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Dr Manazir
Dept of Anaesthesiology & Critical Care
Jawaharlal Nehru Medical College
AMU, Aligarh
 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
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
Pupils: B/L pinpoint, non reacting to light
Tone: Increased
Power: Movement Against gravity
Plantar reflex: Non elicitable
Bowel sounds: Exaggerated
Normal
Size..???
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)
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
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.
What are different types of
organophosphorus compounds?
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
• Nerve agents
• Insecticides
• Glaucoma treatments
• Myasthenia gravis
• Potential uses in alzheimer’s disease and dementia
 How phosphates are different
from Carbamates
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
1. Cutaneous
2. Ingestion
3. Inhalation
4. Injection
14
• Inhibit acetylcholine esterase
enzyme at nerve endings by
phosphorylation
↑ acetylcholine at receptor sites
Mechanism of action
Diarrhea Salivation
Urination Lacrimation
Miosis Urination
Bradycardia Defecation
Bronchospasm G.I upset
Emesis Emesis
Lacrimation
Limp
Sweating
How do you grade the severity??
GRADE SYMPTOMS
MILD NAUSEA, VOMITING
DIARRHOEA
SWEATING
MODERATE LACRIMATION, SALIVATION
MIOSIS
FASCICULATION
SEVERE INCONTINENCE
ARDS, APNOIC SPELLS
AREFLEXIA, SEIZURE,COMA
How long will it take to present with
toxidromes??
 Generally oral or respiratory exposures
within three hours.
 While from dermal absorption may be
delayed up to 12 hours.
How will you confirm your
diagnosis??
 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 .
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
Which enzyme assays correlate
more with poisoning severity??
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
Plasma butyrylcholinesterase activity does not
relate to severity of poisoning
 More easily performed
 A depression of 25% or more – severe .
 Recovers @ 7% per day
These enzymes facilitate the decision
about
 When to stop oxime and
 Allow cautious weaning of a patient
Cholinergic/ OP poisoning
 How will you manage..???
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
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
 Wash at least 3 times with soap (containing
chlorhexidine and alcohol) and water, paying
particular attention to hair, skin folds and
underneath nail beds.
 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
 Lateral position better - delays spont.
Absorption
 No evidence that larger tube better
 Preferably done on awake patients
 ET tube preferred if GCS is low.
 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.
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
 D5 + 10-20% of the total initial dose of
atropine on an hourly basis. (after
stabilization)
 STOP atropine infusion if features of toxicity
 Confusion, delirium, coma
 Urinary retention, Bowel ileus
 Hyperthermia
 Agitation, psychosis
 Flushing
 Tachycardia (>140/min)
 Fixed dilated pupil
 loading dose @ 30mg/kg IV over 10-20mins
 Continuous infusion of 8-10mg/kg/hr.
 Upto when??
 Continue oxime infusion until atropine has
not been needed for 12–24 h and patient
extubated
What are the different phases of
toxicity..?
1. Acute cholinergic crisis
2. Intermediate syndrome (IMS)—major cause
of morbidity and mortality
3. Delayed neuropathy
 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.
 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
 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.
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)
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.
 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.
FRUSEMIDE – for persistent pulmonary
oedema after full atropinization.
 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
 Respiratory
 Airway protection
 Respiratory failure
 Cardiovascular
 Hypotension despite fluid challenge
 Heart block, arrhythmias, QTc
prolongation
 Neurologic
 GCS < 8
 Seizures
 Metabolic
 Hypoglycaemia
 Significant electrolyte abnormalities
 metabolic acidosis
 Hepatic failure
 Coagulopathy with bleeding
What are commonly used nerve
agent antidote kits?
 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.
 A newer model, the ATNAA (Antidote
Treatment Nerve Agent Auto-Injector),[1]
 Has atropine and the pralidoxime in one
syringe
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
Read the label before
selecting and applying
any pesticide.
Organophosphorus poisoning

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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..???
  • 5.
  • 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
  • 16.
  • 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.