Diagnosis and management of Organophosphorus poisoning

1. Dr Manazir
Dept of Anaesthesiology & Critical Care
Jawaharlal Nehru Medical College
AMU, Aligarh

2.  Raju a 27 yr old male, brought to casualty at
1:00 am with history of sudden loss of
consciousness in his room after having a
family quarrel.
 He had 4 episodes of non-bilious vomiting.
No h/o blood in vomitus.
 H/O of incontinence of urine and faeces.
 H/O Alcoholism

3. PR-100/min, low volume
BP- 90/70mmHg
RR- 28/min, shallow
Temperature- 102o F (oral)
GCS – On painful stimuli: Eyes closed,
incomprehensible sounds & withdrawl.
E1V2M4=7/15

4. Pupils: B/L pinpoint, non reacting to light
Tone: Increased
Power: Movement Against gravity
Plantar reflex: Non elicitable
Bowel sounds: Exaggerated
Normal
Size..???

6. C: Clonidine
P: Phenothiazine (Antipsychotics)
R: Resting (deep sleep)
O: Opioids
N: Narcotics (barbiturates)
S: Stroke (pontine)
L: Lomotil (diphenoxylate - anti diarrhoeal)
I: Insceticides (organophosphates, carbamates)
M: Muscarinic Agonist (mushroom)
E: Eye drops (pilocarpine)

7. Feature cluster Likely poison
Coma , hypotension , hypothermia,
shallow breathing ,hypo-tonia , hypo-
reflexia, fast-pulse , watering eyes,
yawing cramps, hallucinations ,
restlessness, diarrhoea
Barbiturates
Benzodiazipines
Alcohol
combinations
TCA poisoning
Bronchorrhea, bradycardia,
hypotension, incontinences of urine and
stool, miosis and hypersalivation
Organophosphates
Carbamates
Nerve agents
Some mushrooms
Blindness Quinine
methanol

8. Feature cluster Likely poison
Small pupil, slow breathing,
unconsciousness, weak pulse ,
hypothermia and vomiting.
opioid
Nausea , vomiting, tinnitus,
deafness, sweating,
hyperventilation, vasodilatation ,
metabolic acidosis.
salicylate
Restlessness, agitation ,
mydriasis, anxiety tremor ,
taachycardia, convulsion ,
arrhythmia, hyperthermia,
hallucinations, fits,
Sympathomimetics
drugs…amphetamines,
cocaine,
Theophylline.

9. What are different types of
organophosphorus compounds?

10. They can be classified as three categories:
A. Derivatives of phosphoric (H3PO4), phosphorus
(H3PO3) & phosphinic acid (H3PO2) e.g
dichlorvos, glufosinate
B. Derivatives of phosphine (PH3).
C. Derivatives of phosphorothioates(c=s) e.g diazinon,
parathion, and bromophos

11. • Nerve agents
• Insecticides
• Glaucoma treatments
• Myasthenia gravis
• Potential uses in alzheimer’s disease and dementia

12.  How phosphates are different
from Carbamates

13. Organophosphates vs. Carbamates
Organophosphates Carbamates
Cholinesterase Non-reversible reversible
Symptoms Vomiting, diarrhea, exhaustion,
convulsion, miosis
Atropine yes Yes
Aging of enzyme Yes No
2-PAM Yes, within a few
hours
No

14. 1. Cutaneous
2. Ingestion
3. Inhalation
4. Injection
14

15. • Inhibit acetylcholine esterase
enzyme at nerve endings by
phosphorylation
↑ acetylcholine at receptor sites
Mechanism of action

17. Diarrhea Salivation
Urination Lacrimation
Miosis Urination
Bradycardia Defecation
Bronchospasm G.I upset
Emesis Emesis
Lacrimation
Limp
Sweating

18. How do you grade the severity??

19. GRADE SYMPTOMS
MILD NAUSEA, VOMITING
DIARRHOEA
SWEATING
MODERATE LACRIMATION, SALIVATION
MIOSIS
FASCICULATION
SEVERE INCONTINENCE
ARDS, APNOIC SPELLS
AREFLEXIA, SEIZURE,COMA

20. How long will it take to present with
toxidromes??

21.  Generally oral or respiratory exposures
within three hours.
 While from dermal absorption may be
delayed up to 12 hours.

22. How will you confirm your
diagnosis??

23.  88% of patients initially deny any exposure history.
 Petroleum or garlic-like odor.
 If doubt exists a trial of atropine (0.01 to 0.02
mg/kg) may be employed
 The absence of s/s of anticholinergic effects
following atropine challenge strongly supports the
diagnosis .

24. 1. Butyrylcholinesterase activity in plasma
2. Acetylcholinesterase in whole blood
3. Other
1. CXR - Evaluate pulmonary oedema
2. ECG - Cardiac arrhythmias
3. ABG & Electrolytes
4. Urea
24

25. Which enzyme assays correlate
more with poisoning severity??

26. Red cell acetylcholinesterase inhibition is a good
marker of severity
 Red cell ACEs ≥ 30% - normal muscle function,
no atropine
 Less than 10% - deranged funct., high dose
atropine
 Between 10-30%- moderate impairment and need
for atropine.
 Recovers @ 1% per day

27. Plasma butyrylcholinesterase activity does not
relate to severity of poisoning
 More easily performed
 A depression of 25% or more – severe .
 Recovers @ 7% per day

28. These enzymes facilitate the decision
about
 When to stop oxime and
 Allow cautious weaning of a patient

29. Cholinergic/ OP poisoning
 How will you manage..???

30. 1. Check airway, breathing, circulation.
2. Monitor Vitals and cardiac rhythm
3. Look for signs & symptoms
4. Obtain IV access
5. Remove contaminated clothes & wash the
skin thoroughly with soap & water.
Management of organophosphate
poisoning

31. 6. Atropine intravenously as soon as possible for
symptomatic patient
7. Pralidoxime (Reactivator)
8. Gastric lavage once the patient is stabilized &
within 2 hours of ingestion with activated
charcoal (50 g in 200 ml)
9. Maintenance atropine infusion

32.  Wash at least 3 times with soap (containing
chlorhexidine and alcohol) and water, paying
particular attention to hair, skin folds and
underneath nail beds.

33.  Gastric lavage decreases absorption by 42% if
done within 20 min
 By 16% if performed at 60 min
 Choice of fluid is tap water @ 5-10 ml/kg
 Performed by first aspirating the stomach and
then repetitively instilling & aspirating fluid

34.  Lateral position better - delays spont.
Absorption
 No evidence that larger tube better
 Preferably done on awake patients
 ET tube preferred if GCS is low.

35.  Start with 1.8-3.0 mg fast iv bolus
 After 3-5minutes check
1. Bronchorroea & bronchospasm
2. Bradycardia ( <60 )
3. Miosis
4. Excessive sweating
5. Hypotension
 If not corrected double the dose of atropine every
5 minutes until signs of atropinization.

36. 1. Clear chest on auscultation with no wheeze
2. Heart rate >80 beats/min
3. Pupils no longer pinpoint
4. Dry axillae
5. Systolic blood pressure >80 mmHg

37.  D5 + 10-20% of the total initial dose of
atropine on an hourly basis. (after
stabilization)
 STOP atropine infusion if features of toxicity

38.  Confusion, delirium, coma
 Urinary retention, Bowel ileus
 Hyperthermia
 Agitation, psychosis
 Flushing
 Tachycardia (>140/min)
 Fixed dilated pupil

39.  loading dose @ 30mg/kg IV over 10-20mins
 Continuous infusion of 8-10mg/kg/hr.
 Upto when??

40.  Continue oxime infusion until atropine has
not been needed for 12–24 h and patient
extubated

41. What are the different phases of
toxicity..?

42. 1. Acute cholinergic crisis
2. Intermediate syndrome (IMS)—major cause
of morbidity and mortality
3. Delayed neuropathy

43.  Excess acetylcholine at NMJ causes downregulation
of nicotinic receptors- muscles affected
 Inadequate oxime therapy,
 Respiratory failure without muscarinic signs
 Muscle necrosis,
 Failure of postsynaptic acetylcholine release, and
oxidative stress-related myopathy.

44.  C/F typically occur within 24 to 96 hours &
persists for 4-18 days
 Affecting conscious patients without cholinergic
signs, and
 Involve the muscles of respiration, proximal
limb muscles, neck flexors, and muscles
innervated by motor cranial nerves

45.  Assess flexor neck strength regularly (head
lift & hold against resistance)
 Weakness is a sign of peripheral respiratory
failure (intermediate syndrome).
 TV checked every 4 hrly.
 TV< 5 mL/kg / VC<15 mL/kg, PaO2<
60mmHg on FiO2 of >60% or apnoeic spells
suggest mechanical Ventilation need.

46. 1. Organophosphate induced delayed neuropathy
(OPIDN)
o 2-3 weeks after large dose
oPeripheral/distal neuropathy (proximal sparing)
oDue to inhib Neuropathy Target Esterases (NTE)
oRecovery can take up to 12 month
2. Chronic organophosphate induced
neuropsychiatric disorder (COPIND)

47. 1. Extrapyramidal manifestations- Dystonia, resting
tremor, rigidity, chorea
2. Neuro-ophthalmic manifestations- Optic
neuropathy, retinal degeneration
3. Rarer manifestations- GBS, Ototoxicity, Sphincter
involvement
4. ARDS, pancreatitis.

48.  Prophylactic diazepam shown to decrease
neurocognitive dysfunction after poisoning.
 Diazepam 0.1-0.2 mg/kg IV, repeat as necessary if
seizures occur.
 Phenytoin has no effect on organophosphate agent-
induced seizures.

49. FRUSEMIDE – for persistent pulmonary
oedema after full atropinization.

50.  Magnesium
 Reduces acetylcholine release
 Block pre-synaptic calcium channel
 Clonidine
 Decrease the presynaptic synthesis and release of acetylcholine
(Central > peripheral synapse)
 NaHCO3
 Reversible Ach esterase - pyridostigmine
 Glutamate antagonist

51.  Respiratory
 Airway protection
 Respiratory failure
 Cardiovascular
 Hypotension despite fluid challenge
 Heart block, arrhythmias, QTc
prolongation

52.  Neurologic
 GCS < 8
 Seizures
 Metabolic
 Hypoglycaemia
 Significant electrolyte abnormalities
 metabolic acidosis
 Hepatic failure
 Coagulopathy with bleeding

53. What are commonly used nerve
agent antidote kits?

54.  It is a dual chamber autoinjector
1. Atropine sulfate and
2. Pralidoxime
 Only effective against the nerve agents tabun
(ga), sarin (gb), soman (gd) and vx.

55.  A newer model, the ATNAA (Antidote
Treatment Nerve Agent Auto-Injector),[1]
 Has atropine and the pralidoxime in one
syringe

56. Signs &
Symptoms
Atropine Dose 2-PAM Dose
Severe Respiratory
Distress,
Agitation
3 Auto-injectors (6
mg)
Monitor every 5
minutes
3 Auto-injectors
(1.8 gms)
Mild Respiratory
Distress
2 Auto-injectors (4
mg)
Monitor every 10
minutes
1 Auto-injector
(600 mg)
Asymptomatic
None
Monitor for signs &
symptoms
every 15 minutes
none

57. Read the label before
selecting and applying
any pesticide.