1. O RGANOPHOSPHATE (OP) P OISINING 1

2. Initial treatment goal should consist of optimizing oxygenation and controlling excessive airway secretions. Tachycardia is neither a contraindication nor an endpoint for atropine administration. Patients exposed to organophosphate (OP) should be observed for at least 12 hours in a high acuity setting. Because of the risk of respiratory depression or recurrent symptoms after resolution of an acute cholinergic crisis, hospitalizing all symptomatic patients for at least 48 hours following resolution of symptoms is recommended. The symptoms of OP poisoning can mimic other toxicities and disease processes. The clinician must keep in mind that misdiagnosis is a potential medicolegal pitfall. 2

3. O RGANOPHOSPHATE (OP) P OISINING Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and industrial settings. 3

4. ANTICHOLINESTERASE anticholinesterase Any substance that inhibits the enzyme cholinesterase, which is responsible for the breakdown of the neurotransmitter acetylcholine at nerve synapses. Anticholinesterases, which include certain drugs, nerve gases, and insecticides, cause a build-up of acetylcholine within the synapses, leading to disruption of nerve and muscle function. In vertebrates, these agents often cause death by paralysing the respiratory muscles.cholinesterase 4

5. cholinesterase (acetylcholinesterase) An enzyme that hydrolyses the neurotransmitter acetylcholine to choline and acetate. Cholinesterase is secreted by nerve cells at synapses and by muscle cells at neuromuscular junctions. Organophosphorus insecticides (pesticide) act as anticholinesterases by inhibiting the action of cholinesterase. acetylcholine synapsesneuromuscular junctionspesticideanticholinesterases 5

6. A CETYLECHOLIE Acetylcholine (ACh) is one of the main neurotransmitters of the vertebrate nervous system. It is released at certain ( cholinergic ) nerve endings and may be excitatory or inhibitory; it initiates muscular contraction at neuromuscular junctions. Acetylcholine receptors ( cholinoceptors ) fall into two main classes: muscarinic and nicotinic receptors. Once acetylcholine has been released it has only a transitory effect because it is rapidly broken down by the enzyme cholinesterase. neurotransmitters neuromuscular junctions muscarinicnicotiniccholinesterase 6

7. P ATHOPHYSIOLOGY The primary mechanism of action of organophosphate pesticides is inhibition of 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 phosphorelation. 7

8. P ATHOPHYSIOLOGY 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. 8

9. P ATHOPHYSIOLOGY 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. 9

11. S IGNS 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, emesis; excess lacrimation; and salivation). 11

12. S IGNS AND SYMPTOMS OF ORGANOPHOSPHATE POISONING Muscarinic effects by organ systems include the following: Cardiovascular - Bradycardia, hypotension Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory distress Gastrointestinal - Hypersalivation, nausea and vomiting, abdominal pain, diarrhea, fecal incontinencepain Genitourinary - Incontinence Ocular - Blurred vision, miosis Glands - Increased lacrimation, diaphoresis 12

13. S IGNS AND SYMPTOMS OF ORGANOPHOSPHATE POISONING 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. 13

14. P HYSICAL Note that clinical presentation may vary, depending on the specific agent, exposure route, and amount. Symptoms are due to both muscarinic and nicotinic effects. 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. 14

15. T REATMENT M EDICAL C ARE 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. 15

16. T REATMENT / M EDICAL C ARE Continuous cardiac monitoring and pulse oximetry should be established; an ECG should be performed. 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. 16

17. T REATMENT M EDICAL C ARE 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. 17

18. M EDICATION The mainstays of medical therapy in organophosphate (OP) poisoning include ATROPINE, pralidoxime, and diazepam Initial management must focus on adequate use of atropine. Optimizing oxygenation prior to the use of atropine is recommended to minimize the potential for dysrhythmias. 18

19. M EDICATION Anticholinergic agents These agents act as competitive antagonists at the muscarinic cholinergic receptors in both the central and the peripheral nervous system. These agents do not affect nicotinic effects. 19

20. A TROPINE (I SOPTO, A TROPAIR ) Adult 1-2 mg IV bolus, repeat q1-5min prn for desire effects (drying of pulmonary secretions and adequate oxygenation) Strongly consider doubling each subsequent dose for rapid control of patients in severe respiratory distress An atropine drip titrated to above endpoints can be initiated until patient's condition stabilized Pediatric 0.05 mg/kg IV, repeat q1-5min prn for control of airway secretions Strongly consider doubling each subsequent dose to rapidly stabilize patients with severe respiratory distress 20

21. C OMPLICATIONS Complications include respiratory failure, seizures, aspiration pneumonia, delayed neuropathy, and death. 21

22. M EDICOLEGAL P ITFALLS Initial treatment goal should consist of optimizing oxygenation and controlling excessive airway secretions. Tachycardia is neither a contraindication nor an endpoint for atropine administration. Patients exposed to organophosphate (OP) should be observed for at least 12 hours in a high acuity setting. Toxicity after this is unlikely. Because of the risk of respiratory depression or recurrent symptoms after resolution of an acute cholinergic crisis, hospitalizing all symptomatic patients for at least 48 hours following resolution of symptoms is recommended. The symptoms of OP poisoning can mimic other toxicities and disease processes. The clinician must keep in mind that misdiagnosis is a potential medicolegal pitfall. 22