What are organophosphates?

Organophosphates are chemicals used in domestic and industrial settings, most commonly as insecticides. Historically, organophosphates have been used in toxic nerve agents by the military in war, or for terrorist activities. Organophosphates can be ingested or inhaled, or absorbed through the skin. The severity and onset of symptoms is dependent on the degree of exposure.

How do organophosphates work?

Organophosphates work by inactivating acetylcholinesterase. Acetylcholinesterase is an enzyme present in human nervous system. Its job is to break down acetylcholine, which is a chemical that carries signals between the nerves and muscle. . Once acetylcholinesterase has been inactivated, acetylcholine builds up in the nerves, and the nerves become over-active. Organophosphate poisoning can occur rapidly or build up over a number of days.

Signs & Symptoms

People affected can display the following signs and symptoms: Mild

Moderate Increased saliva production Nausea & vomiting Abdominal pain Increased sweating Rhinorrhoea (runny nose) Able to walk and talk Headache Dizziness

Severe

Confusion, Anxiety Restlessness Slow heart rate (bradycardia) Blurred vision, small pupils Unable to walk Cramps Diarrhea

Muscle twitching Seizures Low blood pressure (hypotension) Narrowing of the airways (bronchospasm) Increased bronchial secretions Respiratory failure

General Treatment Options

The patient with organophosphate poisoning requires decontamination, and those in contact with the patient must use personal protective equipment (PPE) to avoid absorption of the chemical. This decontamination consists of thoroughly washing the patient, including hair. Clothing must be washed and any leather article discarded (chemical cannot be removed from leather).

Specific treatment will depend upon how the patient became poisoned and their level of symptoms. If the patient has swallowed the poison recently they will receive activated charcoal by mouth to absorb the residual poison.

What Happens in Intensive Care?

Once the patient has been admitted to ICU their care will be focussed on monitoring their level of cholinesterase and the residual effects of the poisoning on the patient. Treament will be supportive. Once in ICU the patient will be cared for in a single room with special ventilation and any staff caring for the patient will continue to wear protective clothing for a number of days. The patient will be placed on a cardiac monitor to monitor their heart rate and rhythm and blood will be taken to check the level of acetyl cholinesterase in their blood. This will need to be done a number of times until the medical staff are satisfied with the recovery of the patient. The medication Atropine will be given at frequent intervals to treat the excessive saliva, bronchial secretions and slow heart rate. Respiratory support using an oxygen mask may be required.Occasionally the patient will experience severe respiratory failure and will require breathing tube (endotracheal tube) is inserted, and the patient is helped with their breathing using a breathing machine (ventilator).

How long will the patient remain in Intensive Care?

The patient will stay in ICU until the signs of respiratory failure have subsided. The degree of exposure to the chemicals, and the symptoms experienced, will determine how long the patient stays in hospital.

Weblinks
Health Surveillance Guideline Poisons Information Centres Across Australia - 131126 Bayer Product Information The information contained in this sheet is general in nature and therefore cannot reflect individual patient variation. It is meant as a back up to specific information which will be discussed with you by the Doctors and Nurses caring for your loved one. ICCMU attests to the accuracy of the information contained here BUT takes no responsibility for how it may apply to an individual patient. Please refer to the Disclaimer. http://intensivecare.hsnet.nsw.gov.au/organophosphate-poisoning
Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and industrial settings. Examples of organophosphates include insecticides (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, ethion), nerve gases (soman, sarin, tabun, VX), ophthalmic agents

(echothiophate, isoflurophate), and antihelmintics (trichlorfon). Herbicides (tribufos [DEF], merphos) are tricresyl phosphatecontaining industrial chemicals. Organophosphate compounds were first synthesized in the early 1800s when Lassaigne reacted alcohol with phosphoric acid. Shortly thereafter in 1854, Philip de Clermount described the synthesis of tetraethyl pyrophosphate at a meeting of the French Academy of Sciences. Eighty years later, Lange, in Berlin, and, Schrader, a chemist at Bayer AG, Germany, investigated the use of organophosphates as insecticides. However, the German military prevented the use of organophosphates as insecticides and instead developed an arsenal of chemical warfare agents (ie, tabun, sarin, soman). A fourth agent, VX, was synthesized in England a decade later. During World War II, in 1941, organophosphates were reintroduced worldwide for pesticide use, as originally intended. Massive organophosphate intoxication from suicidal and accidental events, such as the Jamaican ginger palsy incident in 1930, led to the discovery of the mechanism of action of organophosphates. In 1995, a religious sect, Aum Shinrikyo, used sarin to poison people on a Tokyo subway. Mass poisonings still occur today; in 2005, 15 victims were poisoned after accidentally ingesting ethion-contaminated food in a social ceremony in Magrawa, India. Nerve agents have also been used in battle, notably in Iraq in the 1980s. Additionally, chemical weapons still pose a very real concern in this age of terrorist activity. Exposure to organophosphates (OPs) is also possible via intentional or unintentional contamination of food sources. Although no clinical effects of chronic, low-level organophosphates (OPs) exposure from a food source have been shown, advancements in risk assessment and preparedness are ongoing.

Pathophysiology
The primary mechanism of action of organophosphate pesticides is inhibition of carboxyl ester hydrolases, particularly acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central and peripheral nervous system, neuromuscular junctions, and red blood cells (RBCs). Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. The phosphorylation occurs by loss of an organophosphate leaving group and establishment of a covalent bond with AChE. Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors. Clinical effects are manifested via activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal muscle. Once an organophosphate binds to AChE, the enzyme can undergo one of the following: Endogenous hydrolysis of the phosphorylated enzyme by esterases or paraoxonases Reactivation by a strong nucleophile such as pralidoxime (2-PAM) Irreversible binding and permanent enzyme inactivation (aging) Organophosphates can be absorbed cutaneously, ingested, inhaled, or injected. Although most patients rapidly become symptomatic, the onset and severity of symptoms depend on the specific compound, amount, route of exposure, and rate of metabolic degradation.[3]

History
Signs and symptoms of organophosphate poisoning can be divided into 3 broad categories, including (1) muscarinic effects, (2) nicotinic effects, and (3) CNS effects. Mnemonic devices used to remember the muscarinic effects of organophosphates are SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis) and DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea; emesis; excess lacrimation; and salivation). Muscarinic effects by organ systems include the following:

o o o o o o

Cardiovascular - Bradycardia, hypotension Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory distress Gastrointestinal - Hypersalivation, nausea and vomiting, abdominalpain, diarrhea, fecal incontinence Genitourinary - Incontinence Ocular - Blurred vision, miosis Glands - Increased lacrimation, diaphoresis Nicotinic signs and symptoms include muscle fasciculations, cramping, weakness, and diaphragmatic failure. Autonomic nicotinic effects include hypertension, tachycardia, mydriasis, and pallor. CNS effects include anxiety, emotional lability, restlessness, confusion, ataxia, tremors, seizures, and coma.

Physical
Note that clinical presentation may vary, depending on the specific agent, exposure route, and amount. Symptoms are due to both muscarinic and nicotinic effects. Interestingly, a review of 31 children with organophosphate (OP) poisoning described that, in contrast to adults, the most common presentations were seizure and coma with relatively less muscarinic or nicotinic findings. [8] The authors hypothesized the difference may be due to difficulty in detecting muscarinic findings in infants (eg, crying) and ingestion of contaminated produce instead of organophosphate (OP) directly. Vital signs: Depressed respirations, bradycardia, and hypotension are possible symptoms. Alternatively, tachypnea, hypertension, and tachycardia are possible. Hypoxia should be monitored for with continuous pulse oximetry. Paralysis o Type I: This condition is described as acute paralysis secondary to continued depolarization at the neuromuscular junction. o Type II (intermediate syndrome): Intermediate syndrome was described in 1974 and is reported to develop 24-96 hours after resolution of acute organophosphate poisoning symptoms and manifests commonly as paralysis and respiratory distress. This syndrome involves weakness of proximal muscle groups, neck, and trunk, with relative sparing of distal muscle groups. Cranial nerve palsies can also be observed. Intermediate syndrome persists for 4-18 days, may require mechanical ventilation, and may be complicated by infections or cardiac arrhythmias. Although neuromuscular transmission defect and toxin-induced muscular instability were once thought to play a role, this syndrome may be due to suboptimal treatment. o Type III: Organophosphate-induced delayed polyneuropathy (OPIDP) occurs 2-3 weeks after exposure to large doses of certain organophosphates (OPs) and is due to inhibition of neuropathy target esterase. Distal muscle weakness with relative sparing of the neck muscles, cranial nerves, and proximal muscle groups characterizes OPIDP. Recovery can take up to 12 months. [9, 10] Neuropsychiatric effects: Impaired memory, confusion, irritability, lethargy, psychosis, and chronic organophosphate-induced neuropsychiatric disorders have been reported. The mechanism is not proven. Extrapyramidal effects: These are characterized by dystonia, cogwheel rigidity, and parkinsonian features (basal ganglia impairment after recovery from acute toxicity). Other neurological and/or psychological effects: Guillain-Barrlike syndrome and isolated bilateral recurrent laryngeal nerve palsy are possible. Ophthalmic effects: Optic neuropathy, retinal degeneration, defective vertical smooth pursuit, myopia, and miosis (due to direct ocular exposure to organophosphates) are possible. Ears: Ototoxicity is possible. Respiratory effects: Muscarinic, nicotinic, and central effects contribute to respiratory distress in acute and delayed organophosphate toxicity. Muscarinic effects: Bronchorrhea, bronchospasm, and laryngeal spasm, for instance, can lead to airway compromise. Respiratory failure is the most life-threatening effect and requires immediate intervention. Nicotinic effects: These effects lead to weakness and paralysis of respiratory oropharyngeal muscles. Central effects: These effects can lead to respiratory paralysis.

Rhythm abnormalities: Sinus tachycardia, sinus bradycardia, extrasystoles, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation (often a result of, or complicated by, severe hypoxia from respiratory distress) are possible. Other cardiovascular effects: Hypotension, hypertension, and noncardiogenic pulmonary edema are possible. GI manifestations: Nausea, vomiting, diarrhea, and abdominal pain may be some of the first symptoms to occur after organophosphate exposure. Genitourinary and/or endocrine effects: Urinary incontinence, hypoglycemia, or hyperglycemia is possible.

Medical Care
Airway control and adequate oxygenation are paramount in organophosphate (OP) poisonings. Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures. Immediate aggressive use of atropine may eliminate the need for intubation. Succinylcholine should be avoided because it is degraded by acetylcholinesterase (AChE) and may result in prolonged paralysis. Continuous cardiac monitoring and pulse oximetry should be established; an ECG should be performed. Torsades de Pointes should be treated in the standard manner. The use of intravenous magnesium sulfate has been reported as beneficial for organophosphate toxicity. The mechanism of action may involve acetylcholine antagonism or ventricular membrane stabilization. Remove all clothing and gently cleanse patients suspected of organophosphate exposure with soap and water because organophosphates are hydrolyzed readily in aqueous solutions with a high pH. Consider clothing as hazardous waste and discard accordingly. Health care providers must avoid contaminating themselves while handling patients. Use personal protective equipment, such as neoprene gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolar substances such as latex and vinyl. Use charcoal cartridge masks for respiratory protection when decontaminating patients who are significantly contaminated. Irrigate the eyes of patients who have had ocular exposure using isotonic sodium chloride solution or lactated Ringer's solution. Morgan lenses can be used for eye irrigation.

Deterrence/Prevention
Health care providers must avoid contaminating themselves while handling patients poisoned by organophosphates. The potential for cross-contamination is highest in treating patients after massive dermal exposure. Use personal protective equipment, such as neoprene or nitrile gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolar substances such as latex and vinyl. Use charcoal cartridge masks for respiratory protection when caring for patients with significant contamination.

Complications
Complications include respiratory failure, seizures, aspiration pneumonia, delayed neuropathy, and death.

http://emedicine.medscape.com
Poisoning Overview
If you or someone you know has swallowed or breathed in a poison, and you or they have serious signs or symptoms (nausea, vomiting, pain, trouble breathing, seizure, confusion, or abnormal skin color), then you must either call an ambulance for transport to a hospital emergency department or call a poison control center for guidance. The National Poison Control Center phone number in the U.S. is 1-800-222-1222.

If the person has no symptoms but has taken a potentially dangerous poison, you should also call a poison control center or go to the nearest emergency department for an evaluation. Poison is anything that kills or injures through its chemical actions. Most poisons are swallowed (ingested). The word poison comes from the Latin word - potare - meaning to drink. But poisons can also enter the body in other ways: By breathing Through the skin By IV injection From exposure to radiation Venom from a snake bite

Poisoning Causes
Poisons include highly toxic chemicals not meant for human ingestion or contact, such ascyanide, paint thinners, or household cleaning products. Many poisons, however, are substances meant for humans to eat, including foods and medicines. Foods Some mushrooms are poisonous Drinking water contaminated by agricultural or industrial chemicals Food that has not been properly prepared or handled

When to Seek Medical Care

Call the U.S. National Poison Control Center at 1-800-222-1222 if you have questions about possible poisoning. You can also go directly to your hospital's emergency department. Don't assume over-the-counter medications are safe even if taken in excess. Call the poison control center for advice. With many pills, it may take several hours or longer for symptoms to develop. Do not wait for symptoms to develop, call the poison control center for advice. Go to your hospital's emergency department if any of the following occurs: If someone looks ill after a poisoning or possible poisoning. An infant or toddler who may have ingested a poison, even if the child looks and feels fine.

Anyone who has taken something in an attempt to harm himself or herself, even if the substance used is not known to be harmful. When you go to the hospital's emergency department, take all the medicine bottles, containers (household cleaners, paint cans, vitamin bottles), or samples of the substance (such as a plant leaf) with you.

Self-Care at Home
If you or someone you know has swallowed or breathed a poison and you or they have signs or symptoms, such as nausea, vomiting, pain, trouble breathing, seizure, confusion, or abnormal skin color, then you must call either an ambulance or the U.S. National Poison Control Center at 1800-222-1222 for guidance. This number is routed to the poison control center that serves your area. o Post the telephone number (along with police, fire, and 911 or equivalent) near your home phones. Do not induce vomiting or give syrup of Ipecac. Ipecac was previously used to induce vomiting in poisoned patients where there was a chance to get the toxin out of the body. Several advisory bodies such as the American Association of Poison Control Centers and the American Academy of Pediatrics have recommended that Ipecac NOT be used and that it should not even be kept in the household. For more information on this subject go to:http://www.poison.org/prepared/ipecac.asp

Do not give activated charcoal at home. Allow medical personnel to decide if this treatment is appropriate. The poison control center will instruct you what to do or if an antidote is readily available.

Medical Treatment
Elimination: Get rid of the unabsorbed poison before it can do any harm. If the person is unconscious, the doctor will put a flexible, soft, plastic tube into thewindpipe to protect the person from suffocating in his or her own vomit and to provide artificial breathing (intubation). Once the poison has moved past the stomach, other methods are needed. Activated charcoal acts as a "super" absorber of many poisons. Once the poison is stuck to the charcoal in theintestine, the poison cannot get absorbed into the bloodstream. Activated charcoal has no taste, but the gritty texture sometimes causes the person to vomit. To be effective, activated charcoal needs to be given as soon as possible after the poisoning. It does not work with alcohol, caustics, lithium (Lithobid), or petroleum products. Whole bowel irrigation requires drinking a large quantity of a fluid called Golytely. This flushes the entire gastrointestinal tract before the poison gets absorbed.

Antidotes: Some poisons have specific antidotes. Antidotes either prevent the poison from working or reverse the effects of the poison.

Atropine is an antidote for certain nerve gases and insecticides. During Operation Desert Storm, all military personnel were issued atropine injectors when it was feared that the enemy would use nerve gas. A common antidote is N-acetylcysteine (Mucomyst), which is used to neutralize acetaminophen (Tylenol) overdoses. Acetaminophen, in normal doses, is one of the safest medications known, but after a massive overdose, the liver is damaged, and hepatitis and liver failure develop. Mucomyst works as an antidote by bolstering the body's natural detoxification abilities when they are overwhelmed. It may also be possible to reverse the harmful effect of a drug even if no antidote exists. If a person with diabetes takes too much insulin, a dangerously low blood sugar (hypoglycemia) will cause weakness, unconsciousness, and eventually death. Sugar given by mouth or IV is an effective treatment until the insulin wears off. When the poison is a heavy metal, such as lead, special medicines (chelators) bind the poison in the bloodstream and cause it to be eliminated in the urine. Another "binder" is sodium polystyrene sulfonate (Kayexalate), which can absorb potassium and other electrolytes from the bloodstream.

General supportive measures: When there are no specific treatments, the physician will treat signs and symptoms as needed. If the person is agitated or hallucinating, a sedative can be given to calm the person until the drug wears off. A ventilator can be used to breathe for anyone who has stopped breathing from a poisoning. Antiseizure medicines can be used to treat or prevent seizures.