Organophosphate poisoning

Clinical features
Dr Lamichhane, MBBS, MD
Internal Medicine
 Clinical manifestations
Muscarinic Nicotinic Central receptors
Cardiovascular Cardiovascular Anxiety
Bradycardia Tachycardia Restlessness
Hypotension Hypertension Ataxia
Convulsions
Respiratory Musculoskeletal
Insomnia
Rhinorrhea Weakness
Dysarthria
Bronchorrhea/spasm Fasciculations
Tremors
Cough Cramps
Coma
Gastrointestinal Paralysis
Absent reflexes
Increased salivation CS respiration
Nausea/vomiting Resp. depression
Abdominal pain Circulatory collapse
Diarrhoea
Fecal incontinence
Genitourinary
Urinary incontinence
Ocular
Blurred vision/miosis
Increased lacrimation
 Neurological manifestations
• Neuromuscular weakness/paralysis

• Neuropsychiatric manifestations

• Extrapyramidal manifestations
• Dystonia, resting tremor, rigidity, chorea

• Neuro-ophthalmic manifestations
• Optic neuropathy, retinal degeneration

• Rarer manifestations
• GBS, Ototoxicity, Sphincter involvement
Approach to organophosphate
poisoning
 Management

• Step I: Identify the nature of the poison

• Organophosphate
• Carbamate
• Chloride
• Pyrethroid
• Neonicotinoids
 Management
• Step II: Decontamination

• Skin decontamination

– Important aspect – not to be neglected

– Remove contaminated clothing

– Wash with soap and water (soaps containing 30%

ethanol advocated)
 Management
• Step II: Decontamination

• Care to be taken by health personnel to

avoid contamination

– Reports of occupational illness in staffs caring for

OP poisoned patients
 Management
• Step II: Decontamination

• Gastric decontamination
– Forced emesis if patient is awake and presented
within 2 hours after ingestion
– Gastric lavage if presented within 2 hours after
ingestion
– Activated charcoal
 Reduce absorption

• Gastric lavage

• Gastric lavage decreases absorption by 42% if

done 20 min and by 16% if performed at 60 min
• Performed by first aspirating the stomach and then
repetitively instilling & aspirating fluid
• Left lateral position better - delays spont.
Absorption
• Simplest, quickest & least expensive way - funnel
• Choice of fluid is tap water - 5-10 ml/kg
 Reduce absorption

• Gastric lavage

• Preferrably done on awake patients

• ET tube preferred if GCS is low
 Management
• Step III: Airways and Respiration
• Maintain airway
• Ensure adequate oxygenation
• Watch for intermediate syndrome (diplopia, extra-
ocular muscle weakness/neck muscle weakness)
• Monitor respiratory rate/tidal volume/vital capacity
• Blood gas analysis

• Step IV: Cardiac monitoring

• Hemodynamic and monitor for arrhythmias
 Management
• Step V: Specific therapy
• Atropine
– Initiate as soon as diagnosis is suspected
– Adults 2 mg IV bolus - repeat dose every 5-15
minutes till atropinised
– children - 0.05 mg/kg initially then 0.02-0.05 mg/kg
– Atropinisation
» Heart rate at least 100/min
» Pupils mid position to dilatation
» Bowel sounds just heard
» Clear lung fields
» Dryness of mouth
 Remember
Steps I to V occur simultaneously
Role of oximes
 Organophosphate poisoning

• Are oximes beneficial in human OP

poisoning?

• Subject of much debate & literature

• Systematic review & meta-analysis

 OP - ? benefit with Pralidoxime
Depends on:

• Type of compound
• Poison load & dose
• Time of administration
• Ageing of the compound
OP - ? benefit with Pralidoxime
• Improvements recorded if administered within
12 hours of poisoning. Minimal or no
improvement if treatment delayed more than 26
hours.
• Re-activation of AChe is poor if administered
after 12 hours of poisoning
 Toxicity of oximes
• Pralidoxime can cause dizziness & blurring

• Rapid administration - slow & shallow resps

• Cardiac arrhythmias - AF, VT, VFib, AV block

• Liver function abnormalities

• High dose oximes cause muscle weakness

 Conclusions

• The key to successful management in poisoning

is early recognition and appropriate management

• Remember common toxidromes

• OP poisoning very common in the developing

world

• Role of oximes still not established

Paracetamol (acetaminophen)
poisoning
• Most common form of poisoning in the west
• Common in developing world at present
• Dose necessary to produce toxicity is precisely
known
• 7-10 gm can cause toxic effects
• > 12 gm can be fatal
• Amount is less with any form of liver disease or
with alcohol abuse
• Antidote available
Paracetamol Metabolism
 Acetaminophen
Metabolism
~ 45% ~ 50%
P450

Glucuronidation Sulfation
~ 5% (non toxic)
(non toxic)

NAPQI
N-acetylcysteine (NAC)

Glutathione + NAPQI
= nontoxic product
Liver cell damage
 Paracetamol Toxicity:
• Overdose:
– sulfation and glucuronidation saturated
– increased production of p-450
metabolite
• glutathione eventually depleted
• reactive intermediate NAPQI injures cells
 Clinical Manifestations of
Toxicity:
• Early: non-specific
– anorexia, nausea, vomiting
– May remain asymptomatic
• 24-48 hrs:
– onset of liver injury
• AST, ALT may exceed 10,000 IU
– renal injury (ATN) may also occur
Paracetamol Toxicity, continued:
• 2-5 days:
– liver & kidney injury resolve in most patients
– some patients may develop fulminant liver
failure
• progressive rise in PT/INR, bilirubin
• metabolic acidosis, hypoglycemia
• encephalopathy
• DEATH
Rarely -massive ingestions only
• > 600 mg/kg: early onset metabolic
acidosis
– Not due to liver failure
– Probably mitochondrial poisoning
• In case of massive ingestion >1500 mg/kg
– Coma
– Hypotension
– Acidosis
• Clinical evaluation:
– serum PCM level is best predictor, if available
– levels associated with “probable toxicity”:
• 200 mg/L at 4 hrs after acute ingestion
• 100 at 8 hrs
• 50 at 12 hrs
Treatment Graph
 Management
• General measures including
– ABC assessment
– U&Es, LFTs, glucose, bicarbonate, paracetamol
levels
– Gastric lavage
– Activated charcoal
• Antidote: N-acetylcysteine (NAC)
– provides SH group - binds to NAPQI
- supplies glutathione
• most effective if started within 8-10 hrs after ingestion
– can be given PO or IV
– if vomiting, use IV route or give antiemetic
 Management…
• <8 hours
– Take level after four hours
– Start N-aceylcysteine if above the treatment
line
– Patients are usually declared fit for discharge
from medical care on completion of its
administration. However, check INR,
creatinine and ALT before discharge. Patients
should be advised to return to hospital if
vomiting or abdominal pain develop or recur
 Management…
• >8 hours
– Urgent action required because the efficacy of
NAC declines progressively from 8 hours after the
overdose
– Therefore, if > 150mg/kg or > 12g (whichever is
the smaller) has been ingested, start NAC
immediately, without waiting for the result of the
plasma paracetamol concentration
• >24 hours
– Still benefit from starting NAC
 N-acetylcysteine
• Dosage for NAC infusion - ADULT
– (1) 150mg/kg IV infusion in 200ml 5% dextrose
over 15 minutes, then
– (2) 50mg/kg IV infusion in 500ml 5% dextrose over
4 hours, then
– (3) 100mg/kg IV infusion in 1000ml 5% dextrose
over 16 hours
PO: 140 mg/kg initially then 60 mg/kg q4h for 17
additional doses
• Side-effects
– Flushing, hypotension, wheezing, anaphylactoid
reaction
• Alternative is methionine PO (<12 hours)