A 30-year-old female presented to the emergency department with vomiting, sweating and shortness of breath for 45 minutes after ingesting an unknown substance one hour prior. On examination, she had bradycardia, hypotension, constricted pupils, hyper salivation, diaphoresis and crepitations in both lungs. Based on the history and examination findings, OPC (organophosphorus compound) poisoning was suspected. Treatment for OPC poisoning includes atropine to reverse muscarinic effects, pralidoxime as a specific antidote to reactivate cholinesterase, supportive care and monitoring for complications like intermediate syndrome.

1. Dr. Mir Mohammad Taieb
Indoor Medical Officer
Dept. of Medicine
EMCH
Topic Presentation
OPC poisoning

3. A 30-year-old female brought to the emergency
department with the complaints of vomiting,
sweating and shortness of breath for 45
minutes. One and half hour prior to this
reportedly patient had ingested one bottle of
unknown substance, which was brought along
by relatives. She had a history of family
disharmony for the last 1 month. She had no
other significant past medical history.

4. On general examination
• HR: 46/min, regular
• BP: 80/50 mmHg
• RR: 40/min
• SpO2: 91% in Room air
• GCS: E1V2M4
• Pupils were constricted and sluggishly reactive to
light
• Hyper salivation and diaphoresis present

5. On systemic examination
• Respiratory system: bilateral crepitations all
over the chest
• Cardiovascular system: bradycardia with
regular rhythm
• Alimentary system: nothing significant

7. What will you suspect?

8. OPC poisoning

9. Organophosphorus (OP) compounds
are used in both domestic and
industrial settings
• Insecticides –
– Dimethyl compounds (Dichlorvos, Fenthion, Malathion,
Methamidophos)
– Diethyl compunds (Chlorpyrifos, Diazinon, Parathion-ethyl,
Quinalphos)
• Nerve gases – Soman, sarin, tabun, VX
• Ophthalmic agents – Echothiophate, isoflurophate
• Antihelmintics – Trichlorfon
• Herbicides – Tribufos (DEF), merphos
• Industrial chemical (plasticizer) – Tricresyl phosphate

10. The rate of ‘ageing’ is an important determinant
of toxicity and is more rapid with dimethyl (3.7
hrs) than diethyl (31 hrs) compounds and
especially rapid after exposure to nerve agents
(soman in particular), which cause ‘ageing’
within minutes

11. Background
• OPC were first synthesized in the early 1800s when Lassaigne reacted
alcohol with phosphoric acid.
• Eighty years later, Lange, in Berlin, and, Schrader, a chemist at Bayer AG,
Germany, investigated the use of OPC as insecticides. However, the
German military prevented the use of OPC as insecticides and instead
developed an arsenal of chemical warfare agents (tabun, sarin, soman).
• A fourth agent, VX, was synthesized in England a decade later. During
World War II, in 1941, OPC were reintroduced worldwide for pesticide use,
as originally intended.

12. WHO estimates acute pesticide
poisonings at 3 million cases/ year.
• 1 million accidental & 2 million suicidal; likely underestimate
• 300,000 deaths/ year
• Mostly occur in the developing world.
• OPC agents commonly used as pesticides and is responsible
for over 70% of the cases in most of South Asia.
• Most deaths may occur at home, small towns. Hospital
statistics gross underestimate

14. Skin
Inhalation
Ingestion
Mode of transmission

15. Mode of transmission
• Poisoning may result from ingestion,
absorption from skin and inhalation.
• Fastest absorption takes place through eyes,
scalp, back of the neck, forehead and scrotal
region.
• Inhalation of vaporized pesticides commonly
takes place during mixing, handling and
spraying

16. Clinical Features
• Acute poisoning:
Result from substantial intake of the toxicant in a single
occasion.
• Sub-acute poisoning:
Due to repeated smaller doses through penetration into the
system over a short period of time.
• Chronic poisoning:
Refers to cumulative effect occurring from repeated exposure
to small amount of pesticides over a long period of time.

17. Four clinical syndromes
Acute cholinergic
syndrome
Subacute proximal
weakness (Intermediate
syndrome)
Organophosphate
induced delayed
neuropathy (OPIDN)
Chronic organophosphate
induced neuropsychiatric
disorder (COPIND)

18. Acute cholinergic syndrome starts within a few
minutes of exposure with either muscarinic or
nicotinic features or CNS manifestation

20. Traits Muscarinic features Nicotinic features
Respiratory Bronchorrhoea,
Bronchoconstriction, Rhinorrhea,
cough, severe respiratory distress
Reduced ventilation
Circulation Bradycardia, hypotension Tachycardia, hypertension
Muscle Fasciculation, flaccid
paralysis
Temperature Fever
Eyes Diplopia, miosis, lacrimation Mydriasis
Gastrointestinal - Hypersalivation, nausea and
vomiting, abdominal pain, diarrhea,
fecal incontinence
Mouth Salivation
Saliva Sweating
CNS symptoms Anxiety, delirium, psychosis, Emotional liability, Restlessness,
Confusion, Ataxia, Tremors, Seizures, Coma, Apnea
Complications Coma, seizures, respiratory depression

21. Grading of severity of poisoning
• Clinical grading
• Biochemical grading

22. Clinical grading based on
– Pupil size
– Fasciculation
– Respiratory rate
– Heart rate
– Level of consciousness
– Seizures
*mild (0-3), moderate (4-7), severe (8-11)

24. Biochemical Grading:
Red cell cholinesterase activity (% normal) Category
20-50% Mild
10-20% Moderate
<10% Severe

25. Confirmation of OPC poisoning is based on the
measurement of cholinesterase activity either in
RBC or Plasma: not done routinely
• Sample of used offending pesticide or preferably
container of pesticide as measure of identification is
very important in clinical settings. All patients and
their attendants should be repeatedly encouraged to
bring the sample to the health facility for diagnosis
and management.

26. • CBC (leucocytosis)
• Chest X-ray (pulmonary edema)
• ECG (sinus tachycardia, prolonged QT interval, elevated
ST segments and inverted T waves)
• Blood gases (metabolic or respiratory acidosis)
• Electrolytes (hypokalemia)
• S. amylase levels (maybe elevated)
• RBS (hypoglycemia)
• Troponin levels (maybe elevated)
• Liver function test (increased PT)
• Urine R/M/E (proteinuria)

27. A patient of OPC poisoning should be
hospitalized and the management
consists of
1. Initial stabilization of patient
2. Reduction of exposure
3. Administration of specific antidote
4. Supportive treatment

28. Initial stabilization
• Clear airway
• Adequate ventilation
• High-flow oxygen
• Intravenous access obtained

29. Reduction of exposure
• Dermal spills: wash with soap and water and remove and
discard contaminated clothes. Remove contact lenses and
wash eyes thoroughly for at least 15 minutes with normal
saline or water
• Gastric lavage: within 1 or 2 hours, when the airway is
protected
• Activated charcoal - 50 g may be given orally or by NG tube to
patients who are cooperative or intubated (within one or two
hours or have severe toxicity)

30. Antidotes in the treatment of OPC
poisoning
• Atropine - Reverses the muscarinic features.
• Oxime - Reactivate cholinesterase and
reverses the nicotinic features

31. Atropine
Atropine antagonizes the effect of acetylcholine
by reversing the excessive parasympathetic
stimulation by competing for identical binding
sites at muscarinic receptors

32. Test dose 5 ampoules atropine
No response
Double dose at 15 min interval till
atropinization
Maintenance infusion of atropine 10-20% of total
loading dose/ hour for 24-48 hours
Dosage regimens of Atropine

33. Dosage regimens of Atropine
• Dosage regimens are usually designed
according to the severity of poisoning and to
the signs of atropinisation
• 1 ampoule contains 0.6mg atropine sulphate
• Interval of atropine sulfate dose every 5-
30minutes

34. • A test dose of IV atropine sulfate is provided first.
This therapeutic test provides a measure of severity
of OPC poisoning. If the signs of atropinisation occurs
rapidly, it is unlikely that the poisoning is severe or it
may not be OPC poisoning.
• If atropinisation is achieved by a single dose of
atropine still monitoring should be continued for at
least 24 hours to detect further recurrence of
toxicity.

35. • Test dose of Atropine: It is preferable to
initiate the antidote therapy with a 'test dose'
of parenteral atropine sulphate (1.8-3 mg in
adults (3 to 5 ampoules IV) and 0.01 mg/kg in
children IV)
• When atropinisation has not occurred with
the initial test dose, then more atropine is
required. Double the dose, and continue to
double each time until atropinisation occurs

36. Target end point of therapy
After 5 minutes of atropine administration
record followings :-
(1) air entry into lungs: clear chest
(2) blood pressure: SBP > 80 mm Hg
(3) heart rate: > 80 beats/ min
(4) Pupil: no longer pinpoint
(5) Dry axillae

37. • Mark them on an OPC observation sheet
• A uniform improvement in most of the five parameters
is required, not improvements in just one.
• Pupil dilatation is sometimes delayed. and the other
parameters may improve more rapidly, it is reasonable
to observe air entry on chest auscultation, heart rate,
and blood pressure as the main parameters for
adequate atropinisation.

38. OPC observation sheet
Time Heart
rate
Lungs Pupil
size
Dry
axillae
SBP Bowel
sounds
Confused Temp Atropine
ampoules

39. While waiting for the atropine to have effect,
ensure that two IV drip have been set up
• Other for atropine
• One for fluid and drugs. Give 500–1000 ml (10–
20 ml/kg) of normal saline

40. Maintenance dose of atropine
• Once atropinized set up an infusion using
one of the two IV cannulae. In the
infusion, give 10–20% of the total
atropine that was required to load the
patient every hour
• If very large doses (more than 30mg) is
initially required , then less can be used

41. Observation of the patient:
• Follow up every 15 min with five parameter
• If recurrence of bronchospasm or bradycardia, give further
boluses of atropine
• Once the patient settled then follow up hourly for the first 6
hours to check that the atropine infusion rate is sufficient and
that there are no signs of atropine toxicity
• As the required dose of atropine falls, observation for
recurrence of cholinergic features can be done less often
(every 2–3 hours)
• However, regular observation is still required to spot patients
at risk of, and going into, respiratory failure

42. Atropine toxicity
Peripheral effect
•Dry mouth
•Mydriasis
•Blurred vision
•Hot dry skin
•Tachycardia
•Look for retention of
urine
Central effect
•Hyperpyrexia
•Restlessness
•Anxiety
•Excitement
•Hallucination
•Delirium
•Mania
•Cerebral depression
•Coma

43. Management of Atropine toxicity
• Stop the atropine infusion if signs of gross atropinisation
present like fever, muscle fasciculation, delirium
• Check again after 30 min to see whether the features of
toxicity have settled
• If not, continue to review every 30 min or so
• When they do settle, restart at 70–80% of the previous
rate
• The patient should then be seen frequently to ensure
that the new infusion rate has reduced the signs of
atropine toxicity without permitting the reappearance
of cholinergic signs

44. • Diazepam is given for excitement
• Physostigmine is advocated for peripheral
effects
• Pyrexia should be controlled by cold sponging
and antipyretic

45. Oximes
• Oximes are the specific biochemical antidote
for OPC induced intoxication
• They reactivate the inhibited cholinesterase by
cleavage of phosphorylated active sites.
Oximes are effective only when the
phosphorylated AchE has not undergone
ageing
• Oximes ameliorate the nicotinic, muscarinic &
CNS effects

46. Pralidoxime
Pralidoxime is used in conjunction with atropine in
moderate and severe poisoning. It has a strong
synergistic effect with atropine and provides a dose
sparing effect on the amount of atropine

47. Dosage regimen of pralidoxime
Loading dose 30 mg/kg of pralidoxime over 10–20
min, followed by continuous infusion of 8–10 mg/kg
per hour until clinical recovery (for example 12-
24hours after atropine is no longer required or the
patient is extubated) or 7 days, whichever is later

48. Side effect of pralidoxime
• Mild biochemical signs of liver toxicity.
• Too rapid administration will result in vomiting,
tachycardia and hypertension (especially
diastolic hypertension).

49. Obidoxime
• Currently obidoxime has been introduced. It crosses
blood brain barrier more than pralidoxime
• Where obidoxime is available, a loading dose of 250
mg is followed by an infusion giving 750 mg every 24
hours

50. Pralidoxime Toxicity
• Very few cases of pralidoxime toxicity have been
reported.
• Dizziness, blurred vision, diplopia, headache,
nausea and tachycardia have been reported if the
rate of administration exceeds 0.5 gm. per minute.

51. Supportive Treatment
1. Management of respiratory insufficiency
2. Maintenance of circulation
3. Treatment of convulsion and other complications
4. Fluid and electrolyte balance
5. Control of infections (aspiration pneumonia)
6. Maintenance of nutrition
7. Control of body temperature

52. • Management of respiratory failure represents the
corner stone of treatment.
• Artificial ventilation should be started at the first sign
of respiratory failure.
• For pulmonary edema, high concentration 02 and
diuretic should be used.
• Morphine and aminophyline should be avoided.
• Broad spectrum antibiotic is used as prophylactic
measure for aspiration pneumonia.

53. Diazepam
• Benefits:
– Counteract CNS effects
– Relieves anxiety
– Antagonise convulsions
– Improve morbidity and mortality
• Dose of diazepam: (IV and also may be
repeated if necessary)
– Adult: 10-20mg
– Children – 0.25-0.5mg/kg

54. Disposition
• Consider discharge from ICU to medical ward once
stable for 12 hours after oxime
• Stable for 48 hours after discharge from intensive
care unit- consider disposition and psychiatric review

55. Prognosis of Organophosphorus
Insecticide Poisoning
• Deaths usually occur within the first 24 hours in
untreated cases and within 10 days in treatment
failure cases.
• If there has been no anoxic brain damage, recovery
will usually occur within 10 days, although there may
be residual sequelae.

56. Cause of Death in OPC poisoning
1. Immediate death:
– Seizures.
– Complex ventricular arrhythmias.
2. Death within 24 hours:
- Acute cholinergic crisis in untreated severe case
-Respiratory failure.
3. Death within 10 days of poisoning:
- intermediate syndrome

57. 4. Late death:
- Secondary to ventricular arrhythmias, including
Torsades de Pointes, which may occur up to 15 days
after acute intoxication.

58. Factors related to death in OPC poisoning
• Amount ingested
• Delay in hospitalization
• Delay in starting treatment
• Lack of standardized treatment protocol
• Atropine toxicity
• Lack of frequent monitoring
• Lack of ICU support including financial constrain

59. Intermediate Syndrome (IMS)
• IMS occurs due to dysfunction of the post-synaptic
neuromuscular junction
• Pathogenesis unclear. But thought to be due to persistent
inhibition of acetyl cholinesterase
• IMS develop about 24-96 hours after OPC induced intoxication
about 20% patient develops IMS.
• Respiratory insufficiency may herald the onset of IMS.
• The patient is usually conscious.
• Muscles innervated by cranial nerves show varying degree of
weakness. External ocular muscles are most commonly
affected

60. • Weakness is bilateral and symmetrical. Patient cannot raise the
head from bed.
• There is no sensory impairment.
• Respiratory insufficiency develops over approximately 6 hours.
• There is increased in respiratory rate, sweating, restlessness and
later cyanosis.
• If untreated the patient may soon become unconscious and die.
• The paralytic signs are 2 types. Type 1 (present on admission) and
Type 2 (appearing subsequently and not responding to atropine).
• Management – maintenance of airway and ventilation

61. Organophosphate-induced delayed
polyneuropathy
• Organophosphorus induced delayed polyneuropathy (OPIDN)
occurs following a latent period of 2-4 weeks after exposure
by any route.
• It is a mixed sensory/motor polyneuropathy, affecting long
myelinated neurons especially, and appears to result from
inhibition of enzymes other than AChE.
• It is a feature of poisoning with some OPs such as
triorthocresyl phosphate but is less common with nerve
agents.
• Early clinical features are muscle cramps followed by
numbness and paraesthesiae, proceeding to flaccid paralysis
of the lower and subsequently the upper limbs, with foot and
wrist drop and a high-stepping gait, progressing to paraplegia.

62. • Sensory loss may also be present but is variable.
• Initially, tendon reflexes are reduced or lost but mild
spasticity may develop later
• There is no specific therapy for OPIDN
• Regular physiotherapy may limit deformity caused by
muscle-wasting. Recovery is often incomplete and
may be limited to the hands and feet, although
substantial functional recovery after 1–2 years may
occur, especially in younger patients.

63. Chronic organophosphate induced
neuropsychiatric disorder (COPIND)
• Chronic low dose exposure to OP compounds (usually 40
hours/week or 9months/year)
• No cholinergic symptom
• Extrapyrimdal manifestations:
– Atypical ocular bobbing
– Cerebellar ataxia
– Choreo athetosis
– Chorea with psychiatric changes
– Parkinsonism
• Non responsive to levodopa