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APPROACH TO ORGANOPHOSPHATE MANAGEMENT PPT
- 1. APPROACH TO ORGANOPHOSPHATE AND CARBAMATEPOISONING DR K SIMAYUMBULA MAZABUKA GENERAL HOSPITAL
- 2. OUTLINE • Definition andHistorical note • Epidemiology • Types/ Classification of OPP • Carbamates • Pharmacology and pathophysiology • Clinical manifestations/ progression of OPP • Diagnosis • Management • References
- 3. WHY OPP?????? • Verycommon problem WORLDWIDE. • Cases in Mazabuka have risen of late. • More in males. • Information on the long term survival of OP pt not available. • There are no rules and regulations governing the purchase of these products, and they are therefore readily available "over the counter", despite them being a major cause of morbidity and mortality.
- 4. DEFINITION AND HISTORICALNOTE • Organophosphate poisons are carbon and phosphorus derivatives. They comprise the ester, amide or thiol derivatives of phosphoric acid and are most commonly used as pesticides in commercial agriculture, field sprays and as household chemicals. • Used in both industrial and domestic settings • First synthesed in the 1800 when Lassagaine reacted alcohol with phosphoric acid • In 1862 Lange investigated the use of organophosphates as insecticides. • However the German military prevented that and instead developed for chemical warfare. • In 1941- reintroduced as pesticides. • Massive death in Jamaica led to the discovery of the mechanism of action
- 5. EPIDERMIOLOGY • WHO –Three million people are poisoned every year world wide. • Common in rural regions of the developing world killing • Estimated 200 000 people die every year. • Britain 100 000 / year. Less than 300 die. • UTH – at least 5 cases per week. • MAZABUKA GENERAL HOSPITAL ???? • Unintentional/Accidental poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available.
- 6. MGH STATISTICS ONOPP MWARD FWARD ICU HCOST CWARD JAN 8 2 3 0 FEB 6 0 0 0 MARCH 3 3 1 9 APRIL 4 1 0 0 MAY 8 1 3 0 TOTAL ADM 29 7 4 0 DEATHS 2 0 2 0
- 7. Challenges • Medical managementis difficult, with case fatality generally more than 15%. • 50 years after first use, we still do not know how the core treatments— atropine, oximes, and diazepam—should best be given. • Hospitals in rural areas bear the brunt of this problem, seeing many hundreds of patients poisoned by pesticides each year, with a case fatality of 15–30%. • Most hospitals are frequently not adequately staffed or equipped to deal with these very sick patients—intensive care beds and ventilators are in short supply—so even unconscious patients are managed on open wards.
- 8. TYPES OF ORGANOPHOSPHATES Classifiedbased on their structures and properties: • Pesticides/ Insecticides: Malathion, parathion, diazinon, chlorpyrifos • Nerve Agents: Samorin, sarin, tabun, VX • Herbicides: Tribufos, merphos • Ophthalmic agents: Echothiophate, isoflurophate • Others rare: Antihelmintics,industrial chemicals
- 9. Classification: Cont’d There aremore than a hundred organophosphorus compounds in common use. These are classified according to their toxicity and clinical use: 1. Highly toxic organophosphates: (e.g. tetra-ethyl pyrophosphates, parathion). These are mainly used as agricultural insecticides. 2. Intermediately toxic organophosphates: (e.g. coumaphos, clorpyrifos, trichlorfon). These are used as animal insecticides. 3. Low toxicity: (e.g. diazinon, malathion, dichlorvos). These are used for household application and as field sprays.
- 10. CARBAMATES • Carbamates: Similarto pesticides • i.e Aldicab, carbaryl, methiocarb • Similar to OPP, though typically less severe or requiring a larger amount of the chemical before symptoms appear. • Carbamate poisoning does not cause long-term effects as compared to OPP. • Approach is similar to OPP.
- 11. CAUSES OF POISONING Intentionalor unintentional • Suicidal/ Para-suicidal • Homicidal • Accidental
- 12. PHARMACOKINETICS • OP arehighly lipid soluble compounds hence they are well absorbed through skin, respiratory, injected or ingested in the gastrointestinal mucosa. • Most common route – ingestion • Following absorption OP are distributed to the rest of the body. • Metabolism occurs in the liver. • This high lipid solubility means that they easily cross the blood/brain barrier and therefore produce potent effects on the CNS. • Elimination of organophosphorus compounds and its metabolites occur mainly via urine, bile and faeces, 90% are eliminated mostly as metabolites in the kidneys and faeces within 48 hrs. • Although most patients rapidly become symptomatic , the onset and severity depends on the specific compound , amount, route of exposure and metabolic degradation
- 13. PATHOPHYSIOLOGY • Organophosphorus pesticidesinhibit esterase enzymes, especially acetylcholinesterase in synapses and on red-cell membranes, and butyrylcholin esterase in plasma. • Although acute butyrylcholinesterase inhibition does not seem to cause clinical features, acetylcholinesterase inhibition results in accumulation of acetylcholine and overstimulation of acetylcholine receptors in synapses of the autonomic nervous system, CNS, and neuromuscular junctions. • The subsequent autonomic, CNS, and neuromuscular features of organophosphorus poisoning are well known.
- 14. CLINICAL PRESENTATION • Followingexposure to organophosphorus compounds, the toxic features are usually obvious within 30 minutes to 3 hours. This may be delayed in some cases depending on the rate and amount of systemic absorption. • Signs and symptoms can be divided into muscarinic , nicotinic and central nervous system effects. • Severity assessment with the Peradeniya organophosphate poisoning (POP) score (Mild 0-3), moderate (4-7) and severe ( 8-11) • POP score helps to determine the need for ventilator support, ICU mgt and predict the final clinical outcome. • Parameters include :Pupil size, RR, HR, Fasciculations, GCS, Seizures
- 15. POP SCORING SYSTEM PARAMETERCRITERIA SCORE PUPIL SIZE >2mm < 2mm Pinpoint(miotic) 0 1 2 RR <20 BPM >20 BPM >20 BPM AND CYANOTIC 0 1 2 HR >60 BPM 41-60 BPM <40 BPM 0 1 2 LEVEL OF CONSIOUSNESS CONSCIOUS IMPAIRED RESOUNSE TO VERBAL NO RESPONSE TO VERBAL 0 1 2 FASCICULATIONS NONE GENEREALISED OR CONTINOUS BOTH GEN/CONT 0 1 2 SEIZURES ABSENT PRESENT 0 1
- 16. Clinical Grading MILD MODERATESEVERE Walks and talks headache dizzinnes nausea, Vomiting Abdominal pain Sweating, Salivation Rhinorrhoea Cannot walk Soft voice muscle twitching (fasciculations) Anxiety, Restlessness Small pupils (miosis) Unconscious, no papillary reflex. Muscle twitching, flaccid paralysis. Increased bronchial secretions. Dyspnea crackles / wheeze. Possible convulsions Respiratory failure
- 17. Muscarinic Features Overstimulation ofmuscarinic acetylcholine receptors in the parasympathetic system: DUMBBELS OR SLUDGE • Diarrhoea • Urination • Miosis (Pinpoint pupils) • Bronchospasm /Bronchorrhoea / Bradycardia • Emesis/Vomiting • Lacrimation • Salivation • Others: GI Upset, Hypotension
- 18. BY ORGANS (Muscarinic) • Cardiovascular: Bradycardia, hypotension • Respiratory: Bronchorhea, Rhinorrhea, Bronchospasms, Cough, respiratory distress • GIT: Salivation, Nausea, vomiting, abdominal pains, diarrhea, fecal incontinence • GUT: Urination, urine incontinence • Ocular: Blurred vision, miosis • Glands: Lacrimation, Diaphoresis/ Excessive Sweating
- 19. NICOTINIC FEATURES Overstimulation ofnicotinic acetylcholine receptors in the sympathetic system Neuromuscular junction Muscle Fasciculations/ cramps Muscle weakness Paralysis Respiratory/ Diaphragmatic failure Autononic effects: • Tachycardia, Mydriasis ,Hypertension
- 20. CNS EFFECTS Overstimulation ofnicotinic and muscarinic acetylcholine receptors in the CNS • Confusion • Agitation/ Anxiety/ Restlessness • Ataxia • Tremors • Seizures • Coma • Respiratory failure/ Apnea
- 21. Clinical Progression/ Paralysis •Acute cholinergic crisis/ Type 1 Paralysis FEATURES OF ACUTE CHOLINERGIC CRISIS DUMBBELS/ SLUDGE Nicotinic effects Neurological manifestations can include • altered conscious level, Seizures, Areflexia • extensor planter response • memory deficit • choreothetosis
- 23. Intermediate syndrome /Type2 Paralysis • Develops 12-96hrs after exposure and resolution of acute OPP symptoms and manifests commonly as paralysis and respiratory failure(40%). . • The syndrome involves weakness of proximal muscles sparing the distal muscle groups i.e neck , trunk. CN Palsies can also occur. • Intermediate syndrome usually last 4-18 days, may require ventilation and can be complicated by infections or cardiac arrhythmias. • Pathogenesis unclear but electromyography studies suggest a lesion at the neuromuscular junction AND suboptimal treatment. Cardiac manifestations can include, Sinus tachycardia, sinus bradycardia, Q-T prolongation and ventricular irritability, tachycardia,fibrillation and sudden death.
- 24. Organophosphate induced delayedpolyneuropathy (OPIDP)/ Type 3 Paralysis • Common following exposure to organophoshates which have weak anticholinesterase activity. • Occurs 7-21days after exposure, subacute • Due to exposure and inhibition of neuropathy target esterase, different enzyme not involved in acute OPP. NTE is phosphorylated by OP and undergoes ageing leading to irreversible NTE inhibition. • Distal muscle weaknesss with relative sparing of the neck muscles, CN AND proximal muscle groups characterize OPIDP • Sensorimotor polyneuropathy • Cramping muscle pain followed by sensory disturbances such as numbness and paraesthesia, • Progressive leg weakness • Recovery can take up to 12 months
- 25. Other Neurologic/ Neuropsychiatriceffects • Impaired memory • Significant changes in cognitive abilities (language, memory and abstract thinking) • Chronic organophosphate induced neuropsychiatric disorders: Psychosis, anxiety, insomnia, irritability, depression • Persisting ataxia, chorea • Extrapyramidal effects: dystonia, cogwheel rigidity parkinsonism • Bell s palsy and GBS have been seen. • Opthalmic: optic neuropathy, myopia, retinal degeneration • Ears: Ototoxicity
- 26. DIAGNOSIS • Usually aclinical diagnosis • Smell of pesticides or solvents, and reduced butyrylcholinesterase or acetylcholinesterase activity in the blood. • Patients with severe OPP typically present with pinpoint pupils, excessive sweating, reduced consciousness, and poor respiration. The major differential diagnosis is carbamate poisoning, which is clinically indistinguishable. • RBC acetylcholinesterase is a good marker of synaptic function and hence its more specific than other assays and can be used to assess severity. • Supportive tests: FBC,Metabolic panel, KLFTS CXR –pulmonary edema. ECG – prolonged QT interval, elevated ST segment, sinus tachycardia
- 27. Atropine challenge test Incase clinical presentation is not clear Injection. Atropine 0.6 mg to 1.0 mg may be given IV. Increase in heart rate by more than 20-25 beats/min and flushing would suggest that the patient does not have significant cholinergic poisoning and further observation required. If the opposite occurs then you are dealing with OPP.
- 28. Treatment • Medical emergency •Goals of treatment are rapid diagnosis, prompt treatment with atropine and supportive care. • All patients should be hospitalized atleast for 48 hours due to risk of respiratory compromise in a high dependence unit or ICU depending on severity of symptoms. • Patients who are asymptomatic for atleast 12 hours after OPP exposure can be discharged. • Patients with concomitant trauma trauma should be treated according to the advanced trauma life support (ATLS) protocol • Decontamination of patients should be always done to prevent exposure of medical personnel and re-absorption.
- 29. Emergency Assessment Steps •Medical emergency • Clinical evaluation to confirm the diagnosis and determine if its OPP • Assess clinical severity of condition • Obtain blood and urine samples for lab measurements: FBC/DC, KLFTs, Metabolic screen, Serum and urine toxicology • ABCs • Decontamination • Gastric Lavage • Activated charcoal • 2 IV lines • Medical mgt with atropine, oximes n benzodiazepines • Atropinization is key • Maintenance and observation of respiratory depression
- 30. ABCs General resuscitation: A,B, C • Airway: Secure airway, ensure that the airway is patent. Suction any secretions. Airway control is paramount in OPP. Intubation maybe necessary in cases of severe respiratory distress. • Breathing: Give 100% oxygen to patients with severe respiratory distress or shock • Circulation: Insert 2 IV cannula and take blood samples Provide resuscitative and maintenance crystalloid fluid as indicated. 500- 1000 ml of normal saline (10-20 ml/kg) over 10-20 min to compensate fluid loss due to sweating, diarrhoea and cholinergic hyper-secretion
- 31. Gastric Decontamination • Forcedemesis and syrup Ipecac have no role. • Gastric lavage is indicated once patient is stabilized, calm enough to give consent and in unconscious intubated patient, which is recommended to be repeated after 2-3 hr. Though it has been recommended only to be carried out within 1-2 hours of ingestion of OP/carbamate elsewhere it has been started even after 12 hrs of ingestion and repeated thrice at an interval of 4 hrs • . Repeat stomach wash will remove the residual poison if any/secreted to stomach subsequently from fat stores. After aspirating the contents of stomach through stomach tube, water or normal saline in lots of 300 ml be given and be aspirated. Continue it till the returning fluid is colourless and odourless. ensure that no fluid is left inside the stomach by measuring the fluid taken off. • Contra-indicated if the airway remains compromised.
- 32. Others Important interventions ActivatedCharcoal • Though there is no evidence that either single dose or multiple dose regimens of active charcoal will result in benefit yet a dose of charcoal (50 gm) can be left in the stomach. • Active Cooling And Sedation • Cooling is indicated if the patient is febrile and climate is hot & humid. Agitated patient need to be sedated with Diazepam 10 mg IV slowly which can be repeated up to 30-40 mg/24 hrs. Diazepam will help in allaying anxiety, facilitate gastric lavage, reduce damage to CNS, diminish central respiratory failure and control seizures.
- 33. Antidotes ATROPINE Anticholinergics are competitiveantagonist to Ach and reverse all muscarinic activities both in CnS and peripheral nervous system. Atropine is the only life saving antidote. Full and early atropinisation is an essential and simple part of early management. • Start a Bolus loading dose followed by boluses after a fixed time interval varying from 5-15-30 min till atropinisation or Bolus loading dose followed by infusion. The latter regimen showed improved outcome. 34mls(20mg) OF ATROPINE in 66 mls of NS/HOURLY. • The dose of atropine recommended to be low (1-2 mg) so as to cater for milder cases and then rapidly escalate (doubled each time) to achieve atropinisation quite fast.
- 34. • Alternatively itstarted with a bigger dose (5 mg) to ensure rapid atropinisation. Because of danger of over atropinisation the former practice offers more control by starting with low doses. The peak effect of atropine is seen within three minutes of an IV injection. hence, one need not wait for more than five minutes before giving another bolus. • Infusion is given in severe cases at 0.02-0.08 mg/kg/hr as an infusion or direct iv . Cardiac monitoring is required • Atropine administration by nebulisation also improves respiratory distress and oxygenation. It can also be given through endotracheal tube initially before securing a venous route.
- 35. Criteria of Atropinisation Thetarget end points for atropine injection is Atropinisation. • Clear chest on auscultation with no wheeze • Heart rate> 80 beats/min • Pupil no longer pin point • Dry axilla • Systolic blood pressure > 80 mm of hg
- 36. Atropine maintenance • Targetend point once achieved is to be maintained by atropine infusion. • Infusion of atropine reduces the fluctuation in atropine concentration associated with repeated bolus doses. • The rate of infusion is set at 10 -20 % of the total atropine required to load the patient every hour. • Duration of maintenance atropine therapy: - This depends on the severity and response to therapy. Usually it is maintained for 24- 48 hrs or longer in severe cases, and gradually withdrawn over 3-5 days. Frequent observation is required to detect early signs of intermediate syndrome. Tidal volume and blood gases are to be measured.
- 37. Observation • Observations madeinitially after each atropine dose is entered in the observation sheet. • Once atropinisation has been attained, those five parameters are to be monitored every 15 minutes initially which can be gradually increased to 1-2-3 hours depending on the state of atropinisation. • Close observation and monitoring plays not only a vital role in the management but also can contribute to the learning process by gathering new symptoms and signs and can anticipate recurring cholinergic crisis which may occur with little notice.
- 38. Atropine/ Carbamate ObservationChart TIME HR CLEAR LUNGS PUPIL SIZE DRY AXILLA BP MENTAL STATE SPO2 ATROPIN E DOSE FEVER >37.5
- 39. Atropine Toxicity • Confusion,agitation • Hyperthermia, • Ileus, • Tachycardia Discontinuation of the atropine infusion, followed by frequent observation. When they settle down the infusion is to be started at 70- 80 % of the previous rate, hyperthermia is a serious complication in hot wards which needs prevention.
- 40. Alternative Drugs ToAtropine • Glycopyrrolate: Equally effective with fewer central nervous system side effects and better control of secretions.7.5 mg of glycopyrolate in 200ml of saline is started as infusion and is titrated to the desired effects of dry mucus membranes. • Diphenhydramine can be an alternate centrally acting anticholinergic agent if atropine is not available • Magnesium Therapy: - magnesium therapy in addition to atropine and oximes has been found to benefit. The mechanism appears to be inhibition of AChe and OP antagonism.
- 41. Oximes/Cholinesterase Reactivators • Theseagents known as oximes get attached to the free anionic site of the enzyme Che. The oxime end then reacts with the phosphorus atom of OP attached at the esteratic site of the enzyme. This oxime phosphate so formed diffuses away leaving the enzyme intact. • In addition to reactivation they also slow the ageing of the phosphoylated enzyme complex and has a direct action in converting the OP to a harmless compound. • Reactivation of CHE is more marked in the skeletal muscle than at autonomic site and not at all in CnS (Do not enter CnS). Thus their use in OP poisoning is secondary to that of atropine.
- 42. • (Pralidoxime, Obidoxime) •Widely used in OPP poisoning along with atropine within 24-48 hours post ingestion as pralidoxime chloride 1 gm every 3-4h for 1-3 days. WhO guidelines recommended giving a 30 mg/kg loading dose of Pralidoxime over 10-20 min followed by a continuous infusion of 8-10 mg/kg/hr until clinical recovery or seven days have elapsed whichever is later. • Where obidoxime is available a loading dose of 250 mg is followed by an infusion of 750 mg every 24 hrs.
- 43. • Furosemide: -It is recommended if pulmonary oedema persists, even after full atropinisation. • Antibiotics:- Broad spectrum antibiotics are to be instituted as per antibiotics policy of the institution as per antibiotics policy of the institution, considering the risk of infection due to frequent and multiple interventions. Othersise no role for antibiotics in OPP • No role of omeprazole
- 44. TAKE HOME POINTS •OPP is a worldwide problem, and cases are on the rise in Mazabuka. • OPP and carbamate poisoning usually present the same way, and are difficult to differentiate, but they are treated the same way. • It’s a medical emergency hence it requires rapid diagnosis, prompt treatment with atropine and supportive care. If not promptly managed it leads to mortality and long-term complications. • It’s a clinical diagnosis, if not sure do atropine challenge test. • Do gastric lavage regardless of timeframe, helps with good outcomes. • Airway support is also key, if not properly managed patients die from respiratory failure. • Severe cases should be managed in ICU, lookout for ventilation.
- 45. References • Zambia NationalGuidelines 2025 • NK Sundaray, Ratheesh Kumar J, ORGAnOPhOSPhORUS POISOnInG: CURRenT mAnAGemenT GUIDelIneS • Haddad LM. Organophosphates and other insecticides. In: Haddad LM, Winchester J, Eds. Clinical management of poisoning and drug overdose. W.B. Saunders Company 1990; 1076-87 • Tafuri J,Roberts J.Oraganophosphate poisoning. Ann Emerg Med 1987; 16:193-202 • Katz Kenneth D, Brooks Daniel E. Toxicity, Organophosphate. Last updated May 13 2009 http/www.emedicine.medscape. com
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