyrylcholinesterase activity (plasma).⁵ While acetylcholinesterase activity is a good indicator of initial poisoning severity, daily butyrylcholinesterase measurements are useful in monitoring OP elimination.⁵ Organophosphate exposure may also be identified via urinalysis for OP metabolites, as was performed in our postmortem examination.¹¹

Postmortem Off-Gassing Exposure

Despite the postmortem examination occurring several hours after the patient's death, off-gassing effects resulted in OP exposure of postmortem personnel. Several postmortem personnel reported symptoms such as severe headache, confusion, salivation, increased bowel motility, and miosis, all of which are consistent with OP exposure. Therefore, we suggest several additional precautions be taken in cases of possible OP exposure. In addition to standard universal precautions, such as personal protective equipment, additional potential precautions during the autopsy procedure include backdraft workstations, powered air-purifying respirators, and decontamination procedures prior to patient arrival. Personal protective equipment should be vapor and fluid impermeable and should be protected from skin, mucous membrane, and respiratory exposures.¹³

CONCLUSIONS

Although self-poisoning by OPs is more common in developing countries, its use in standard household products, such as pesticides, cleaning products, germicides, and pest control poisons, makes it an easily accessible and low-cost method of self-harm. Considering OP potency, postmortem examination personnel should take extra precautions to prevent exposure to off-gassing in cases of OP toxicity.