Toxicology Case Presentation

1
Toxicology Case Presentation

• Ng Fu
• AE, QMH

2
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

3
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

4
Progress in AE

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

5
Investigation in AE

• ECG Sinus tachycardia 147/min
• Hb 14 Hstix 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

6
Types of Insecticide

• Pyrethrins
• e.g.Mosquito coils Raid Roach Ant Killer
• 2. Chlorinated hydrocarbon insecticides
• e.g. DDT analogue (Raid Moth Proofer)
• 3. Thiocyanate Insecticides
• 4. Organophosphate Insecticides
• e.g. chlorpyrifos (Baygon Roach Bait)
  Fenitrothion (Zoro Zoro Cockroach Bait)
• 5. Carbamate Insecticides
• e.g. Propoxur (No Frills, Baygon Insect Spray)

7
Common Insecticides in HK Supermarket
Brand Name Use Active ingredient antidote Group Brand Name Use Active ingredient antidote Group
No Frills ?? Propoxur Carbamate Raid Liquid Electric Mosquito Repeller Prallethrin pyrethroid
Tetramethrin pyrethroid
Raid Ant Bait Abamectin Botanical
Baygon ???? Propoxur Carbamate Raid Roach Bait Abamectin Botanical
cyfluthrin pyrethroid
Raid PBO 0.5 unclassified
Baygon Ultra Roach Gel Imidacloprid Nil Chloronicotinyl pyrethrin pyrethroid
Permethrin pyrethroid
Baygon Roach Bait Chlorpyrifos Atropine Organophosphate
Zoro Zoro ?? Heavy duty Cockroach Bait Fenitrothion Organophosphate
Baygon Electric Liquid Vaporiser Transfluthrin pyrethroid
S.T. Chemical Mushuda Mothproofer Empenthrin pyrethroid
Raid Roach Ant Killer Cypermethrin pyrethroid ??? ????????
Imiprothrin pyrethroid
Mosquito Coils Allethrin pyrethroid
8
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 salicylate
  and no ethanol
• Further Hx confirmed carbamate poisoning
  resulting in muscle paralysis.

9
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

10
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)

11
Pathophysiology
12

• Carbamate Poisoning
• Reversibly binds to cholinesterase
• The carbamate-cholinesterase bond reverses
  spontaneously in 4-8 h, yielding a normal
  cholinesterase.

• Organophosphate
• Permanently bind to cholinesterase
• Pralidoxime reverses the organophosphate-cholinest
  erase bond if it is given within 24 to 36 h of
  acute exposure.

13
Clinical Features

• Due to cholinergic excess causing
• Muscarinic overstimulation (hyperactivity of
  parasympathetic system)
• - SLUDGE
• Overstimulation of nicotinic receptors in
  sympathetic system
• - tachycardia, HT, stimulation of adrenal
  medulla
• Overstimulation of nicotinic receptors in NM
  junction
• - muscle faciculation, cramping, weakness
• Cholinergic excess in CNS
• - delirium, confusion, coma, seizure

14
Classification of s/s of acute carbamate
poisoning according to Receptor Site and Type

• Muscarinic
• Miosis
• Blurred vision
• Nausea Vomiting
• Diarrhoea
• Salivation
• Lacrimation
• Bradycardia
• abdominal pain
• Diaphoresis
• Wheezing
• Urinary incontinence
• Fecal incontinence

• 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

15
Clinical Features

• Usual cause of DEATH is
• Respiratory failure due to
• CNS resp. centre depression
• Resp. muscle weakness
• Increased bronchial secretions

16
Investigations

• Non-diagnostic
• ?sugar ?K ?WBC ?amylase
• Glycosuria proteinuria
• ECG changes
• CXR usu unremarkable but may show pulmonary edema
  in severe cases
• Serum cholinesterase vs RBC cholinesterase
  activities diagnostic aids only, no specific
  value in the Mx

17
Management

• If asymptomatic ?observe 6-8 h
• For seriously poisoned patients,
• Vigorous decontamination
• Respiratory support
• Use of specific antidotes

18
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

19
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 (mydriasis, tachycardia, flushing,
  xerostomia, anhydrosis,etc)
• Difficult to use pupils size as a guide
• Should be given aggressively esp. in case of
  organophosphate poisoning (atropine
  refractoriness)

20

• Should Atropine be used more liberally in this
  patient ?
• Tachycardia is usu due to hypoxia or ganglionic
  stimulation
• Tachycardia gt140 ?contraindication to atropine
  use

21
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
  phosporylated by an organophosphate if given in
  24 to 36h
• 2. 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.

22
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

23
Should Pralidoxime be used in this patient ?

• FOR
• Not harmful
• Severe s/s with impending resp failure
• Prominent muscle weakness
• May be mixture of organophosphate and carbamate
  poisoning

• AGAINST
• The carbamate-cholinesterase bond reverses spont.
  in 4-8 hrs
• Not without side effects
• Atropine not fully given
• Use is controversial

24
Use of Pralidoxime in Carbamate Poisoning

• Its use is still controversial
• After aequate atropinization, pralidoxime may be
  indicated in (Consensus, 1986)
• life-threatening symptoms with severe muscle
  weakness, fasciculations, paralysis, or decreased
  resp effort
• Continued excessive requirement of atropine
• Concomitant organophosphate and carbamate exposure

25
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.

26
Learning Points

• Succinylcholine should be used with caution or
  avoided because
• Hydrolysis of Sch by plasma cholinesterase is
  delayed
• Increased levels of Ach at neuromuscular junction
  may aggravate the neuromuscular blocking effect