Toxicology Case Presentation

Ng Fu

A&E, QMH

History

• F/30, Indonesian Maid

• Found collapse at home by employer

• With an insecticide spray beside her

• Good past health, no history of suicide

• Good relation with present family

Physical Examination

• GCS E4V2M4 10/15; confused

• BP 148/89; P 123/min; T 36oC; SpO2 90%

• Flaccid 4 limbs

• Smell of insecticide

• Bronchorrhea noted; air entry good

• Pin point pupils both sides

• No external wounds

Progress in A&E

• GCS decreased to E4M1V1 6/15• Atropine 0.6mg iv x 1 → P 147• Patient intubated after given Dormicum 3mg iv fo

llowed by Suxamethonium 25mg iv• Pralidoxime 1g in100ml NS over 15min• Another dose of Dormicum 2mg iv• P122/min → another dose of atropine 0.6mg iv• Medical ICU consulted• Ryles tube, Foley inserted

Investigation in A&E

• ECG : Sinus tachycardia 147/min

• Hb 14; H’stix 14.3; urine x PT neg

• Istat before intubation :

Na 139; K 2.9; pH 7.235; pCO2 6.87

pO2 11.9; HCO3 22

• CXR : ET tube in position, no active lung consolidation

Types of Insecticide

1. Pyrethrins e.g.Mosquito coils; Raid Roach & Ant Killer

2. Chlorinated hydrocarbon insecticidese.g. DDT analogue (Raid Moth Proofer)

3. Thiocyanate Insecticides4. Organophosphate Insecticides

e.g. chlorpyrifos (Baygon Roach Bait); Fenitrothion (Zoro Zoro Cockroach Bait)

5. Carbamate Insecticidese.g. Propoxur (No Frills, Baygon Insect Spray)

Common Insecticides in HK Supermarket

Brand Name UseActive ingredient antidote Group 　 Brand Name Use Active ingredient antidote Group

No Frills 特惠 　 Propoxur Carbamate 　 RaidLiquid Electric Mosquito Repeller Prallethrin 　 pyrethroid

　 　 Tetramethrin pyrethroid 　 　 　 　 　

　 　 　 　 　 　 Raid Ant Bait Abamectin 　 Botanical

Baygon 滅蟲噴霧 Propoxur Carbamate 　 Raid Roach Bait Abamectin 　 Botanical

　 　 cyfluthrin pyrethroid 　 　 　

　 　 　 　 　 Raid PBO 0.5% 　unclassified

BaygonUltra Roach Gel Imidacloprid Nil

Chloronicotinyl 　 pyrethrin 　 pyrethroid

　 　 　 　 　 Permethrin 　 pyrethroid

Baygon Roach Bait Chlorpyrifos AtropineOrganophosphate 　 　 　 　 　 　

　 　 　 Zoro Zoro 來來Heavy duty Cockroach Bait Fenitrothion 　

Organophosphate

BaygonElectric Liquid Vaporiser Transfluthrin 　 pyrethroid 　 　 　 　 　 　

　 　 　 　 　 　 S.T. ChemicalMushuda Mothproofer Empenthrin 　 pyrethroid

RaidRoach & Ant Killer Cypermethrin pyrethroid 　 雞仔牌 無味得衣櫃防蟲片 　 　 　

　 　 Imiprothrin 　 pyrethroid 　 　 　 　 　 　

　 　 　 　 　 Mosquito Coils 　 Allethrin 　 pyrethroid

Progress in Ward

• Admitted medical ICU• Developed aspiration pneumonia with WCC 24.9

and neutrophil 22.2• Plasma Cholinesterase 2175 (4650 – 10440)• CK elevated temporarily (483) then in downward

trend later• Amylase increased to 499 then decreased.• Toxicology screen : no paracetamol, no salicylat

e and no ethanol• Further Hx confirmed carbamate poisoning resul

ting in muscle paralysis.

Progress in ward

• Discharge to general ward on Day 4• Psychiatrist consulted : admitted that she

had an argument with her father and boyfriend in Indonesia for her plan at the end of current contract one month later. She wanted to stay in HK but her family disagreed. She then drank the insecticide at home

• Finally discharged on Day 7

Carbamate Poisoning

c.f. Organophosphate insecticide

- Widespread agricultural and home use

- Rapid hydrolysis into harmless cpds with little long-term accumulation in the environment.

- Propoxur (Baygon); Aldicarb (Temik)

Pathophysiology

Carbamate Poisoning- Reversibly binds to ch

olinesterase- The carbamate-cholin

esterase bond reverses spontaneously in 4-8 h, yielding a normal cholinesterase.

Organophosphate- Permanently bind to c

holinesterase- Pralidoxime reverses

the organophosphate-cholinesterase bond if it is given within 24 to 36 h of acute exposure.

Clinical Features

- Due to cholinergic excess causing :1. Muscarinic overstimulation (hyperactivity of parasympa

thetic system) - SLUDGE2. Overstimulation of nicotinic receptors in sympathetic sy

stem- tachycardia, HT, stimulation of adrenal medulla

3. Overstimulation of nicotinic receptors in NM junction- muscle faciculation, cramping, weakness

4. Cholinergic excess in CNS- delirium, confusion, coma, seizure

Classification of s/s of acute carbamate poisoning according to Receptor Site and Type

Muscarinic- Miosis**- Blurred vision- Nausea & Vomitin

g- Diarrhoea- Salivation- Lacrimation- Bradycardia- abdominal pain- Diaphoresis- Wheezing- Urinary incontinen

ce- Fecal incontinenc

e

Nicotinic- Muscle fasciculations**(striated muscle)-Paralysis-Muscle weakness-Hypertension-Tachycardia-Pallor-Mydriasis (rare)

Central

-Unconsciousness

-Confusion

-Toxic psychosis

-Seizures

-Fatigue

-Respiratory depression

-Dysarthria

-Ataxia

-anxiety

Clinical Features

Usual cause of DEATH is

Respiratory failure due to :

1. CNS resp. centre depression

2. Resp. muscle weakness

3. Increased bronchial secretions

Investigations

• Non-diagnostic• ↑sugar; ↓K; ↑WBC; ↑amylase• Glycosuria; proteinuria• ECG changes• CXR usu unremarkable but may show pul

monary edema in severe cases• Serum cholinesterase vs RBC cholinester

ase activities – diagnostic aids only, no specific value in the Mx

Management

If asymptomatic →observe 6-8 h

For seriously poisoned patients,

1. Vigorous decontamination

2. Respiratory support

3. Use of specific antidotes

Management

1. Rescuers’ safety

2. Establishment of Airway and adequate ventilation

3. Use of atropine

4. Decontamination

5. Gastric larvage / activated charcoal

6. Use of Pralidoxime

Atropine

• Acts as a physiologic antidote by competitively blocking the action of Ach at muscarinic (but not nicotinic) receptors.

• No effect on the nicotinic receptors at skeletal myoneural junctions or within the sympathetic ganglia.

• May be therapeutic for CNS symptoms esp. in children• 2 mg iv every 5 to 15min until signs of atropinization (my

driasis, tachycardia, flushing, xerostomia, anhydrosis,etc)

• Difficult to use pupils size as a guide• Should be given aggressively esp. in case of organophos

phate poisoning (atropine refractoriness)

Should Atropine be used more liberally in this patient ?

- Tachycardia is usu due to hypoxia or ganglionic stimulation

- Tachycardia >140 – ?contraindication to atropine use

Pralidoxime

• A biochemical antidote for organophospate poisoning but probably not for pure carbamate poisoning.

• Little toxicity• 3 beneficial effects :1. Reactivate the cholinesterase that has been phosporylat

ed by an organophosphate if given in 24 to 36h2. Reverses the cholinergic nicotinic effects not affected by

the use of atropine alone (i.e. muscle fasciculation, weakness and stimulation of sympathetic ganglia.

3. Direct reaction and detoxification of unbounded organophosphate molecules.

Pralidoxime

• 1 g iv over 15-30 min, repeated 1 to 2 h after the initial dose, then every 10 to 12 h as needed. (Paed. 20-50mg/kg)

• OR continuous iv infusion 0.5g/h in adult or 10-20mg/kg/h in children

• Reversal of muscle weakness and fasciculation usu begins in 10-40min

• Rx is usu continued for 24-48h

Should Pralidoxime be used in this patient ?

FOR- Not harmful- Severe s/s with impen

ding resp failure- Prominent muscle we

akness- May be mixture of org

anophosphate and carbamate poisoning

AGAINST- The carbamate-cholin

esterase bond reverses spont. in 4-8 hrs

- Not without side effects

- Atropine not fully given

- Use is controversial

Use of Pralidoxime in Carbamate Poisoning

• Its use is still controversial

After aequate atropinization, pralidoxime may be indicated in (Consensus, 1986)

1. life-threatening symptoms with severe muscle weakness, fasciculations, paralysis, or decreased resp effort

2. Continued excessive requirement of atropine

3. Concomitant organophosphate and carbamate exposure

Learning Points

• Atopine should be used aggressively in organophosphate and carbamate poisoning. The therapeutic end-point should be clearing up of bronchial secretions. Tachycardia alone should not be a contra-indication to adequate atropinization.

• Pralidoxime can be given in carbamate poisoning when severe toxicity occurs, as in this case.

Learning Points

• Succinylcholine should be used with caution or avoided because:

1. Hydrolysis of Sch by plasma cholinesterase is delayed

2. Increased levels of Ach at neuromuscular junction may aggravate the neuromuscular blocking effect