OP Poisoning - Dr. Ajith Venugopalan, EM, MOSC Medical College Hospital, Kolenchery, Ernakulam, Kerala, India
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Organophosphate Poisoning - Evaluation & Management Toxicology Emergency Medicine - Dr. Ajith Venugopalan, EM, MOSC Medical College Hospital, Kolenchery, Ernakulam, Kerala, India
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OP Poisoning - Dr. Ajith Venugopalan, EM, MOSC Medical College Hospital, Kolenchery, Ernakulam, Kerala, India
- 1. Dr. Ajith Venugopalan. MBBS, MD(Emergency Medicine), Fellow of Academic College of Emergency Experts (FACEE), Fellowship in Intensive Care Medicine (FICM). Head of the Department Department of Emergency Medicine MOSC Medical College Hospital, Kolenchery, Ernakulam, Kerala Lead, National EM Residency Network, Emergency Medicine Association (EMA) of India ORGANOPHOSPHATE (OP) POISONING
- 2. CASE SCENARIO 48yr / female, Otherwise healthy Presented to ER in a drowsy state. Bystanders gives history of a presence of an empty bottle near her. (Content - Unknown) Vomited, pungent odour, sweating, breathing difficulty is present OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 3. HOW DO WE PROCEED….????? OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 4. MAJOR CONCERNS Inhaled toxin Gastric lavage Tight ligature Excision of wound Induced emesis Hypotension management Oxygen delivery Antidotes OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 6. AGENDA • INTRODUCTION • CLINICAL MANAGEMENT • EVALUATION • MANAGEMENT OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 7. ORGANOPHOSPHORUS COMPOUNDS Widely used Pesticide Available as – Dust, Granules, Liquids Also called the NERVE AGENTS Case Fatality – 5 – 20% OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 9. ORGANOPHOSPHATES Organophosphates and carbamates are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity Acetylcholinesterase (AChE) deficiency leading to the accumulation of acetylcholine (ACh) in the body AChE is critical for nerve function, so the irreversible blockage of this enzyme, which causes acetylcholine accumulation, results in muscle overstimulation. This causes disturbances across the cholinergic synapses OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 10. MOA
- 15. NICOTINIC ACETYLCHOLINE RECEPTORS Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction leads to fasciculation, fatigue, muscle cramps, muscle weakness,, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system leads to tachycardia, hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and coma. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 16. MUSCARINIC ACETYLCHOLINE RECEPTORS When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors Salivation, Lacrimation, Urination, Diarrhea/Defecation, Gastric Emesis/Vomiting, Diaphoresis, Bronchorrhea, Bronchoconstriction Miosis, BradycardiaOP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 17. AGENTS Nerve agents Tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX. VR Insecticides Dimethyl compounds Dichlorvos Parathion Fenthion Malathion Methamidophos Diethyl compounds Chlorpyrifos Diazinon Parathion-ethyl Quinalphos OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 18. CLINICAL FEATURES OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 19. ACUTE CHOLINERGIC PHASE Starts in minutes, usually within one hour It lasts up to 48-72 hours OPs produce muscarinic, nicotinic & CNS effects Nicotinic Muscle twitching, fasciculation, weakness, respiratory paralysis Hypertension, tachycardia CNS Anxiety, restlessness, weakness Confusion, Convulsions, Coma Muscarinic – SLUDGE BBB/DUMBLES All secretions increased Sweating, Salivation, Lacrimation Increased urination Increased bronchial secretion, Pulmonary oedema Miosis – constricted pupil Bradycardia (tachycardia in 20 % cases) Heart blocks, hypotension ----QT prologation / arrythymias OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 20. INTERMEDIATE SYNDROME It begins after 48 hours ( in 20% cases ),it may be delayed up to 72 - 96 hours Patient will have muscle weakness due to receptor dysfunction at neuromuscular junction Muscles involved are – Ocular muscles, neck muscles, proximal limb muscles, respiratory muscles Patient also have anxiety, sweating, cyanosis and may develop coma OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 21. ORGANOPHOSPHATE INDUCED DELAYED POLYNEUROPATHY This occurs after 1 to 3 weeks of exposure due to degeneration of myelinated nerve fibers Clinical features Symmetrical, flaccid, distal muscle weakness and foot drop Absent deep tendon reflexes Sensory loss – All starts in distal parts of lower limb; then upper limb also OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 22. DIAGNOSIS Pungent garlic like smell Toxicology analysis for OPs in blood, gastric secretions, urine OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 23. INVESTIGATIONS Serum cholinesterase levels - Reduced ABG Blood glucose RFT ECG Electromyogram NCS Histopathology of the nerve . OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 24. MANAGEMENT A – Airway B – Breathing C – Circulation D – Disability / neurological E – Exposure reduction F – Ph(F)ysical Examination S – Special therapy – Supportive care OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 25. SAFETY OF CAREGIVERS – UTMOST IMPORTANCE
- 26. AIRWAY Airway takes priority Clearing the airway RSI if required. Non depolarisation agent Depolarisation agent – Not in OP C – Spine protection – if required Issue: Not given priority nor the needed importance. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 27. BREATHING Monitor – RR, SpO2, chest signs Oxygen - SpO2 > 94% Risk of Aspiration – High Bronchodilators as required Issues • How to monitor • How much O2 to give • O2 delivery devices • When to go for definitive airway OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 28. CIRCULATION Monitor PR, BP, ECG Targets MAP >65mmHg, CRT < 2sec, Urine O/P > 0.5ml/kg/hr Issues • How to monitor • Targets • IV access • Fluid of choice • Vasoactive agents OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 29. CIRCULATION Hypotension management Large bore cannula – 14 / 16 / 18 G Identify type of shock Fluids – Crystalloids (NS / RL) – 10 – 20mL/kg bolus Inotropic agents Arrhythmias - Lignocaine OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 30. DISABILITY Monitor – Level of awareness Pupils Lateralising signs GRBS Issues • How to evaluate • Management OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 31. DECONTAMINATION Remove cloths Thorough wash of body Deliver100 percent oxygen via facemask; Gastric lavage --- activated charcoal --- 1g/kg --- 12.5 g every hr / 25g ever 2 hr (3 times) / 50g every 4 hr (2 times) OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 32. ATROPINE Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally Atropine reverses Ach induced bronchospasm, bronchorrhoea, bradycardia and hypotension Atropine competes with acetylcholine at muscarinic receptors, preventing cholinergic activation. Atropine does not bind to nicotinic receptors, it is ineffective in treating neuromuscular dysfunction. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 33. ATROPINE Initial dose 1 mg IV, if no adverse effects 2 mg IV bolus (0.05 mg/kg IV in children). Double the dose every 5 - 10 mts till bronchorea and bronchospasm settles HR > 80/mt, secretions controlled, skin is dry Then start atropine infusion OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 34. ATROPINE Excessive dose can produce anticholinergic effect Atropine – S/E – Atropine induced Psychosis OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 35. GLYCOPYRROLATE Glycopyrrolate is a medication of the muscarinic anticholinergic group. It does not cross the blood brain barrier and consequently has no to few central effects. It is used as an alternative to atropine when atropine produces psychological adverse effects Injection - Each 1 mL contains: Glycopyrrolate 0.2 mg OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 36. DIAZEPAM Patient with convulsions. In a potentially severe exposure, prophylacaly Diazepam is also useful for sedation in patients with anxiety and has been used to reduce muscle fasciculations. If artificial ventilatory support is indicated, even without fasciculation or convulsions, it seems justified to use diazepam for sedation. Dose : 10-20 mg i.v. slowly in adults and 0.3 – 0.4 mg/kg i.v. in children, repeated as necessary. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 37. PRALIDOXIME Oximes – They reactivates phosphorylated AChE,It is effective in treating both muscarinic and nicotinic symptoms Pralidoxime, typically used in cases of organophosphate poisoning (which causes Achase inhibition), attaches to the site where a cholinesterase inhibitor has attached, then attaches to the inhibitor, removing the organophosphate from cholinesterase, allowing it to work normally again. This is known as "regenerating" or "reactivating" acetylcholinesterase allowing the breakdown of Ach at the synapse. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 40. PAM – REGENERATED CHOLINESTERASE
- 41. PRALIDOXIME Pralidoxime should NOT be administered without concurrent atropine in order to prevent worsening symptoms due to transient oxime-induced acetylcholinesterase inhibition OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 42. PRALIDOXIME – LOADING DOSE Adult : 30mg/kg over 30mts Children : 25 – 50mg/kg Infusion --- 8mg/kg/ hr adult Children 10- 20mg/kg/hr Pralidoxime should be administered slowly over 30, minutes since rapid administration has occasionally been associated with cardiac arrest, and slow administration prevents the muscle weakness that results from the transient inhibition of acetylcholinesterase as pralidoxime binds to the enzyme.OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 43. PRALIDOXIME – IN IS /OIDN Although no treatments have been shown to prevent the intermediate syndrome or organophosphorus agent-induced delayed neuropathy (OIDN), early oxime treatment may be of benefit in this situation OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 44. PRALIDOXIME – DIETHYL COMPOUNDS Evidences show that patients poisoned with diethyl compounds (eg Chlorpyrifos, Parathion) had significantly lower mortality and intubation rates following treatment with pralidoxime than those poisoned with dimethyl agents (eg dimethoate, monocrotophos and oxydemeton-methyl,) OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 45. WORLD HEALTH ORGANIZATION The World Health Organization has published a recommendation to use oximes to treat all symptomatic patients who need atropine Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. This is why atropine, which has excellent blood–brain barrier penetration, is concomitantly administered with pralidoxime during the treatment of organophosphate poisoning. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 46. ATROPINE + PAM
- 47. PUTTING IT ALL TOGETHER… A, B, C, D, E, Ph(F,) S method Toxidromal Approach Helps Save Life…. OP POISONING - DR. AJITH VENUGOPALAN, EM, KERALA, INDIA
- 48. 52 Q & A
- 49. ThankYou….. Dr. Ajith Venugopalan 9496339347 ajith.v123@gmail.com Dr. Ajith Venugopalan Head, Dept. of Emergency Medicine MOSC Medical College Hospital, Kolenchery, Ernakulam, Kerala, India +919496339347 / Ajith.v123@gmail.com
Editor's Notes
- Organophosphates and carbamates are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity following cutaneous exposure, inhalation, or ingestion. Although structurally distinct , organophosphate and carbamate manifest similar clinical manifestations with toxicity and management is also similar Organophosphates have been used as insecticides worldwide for the past 50 years. Medical applications of organophosphates and carbamates include reversal of neuromuscular blockade (neostigmine,pyridostigmine, edrophonium) and treatment of glaucoma, myasthenia gravis, and Alzheimer disease (echothiophate, pyridostigmine, tacrine, anddonepezil).
- Organophosphorous compounds contain carbon and phosphorous acid derivatives. These agents are well absorbed through the skin, lungs, and gastrointestinal tract. They bind to acetylcholinesterase (AChE), also known as red blood cell (RBC) acetylcholinesterase, and render this enzyme non-functional. AChE is the enzyme responsible for hydrolysis of acetylcholine to choline and acetic acid, and inhibition leads to an overabundance of acetylcholine at the neuronal synapses and the neuromuscular junction . After some period of time (dependent on the chemical structure of the organophosphorous agent), the acetlycholinesterase-organophosphorous compound undergoes a conformational change, known as "aging," which renders the enzyme irreversibly resistant to reactivation by an antidotal oxime . In addition, plasma cholinesterase (also called butylcholinesterase [BuChE] or pseudocholinesterase) and neuropathy target esterase (NTE) are inhibited by organophosphorous agents; however, the clinical significance of these interactions are less certain Carbamate compounds are derived from carbamic acid . Like organophosphorous agents, carbamates are rapidly absorbed via all routes of exposure. Unlike organophosphates, these agents are transient cholinesterase inhibitors, which spontaneously hydrolyze from the cholinesterase enzymatic site within 48 hours. Carbamate toxicity tends to be of shorter duration than that caused by equivalent doses of organophosphates, although the mortality rates associated with exposure to these chemical classes are similar .
- Nicotonic expression in NMJ ------ Fasciculation – fatique – muscle cramp --- weakness --- paralysis Autonomic ganglia ---- tachycardia --- hypertension ---– hypoglycemia---pallor CNS --- Anxiety --- headache---tremors--- ataxia --confusion----restlessness---- convulsions --- depression of respiration n circulation ---general weakness---coma AAA CCC – Ataxia / Agitation /Anxiety / / Confusion /convulsion /coma
- Muscarinic overstiimulation ----– increased lacrimation --salivation---bronchoria --- urination – peristalsis ----sweating Miosis --- visual disturbace --- bronchoconstriction SLUDGE BBB--- salivation / lacrimation / urination / diarrhea / GI upset / emesis / Bronchorea / bronchial constriction / bradycardia.
- Onset and duration of AChE inhibition varies depending on the organophosphorous agent's rate of AChE inhibition, the route of absorption, enzymatic conversion to active metabolites, and the lipophilicity of the organophosphorous agent. For most agents, oral or respiratory exposures generally result in signs or symptoms within three hours, while symptoms of toxicity from dermal absorption may be delayed up to 12 hours. Lipophilic agents such as dichlofenthion, fenthion, and malathion are associated with delayed onset of symptoms (up to five days) and prolonged illness (greater than 30 days), which may be related to rapid adipose fat uptake and delayed redistribution from the fat stores . The great variability in toxicity and treatment response among organophosphorous agents, however, is not well understood, leading some to suggest that each agent be considered independently in future studies
- 1 hr – 48hrs …can go upto 72hrs Nicotinic , ANS , CNS , Muscarnic effect SLUDGE = Salivation, Lacrimation, Urination, Defecation, Gastric Emptying BBB = Bradycardia, Bronchorrhea, Bronchospasm DUMBELS - Defecation, Urination, Miosis, Bronchorrhea/Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation
- 48hrs –delayed upto 72 -96 hrs Muscle weakness due to receptor dysfunction at NMJ It can due to exposure of fat soluable OP agents ---n also inadequate dose of oximes Diagnosis : Nerve conduction study – demonstrate unique post synaptic abnormalities Treatement : Supportive care Prolonged mechanical ventilation Can recover within 2 – 3 weeks
- Degeneration of myelinated nerve fibers Also damage to neuropathy target esterase . Months to yrs after exposure Transient painful “stocking glove “ paresthesia. Symmetrical flaccid weakness of the muscles ---- distal followed by proximal ---- footdrop ---absent DTR n sensory loss Diagnosis : Electromyograms , NCS --- decreased firing of motor conduction units. Histopathology reveals --- peripheral nerve – wallerian degeneration of large distal axons .
- Atropine challenge if diagnosis is in doubt (1 mg IV in adults, 0.01-0.02 mg/kg in children) Absence of anticholinergic signs (tachycardia, mydriasis, decreased bowel sounds, dry skin) strongly suggests poisoning with organophosphate or carbamate RBC acetylcholinesterase activity to confirm diagnosis
- Remove cloths Thorough wash of body Deliver 100 percent oxygen via facemask; early intubation often required; avoid succinylcholine Gastric lavage --- activated charcoal --- 1g/kg --- 12.5 g every hr / 25g ever 2 hr (3 times) / 50g every 4 hr (2 times)
- Initiated in patients with OP toxicity who present with muscarinic symptoms. (SLUDGE BBB ) Competitive inhibitor at autonomic postganglionic cholinergic receptors, including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eye. The endpoint for atropinization is dried pulmonary secretions and adequate oxygenation. And drying up of secretions. S/E : CNS depression (?) atropine psychosis Infusion : 20% of the maximum dose at which atropinisatiton occurred is taken and started as per hour infusion.
- give 2 mg every 15 minutes till the patient develops atropinization ( drying of secretions, tachycardia, dry mouth, and dilated pupil , temp :) Injection(Vial) - 1 mL contains: atropine 1 mg, (Ampule – 1ml = 0.6mg) Atropine also can be used as infusion ( The average patient requires approximately 40 mg/d ) Monitor the patient – heart rate, pupil size, fasciculations, secretions, lung crepitation
- 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.
- Indicated for use as an antimuscarinic agent to reduce salivary, tracheobronchial, and pharyngeal secretions. Can be considered in patients at risk for recurrent symptoms (after initial atropinization) but who are developing central anticholinergic delirium or agitation.
- Convulsions Anxiety reduction Muscle fasciculations reduces.
- Pralidoxime is typically used in cases of organophosphate poisoning. The Acetylcholinesterase enzyme has two parts to it. An acetylcholine molecule bound at both ends to both sites of the enzyme, is cleaved in two to form acetic acid and choline. In organophosphate poisoning, an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ], blocking its activity. Pralidoxime is able to attach to the other half [ the unblocked, anionic site ] of the acetylcholinesterase enzyme. It then binds to the organophosphate, the organophosphate changes conformation, and loses its binding to the acetylcholinesterase enzyme. The conjoined poison / antidote then unbinds from the site, and thus regenerates the enzyme, which is now able to function again. After some time though, some inhibitors can develop a permanent bond with cholinesterase, known as aging, where oximes such as pralidoxime can not reverse the bond.[citation needed] Pralidoxime is often used with atropine (a muscarinic antagonist) to help reduce the parasympathetic effects of organophosphate poisoning. Pralidoxime is only effective in organophosphate toxicity (i.e. it does not have an effect if the acetylcholinesterase enzyme is carbamylated, as occurs with neostigmine or physostigmine). Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. This is why atropine, which has excellent blood–brain barrier penetration, is concomitantly administered with pralidoxime during the treatment of organophosphate poisoning.
- Adult : 30mg/kg over 30mts Children : 25 – 50mg/kg Infusion --- 8mg/kg/ hr adult Children 10- 20mg/kg/hr