Emergency treatment ofEmergency treatment ofAcute Organophosphate Pesticides Poisoning

(A O P P)

Emergency department

Wenzhou People’s hospital

吴瑞克

ContentContent

ClassificationClassification PathogenesyPathogenesy ManifestationManifestation ManagementManagement

CharacteristicsCharacteristics

OilyOily

Smell like garlic.Smell like garlic.

It can easily be It can easily be decomposed under decomposed under alkaline conditions.alkaline conditions.

CharacteristicsCharacteristics

TheThe patientspatients withwith AOPPAOPP areare sometimessometimes inin criticalcritical condition.condition.

AfterAfter properproper treatmentstreatments inin timetime mostmost ofof thethe patient’spatient’s liveslives cancan bebe rescued.rescued.

ClassificationClassificationLD50

mg/kg Regularly used organophosphorus

Extremely

hazardous

≤10 Phorate, Parathion(1605)

Highly hazardou

s

10~

100

Parathion-methyl,

Methamidophos, Omethoate, DDWP

Moderately

hazardous

100~

1000Rogor, Dipterex

Slightly hazardou

s

1000~5000

Malathion, Chlorthion

Routes of entry ： Skin Resp. tract GI. tract

浓度最高 其次：肾、 肺、脾等

Enterohepatic circulation

PathogenesyPathogenesy

The primary mechanism of action of OP The primary mechanism of action of OP

is inhibition of is inhibition of

acetylcholinesterase(AChE): acetylcholinesterase(AChE):

Phosphate+AChEPhosphate+AChE

→ →Phospharylated AChEPhospharylated AChE→→ The Acetylcholine(ACh) The Acetylcholine(ACh) ↑↑↑↑

PathogenesyPathogenesy

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

Normal Nerve FunctionNormal Nerve Function

AChAChSynapse Neuromuscular junction

Presynaptic membrane Postsynaptic membraneMotor end-plate

Normal Nerve FunctionNormal Nerve Function

AChACh

Synapse Neuromuscular junction

M and N receptor

Postsynaptic membraneMotor end-plate Presynaptic membrane

Normal Nerve FunctionNormal Nerve Function

AChACh

AChEAChE

Synapse Neuromuscular junction

Hydrolyze acetylcholine

How OP Works: How OP Works: Reversible & Aged Reversible & Aged BindingBinding

AChEAChE

AChACh OPsOPsSynapse Neuromuscular junction

CNS effects

Nicotinic effects

Muscarinic effects

ManifestationsManifestations 1.Cholinergic crisis1.Cholinergic crisis

Muscarinic effectsMuscarinic effects

Nicotinic effectsNicotinic effects

CNS effectsCNS effects

2.Intermediate syndrome(IMS)2.Intermediate syndrome(IMS)

3.Organophosphate-induced 3.Organophosphate-induced

delayed polyneuropathy delayed polyneuropathy (OPIDP)(OPIDP)

Signs and Signs and symptoms of OPs symptoms of OPs poisoning can be poisoning can be divided into 3 divided into 3 broad categories. broad categories.

Muscarinic effects Muscarinic effects is duo to is duo to excessive parasympathetic activation. excessive parasympathetic activation.

Smooth muscle spasmSmooth muscle spasm GI: nausea, vomite, abdominal pain, increased peristaltic sounds.GI: nausea, vomite, abdominal pain, increased peristaltic sounds.

Urinary tract: frequency of urination, urinary incontinence.Urinary tract: frequency of urination, urinary incontinence.

Bronchus: tachypnea, dyspnea.Bronchus: tachypnea, dyspnea.

OcularOcular: pinpoint pupil(: pinpoint pupil(miosismiosis), b), blurred vision.lurred vision.

Sphincter relaxationSphincter relaxation Incontinence of urine and fecesIncontinence of urine and feces

Cardiovascular symptoms Cardiovascular symptoms Bradycardia, hypotensionBradycardia, hypotension

Over active Over active GlandsGlands(sympathetic cholinergic (sympathetic cholinergic nervous ) nervous ) Increased lacrimationIncreased lacrimation, , diaphoresisdiaphoresis Sputum and moist rale, diarrheaSputum and moist rale, diarrhea

Nicotinic effects

Stimulation of muscle motor end-plateStimulation of muscle motor end-plate– Fasciculation Fasciculation → Weakness Weakness → ParalysisParalysis– Respiratory muscle paralysis Respiratory muscle paralysis → peripheral peripheral

respiratory failurerespiratory failure

Stimulation of sympathetic nervous Stimulation of sympathetic nervous systemsystem– Tachycardia Tachycardia – Hypertension Hypertension – ArrhythmiaArrhythmia

CNS symptomCNS symptom

Serious effectsSerious effects– ComaComa– Respiratory centre depression(Central RF) Respiratory centre depression(Central RF) – SeizuresSeizures

Other effectsOther effects– ConfusionConfusion– Memory lossMemory loss– DisorientationDisorientation– DeliriumDelirium

Intermediate Intermediate syndromesyndrome(IMS)(IMS)

Typically Typically 1-3 days 1-3 days after after cholinergic crisis has resolved, cholinergic crisis has resolved, and before and before delayed delayed polyneuropathypolyneuropathy..

Proximal muscle Proximal muscle weaknessweakness and and cranial nerve lesionscranial nerve lesions..

Delayed Delayed Respiratory FailureRespiratory Failure..

Mechanism of IMSMechanism of IMS

Prolonged Effects on Nicotinic Prolonged Effects on Nicotinic receptors because of the receptors because of the accumulation of Ach in the accumulation of Ach in the neuromuscular junctionneuromuscular junction

→ → Motor end-plate degeneration Motor end-plate degeneration

→ → Neuromuscular blockNeuromuscular block

→ → Peripheral respiratory failurePeripheral respiratory failure

Clinical importance of Clinical importance of IMSIMS

Delayed respiratory failure leads to Delayed respiratory failure leads to death if not aware of it or prepared death if not aware of it or prepared for it.for it.

MM echanical echanical ventilation ventilation may be the may be the only effective emergency measures.only effective emergency measures.

Organophosphate-induced Organophosphate-induced delayed polyneuropathy delayed polyneuropathy (OPIDP) (OPIDP) OOccurs ccurs 11 --55 weeks weeks after exposure to large doses oafter exposure to large doses o

f certain OPsf certain OPs..

– Begin with Begin with shooting pains shooting pains in both legs, in both legs,

then upper extremities.then upper extremities.

– QuadriplegiaQuadriplegia..

– Standard treatments are ineffective.Standard treatments are ineffective.

ComplicationsComplications

1.Respiratory failure1.Respiratory failure

2.Shock2.Shock myocardial injury, cardiac contractility reduced, cardiac myocardial injury, cardiac contractility reduced, cardiac

arrhythmiaarrhythmia..

Peripheral circulatory failure, angiectasis.Peripheral circulatory failure, angiectasis.

Inhibition of the cardiovascular central.Inhibition of the cardiovascular central.

Hypovolemic shock due to dehydrationHypovolemic shock due to dehydration..

3.Malignant arrhythmia.3.Malignant arrhythmia.

4.Brain edema.4.Brain edema.

Measurement of Measurement of acetylacetylcholinesterasecholinesterase (AChE) (AChE) activiactivityty..

Most widely used for a diagnosis of OP, for Most widely used for a diagnosis of OP, for

judgement of judgement of severityseverity and and effect of treatment.effect of treatment.

It is an objective indicator which can be a It is an objective indicator which can be a

guidance for the dosage of guidance for the dosage of antidote.antidote.

Laboratory StudiesLaboratory Studies

ManagementManagement

The priority in management is :The priority in management is :

Resuscitation!Resuscitation!

ResuscitationResuscitation

Recognition of life threatening events Recognition of life threatening events when you work in ED.when you work in ED.

The ABCDE approach is the prior The ABCDE approach is the prior task we have to do in early task we have to do in early treatment of critical illness.treatment of critical illness.

The The ABCDE approachABCDE approach

Airway &assessment

Breathing , ventilation & oxygenation

Circulation & shock management

Disability due to neurological deterioration

Exposure & examination

1. 1. Gastric lavageGastric lavage ：： Usualy use warm water. Usualy use warm water.

Every time 300-500ml,Every time 300-500ml, 10,000-30,000ml in 10,000-30,000ml in

totaltotal ，， until the liquid washing out is clear and until the liquid washing out is clear and

without the smell of OPs.without the smell of OPs. Feed Activated Charcoal Feed Activated Charcoal

via nasal-gastric tubevia nasal-gastric tube after gastric lavage.after gastric lavage.

2%2%sodium bicarbonatesodium bicarbonate （（ dipterexdipterex ）） 1:50001:5000potassium permanganatepotassium permanganate （（ parathion, parathion,

malathionmalathion ）） 2. 2. CatharsisCatharsis:: 20% 20%Mannitol NaMannitol Na22SOSO44

The effect maybe not obvious becauseThe effect maybe not obvious because

of a high dose of atropine. of a high dose of atropine.

Gastrointestinal Gastrointestinal DecontaminationDecontamination

GI Decontamination is GI Decontamination is NOTNOT a life a life saving procedure!saving procedure!– Should not be performed before Should not be performed before

resuscitationresuscitation

Gastrointestinal Gastrointestinal DecontaminationDecontamination

Risks

•Aspiration

•Trauma

•Electrolyte Imbalances

•Cardiac Arrest

Benefits

•Removal of poison load

•Prevention of ongoing poison absorption

Gastrointestinal Gastrointestinal DecontaminationDecontamination

Cholinesterase reactivator — PCholinesterase reactivator — Pralidralidoximeoxime

Anticholinergic drugs — Atropine,Anticholinergic drugs — Atropine, Scopolamine Scopolamine

MedicationMedication

PP ralidoximeralidoxime——release nicotinic ——release nicotinic

effect.effect.

– Giving the pGiving the pralidralidoxime oxime

sufficiently and in time can sufficiently and in time can

improve the prognosis.improve the prognosis.

– PP ralidoxime ralidoxime –chloride(PAM-Cl) –chloride(PAM-Cl)

11 、、 Cholinesterase Cholinesterase reactivatorreactivator

CharacteristicCharacteristic of PAM- of PAM-CLCL The effect of pralidoxime The effect of pralidoxime

depends on the first time of depends on the first time of

administration and the dose. administration and the dose.

The sooner the better.The sooner the better.

It is not effective once the OP compouIt is not effective once the OP compound has bound AChE irreversibly (agednd has bound AChE irreversibly (aged pphosphorylated AChE).hosphorylated AChE).

For the “aging” time is about 24~36h For the “aging” time is about 24~36h after poisoning,the pralidoxime should after poisoning,the pralidoxime should be used within 48h, be used within 48h, preferably within preferably within

30 minutes. 30 minutes.

CharacteristicCharacteristic of PAM- of PAM-CLCL

Characteristic of PAM-Characteristic of PAM-CLCL

T1/2 ＝＝ 1-1.5h

Usage: iv. or im.

iv gtt.

22 、、 Anticholinergic drugs—AtropineAtropine

Competitively inhibit ACh receptors including receptoCompetitively inhibit ACh receptors including receptors found in GI and pulmonary smooth muscle, exocrine rs found in GI and pulmonary smooth muscle, exocrine glands, heart, and eyeglands, heart, and eyes.s.

IIn order to n order to relieve the relieve the muscarinic symptoms and muscarinic symptoms and anti respiratory inhibition.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 Dosage of anticholinergic drugsdrugs

AtropinisationAtropinisation

AtropinisationAtropinisation endpointendpoint– Dry axillae;Dry axillae;– HR 90-100bpm;HR 90-100bpm;– Slight fever,T37.3-37.5℃;Slight fever,T37.3-37.5℃;– Slight dysphoria;Slight dysphoria;– Pupils no longer pinpoint, facial flushing and chest Pupils no longer pinpoint, facial flushing and chest

clear with no rale are reference indexes.clear with no rale are reference indexes. What if you give too much Atropine ?What if you give too much Atropine ?

– Anticholinergic Syndrome Anticholinergic Syndrome ：： Delirium,Delirium, restless,restless, hallucination,hallucination, convulsion,convulsion, highhigh

fever,fever, Facial flushing,Facial flushing, tachycardia,tachycardia, urinary retention.urinary retention. SedativesSedatives may help to relieve it. may help to relieve it.

Proper usage of Proper usage of antidotesantidotes Administer as soon as possible.

Use a combination of a variety of Use a combination of a variety of

antidotesantidotes.

Use adequate dosage for the first timeUse adequate dosage for the first time.

Repeated administration according

to the patient’s condition.

Comprehensive supportive Comprehensive supportive therapy 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.

Charcoalfilter

3.Keep a patent airway; Inhale O2; 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 Comprehensive supportive therapy therapy