organophosphate poisoning

1. Case presentation
By
Dr. Suleman Bashir

2. Patient Details
• Name- Ijaz
• Age/Gender- 30 years/Male
• Address- Kharian
• Maritial Status- Unmarried
• Education- Primary
• History taken from attendants

3. Presenting Complaints
• Loss of consciousness for 10 hours.
• Difficulty in breathing for 6 hours.

4. HOPI
• My patient a farmer by profession with no past
medical history was found unconscious in the
fields by his brother on the day of admission 2
hours after going to his farm. Patient had no
symptoms preceding this event. There is no
history of fever, headache, any drug or food
intake from outside. There in no history of illicit
drug abuse or addiction. There is no evidence of
any vomiting at the scene.

5. HOPI contd
• Patient was taken to local hospital where he was
given first aid and was referred to Mayo Hospital
• On his way to hospital, patient became
tachypoenic and had difficulty in breathing with
crackling sounds. There is also history of
frothing from mouth. But there is no history of
vomiting, fits, urinary or fecal incontinence or
any weakness/focal deficit.

6. Systemic Inquiry
• No history of chronic headache,fits,visual
disturbances,blackouts,abnormal behavior,
psychosis ,numbness or tingling sensations.
• No history of exertional dyspnoea,chest
pain,body swelling, orthopnea,PND.
• No history of cough, plurisy, wheezing or nasal
discharge
• There is no history of pain abdomen, vomiting,
diarrhoea or food poisoning.

7. Past History
• NOT SIGNIFICANT
• NO HISTORY OF TUBERCULOSIS OR ANY
CHRONIC SYSTEMIC ILLNESS

8. Family History
• There is no any significant history of TB, HTN,
DM or any other illnesses in his family.

9. Drug History
• NO HISTORY OF USE OF ANY ILLICIT
SUBSTANCE OR DRUG ADDICTION
• No known allergy to any drugs

10. Personal and social history
• LOW SOCIOECONOMIC STATUS
• UNMARRIED
• EDUCATION LEVEL(UPTO Primary)

11. Occupational History
• Farmer by profession.

12. Summary of History
• Altered Sensorium for 10 hours
• Difficulty in breathing with frothing from mouth
• No history of any drug intake
• No history of any food poisoning
• No history of headache, fits, vomiting or fever
• Farmer by profession.
• No history of any social conflict

13. Differential diagnosis
• Cerebro-vascular Accidents
• Poisoning/drug overdose
• Cardiac arrythmias with brain hypoxia
• Metabolic encephalopathy
• Meningoencephalitis

14. Physical Examination
• A young man lying in bed with respiratory
distress, having cannulae in right hand with
following vitals
• P/R- 100/min
• BP- 100/60 mm Hg
• T-98
• R/R- 28/min

15. • Pallor-
• Icterus-
• Edema-
• Lymhadenopathy-
• Cyanosis-
• Bruises-
• rash-
• Thyroid not enlarged
• Patechiae –
• JVP not raised

16. CNS examination
• GCS- E2V2M5 - 9/15
• HMF couldn’t be assessed
• Speech couldn’t be assessed
• CN- couldn’t be assessed
• Pupils- B/L pinpoint
• Sensory- Couldn’t be assesed
• Motor
▫ Patient moving all 4 limbs but power couldn’t be assesed
▫ Reflexes- all reflexes present ++
▫ Tone- Seems to be normal
▫ Plantar- B/L downgoing
▫ Co-ordination couldn’t be assesed
• Cerebellar signs couldn’t be assesed
• SOMI absent

17. Respiratory System
• On inspection-
▫ Chest moving equally with respiratory rate of 28/min.
▫ Abdomio-thoracic type of respiration
▫ No chest deformity or scar marks noted
• Palpation
▫ No tenderness or crepitus noted
▫ Chest movement and expansion normal
▫ Vocal fremitus absent
• Percussion
▫ Normal
• Ascultation
▫ B/L harsh vesicular breathing with b/l coarse crepts and
rhonci.

18. Systemic examination contd
• GIT- NAD
• CVS-NAD

19. History and examination summary
History Examination
• Altered Sensorium for 10
hours
• Difficulty in breathing with
frothing from mouth
• No history of any drug intake
• No history of any food
poisoning
• No history of headache, fits,
vomiting or fever
• Farmer by profession.
• GCS- 9/15
• P/R- 100/min R/R- 28/Min
• Pin point pupil
• Frothing from mouth
• No focal deficit
• SOMI absent
• Plantar downgoing
• Chest- B/l coarse crepts with
ronchi

20. Differentials
• Poisoning
▫ Organophosphate
▫ Opiod Poinosing/overdose
• Brainstem CVA (Pontine)

21. INVESTIGATIONS
• CBC
▫ Hb 11.1
▫ wbc 10.5
▫ plt 199
• RFT-N
• LFT-N
• S/E-N
• CARDIAC ENZYMES- N
• ABG-Respiratpry alkalosis

22. INVESTIGATIONS contnd.
• PT/APTT-N
• CT SCAN BRAIN-N
• ECG- INITIALLY SINUS TACHYCARDIA THEN
SINUS BRADYCARDIA

24. FINAL DIAGNOSIS
• ORGANOPHOSPHATE POISONING

25. MANAGEMENT IN EMERGENCY
• Prop up with left lateral position
• IV Access obtained
• Cardiac monitor attached
• Ecg done
• Inj atropine 1cc given at interval of 2 to 3 mints
till pts chest was dry and clear and Spo2
improved and pupils fully dilated.
• Inj pralidoxime 1gm in 100 cc N/SALINE given
over ½ hour

26. Management
• Inj Ringer lactate IL GIVEN
• Inj Ulcerex + Marzine
• Inj C-Trox 1 gm stat
• All baselines with cardiac enzymes and ABGs
sent
• Chest X-Ray and USG Abdomen were done
• CT Head Done

27. Treatment in Ward
• Cardiac Monitoring done
• Atropine chart maintained at regular intervals
• Inj Pralidoxime @ 200mg/ hr continous
infusion given
• IV fluids 3 Litres
• Antibiotics Inj sulzone 1 gm BD
• PPI
• NPO

28. Organoposphate Poisoning
• Organophosphate (OP) compounds are a diverse
group of chemicals used in both domestic and
industrial settings. Examples of organophosphates
include insecticides (malathion, parathion,
diazinon, fenthion, dichlorvos, chlorpyrifos, ethion),
nerve gases (soman, sarin, tabun, VX),
ophthalmic agents (echothiophate,
isoflurophate), and antihelmintics (trichlorfon).
• Organophosphate compounds were first synthesized
in the early 1800s when Lassaigne reacted alcohol
with phosphoric acid.

29. • Nerve agents have also been used in battle, notably
in Iraq in the 1980s. Additionally, chemical weapons
still pose a very real concern in this age of terrorist
activity.
• Exposure to organophosphates (OPs) is also
possible via intentional or unintentional
contamination of food sources. Although no clinical
effects of chronic, low-level organophosphates (OPs)
exposure from a food source have been shown,
advancements in risk assessment and preparedness
are ongoing.

30. Pathophysiology
• The primary mechanism of action of organophosphate pesticides is
inhibition of carboxyl ester hydrolases, particularly
acetylcholinesterase (AChE). AChE is an enzyme that degrades the
neurotransmitter acetylcholine (ACh) into choline and acetic acid.
ACh is found in the central and peripheral nervous system,
neuromuscular junctions, and red blood cells (RBCs).
• Organophosphates inactivate AChE by phosphorylating the serine
hydroxyl group located at the active site of AChE. The
phosphorylation occurs by loss of an organophosphate leaving
group and establishment of a covalent bond with AChE.
• Once AChE has been inactivated, ACh accumulates throughout the
nervous system, resulting in overstimulation of muscarinic and
nicotinic receptors. Clinical effects are manifested via activation of
the autonomic and central nervous systems and at nicotinic
receptors on skeletal muscle.

31. • Once an organophosphate binds to AChE, the enzyme
can undergo one of the following:
▫ Endogenous hydrolysis of the phosphorylated enzyme by
esterases or paraoxonases
▫ Reactivation by a strong nucleophile such as pralidoxime
(2-PAM)
▫ Irreversible binding and permanent enzyme inactivation
(aging)
• Organophosphates can be absorbed cutaneously,
ingested, inhaled, or injected. Although most patients
rapidly become symptomatic, the onset and severity of
symptoms depend on the specific compound, amount,
route of exposure, and rate of metabolic degradation.[3]

32. Clinical Presentation
•
Signs and symptoms of organophosphate poisoning can
be divided into 3 broad categories, including
▫ (1) muscarinic effects,
▫ (2) nicotinic effects, and
▫ (3) CNS effects.
• Mnemonic devices used to remember the muscarinic
effects of organophosphates are SLUDGE (salivation,
lacrimation, urination, diarrhea, GI upset, emesis) and
DUMBELS (diaphoresis and diarrhea; urination;
miosis; bradycardia, bronchospasm, bronchorrhea;
emesis; excess lacrimation; and salivation).
•

33. • Muscarinic effects by organ systems include the
following:
▫ Cardiovascular - Bradycardia, hypotension
▫ Respiratory - Rhinorrhea, bronchorrhea,
bronchospasm, cough, severe respiratory distress
▫ Gastrointestinal - Hypersalivation, nausea and
vomiting, abdominal pain, diarrhea, fecal
incontinence
▫ Genitourinary - Incontinence
▫ Ocular - Blurred vision, miosis
▫ Glands - Increased lacrimation, diaphoresis

34. • Nicotinic signs and symptoms include muscle
fasciculations, cramping, weakness, and
diaphragmatic failure. Autonomic nicotinic
effects include hypertension, tachycardia,
mydriasis, and pallor.
• CNS effects include anxiety, emotional lability,
restlessness, confusion, ataxia, tremors,
seizures, and coma.

35. Physical Examination
• Clinical presentation may vary, depending on
the specific agent, exposure route, and amount.
Symptoms are due to both muscarinic and
nicotinic effects.
• Vital signs: Depressed respirations, bradycardia,
and hypotension are possible symptoms.
Alternatively, tachypnea, hypertension, and
tachycardia are possible. Hypoxia should be
monitored for with continuous pulse oximetry.

36. • Paralysis
▫ Type I: This condition is described as acute paralysis secondary to
continued depolarization at the neuromuscular junction
▫ Type II (intermediate syndrome): Intermediate syndrome was
described in 1974 and is reported to develop 24-96 hours after
resolution of acute organophosphate poisoning symptoms and
manifests commonly as paralysis and respiratory distress. This
syndrome involves weakness of proximal muscle groups, neck,
and trunk, with relative sparing of distal muscle groups. Cranial
nerve palsies can also be observed. Intermediate syndrome
persists for 4-18 days, may require mechanical ventilation, and
may be complicated by infections or cardiac arrhythmias.
Although neuromuscular transmission defect and toxin-induced
muscular instability were once thought to play a role, this
syndrome may be due to suboptimal treatment.

37.  Type III: Organophosphate-induced delayed
polyneuropathy (OPIDP) occurs 2-3 weeks after
exposure to large doses of certain organophosphates
(OPs) and is due to inhibition of neuropathy target
esterase. Distal muscle weakness with relative sparing
of the neck muscles, cranial nerves, and proximal
muscle groups characterizes OPIDP. Recovery can
take up to 12 months.

38. • Neuropsychiatric effects: Impaired memory, confusion, irritability,
lethargy, psychosis, and chronic organophosphate-induced
neuropsychiatric disorders have been reported. The mechanism is
not proven.
• Extrapyramidal effects: These are characterized by dystonia,
cogwheel rigidity, and parkinsonian features (basal ganglia
impairment after recovery from acute toxicity).
• Other neurological and/or psychological effects: Guillain-Barré–like
syndrome and isolated bilateral recurrent laryngeal nerve palsy are
possible.
• Ophthalmic effects: Optic neuropathy, retinal degeneration,
defective vertical smooth pursuit, myopia, and miosis (due to direct
ocular exposure to organophosphates) are possible.
• Ears: Ototoxicity is possible.

39. • Respiratory effects: Muscarinic, nicotinic, and central
effects contribute to respiratory distress in acute and
delayed organophosphate toxicity.
• Muscarinic effects: Bronchorrhea, bronchospasm, and
laryngeal spasm, for instance, can lead to airway
compromise. Respiratory failure is the most life-threatening
effect and requires immediate intervention.
• Nicotiectsnic eff: These effects lead to weakness and
paralysis of respiratory oropharyngeal muscles.
• Central effects: These effects can lead to respiratory
paralysis.
• Rhythm abnormalities: Sinus tachycardia, sinus
bradycardia, extrasystoles, atrial fibrillation, ventricular
tachycardia, and ventricular fibrillation (often a result of,
or complicated by, severe hypoxia from respiratory
distress) are possible.

40. • Other cardiovascular effects: Hypotension,
hypertension, and noncardiogenic pulmonary
edema are possible.
• GI manifestations: Nausea, vomiting, diarrhea,
and abdominal pain may be some of the first
symptoms to occur after organophosphate
exposure.
• Genitourinary and/or endocrine effects: Urinary
incontinence, hypoglycemia, or hyperglycemia is
possible.

41. Differential Diagnoses
▫ Gastroenteritis, Viral
▫ Toxicity, Mushroom

42. Laboratory Studies
• Organophosphate (OP) toxicity is a clinical diagnosis. Confirmation
of organophosphate poisoning is based on the measurement of
cholinesterase activity; typically, these results are not readily
available. Although RBC and plasma (pseudo) cholinesterase
(PChE) levels can both be used, RBC cholinesterase correlates better
with CNS acetylcholinesterase (AChE) and is, therefore, a more
useful marker of organophosphate poisoning.
• The portable Test-mate ChE field test measures RBC AChE and
PChE within 4 minutes.
• If possible, draw blood for measurement of RBC and plasma
cholinesterase levels prior to treatment with pralidoxime (2-PAM).
Monitoring serial levels can be used to determine a response to
therapy.
• RBC AChE represents the AChE found on RBC membranes, similar
to that found in neuronal tissue. Therefore, measurement more
accurately reflects nervous system OP AChE inhibition.

43. • Plasma cholinesterase is a liver acute-phase protein
that circulates in the blood plasma. It is found in
CNS white matter, the pancreas, and the heart. It
can be affected by many factors, including
pregnancy, infection, and medical illness.
Additionally, a patient's levels can vary up to 50%
with repeated testing.
• RBC cholinesterase is the more accurate of the 2
measurements, but plasma cholinesterase is easier
to assay and is more readily available.
• Cholinesterase levels do not always correlate with
severity of clinical illness.

44. • Falsely depressed levels of RBC cholinesterase
can be found in pernicious anemia,
hemoglobinopathies, use of antimalarial drugs,
and oxalate blood tubes.
• Falsely depressed levels of plasma cholinesterase
are observed in liver dysfunction, low-protein
conditions, neoplasia, hypersensitivity reactions,
use of certain drugs (succinylcholine, codeine,
morphine), pregnancy, and genetic deficiencies.

45. • Other laboratory findings include:
▫ leukocytosis
▫ Hemoconcentration
▫ metabolic and/or respiratory acidosis
▫ Hyperglycemia/hypoglycemia
▫ hypokalemia
▫ hypomagnesemia and
▫ elevated amylase and liver function studies

46. • ECG findings include prolonged QTc interval,
elevated ST segments, and inverted T waves.
Although sinus tachycardia is the most common
finding in the poisoned patient, sinus
bradycardia with PR prolongation can develop
with increasing toxicity due to excessive
parasympathetic activation.

47. • Procedures
• Endotracheal intubation and mechanical ventilation
may be necessary in patients with organophosphate
poisoning for airway protection and management of
bronchorrhea and seizures.
• Central venous access and arterial lines may be
needed to treat the patient with organophosphate
toxicity who requires multiple medications and
blood-gas measurements.

48. Treatment
• Medical Care
• Airway control and adequate oxygenation are paramount in
organophosphate (OP) poisonings. Intubation may be necessary in
cases of respiratory distress due to laryngospasm, bronchospasm,
bronchorrhea, or seizures.
• Immediate aggressive use of atropine may eliminate the need for
intubation. Succinylcholine should be avoided because it is
degraded by plasma cholinesterase and may result in prolonged
paralysis.
• Continuous cardiac monitoring and pulse oximetry should be
established; an ECG should be performed. Torsades de Pointes
should be treated in the standard manner. The use of intravenous
magnesium sulfate has been reported as beneficial for
organophosphate toxicity. The mechanism of action may involve
acetylcholine antagonism or ventricular membrane stabilization.

49. • Remove all clothing and gently cleanse patients suspected of
organophosphate exposure with soap and water because
organophosphates are hydrolyzed readily in aqueous solutions
with a high pH. Consider clothing as hazardous waste and
discard accordingly.
• Health care providers must avoid contaminating themselves
while handling patients. Use personal protective equipment,
such as neoprene gloves and gowns, when decontaminating
patients because hydrocarbons can penetrate nonpolar
substances such as latex and vinyl. Use charcoal cartridge
masks for respiratory protection when decontaminating
patients who are significantly contaminated.
• Irrigate the eyes of patients who have had ocular exposure
using isotonic sodium chloride solution or lactated Ringer's
solution. Morgan lenses can be used for eye irrigation.

50. Medication Summary
• The mainstays of medical therapy in organophosphate (OP)
poisoning include
▫ atropine,
▫ pralidoxime (2-PAM), and
▫ benzodiazepines (eg, diazepam).
• Initial management must focus on adequate use of atropine.
Optimizing oxygenation prior to the use of atropine is
recommended to minimize the potential for dysrhythmias.
• A meta-analysis and review of the literature performed by
Peter et al emphasized optimal supportive care along with
discriminate use of 2-PAM, especially early in the course of
treatment of moderately to severely OP poisoned patients, are
the hallmarks of treatment. More prospective data are
required.

51. • Intravenous glycopyrrolate or diphenhydramine
may provide an alternative centrally acting
anticholinergic agent used to treat muscarinic
toxicity if atropine is unavailable or in limited
supply.
• In a single-center, randomized, single-blind study by
Pajoumand et al found a benefit to magnesium
therapy in addition to standard oxime and atropine
therapy in reducing hospitalization days and
mortality rate in patients with organophosphate
poisoning.The mechanisms appear to be inhibition
of acetylcholine (ACh) and organophosphate
antagonism.

52. Anticholinergic agents
• Class Summary
• These agents act as competitive antagonists at the muscarinic cholinergic receptors in both the
central and the peripheral nervous system. These agents do not affect nicotinic effects.
• Atropine IV/IM (Isopto, Atropair)
• Initiated in patients with OP toxicity who present with muscarinic symptoms.
• Competitive inhibitor at autonomic postganglionic cholinergic receptors, including receptors
found in GI and pulmonary smooth muscle, exocrine glands, heart, and eye.
• The endpoint for atropinization is dried pulmonary secretions and adequate oxygenation.
Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. The
main concern with OP toxicity is respiratory failure from excessive airway secretions.
• Glycopyrrolate (Robinul)
• Indicated for use as an antimuscarinic agent to reduce salivary, tracheobronchial, and pharyngeal
secretions. Does not cross the blood-brain barrier. Can be considered in patients at risk for
recurrent symptoms (after initial atropinization) but who are developing central anticholinergic
delirium or agitation.
• Since glycopyrrolate does not cross BBB, it is not expected to control central cholinergic toxicity.
Bird et al suggested that atropine (rather than glycopyrrolate) was associated with lower, early
OP-induced mortality

53. Antidotes
• Class Summary
• These agents prevent aging of AChE and reverse muscle paralysis with OP poisoning.
• Pralidoxime (2-PAM, Protopam)
• Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP
molecule. Used as an antidote to reverse muscle paralysis resulting from OP AChE
pesticide poisoning but is not effective once the OP compound has bound AChE irreversibly
(aged). Current recommendation is administration within 48 h of OP poisoning. Because it
does not significantly relieve depression of respiratory center or decrease muscarinic effects
of AChE poisoning, administer atropine concomitantly to block these effects of OP
poisoning.
• Signs of atropinization might occur earlier with addition of 2-PAM to treatment regimen. 2-
PAM administration is not indicated for carbamate exposure since no aging occurs.
•

54. Benzodiazepines
• Class Summary
• These agents potentiate effects of gamma-aminobutyrate
(GABA) and facilitate inhibitory
GABA neurotransmission.
• Diazepam (Valium, Diastat, Diazemuls)
•
• For treatment of seizures. Depresses all levels of
CNS (eg, limbic and reticular formation) by
increasing activity of GABA.

55. Deterrence/Prevention
• Health care providers must avoid contaminating
themselves while handling patients poisoned by
organophosphates. The potential for cross-contamination
is highest in treating patients after
massive dermal exposure.Use personal protective
equipment, such as neoprene or nitrile gloves and
gowns, when decontaminating patients because
hydrocarbons can penetrate nonpolar substances
such as latex and vinyl.
• Use charcoal cartridge masks for respiratory
protection when caring for patients with significant
contamination.

56. Complications
• Complications include
▫ respiratory failure,
▫ seizures,
▫ aspiration pneumonia,
▫ delayed neuropathy, and
▫ death.

57. •THANK YOU