Pesticide and

Herbicide Poisoning
SANGEETHA
GROUP D

1/12/2020
 PESTICIDES
Mainstay of
INSECTICIDES treatment is
supportive care
and some
antidotes are
essential
PESTICIDES

HERBICIDES RODENTICIDES
INSECTICIDES

ORGANOPHOSPHATES
INSECTICIDES:
1. Organophosphate
2. Carbamates
3. Organochlorines
4. Pyrethrins/pyrethroids
5. Neonicotinoids
6. Nereistoxin analogs
ORGANOPHOSPHATES
1 INTRODUCTION

2 ABSORPTION PATHOPHYSIOLOGY
3

4 CLINICAL SYNDROME

6 MANAGEMENT

DIAGNOSIS
5
INTRODUCTION
 Commonly used OPs:
1. Malathion
2. Parathion
3. Diazinon
4. Acephate
5. Chlorpyrifos

 Most commonly from deliberate self-poisoning

ABSORPTION

INGESTION INHALATION

DERMAL
PATHOPHYSIOLOGY
Pseudocholinesterase/
TRUE / RBC
Plasma
Acetylcholinesterase
Acetylcholinesterase

Serum
Liver
Pancreas
RBC Heart
Nervous tissue Brain
Skeletal muscle
How it becomes toxic?
1. Toxicity is produced through binding and
inhibition of Acetylcholinesterase
2. That causes excess accumulation of
acetylcholine and simulations of cholinergic
receptors (both muscarinic and nocotinic receptor
types).
∞ Muscarinic → Post ganglionic parasympathetic
nerve ending
∞ Nicotinic → Neuromuscular junction
AGING
1. Describes the permanent irreversible binding of
OP to acetylcholinesterase

2. Once aging occurs, the enzymatic activity of

acetylcholinesterase is permanently destroyed
 Organophosphate inhibits
Acetylcholinesterase

Accumulation of acetylcholine

MUSCARINIC NICOTINIC

Central Nervous System Peripheral Nervous System Neuromuscular Junction

Neurotoxicity

Clinical Manifestation

Initial Cholinergic Crisis Intermediate Syndrome Delayed Polyneuropathy

CLINICAL SYNDROME
1. Acute poisoning (cholinergic crisis)
2. Intermediate syndrome
3. Chronic toxicity
4. Organophosphate-induced delayed neuropathy
CHOLINERGIC CRISIS
1 MUSCARINIC EFFECTS

D Diarrhoea
U Urination KILLER
BEES
M Miosis
B Bradycardia, Bronchorrhea , Bronchospasm
E Emesis
L Lacrimation
S Salivation
CHOLINERGIC CRISIS
1 MUSCARINIC EFFECTS

S Salivation
L Lacrimation
U Urinary in continence
D Defecation
G GI pain
E Emesis
CHOLINERGIC CRISIS
CHOLINERGIC CRISIS
2 NICOTINIC EFFECTS

M Mydriasis MTWTHF (Days of the

T Tachycardia Week)
W Weakness
T Twitching
H Hypertension
F Fasciculation
CHOLINERGIC CRISIS
3 CNS EFFECTS

● Anxiety, restlessness, emotional lability

● Tremor, headache, dizziness
● Confusion, delirium, hallucinations
● Seizures, coma
ONSET OF SYMPTOMS
∞ Minutes to hours
∞ Varies base on amount and route of exposure

∞ Most patients become symptomatic within 8

hours of acute exposure.

∞ BUT Fat-soluble agents (eg FENTHION) can

cause delayed symptoms with dermal exposure
Effects of nicotinic receptor
stimulation
Nicotinic receptor simulation leads to :
∞ Fasciculation and muscle weakness .
 Most pronounced in the respiratory muscles
 Leads to worsening pulmonary dysfunction caused by bronchorhea from
muscarinic effects

∞ Nicotinic effects can also cause tachycardia and mydriasis

 Paradoxical to the expected muscarinic cholinergic effects

∞ CNS Effects  predominate in children

 Tremors/restlessness/confusion/seizures/coma
 Intermediate OP Induce Delayed
Chronic Toxicity
Syndrome Neuropathy
• 1-5 days after • Daily exposure in • 1-3 weeks after
exposure agriculture workers exposure
• Clinical features – • Symmetrical sensory • Cognitive
Paralysis of motor axonopathy dysfunction
• neck flexor muscle • Impaired memory
• muscle innervated • Mood changes
by cranial nerves • Autonomic
• proximal limbs dysfunction
muscle
• respiratory muscle
• Resolved within 7
days
Severity of Effects with OP
Poisoning
 Intermediate syndrome → 5 -7 days after acute poisoning
∞ Paralysis/weakness of neck/fascial/respiratory muscles
∞ Can result in respiratory arrest if not treated

 OP induced delayed neuropathy → 1-3 weeks after acute

poisoning
∞ Results in distal motor-sensory polyneuropathy with leg
weakness and paralysis
 DIAGNOSIS
LAB DIAGNOSIS

Direct measurement
Plasma
RBC
cholineseterase
Acetylcholinesterase

 Measure the degree  Does not measure

of toxicity degree of toxicity
 Determine effect of  Does not determine
treatment effect of treatment
DIAGNOSIS
∞ OP poisoning typically a clinical diagnosis based on
toxidrome and history of exposure

∞ Lab cholinesterase assay → Helps in diagnosis

∞ ECG is very useful → Monitor prolonged QT

(associated with increased morbidity and mortality in
OP poisoning )
OP DIAGNOSIS
MAINLY CLINICAL DIAGNOSIS
MANAGEMENT

DECONTAMINATION PRALIDOXIME

2 4
SEIZURE
CONTROL
5
1 3
ABC ATROPINE
MANAGEMENT
∞ Check airway, breathing, circulation.
∞ Monitor arterial oxygen saturation, cardiac rhythms, BP, PR
∞ Look for signs & symptoms.
∞ Get IV access.
∞ Remove the contaminated clothes & wash the skin thoroughly
with soap & water
∞ Give atropine intravenously as soon as possible for symptomatic
patient
∞ Gastric decontamination with gastric lavage once the patient is
stabilized & within two hours of ingestion.
∞ Give activated charcoal (50 g in 200 ml)
∞ Maintainance atropine infusion
∞ Give pralidoxime.
MANAGEMENT
DECONTAMINATION

∞ Wear PPE
∞ Remove and disposed clothes
∞ Wash patient with soap and water
∞ Handle and disposed water runoff
MANAGEMENT
ATROPINE Adequate Atropinization
1. Clear chest on
∞ Bolus: IV Atropine 1.2-3mg auscultation
2. HR >80bpm
(children 0.05mg/kg) – double 3. SBP > 80mmHg
the dose every 5 minutes until 4. Dry Axilla
adequate atropinization
Atropine Toxicity
∞ Maintenance: 10-20% of initial 1. Absent bowel sound
2. Hyperthermia
dose of atropine required to 3. Delirium
achieve adequate
atropinization
MANAGEMENT
ATROPINE

Maintenance infusion
 Once the patient is stable start an infusion of 5% dextrose
containing 10-20% of the total initial dose of atropine on an hourly
basis
 Stop atropine infusion if features of toxicity appears:
confusion tachycardia agitation flushing urinary retention
hyperthermia bowel ileus
MANAGEMENT
PRALIDOXIME

∞ Give ASAP

∞ Dose:
 IV 30mg/kg infused over 5-10 minutes
 Maintenance: IV 8mg/kg/hr for 24-48H
∞ Mechanism of Action
 Displaced OP from active site of acetylcholinesterase
→ reactivating enzymes
ED Principle of Management :
∞ Treatment should not be delayed
∞ Should not delay in management while awaiting for pending
confirmation tests

In symptomatic patients
∞ Administer 100% oxygen and focus on airway management
∞ Gentle suctioning of secretions
∞ Non depololarizing agents should be used for RSI
∞ Use of succinylcholine for intubation → metabolized by
plasma cholinesterase may result in prolonged paralysis
Key treatment is :
Large amount of ATROPINE
∞ Titrated to attenuation of tracheobronchial secretions
∞ Tachycardia and dilated pupils are not contraindications to
additional atropine
∞ Atropine will only reverse the muscarinic effects , but NOT
the Nicotinic effects of excess acetylcholine
∞ Minimal exposure requires only 6-8 hours of observation
∞ Some may develops symptoms again if re-exposure to
contaminated clothing( particularly leather )
∞ Significant poisonings require intensive care monitoring.
Mortality rates depend on
∞ Typed of compound used
∞ Amount ingested
∞ General health of patient
∞ Delay in discovery and transport
∞ Insufficient respiratory management
∞ Delay in intubation
∞ Failure of weaning off ventilatory support
GLYPHOSPHATE
SURFACTANT HERBICIDES
(ROUNDUP©)
∞ Mechanism poorly understood
∞ Symptoms same as OP poisoning
∞ Mainly GI symptom and corrosive effect on GI tract
∞ Present of surfactant = severe metabolic acidosis ,
hyperkalemia, CVS collapse
∞ No antidote
∞ Supportive treatment only
∞ Admissions for observations, multi-organ failure
might need ICU
∞ Intubations if present of respiratory distress or
stridors related to oropharyngeal injury
∞ Hypotension – give fluid and vasopressors
∞ GI symptoms – antiemetic
HERBICIDES

Most dangerous are BIPYRIDYL HERBICIDES

PARAQUAT
PARAQUAT
1 INTRODUCTION

2 PATHOPHYSIOLOGY CLINICAL FEATURES

3

DIAGNOSIS
4

5 MANAGEMENT
INTRODUCTION
∞ Agents used to kill weed

∞ Addition to intrinsic toxicity, they may also be

packaged with surfactants/solvents with their
own toxic effects

∞ Most dangerous are BIPYRIDYL HERBICIDES

→ PARAQUAT
INTRODUCTION
∞ Rapidly acting, non selective herbicide
∞ Inexpensive
∞ Dermal exposure → Limited localised injury
∞ Ingestion → High case fatality rate
∞ Especially toxic with lethality seen with oral doses of 10-
20ml in an adult and 4-5ml in children ( 20% solution)
INTRODUCTION
∞ Decontamination of skin is important to prevent
continued absorption

∞ Early after ingestion → GI decontamination with

activated charcoal/fuller's earth may be helpful

∞ Charcoal hemoperfusion may remove paraquat

∞ Because of poor prognosis, patients will be admitted for

further observation and treatment
PATHOPHYSIOLOGY
 PATHOPHYSIOLOGY
Concentrated
Redox cycling Cell anaerobic
inside cells

Oxidative stress

Secondary Multi-organ failure

Cellular damage
inflammatory
ABSORPTION Lungs Heart Kidneys
response
Liver

∞ Renal, cardiac and hepatic failure along with pulmonary fibrosis

from oxidative damage
∞ Thus, treatment often includes restriction of supplemental oxygen
accept for severe hypoxia
CLINICAL FEATURES
MILD
∞ Asymptomatic or GI symptoms
<20mg/kg ∞ Complete recovery
<7.5mls of 20% concentration

SEVERE ∞ Initial: GI symptoms, mouth ulceration

∞ 1-4days: Renal failure, liver impairment
20-40mg/kg
∞ 1-2 weeks: Hemoptysis, lung fibrosis
7.5-15mls of 20% concentration
∞ Majority die within 1-3 weeks from
pulmonary failure

FULMINANT
∞ Initial: GI symptoms
>40-50mg/kg
∞ 1-4 days: Death from cardiogenic shock
>15-20mls of 20% concentration
and multiorgan failure
CLINICAL FEATURES
∞ History:
 Strength and dose are important
 Can be lethal
 Kidney disease and age >50yo → Bad prognosis
 Time of ingestion

∞ Painful mouth , difficulty in swallowing, nausea,

vomiting, abdominal pain
∞ Burning skin sensation
∞ Respiratory complains → Systemic poisoning
PHYSICAL EXAMINATION
∞ Mouth & Pharynx – Necrosis , inflammation, ulceration
 (maybe delayed up to 12 hours, peak severity in some days later)
∞ Dehydration – vomiting
∞ Monitor RR, SpO2 – supplementation oxygen only if SpO2
<90%
∞ HR, BP → Refractory hypotension
∞ Chest – Dyspnoeic/tachypnoeic/crackcles (alveolitis),
subcutaneous emphysema
∞ Abdominal pain
∞ Topical contact – corneal ulceration/non specific dermatitis
DIAGNOSIS
∞ Specific testing: Urine paraquat
 Inexpensive
 Positive within 6 hrs after large ingestion,remains positive for
several days.
 Positive test - 40% mortality.
 Negative - 100 % survival
DIAGNOSIS

RENAL
∞ AKI
∞ Increase creatinine >4.4mmol/L/hr over
PROFILE 6 hours = DEATH

SERUM ∞ >4.4mmol/L = DEATH

LACTATE ∞ 82% sensitivity, 88% specificity

∞ Diffuse pulmonary infiltrate

CXR ∞ Pneumothorax and pneumomediastinum →
corrosive ruptured of esophagus
DIAGNOSIS
 Blood investigation
 On admission, every 6 to 12th hourly for first 48 hours
 Then based on clinical severity

∞ Serum electrolytes → may be altered due to vomiting, diarrhea, acute kidney

injury and multi organ dysfunction.
∞ Renal function → AKI suggests significant poisoning-acute tubular
necrosis/volume depletion-increased mortality
∞ Blood gas
• Alkalemia - vomiting, early in the course
• Acidemia - respiratory acidosis( alveolitis, pneumonitis)
- metabolic acidosis( diarrhea, AKI, mitochondrial toxicity,
∞ Arterial Lactate → MODS, hypotension, ARDS. Lactate concentration
>40mg%-fatal outcome- helps determine prognosis

 If prognosis is poor - palliative measures

DIAGNOSIS
∞ Chest radiograph
 For assessing acute lung injury (hypoxia/hyperventilation/crackles)
 Direct effect of paraquat (bilateral) / aspiration( focal - mostly right
lung)
 Phase:
 Early phase (1-2 weeks) - Diffuse alveolar infiltrates-ARDS
 Late phase - Reticulointerstitial infiltrates - Progressive fibrosis

∞ Toxicology screen
 For patients in altered mental status
 Usually not caused by paraquat- but by acetaminophen exposure etc
MANAGEMENT
∞ ABC
∞ Decontamination
 Wear PPE
 Remove and disposed clothes
 Wash patient with soap and water
 Handle and disposed water runoff
 Activated charcoal (if present within 2 hours)
∞Do not administer oxygen!!!
∞ HD
MANAGEMENT
∞ Fullers earth (non-plastic clay): 30%, 250mL Q 4 hourly → until comes out in stools
OR
Activated Charcoal
∞ Early NGT recommended (due to mucosal injury)
∞ Avoid gastric lavage (caustic injury, and unlikely to provide any benefit)
∞ Titrate O2 (can worsening pulmonary fibrosis, mild hypoxia is acceptable e.g. SpO2
>88%)
∞ Immediate plasma exchange or haemofiltration (not likely to change outcome –
distribution to the lungs occurs <2h)
∞ Immune suppression with cyclophosphamide, MESNA, methylprednisolone and
dexamethasone to dampen inflammatory reaction (unproven)
∞ Antioxidants such as acetylcysteine and salicylate might be beneficial through free
radical scavenging, anti-inflammatory and NF-κB inhibitory actions (no evidence)
∞ Patients in extremis should be palliated
 8
1–8: Potential sites of
action by available
treatment options.
3
1: Activated charcoal
and Fuller's earth;
2: Dialysis;
3, 4, 6 and 8:
7 Salicylates;
5 and 8:
N‐acetylcysteine;
7 (P‐glycoprotein
induction):
5 Dexamethasone;
1 2 4 4:
Immunosuppression
6

Figure: Graphical representation of paraquat toxicity inside a pneumocyte and potential sites of
antidotal therapy.
SOD, superoxide dismutase; CAT, catalase; Gred, glutathione reductase; Gpx, glutathione peroxidase; FR, Fenton reaction; HWR,
Haber‐Weiss reaction.
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REFERENCES
 Tintinalli Emergency Medicine 9th Edition
 Uptodate