presenatation on MV prepared by Dr nigat

1. Case presentation on
organophosphate
poisoning
Presenter –Dr Nigat Endalamaw
moderator- Dr Rediet EMCC senior

2. Out line of presentation
• Identification of patient
• Case analysis with progress and investigation
• Introduction to OP poisoning
• Pathophysiology of OP poisoning
• Effect of OP poisoning on different organs
• OP poisoning severity grading
• Work up of patient with OP poisoning
• Management principles and medications
• Prevention and complication of OP poisoning

3. Name=papi solomon
Age/gender=2yr/m
Address=Addis ababa
Education=not yet
History taken=family
MRN=071353

4. 2Yr/m child presented with malathion ingestion of
2hour duration on RED side on 05/13/12 E.C
A=not patent not protected full of secretion
done=secretion sucked out and intubated with ETT 4.5
B=RR-10 PSO2-80 % on face mask o2
-bilateral diffuse crepitation on both lung field
-put on PCV-AC FIO2-60% Rate-20 PEEP- 5

5. C=PR-114 normal capilary refill
-IV line secured and atropine 0.05 mg/kg
diluted with normal saline started every 5 minutes.
D= GCS E2V1M3=6/15
-Reactive pin point pupil bilaterally
E=no sign of trauma and clothes removed and
decontaminated

6. 2 Survey
A 2yr/m chiled who presented with unintesional
ingestion of malathion after he got it in glass in the
home for 2hours.The amount can not be estimated but
he had history of loss of consiousness and has fast
breathing and frequent vomiting and excessive
secretion.He was intially seen in amanuel after GI
decontamination they Refer it to Aabet.

7. ASL PR=114 normal capillary refill
pso2=98% after intubation
diffuse crepitation on both lung field
GCS E2V1M3 =6/15
Pin point reactive pupil bilaterally
ASST=coma 2 to organophosphate poisoning + immediate
post intubation
plan-continue atropine
-Ranitidine 12.5mg iv tid
-ETT care
-insert NG tube and
start feeding
-catheterize
-ICU admission

8. Revised order
-ketamine infusion 5ug/kg/min started
-atropine 1.8mg every 1hour to be
descalated based on response
-Ranthidine 12.5 mg iv tid
-NG tube feeding 50ml every 3hour
-put on cardiac monitor
-follow input out put

9. ADMMITED TO ICU ON 1/1/13 E.C
A=Protected with ETT 4.5 no secretion and on ETT care
B=RR-20 PSO2-98 on mechanical ventilation PCV-CPAP
FI02 -60% PEEP-5
C=PR-98 normal capillary refill
D=GCS E3V1TM5=9T/15
-Pupil dilated and reactive to light
E= no sign of trauma
2 survey
secretion decreased
normal vital sign
ASST= improving
plan-RFT,Serum electrolyte,CBC

10. Progress on 02/01/13 E.C
A=protected with ETT 4.5 on suctioning
B=RR-22 PSO2-99% on PCV-AC mood
-transmitted sound all over chest
C=BP-130/68 PR -62
D=GCS E1V1TM4=6T/15 pupil are dilated and reactive
2 survey
no new complaint
normal vital sign
ASST=improving
plan-pcm 125mg supp PRN
-Diazepam 2mg iv PRN
-UFH 1000 IU sc bid
-Put on M.F calculated

11. Progress on 04/01/12 E.C
A=patent and protected with ETT 4.5
B=RR-27 PSO2 -99% on PCV-AC
-clear and resonant
C=BP -108/78 PR=108
D=GCS E2V1TM5=8T/15
-Pupil dilated reactive to light
2 survey
-Distended abdomen
-potassium is 3.25
Asst=improving +mild hypokalemaia
plan-Descalate atropine 0.01mg/kg
-kcl 150 mg po tid
-NG tube decompression

12. Progress on 05/01/13 E.C
-Same as 04/01/13 E.C
Progress on 06/01/13 E.C
-Same as o4/o1/13 E.C
-Dexametasone 2mg iv QID
started for extubation
-DIC Atropine and KCL
progress 07/01/13 E.C
-The patient extubated
progress 09/01/13 E.C
-The patient discharged

13. INVESTIGATION
on 05/13/12 E.C
wbc-8.4 Hgb-13 plt-322
-urea-25 creatinine-0.35
sgot-37 sgpt-21
sodium-138 potasium-3.96
on 03/01/13 E.C
wbc-6.6 Hgb-11 plt-277
-potasium-3.25 sodium-150
urea-14
creatinine-0.2

14. 05/01/13 EC
wbc-7.6 Hgb-12 plt-276
-urea-11 creatinine-0.22
sodium-142 potasium-4
07/01/13 E.C
wbc-8.6 Hgb-11 plt-241
-urea-10 creatinine-0.17
sodium-139 potasium-3.8

15. Organophosphates
- are a diverse group of chemicals used in both
domestic and industrial settings.
Examples are
Insecticides – Malathion, parathion, diazinon,
fenthion, dichlorvos, chlorpyrifos, ethion
Nerve gases – Soman, sarin, tabun, VX
Ophthalmic agents – Echothiophate, isoflurophate
Antihelmintics – Trichlorfon
Herbicides – Tribufos (DEF), merphos
Industrial chemical (plasticizer) – Tricresyl phosphate

16.  organophosphate toxicity can result from
-household or
-occupational exposure,
- military or terrorist action
Exposure to organophosphates is also possible via
intentional or unintentional contamination of food
sources.
Although no clinical effects of chronic, low-level
organophosphate exposure from a food source have
been shown.

17. Pathophysiology
-The primary mechanism of action of
organophosphate pesticides is inhibition of
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 .

18. - Organophosphates inactivate AChE by
phosphorylating the serine hydroxyl
group located at the active site of AChE.
-Over a period of time, phosphorylation is
followed by loss of an organophosphate
leaving group and the bond with AChE
becomes irreversible, this process known as
aging.

19. -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.

20. Once an organophosphate binds to AChE, the
enzyme can undergo one of the following:
1)-Endogenous hydrolysis of the phosphorylated
enzyme by esterases or paraoxonases
2)-Reactivation by a strong nucleophile such as
pralidoxime (2-PAM)
3)-Irreversible binding and permanent enzyme
inactivation (aging)

21. Organophosphates exposure can be
-cutaneously
-ingestion
-inhaletion
-injection
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.

22. Approach to patient with
organophosphate poisoning
History
Signs and symptoms of organophosphate
poisoning can be divided into the following three
broad categories:
1) Muscarinic effects
2) Nicotinic effects
3) Central nervous system effects

23. Muscarinic 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). :

24. Muscarinic effects by organ system 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

25. Nicotinic effects
-Nicotinic signs and symptoms include muscle
fasciculations, cramping, weakness, and
diaphragmatic failure.
-Autonomic nicotinic effects include
hypertension, tachycardia, mydriasis, and
pallor.

26. CNS effect
Anxiety ,Emotional lability ,Restlessness
,Confusion ,Ataxia ,Tremors ,Seizures ,Coma
Apnea.

27. A review of 31 children with organophosphate
poisoning described that, in contrast to adults, the
most common presentations were seizure and coma
with relatively less muscarinic or nicotinic finding.
This difference may be due to difficulty in detecting
muscarinic findings in infants (eg, crying) and ingestion
of contaminated produce instead of direct exposure to
organophosphates.

28. The most common signs in children were miosis,
excessive salivation, muscle weakness, and lethargy.
Approximately 49% of these children presented with
tachycardia.
Symptoms included salivation, lacrimation, urination,
defecation, GI distress, and emesis (SLUDGE) and were
more commonly observed in adults than in children.

29. Physical examination
Vital signs
Depressed respirations, bradycardia, and
hypotension are possible findings.
Alternatively, tachypnea, hypertension, and
tachycardia are possible.
Hypoxia should be monitored for with continuous
pulse oximetry.

30. Paralysis
Three types of paralysis may result from
organophosphate poisoning.
Type I- is described as acute paralysis secondary to
continued depolarization at the neuromuscular
junction.
Type II (intermediate syndrome) -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.

31. -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.

32. Type III paralysis or organophosphate-induced delayed
polyneuropathy (OPIDP)
-occurs 2-3 weeks after exposure to large doses of
certain organophosphates 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.

33. Op poisoning severity grading

34. Unless pralidoxime is given before aging occurs,
plasma butyrylcholinesterase takes up to 4 to 6 weeks
and red blood cell acetylcholinesterase takes as long as
90 to 120 days to return to baseline after exposure.

35. Neuropsychiatric effects of
organophosphate poisoning include:
-Impaired memory ,Confusion,Irritability
,Lethargy,Psychosis
Chronic organophosphate-induced
neuropsychiatric disorders

36. -Extrapyramidal effects are characterized by
dystonia, cogwheel rigidity, and parkinsonian
features (basal ganglia impairment after
recovery from acute toxicity).
-Other possible neurologic and/or psychological
effects include Guillain-Barré–like syndrome and
isolated bilateral recurrent laryngeal nerve palsy.

37. Other effects
Organophosphate toxicity may affect other organ
systems as follows:
Ophthalmic: Optic neuropathy, retinal
degeneration, myopia, and miosis (due to direct
ocular exposure to organophosphates).

38. Ears: Ototoxicity is possible
Respiratory: 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.

39. Nicotinic effects:These effects lead to
weakness and paralysis of respiratory oropharyngeal
muscles.
Central effects: These effects can lead to
respiratory paralysis
Cardiac 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
Gastrointestinal 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. Work up of patient with
organophosphate poisoning
-complete blood count with differential
to rule out infection
-liver and renal function with serum
electrolyte
- plasma and RBC cholinesterase

42. -Chest radiography may be performed to evaluate
pulmonary edema.
-Nonenhanced head computed tomography (CT)
scanning may be required to assess structural
lesions if the patient has an altered mental status.
-Perform an electrocardiogram (ECG) to evaluate for
cardiac arrhythmias.

43. Cholinesterase test
-Confirmation of organophosphate poisoning is based
on the measurement of cholinesterase activity.
-But these results are not readily available in a clinically
relevant timeframe.
- Although red blood cell (true) and plasma (pseudo)
cholinesterase (PChE) levels can both be used.
- RBC cholinesterase correlates better with central
nervous system (CNS) acetylcholinesterase (AChE) and
is, therefore, a more useful marker of organophosphate
poisoning.

44. -The portable Test-mate ChE field test measures RBC
AChE and PChE within 4 minutes.
-Results show the Test-mate ChE field kit is a reliable
test that provides rapid measurement of RBC AChE in
acute organophosphorus poisoning.

45. -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.

46. - 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.

47. -RBC cholinesterase is the more accurate of the two
measurements, but plasma cholinesterase is easier to
assay and is more readily available.
-Cholinesterase levels do not always correlate with
severity of clinical illness.
-Moreover, a variety of conditions can result in falsely
lowered cholinesterase levels .

48. -Plasma butyrylcholinesterase levels may be
depressed in genetic variants chronic disease liver
dysfuction ,cirrhosis,
malnutritin and low serum albumin states,
neoplasm, infection, and pregnancy.
-Red blood cell acetylcholinesterase is affected
by factors that influence the circulating life of
erythrocytes such as hemoglobinopathies

49. -The level of cholinesterase activity is relative and is
based on population estimates.
- Neonates and infants have baseline levels that are
lower than adults.
- Because an individual patient's baseline levels are
rarely available, the diagnosis can be confirmed by
observing a progressive increase in the cholinesterase
value until the values plateau over time.

50. Other laboratory findings include
the following:
Leukocytosis ,Hemoconcentration
Metabolic and/or respiratory acidosis
Hyperglycemia ,Hypokalemia ,Hypomagnesemia
,Elevated troponin levels ,Elevated amylase levels
,Elevated liver function test results.

51. Electrocardiography
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.

52. Prehospital care includes the
following:
-Ensure airway support and ventilation and perform
endotracheal intubation, if necessary, in patients with
respiratory failure.
-Circulatory support with intravenous (IV) access,
fluids, and cardiac and pulse oximetry monitoring can
facilitate safe transport.
-Decontamination is of the utmost importance in
minimizing continued exposure and to protect
providers and other patients from contamination

53. Emergency department care
Assess the patient's airway, breathing, and
circulation (ABCs). Secure the airway and perform
cardiovascular resuscitation if needed.
But avoid using succnilecholine during RSI that
exacerbate further neuro mascular blockage.
Endotracheal intubation may be necessary for
airway protection and ventilatory support.
If the patient's condition is stable,
decontamination is the next priority.

54. treatment

55. Treatment begins with decontamination.
Airway control and oxygenation are paramount.
The mainstays of pharmacological therapy 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.

56. They found that atropine seemed to be as
effective as atropine plus 2-PAM in the treatment
of acute OP poisoning.
If atropine is unavailable or in limited supply,
intravenous glycopyrrolate or diphenhydramine
may provide an alternative anticholinergic agent
for treating muscarinic toxicity; however,
glycopyrrolate does not cross the blood-brain
barrier and cannot treat central effects of OP
poisoning.

57. -Possible future interventions include
neuroprotective agents used to prevent nerve damage
and bioscavengers aimed to prevent AChE inhibition by
nerve agents.
- In a child with acute, severe organophosphate
poisoning that was unresponsive to standard
treatments, successful treatment with high-volume
continuous venovenous hemodiafiltration and
therapeutic plasma exchange combined with lipid
infusion is important.

58. Anticholinergic agents
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.
-Atropine is indicated when evidence of bronchorrhea
and other secretions is present.

59. -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.

60. Glycopyrrolate (Robinun)
-Indicated for use as an antimuscarinic agent to
reduce salivary, tracheobronchial, and pharyngeal
secretions.
-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.

61. Antidotes, OP poisoning
Pralidoxime (2-PAM, Protopam)
-Nucleophilic agent that reactivates the phosphorylated
AChE by binding to the OP molecule.
-Administer 2-PAM to patients with organophosphate
exposure and signs of muscle and respiratory muscle
weakness.
-Used as an antidote to reverse muscle paralysis
resulting from OP AChE pesticide poisoning but is not
effective once the OP compound has aged.
-Current recommendation is administration within 48 h
of OP poisoning.

62. - Because it does not significantly relieve
depression of the 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.

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

64. Further Inpatient Care
-Because of risks of respiratory compromise or
recurrent symptoms, hospitalizing all symptomatic
patients for at least 48 hours in a high acuity setting is
recommended.
-Patients who are asymptomatic 12 hours after
organophosphate exposure can be discharged since
symptom onset should usually occur within this time
frame.

65. Prevention
- 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.

66. Complication of op poisoning
Respiratory failure,siezure,Aspiration
pneumonia,delayed neuropathy
metabolic disorders, such as hyperglycemia (high
blood sugar) and glycosuria (excess sugar in urine)
pancreatitis, or inflammation of the pancreas and
cancer
neurological problems, such as muscle weakness and
twitching, poor concentration, poor memory, and post-
traumatic stress disorder and fertility problems and
paralysis

67. What OP poisoning
Toxidromes the patient has?
-He has excessive secretion
-He has altered mentation
-He has papillary constriction
-He has tachypnea and tachycardia
-He has gastric emesis and family told
that he took malathion
-He responded for atropine treatment
so this are organophosphate toxidromes but
typical presentation is not like adults.

68. What are the strength in patient
management
-Decontaminated
-early intubated
-early atropine initiated
-GI and DVT prophylaxis was given
-sedated on MV
-catheterized and feeding started
-ETT care given and on cardiac monitor
-admitted to ICU
-Dexametasone was given before extubation

69. What are weakness in patient
management
-Difficult to get and estimate amount of poison
and to get psychosocial history
-chest x-ray and CT was not done for altered
mental status patient
-ECG was not done to rule out arrhythmia
-GCS was not well documented
-paracetamol was only antipain given for patient
on mechanical ventilation
-Other options of medical management like
pralidoxime and glycopyrrolate was not considered

70. REFERENCE