Emergency treatment of Emergency treatment of Acute Organophosphate Pesticides Poisoning (A O P P) Emergency department Wenzhou People’s hospital 吴瑞克

Content Classification Classification Pathogenesy Pathogenesy Manifestation Manifestation Management Management

Characteristics Oily Oily Smell like garlic. Smell like garlic. It can easily be decomposed under alkaline conditions. It can easily be decomposed under alkaline conditions.

Characteristics The patients with AOPP are sometimes in critical condition. The patients with AOPP are sometimes in critical condition. After proper treatments in time most of the patient’s lives can be rescued. After proper treatments in time most of the patient’s lives can be rescued.

Classification LD 50 mg/kg Regularly used organophosphorus Extremely hazardous ≤10 Phorate, Parathion(1605) Highly hazardous 10~ 100 Parathion-methyl, Methamidophos, Omethoate, DDWP Moderately hazardous 100~ 1000 Rogor, Dipterex Slightly hazardous 1000~ 5000 Malathion, Chlorthion

Routes of entry ：  Skin  Resp. tract  GI. tract 浓度最高 其次：肾、 肺、脾等 Enterohepatic circulation

Pathogenesy The primary mechanism of action of OP is inhibition of acetylcholinesterase(AChE): The primary mechanism of action of OP is inhibition of acetylcholinesterase(AChE): Phosphate+AChE Phosphate+AChE →Phospharylated AChE→ →Phospharylated AChE→ The Acetylcholine(ACh) ↑↑ The Acetylcholine(ACh) ↑↑

Pathogenesy The Ach accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic recepters which can be found in the nervous system and neuromuscular junction. The Ach accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic recepters which can be found in the nervous system and neuromuscular junction.

Normal Nerve Function ACh Synapse Neuromuscular junction Presynaptic membrane Postsynaptic membrane Motor end-plate

Normal Nerve Function ACh Synapse Neuromuscular junction M and N receptor Postsynaptic membrane Motor end-plate Presynaptic membrane

Normal Nerve Function ACh AChE Synapse Neuromuscular junction Hydrolyze acetylcholine

How OP Works: Reversible & Aged Binding AChE ACh OPs Synapse Neuromuscular junction

CNS effects Nicotinic effects Muscarinic effects

Manifestations  1.Cholinergic crisis  Muscarinic effects  Nicotinic effects  CNS effects  2.Intermediate syndrome(IMS)  3.Organophosphate-induced delayed polyneuropathy (OPIDP) Signs and symptoms of OPs poisoning can be divided into 3 broad categories.

Muscarinic effects is duo to excessive parasympathetic activation.  Smooth  Smooth muscle spasm GI: nausea, vomite, abdominal pain, increased peristaltic sounds. Urinary tract: frequency of urination, urinary incontinence. Bronchus: tachypnea, dyspnea.  Ocular: Ocular: pinpoint pupil(miosis), pupil(miosis), blurred blurred vision.  Sphincter  Sphincter relaxation  Incontinence  Incontinence of urine and feces  Cardiovascular  Cardiovascular symptoms Bradycardia, hypotension  Over  Over active Glands(sympathetic Glands(sympathetic cholinergic nervous )  Increased  Increased lacrimation, lacrimation, diaphoresis  Sputum  Sputum and moist rale, diarrhea

Nicotinic effects Stimulation Stimulation of muscle motor end-plate –Fasciculation –Fasciculation → Weakness Paralysis → Paralysis –Respiratory –Respiratory muscle paralysis peripheral → peripheral respiratory failure Stimulation Stimulation of sympathetic nervous system –Tachycardia –Hypertension –Arrhythmia

CNS symptom Serious effects Serious effects –Coma –Respiratory centre depression(Central RF) –Seizures Other effects Other effects –Confusion –Memory loss –Disorientation –Delirium

Intermediate syndrome (IMS) Typically 1-3 days after cholinergic crisis has resolved, and before delayed polyneuropathy. Typically 1-3 days after cholinergic crisis has resolved, and before delayed polyneuropathy. Proximal muscle weakness and cranial nerve lesions. Proximal muscle weakness and cranial nerve lesions. Delayed Respiratory Failure. Delayed Respiratory Failure.

Mechanism of IMS Prolonged Effects on Nicotinic receptors because of the accumulation of Ach in the neuromuscular junction Prolonged Effects on Nicotinic receptors because of the accumulation of Ach in the neuromuscular junction → Motor end-plate degeneration → Motor end-plate degeneration → Neuromuscular block → Neuromuscular block → Peripheral respiratory failure → Peripheral respiratory failure

Clinical importance of IMS Delayed respiratory failure leads to death if not aware of it or prepared for it. Delayed respiratory failure leads to death if not aware of it or prepared for it. Mechanical ventilation may be the only effective emergency measures. Mechanical ventilation may be the only effective emergency measures.

Organophosphate-induced delayed polyneuropathy (OPIDP) Occurs 1-5 weeks after exposure to large doses of certain OPs. Occurs 1-5 weeks after exposure to large doses of certain OPs. –Begin with shooting pains in both legs, then upper extremities. –Quadriplegia. –Standard treatments are ineffective.

Complications 1.Respiratory failure 1.Respiratory failure 2.Shock 2.Shock  myocardial injury, cardiac contractility reduced, cardiac arrhythmia.  Peripheral circulatory failure, angiectasis.  Inhibition of the cardiovascular central.  Hypovolemic shock due to dehydration. 3.Malignant arrhythmia. 3.Malignant arrhythmia. 4.Brain edema. 4.Brain edema.

Measurement of acetylcholinesterase (AChE) activity. Measurement of acetylcholinesterase (AChE) activity. Most widely used for a diagnosis of OP, for judgement of severity and effect of treatment. Most widely used for a diagnosis of OP, for judgement of severity and effect of treatment. It is an objective indicator which can be a guidance for the dosage of antidote. It is an objective indicator which can be a guidance for the dosage of antidote. Laboratory Studies

Management The priority in management is : Resuscitation! Resuscitation!

Resuscitation Recognition of life threatening events when you work in ED. Recognition of life threatening events when you work in ED. The ABCDE approach is the prior task we have to do in early treatment of critical illness. The ABCDE approach is the prior task we have to do in early treatment of critical illness.

The ABCDE approach Airway & assessment Breathing, ventilation & oxygenation Circulation & shock management Disability due to neurological deterioration Exposure & examination

 1. Gastric lavage ： Usualy use warm water. Every time ml, 10,000-30,000ml in total ， until the liquid washing out is clear and without the smell of OPs. Feed Activated Charcoal via nasal-gastric tube after gastric lavage. 2% sodium bicarbonate （ dipterex  ） 2% sodium bicarbonate （ dipterex  ） 1:5000 potassium permanganate （ parathion, malathion  ） 1:5000 potassium permanganate （ parathion, malathion  ）  2. Catharsis : 20% Mannitol Na 2 SO 4 The effect maybe not obvious because The effect maybe not obvious because of a high dose of atropine. of a high dose of atropine. Gastrointestinal Decontamination

GI Decontamination is NOT a life saving procedure! GI Decontamination is NOT a life saving procedure! –Should not be performed before resuscitation Gastrointestinal Decontamination

Risks Aspiration Trauma Electrolyte Imbalances Cardiac Arrest Benefits Removal of poison load Prevention of ongoing poison absorption Gastrointestinal Decontamination

Cholinesterase reactivator — Pralidoxime Cholinesterase reactivator — Pralidoxime Anticholinergic drugs — Atropine, Scopolamine Anticholinergic drugs — Atropine, Scopolamine Medication

Pralidoxime——release nicotinic effect. Pralidoxime——release nicotinic effect. – Giving the pralidoxime sufficiently and in time can improve the prognosis. – Pralidoxime –chloride(PAM-Cl) 1 、 Cholinesterase reactivator

Characteristic of PAM-CL  The effect of pralidoxime depends on the first time of administration and the dose. The sooner the better.

 It is not effective once the OP compound has bound AChE irreversibly (aged phosphorylated AChE).  For the “aging” time is about 24~36h after poisoning,the pralidoxime should be used within 48h, preferably within 30 minutes. Characteristic of PAM-CL

 ＝  T1/2 ＝ 1-1.5h   Usage: iv. or im.  iv gtt. 

2 、 Atropine 2 、 Anticholinergic drugs — Atropine Competitively inhibit ACh receptors including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eyes. Competitively inhibit ACh receptors including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eyes. In order to relieve the muscarinic symptoms and anti respiratory inhibition. In order to relieve the muscarinic symptoms and anti respiratory inhibition.

Atropine   Is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally   Competitive inhibitor at ACh receptors   No obvious effect on central nicotinic receptors—— The effect on convulsion, and respiratory centre depression is poor.

Mild (mg) Moderate(mg) Severe(mg)  Atropine 2~4 4~10 10~20 Administer repeatedly until atropinisation. Dosage of anticholinergic drugs

Atropinisation Atropinisation endpoint Atropinisation endpoint –Dry axillae; –HR bpm; –Slight fever,T ℃ ; –Slight dysphoria; –Pupils no longer pinpoint, facial flushing and chest clear with no rale are reference indexes. What if you give too much Atropine ? What if you give too much Atropine ? –Anticholinergic Syndrome ： Delirium, restless, hallucination, convulsion, high fever, Delirium, restless, hallucination, convulsion, high fever, Facial flushing, tachycardia, urinary retention. Facial flushing, tachycardia, urinary retention. Sedatives may help to relieve it. Sedatives may help to relieve it.

Proper usage of antidotes   Administer as soon as possible.  Use a combination of a variety of antidotes  Use a combination of a variety of antidotes.  Use adequate dosage for the first time  Use adequate dosage for the first time.   Repeated administration according to the patient’s condition.

Comprehensive supportive therapy 1.Eliminate the source of poisons. 2.Eliminate the poisons which have been absorbed. – –Hemoperfusion Should be carried out within 24h,and repeated for 1-2 times. Indication:   Severe poisoning;   Patient’s condition deteriorate with routing therapy;   Liver dysfunction. Charcoal filter

3.Keep a patent airway; Inhale O 2 ; Provide adequate oxygenation and ventilation; And administer mechanical ventilation if it is necessary. 4. Prevent cerebral edema, and use naloxone to ease disturbance of consciousness. 5.Monitor vital sign; Monitor fluid input and output; Treat metabolic disturbances such as electrolyte abnormalities. Comprehensive supportive therapy