Mr. S was brought to the emergency department (ED) by ambulance after a presumed suicide attempt. Earlier in the day, he had an argument with his 13-year-old daughter, who was threatening to hurt herself after being bullied at school.
When questioned in the ED, Mr. S admitted to drinking three 12-oz cans of beer and ingesting four packets of a substance known to be rat poison just prior to arrival. During preliminary examination, Mr. S complained of shortness of breath, dizziness, and excess secretions in his mouth. He displayed fecal and urinary incontinence, and muscular spasms in his abdomen and both legs.
The patient denied any prior psychiatric history, other drug use or active suicidal ideation. He also claimed to have no history of chest pain, alcohol withdrawal or seizures. Medical history was significant for alcohol use (a minimum of two 6-packs of beer every weekend). Mr. S was hospitalized for pancreatitis in 2002 and a subsequent cholecystectomy.
Vital signs in the ED were as follows: temperature 36.7, BP 125/93, heart rate 56, respiratory rate of 16 beats per minute and oxygen saturation was 87% on room air. Head exam was notable for pinpoint pupils; there was noticeable hypersalivation. Lungs were clear. Heart sounds were normal. Abdomen was mildly distended and tender to palpation in epigastrium. Extremities were warm and without edema. Calf muscle fasciculations were noted bilaterally.
3. Laboratory Results
ECG showed sinus rhythm at a rate of 68 with no ischemic changes. QTc was 433 msec.
WBC was 14,800/uL with hemoglobin 16.6 g/dL. International normalized ratio was 0.91. Liver panel showed aspartate transaminase 33 units/L, alanine aminotransferase 84 units/L, and alkaline phosphatase 80 units/L. Urine toxicology screen was notable for amphetamines. Alcohol level was 23 mg/dL. Chest x-ray was unremarkable.
Taking a detailed history and recognition of the physical symptoms of cholinergic crisis are most important in diagnosis, as toxicology screens will be of little utility.1 Many chemical agents have a characteristic petroleum or garlic-like odor. The clinical features of cholinergic excess — best remembered by the mnemonic SLUDGE (Salivation, Lacrimation, Urination, Defecation, Gastrointestinal Distress, Emesis) or DUMBELS (Diarrhea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation) — should raise the question of organophosphate poisoning.1
Children present differently from adults, with the most common manifestations being seizures (in 22%-25%), and mental status changes including lethargy and coma (in 54%-96%) one study noted.2 Every attempt should be made to identify the toxic agent.
When diagnosing, laboratory tests are generally not helpful. RBC acetylcholinesterase and plasma pseudocholinesterase levels will be depressed, if these tests are available. Therefore, it is important to administer treatment prior to laboratory confirmation of toxicity. Chest radiographs may reveal pulmonary edema. Sinus tachycardia is the most common finding seen on ECG, although sinus bradycardia with PR prolongation can develop secondary to increased parasympathetic activation.
The case was immediately discussed with the New York City Poison Control Center. Recommendation was to administer IV atropine intermittently until secretions improved. Mr. S was given a total of 14 mg atropine and 1 g IV pralidoxime (2-PAM), which resulted in rapid improvement in secretions and respirations. No activated charcoal was given. The patient was admitted to intensive care.
After admission, the patient was seen by psychiatry and inpatient psychiatric treatment was recommended. Mr. S did not require any additional atropine or 2-PAM.
Severe organophosphosphate and carbamate poisoning is a medical emergency. Treatment for such patients includes airway management, including oxygen and intubation in patients with excessive secretions.3 Succinylcholine should not be used when performing rapid sequence intubation as it is metabolized by acetylcholinesterase, leading to prolonged neuromuscular blockade/paralysis.3 In addition, continuous cardiac monitoring and pulse oximetry should be employed.3 Hypotension, if it occurs, can be managed with fluid resuscitation — either normal saline or lactate ringer’s solution.
Specific antidotes such as a muscarinic antagonist (usually atropine) and 2-PAM should be used. In cholinergic excess, atropine competes with acetylcholine, and should be administered until signs and symptoms are resolved. Atropine can be given usually in doses of 2 mg to 5 mg at a time with no ceiling; it should be uptitrated until respiratory secretions are eliminated and there is adequate oxygenation, and this means up to hundreds of milligrams can be given over the next several days.
Since it works on the nicotinic receptors that atropine does not bind to, 2-PAM is used. Typically, we administer about 2 g for the average adult over 30 minutes in addition to atropine to provide antidotal effects. The clinical response to 2-PAM is quite variable and not well understood.
Health-care providers should utilize personal protective equipment such as neoprene gloves and gowns. Hydrocarbons can penetrate nonpolar substances such as latex and vinyl. Discarding patient clothes and cleansing the patient with soap and water is typically recommended.
Gastric lavage is not performed, as this is only helpful if it can be completed within one hour after ingestion and only after other measures such as atropine and 2-PAM are given.3 For clinicians, this window of opportunity is narrow, and also involves risk of aspiration.
Activated charcoal (again, after initial resuscitation and treatment with atropine and 2-PAM) can be given, but this too is only shown to be useful within the first hour after ingestion, with questionable effectiveness thereafter. The standard dose is 1 g/kg (maximum dose 50 g). However, the risk is high for aspiration and would not be indicated if the patient is not awake enough or not intubated.
Remember that emergent consultation with the U.S. Poison Control Network can and should be obtained. The national number, 800.222.1222, will automatically reroute all calls to a local poison-control center.
Organophosphate compounds have been widely used in domestic and industrial settings for the past 50 years. Organophosphates are commonly used in insecticides, such as the widely available, commercial “RAID” insecticides. Organophosphate use has decreased in the last 10 to 20 years, in part due to the development of carbamate insecticides such as “Tres Pasitos.”
Organophosphate poisoning is the most prominent cause of death from acute poisoning worldwide with an estimated 300,000 deaths occurring globally, particularly in rural Asia.4 In developed countries such as the United States, by comparison, more then 8,000 patients sought medical attention in 2008 for organophosphate poisoning and fewer than 15 died.1
Organophosphates are nerve agents developed in the 1940’s, but became widely known when the Japanese religious cult, Aum Shinrikyo, carried out a sarin gas attack in 1995 in the Tokyo subway system. That incident killed 13 people, severely injuring 50 others and caused temporary vision problems for nearly a thousand people in the vicinity.
Organophosphate agents bind to and disable acetylcholinesterase, the enzyme responsible for breaking down acetylcholine.3 Specifically, they phosphorylate the serine hydroxyl group of acetylcholinesterase. This results in a buildup of acetylcholine leading to recognizable symptoms (SLUDGE or DUMBELS).
Recognizing these signs of cholinergic excess is important in diagnosis. Also seen are nicotinic effects such as muscular fasciculations from acetylcholine stimulation at the neuromuscular junctions and respiratory depression. Central nervous system effects can include anxiety, confusion, tremors, seizures, coma and ataxia, as there are nicotinic and muscarinic receptors in the brain. Death generally results from acute respiratory failure, but can also result from cardiovascular collapse due to an unclear mechanism.
The mechanism of carbamate compounds is identical to that of organophosphate agents except that carbamate compounds are transient cholinesterase inhibitors, which spontaneously hydrolyze from the cholinesterase enzymatic site within 48 hours. Cases involving carbamate toxicity tend to have shorter duration, but similar mortality rate.
Intermediate syndrome affects 10% to 40 % of individuals poisoned by organophosphates within 24 to 96 hours after exposure. It is characterized by acute respiratory failure and by muscle weakness primarily in the facial, neck, and proximal limb muscles. Decreased deep tendon reflexes and cranial nerve palsies are typically noted.
Organophosphate-induced delayed polyneuropathy can occur two to three weeks after exposure to certain agents, such as chlorpyrifos. Distal muscle weakness with relative sparing of the neck muscles, cranial nerves, and proximal muscle groups is noted, and recovery may take up to one year. Transient, painful stocking glove paresthesias followed by a symmetrical motor polyneuropathy (flaccid weakness of the lower extremities that ascends to include the upper extremities) can manifest as well. Carbamate compounds are rarely associated with this entity.
“Tres Pasitos,” the brand name of the substance Mr. S ingested, is an illegally imported and highly-toxic rodenticide. It is produced and sold legally only in the Dominican Republic and in Mexico. “Tres Pasitos” literally translated signifies the three little steps that a rat can take before death after ingestion.
The main ingredient in this poison is aldicarb, a potent carbamate insecticide that causes fulminant cholinergic crisis. Aldicarb causes reversible carbamylation of the acetylcholinesterase enzyme. The poison consists of brown grains and is typically sold in unlabeled plastic bags. It can easily be mistaken for food.
An alert from the New York City Department of Health and Mental Hygiene publicized that there were 15 reported cases of human poisoning by Tres Pasitos in 2006.5 The alert also noted one in three households in New York City used pesticides that may be hazardous to human health.
Organophosphate and carbamate poisoning is a worldwide health problem. In the developed world, such poisoning is usually the result of accidental ingestion or suicide attempts. This case has relevance for emergency clinicians as carbamates and organophosphates are still used as insecticides and emergency clinicians working in rural areas may have to evaluate and manage patients with these types of poisoning.
Recognizing and diagnosing toxicity is clinically essential for patient survival. The case presented here illustrates the need to recognize signs and symptoms of cholinergic excess, which may involve the autonomic nervous system, neuromuscular junction and central nervous system. If there are strong indications or suspicion of acute poisoning, the patient should be treated immediately.
Acute toxicity is a medical emergency. All symptomatic patients should receive oxygen, atropine, 2-PAM and benzodiazepine. Further research is needed to demonstrate how these therapies should be best administered.
Eugene Wong, MD, is an attending physician in internal medicine at New York-Presbyterian-The Allen Hospital. Jeffrey Reyes, PA, is a physician assistant at New York-Presbyterian-The Allen Hospital. Jonathan Rieber, MD, is a gastroenterologist in private practice in New York City.
1. Senanayake N, Karalliedde, L. Neurotoxic effects of organophosporus insecticides. An intermediate syndrome. N Engl J Med. 1987;316:761-763.
2. Zweinter RJ, Ginsburg CM. Organophosphate and carbamate poisoning in infants and children. Pediatrics. 1988;81:121-126.
3. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisioning. Lancet. 2008;371:597-607.
4. Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health. 2003;58:484-497.
5. The City of New York Department of Health and Mental Hygiene. 2006 Alert #38: Poisonings associated with the use of an illegal pesticide Tres Pasitos, in New York City. November 1, 2006