Toxicologic Emergencies

1. Organophosphate
and carbamate
poisonings
Presenter: Molalign Ab.ECCM RI
Moderator: Dr.Tekiy.ECCM RII
Advisor: Dr.Mariamawit.ECCM Specialist

2. Seminar outlines
• Introduction
• Epidemiology
• Pathophysiology
• Clinical syndromes
• Diagnosis
• Management

3. Introduction
• CENTRAL NERVOUS SYSTEM NEURON:
THE BASIC FUNCTIONAL UNIT
• The central nervous system is estimated to contain 80
to 100 billion neurons.
• The synapse is the junction point from one neuron to
the next.
• There are two major types of synapses:-
1. Chemical
• Most synapses in CNS
• Neurotransmitters
2. Electrical
• In smooth muscle
• Gap junctions

4. • More than 50 chemical substances have been proved
or postulated to function as synaptic transmitters.
• Some of the best known are acetylcholine,
norepinephrine, epinephrine, histamine,
gamma-aminobutyric acid (GABA), glycine,
serotonin, and glutamate.

5. • Acetylcholine
• The primary transmitter in:-
• ANS ganglia
• Somatic neuromuscular junction, and
• Parasympathetic postganglionic nerve endings
• Two principal types of acetylcholine receptors
– Muscarinic receptors
– Nicotinic receptors
• Acetylcholine activates both of them.

6. Some anatomic and neurotransmitter
features of autonomic and somatic motor
nerves

7. Table 2 Major autonomic receptor types

8. Table 3:Direct effects of autonomic nerve activity on
some organ systems

9. • Once secreted, acetylcholine persists in the tissue for
a few seconds & then it is split into an acetate ion and
choline, catalyzed by the enzyme
acetylcholinesterase.
• Most cholinergic synapses are richly supplied with
acetylcholinesterase; the half-life of acetylcholine
molecules in the synapse is therefore very short (a
fraction of a second)

10. • Organophosphate and carbamate poisonings are
poisonings caused by organophosphate and carbamate
compounds that inhibit the enzyme cholinesterase.

11. Organophosphate
Poisonings

12. • Organophosphate compounds are the organic
derivatives of Phosphorous containing acids.
• Commonly used organophosphates include:-
– Diazinon
– Malathion
– Parathion, and
– Chlorpyrifos
• Organophosphorus insecticides variable chemical
nature.

13. • Route of Exposure:
• Oral ingestion
–most common(88.9%)
• Inhalation
• Skin contact
• Organic phosphorus compounds are extremely well
absorbed from the lungs, gastrointestinal tract, skin,
mucous membranes, and conjunctiva.
• Result in organophosphate poisonings.

14. Epidemiology
• OP poisoning due to self poisoning or suicidal
poisoning accounts for at least 40-60% of all
cases in some African countries.
• In an analysis of admissions to the Tikur
Anbesa Hospital (TAH) over a period of
four years organophosphate poisoning
accounted for 50% of all poisonings.

16. • Results
– The most commonly consumed OP was Malathion
(41.1%), which is similar with some other studies ,
the remaining 58.9% was unknown OPCs.
– The majority of the patients (81.1%), were in the
age group 11–30 years.
– The majority of poisoning cases are women (60%),
with a male to female ratio of 1:1.5
– The majority of the cases reached the hospital with
3–12 h with a mean time interval of 5.13 h.

17. • The main reasons stated by patients for their suicide
attempt were;
• Conflict among families (5.8%)
• Marital disharmony (16.9%)
• Unsuccessful love affair (7.3%)
• Mental disorder (8.4%)
• For treatment of a disease (2.4%)
• Being HIV positive (4.8%) and
• Unplanned pregnancy (4.8%)

18. Ops/carbamates identified in one Cross-Sectional
Comparative Study on Knowledge Attitude and Practice of
Farmers and Farm Workers Ethiopia
COMMON NAME CHEMICAL CLASS WHO CLASS
Malathion Organophosphate (diM) III (slightly hazardous)
Methyl parathion Organophosphate (diM) Ia (extremely or highly
hazardous)
Profenofos Organophosphate II (moderately hazardous)
Chlorpyrifos Organophosphate (diE) II (moderately hazardous)
Diazinon Organophosphate (diE) II (moderately hazardous)
Dimethoate Organophosphate II (moderately hazardous)
Propamocarb
hydrochloride
Carbamate U (unlikely to present acute
hazard)
Mancozeb Dithiocarbamate U (unlikely to present acute
hazard)

19. Pathophysiology
Inhibition of cholinesterase
Acetylcholine accumulation at nerve synapses
and neuromuscular junctions
Overstimulation of acetylcholine receptors

20. Paralysis of cholinergic synaptic transmission:
• CNS
• Autonomic ganglia
• parasympathetic
• Some sympathetic nerve endings (e.g., sweat glands),
and
• Somatic nerves

21. Cont.…
• There are in multiple important chemical
nature of Op compounds in the
pathophysiology of OP poisoning, including:-
• Lipid solubility
• Rate of activation
• Chemical structure

22. 1.Lipophilicity
– Lipophilic compounds
• Results in relatively
– Minor early clinical features
– Recurrence of toxicity
– Delayed respiratory failure, and
– Prolonged cholinesterase inhibition
• Eg Chlorpyrifos, profenofos, malathion,
fenthion

23. – Nonlipophilic compounds
• Produces relatively acute poisoning with
rapid resolution if the patient survives
• Eg. Dimethoate
• Lipid solubility markedly affects the volume of
distribution, the acuteness of toxicity, and both
the duration and recrudescence of toxicity.

24. 2.Rate of activation
– “Direct”-acting OP insecticides (“oxons”)
–Inhibit acetylcholinesterase (AChE) without
being metabolized in the body
– “Indirect” inhibitors (prodrugs or “thions”)
– Require partial metabolism within the body to
become active.
– Many pesticides, such as parathion and malathion,
are “indirect” inhibitors eg (to paraoxon and
malaoxon, respectively)

25. 3.Chemical groups attached to the
phosphorus
– Major implications for the speed of aging and
therefore the efficacy of oxime treatment.
– There are generally 3 classes of OP
• Dimethyl: Malathion, methyl parathion,
Dichlorovos(DDVP)
• Diethyl: Parathion, chlorpyrifos
• Atypical: Profenofos

26. • Inhibited acetylcholinesterase reactivates
spontaneously but slowly.
• The half-life of reactivation varies according to
the organophosphorus:
• If dimethyl, the half-life is about 3.7 h.
• If diethyl, the half-life is around 33 h.
• Oximes speed up this reactivation

27. • Aging is irreversible binding of the
organophosphorus compound to the
cholinesterase. .
• Once aging occurs, the enzymatic activity of
cholinesterase is permanently destroyed, and
new enzyme must be resynthesized over a
period of weeks before clinical symptoms
resolve and normal enzymatic function returns.
• Antidotes must be given before aging occurs to
be effective.

28. Clinical Features
• Clinical presentations (onset & severity) depends on:-
– Specific agent (predominance of nicotinic versus
muscarinic effects)
– Quantity absorbed
– Route of exposure
– Amount and character of additives (including
solvents) in any preparation
– Location of the receptors affected
– Rate of metabolic degradation

29. Clinical Features
• Excess acetylcholine results in a cholinergic crisis
that manifests as a central and peripheral clinical
toxidrome.
• Four clinical syndromes are described following
organophosphate exposure:
– Acute poisoning
– Intermediate syndrome
– Chronic toxicity
– Organophosphate induced delayed neuropathy

30. 1.Acute Organophosphate
Poisoning
• Most poisoned patients are symptomatic within the
first 8 hours and nearly all within the first 24 hours
• Acute exposure results in
– Muscarinic
– CNS
– Nicotinic
– Somatic motor manifestations

31. Muscarinic overstimulation in the parasympathetic
system
• Bronchospasm
• Bronchorrhoea
• Miosis
• Lachrymation
• Urination
• Diarrhoea
• Hypotension
• Bradycardia
• Vomiting
• Salivation

33. Nicotinic overstimulation in
the sympathetic system
• Tachycardia
• Mydriasis
• Hypertension
• Sweating
Nicotinic and muscarinic
overstimulation in the CNS
• Headache
• Confusion
• Agitation
• Coma
• Depression of
respiratory and
circulatory centers may
result

34. Nicotinic overstimulation in somatic nerves
• At neuromuscular junctions results in muscle
– Cramps
– Fasciculation
– muscle weakness
• This syndrome may progress to paralysis and
areflexia, making it difficult to detect seizure activity.
• Respiratory muscle paralysis can lead to ventilatory
failure.

35. Classfication based on severity……
Mild Moderate Severe
• Lightheadedness
• Nausea
• Headache
• Dyspnea
• Lacrimation
• Rhinorrhea
• Salivation, and
• Diaphoresis
• Autonomic instability
• Confusion
• Vomiting
• Muscle spasms
• Bronchorrhea and
• Bronchospasm
• Pinpoint pupils
• Excessive sweating
• Reduced
consciousness
• Poor respiration
• Coma
• Seizures
• Flaccid paralysis
• Urinary and fecal
incontinence, and
• Respiratory arrest

36. • Poisoning severity is also measured using the
Peradeniya Organophosphorus Poisoning (POP)
scale.
• The POP scale was first introduced in 1993 and
analyzed many variables on admission
• Mortality rates are relatively low for mild to moderate
disease.
• Severe disease as calculated by the POP carries an
exceptionally high mortality rate.

37. The Peradeniya Organophosphorus Poisoning (POP) scale

39. • Conclusions:
– The POP was a useful tool in prognosticating OP
poisoning outcomes and management.
– Mild to moderate disease had an excellent survival
rate at 28 days.
– Nearly half of the patients with severe disease died
within the same period.
– Peradeniya score of >7 is an indication for
ventilation.

40. 2.Intermediate Syndrome
• The syndrome is defined as occurring 24 to 96 hours
after acute OP poisoning, and after resolution of the
cholinergic crisis.
• It reflects a prolonged action of acetylcholine on the
nicotine receptors.
• Clinical features
– Paralysis of neck flexor muscles
– Paralysis of muscles innervated by the cranial nerves
– Paralysis of proximal limb muscles, and respiratory
muscles

41. • The first sign is often weakness of neck flexion such
that patients cannot lift their head off the bed.
• Symptoms or signs of cholinergic excess are absent in
this syndrome.
• Seen in up to 40% of patients following ingestion.
• Most feared syndromes & symptoms usually resolve
within 7 days.

42. • The diagnosis is clinical.
• It should be suspected when a patient who is
recovering from the cholinergic crisis develops
respiratory difficulty.
• Aggressive, early antidote therapy and supportive
measures may prevent or ameliorate the severity of
this syndrome.

43. 3.Chronic Toxicity
• Seen primarily in agricultural workers with daily
exposure.
• Manifests as symmetrical sensorimotor axonopathy.
• This mixed sensorimotor syndrome may begin with
leg cramps and progress to weakness and paralysis,
mimicking features of the GBS.

44. 4.Organophosphate-induced
delayed neuropathy
• Typically a subacute sensory motor nerve disease
occurring 2-4 weeks after OPC poisoning.
• It is characterized by:
– Cognitive dysfunction
– Impaired memory
– Mood changes
– Autonomic dysfunction
– Peripheral neuropathy
– Extrapyramidal signs
– Chronic fatigue syndrome

45. Diagnosis
• The diagnosis of OP poisoning is made on:
– Basis of history of poisoning
– Smell of pesticides
• Characteristic hydrocarbon or garlic-like odor may assist in
diagnosis
– Characteristic clinical signs and
• Majority of patients severely poisoned will have altered mental
status, pinpoint pupils, excessive sweating, and difficulty
breathing
• Miosis (papillary constriction) and muscle fasciculation are the
most reliable signs of organophosphate toxicity and help in
diagnosis.
– Reduced cholinesterase activity (tests are highly unlikely to be
available)

46. • Routine laboratory test abnormalities are
nondiagnostic.
– Hyperglycemia and ketosis (mistaken for DKA)
– Leukocytosis
– Elevations of hepatic enzymes
– Hyperamylasemia appears to be relatively common
• In severe cases, a chest radiograph may show
pulmonary edema.

47. • ECG changes include ST-segment changes, peaked T
waves, atrioventricular block, and prolongation of the
QT interval.
– Common abnormalities include torsades de pointes,
ventricular tachycardia, and ventricular fibrillation

48. • In case clinical presentation is not clear, Inj. Atropine
0.6 mg to 1.0 mg (0.05 mg/kg in children) IV
challenge may be helpful
– Classic antimuscarinic findings in particular tachycardia
(by more than 20-25 beats/min), mydriasis, and dry mucous
membranes Not significant cholinergic poisoning
and further observation required.
– Persistent cholinergic signs and symptoms strongly
suggests the presence of anticholinesterase poisoning.

49. Management of OP poisonings
• Airway protection
• Intensive respiratory support
• General supportive measures
• Decontamination, prevention of
absorption
• Administration of antidotes
• Other therapies

50. Airway protection
– Death occurs in untreated patients through a
combination of bronchorrhea, respiratory
muscle paralysis, and CNS depression.
– Gentle suction (clear airway secretions )
• Hypersalivation
• Bronchorrhea, or
• Emesis
– Endotracheal intubation
• Coma
• Seizures
• Respiratory failure
• Excessive respiratory secretions, or
• Severe bronchospasm

51. Intensive respiratory support
– Ideally, oxygen should be provided at the
first opportunity.
• A 100% nonrebreather mask will optimize oxygenation
in the patient with excessive airway secretions and
bronchospasm
– Respiratory support through endotracheal intubation
and artificial ventilation is required in severe poisoning.
• Patients with the following criteria may
need ventilator support.
» History of intake of large dose
» Copious secretions
» Disturbed level of consciousness
» Signs of hypoventilation or respiratory
obstruction by secretions

52. General supportive measures
– A cardiac monitor, and pulse oximeter
– Establish an IV line with baseline blood sampling
– Hypotension is initially treated with fluid boluses
of isotonic crystalloid
• Set up an infusion of 0·9% normal saline; aim to keep
the systolic blood pressure above 80 mm Hg and urine
output above 0·5 mL/kg/hr..
– The patient should be placed in the left lateral
position, with the neck extended.
– Insulin to control Blood glucose.

53. – Antibiotics as prophylaxis (controversial)
– Benzodiazepines to treat agitation and tremor
symptom
– Antiemetic to treat vomiting
– Proton pump inhibitors and Histamine receptor 2
blockers to decrease gastric mucosa erosion

54. Decontamination
– All clothes and accessories must be removed
completely, placed in plastic bags, and disposed of
as hazardous materials.
– Wash patient with soap and water.
– Handle and dispose of water runoff as hazardous
waste.
– Body fluids should be treated as contaminated.
– Activated charcoal is sometimes recommended
• The standard dose is 1 g/kg (maximum dose 50 g)

55. Gastric lavage

56. • Conclusion: Despite widespread use of multiple
gastric lavages for OP pesticide poisoning across
Asia, there is currently no high-quality evidence to
support its clinical effectiveness.
• Gastric lavage undertaken within 1 hour of a very
large may be beneficial.

57. Administration of antidotes
• Atropine therapy
– Atropine is considered the most acceptable and
widely used treatment for OP and CRB poisoning.
– It is a competitive inhibitor of the muscarinic Ach
receptor; therefore, it diminishes some of the
pathological cholinergic effect but has no effect on
the AchE-OP complex.
– Atropine binds muscarinic receptors; prevents
activation

58. – Atropine will reduce fluid in the lungs and
improve oxygenation as well as treat hypotension
and bradycardia.
– Atropine has well documented effects on bronchial
smooth muscle tone with bronchodilation lasting
for hours following intravenous administration
(half life 1-2 hours)
– The peak effect of atropine is seen within three
minutes of an IV injection.

59. • Atropine therapy
• Rapid loading dose of intravenous
atropine:
• Initial bolus of 1.2–3.0 milligrams IV in an
adult depending on severity of symptoms (doses
in children should start at 0.05 milligram/kg IV)

60. • A recent trial from Bangladesh showed markedly
more rapid atropinization of OP-poisoned patients
with a doubling dose regimen of atropine rather than
a standard bolus dose regimen.
– The time to stabilization was reduced from a mean of 152
min to 24 min in those receiving the doubling regimen; this
faster stabilization was associated with a mortality
reduction from 22.5% to 8%.
– This study demonstrates a clear clinical benefit achieved by
administering atropine rapidly to sick patients with
anticholinesterase insecticide poisoning.

61. • Atropine therapy
– Criteria of Atropinization:
• The dose is doubled every 5 minutes until the following
are achieved:
» Chest clear on auscultation
» HR >80 beats/min, and
» SBP >80 mm Hg
» Dry axillae and wider than pinpoint pupils as additional
goals(some authors)
• Large amounts of atropine, on the order of hundreds of
milligrams, may be necessary in massive ingestions.

62. Muscarinic Effects
Heart rate
SBP
Sweating
Secretion
Pupils
Atropine

63. • Atropine therapy
– Resistant to High dose Atropine:
• Some patients are resistant to the effects of
atropine and need large doses possibly up to
100mg in 24 hours.
– HR< 80 bpm
– Hypotension with adequate HR(eg 80-100 bpm)
• Treatment: Epinephrine
– Most patients need epinephrine for <12 hrs.
– No mortality benefit.

64. – Clinical judgment is needed about additional doses
of atropine if the heart rate and blood pressure are
slightly below their targets but the chest is clear.
More atropine at this point might not be needed.
– Severe hypotension might benefit from
vasopressors.
– The value of vasopressors versus higher doses of
atropine is not yet clear.

65. – The studies concluded that patient who
receive aggressive heavy dose of atropine,
survived more frequently than those who
received inadequate doses or none at all.
– Also studies observed that continuous high
dose atropine infusion is more effective than
intermittent bolus doses

66. • Atropine therapy
– Maintenance dose:
• Once the patient was atropinized, then atropine
infusion was started and maintained at 10-20%
of total atropine dose used for achieving
atropinization in every hour (10-20% of loading
dose/hour).

67. • Atropine therapy
– Maintenance dose:
• For example:
– If a patient received atropine 2 mg IV, then 4
mg in 5 minutes, and 8 mg in 5 minutes
– When improvement in bronchorrhea is
noticeable, the total loading dose to initial
control would be 14 mg in 10 minutes
– The initial IV infusion dose of atropine would be
1.4 mg/h.

68. • Atropine therapy
– Duration of maintenance atropine
therapy:
• This depends on the severity and response to
therapy.
• Usually it is maintained for 24- 48 hrs. or longer
in severe cases.
• Tapering dose: reduce the dose by 1/4th of
previous day’s dose and gradually withdrawn
over 3-5 days (some over 5-10 days).

69. • Out of 38 protocols prescribed in literature a protocol
of starting with dose of 1-2 mg followed by bolus
doses, every 5 min, with double of previous dose, in
case of no response, to achieve the target end point is
recommended.
• Here after it is to be maintained through Atropine
infusion (at a rate of 10-20% of total atropine
required to load the patient per hour) for 24-48 hrs.
and gradually withdrawn over next 3-5 days.

70. • Atropine therapy
–Observation: -
• Observations made initially after each atropine dose is
entered in the observation sheet.
• The need of close observation through OP observation
sheet has been stressed
• With regard to management, patients with OP and CRB
poisoning must be kept under continuous observation
even after atropinization.

71. Table-2: OP / Carbamate Observation
Sheet
Ti
me
BP HR T0 So
2
Lu
ng
GC
S
Pu
pil
siz
e
Axi
lla
flexo
r
neck
stren
gth
B
o
w
el
s
o
u
n
d
Inp
ut
Ou
tpu
t
Atr
opi
ne
do
se

72. • During observation: -
-Recurrent cholinergic features
• If too little is given, cholinergic features will re-
emerge after sometime.
• Fat-soluble organophosphorus
• Such crises can occur for several days to weeks
after ingestion of some organophosphorus.
• Management :-retreatment with atropine and
oxime

73. • During observation: -
– Atropine Toxicity
• Tachycardia,Confusion, agitation, fever, ileus,
tachycardia etc. (confusion, pyrexia, absent bowel
sounds; all three should be present), would suggest
over atropinization.
• Management :
• Discontinue atropine infusion
• Wait 30–60 min for these features to settle
• When symptoms settle, restart infusion at 70- 80 % of
the previous rate.

74. Atropine therapy algorism

75. • During observation: -
– Intermediate syndrome
• Develops around 3-5 days after poisoning
• Rapid onset of weakness of muscles (respiratory, ocular,
limb, neck, back) seen
as inability to raise head from pillow and difficulty in
respiration
• Any sign of weakness is a sign that the patient is at risk
of developing peripheral respiratory failure.
• Management: Respiratory support

76. • Atropine does not alleviate the nicotinic
cholinergic effects, such as muscle
fasciculations and muscle paralysis, so death
from massive overdoses of OPs can still occur.

77. • During observation: -
– Agitation
• The cause is complex, with contributions from
multiple factors:-
– Pesticide itself
– Atropine toxicity
– Hypoxia
– Alcohol ingested with the poison, and
– Medical complications

78. – Management of Agitation:-
• Prevention or treatment of underlying causes
• Reviewing the dose of atropine being given
• Physical restraint of agitated patients in warm
conditions risks severe hyperthermia, which is
exacerbated greatly by atropine because it inhibits
normal thermoregulatory responses, including sweating.
• Pharmacotherapy
– Acutely agitated patients will benefit from treatment with
diazepam

79. • During observation: -
– Seizure
• Treated with airway protection,
• Oxygen
• Atropine
– Atropine may prevent or abort seizures (due to
cholinergic overstimulation) that occur within
the first few minutes of exposure.
• Benzodiazepines

80. Oxime therapy
• Oximes reactivate acetylcholinesterase by attaching
to the phosphorus atom and forming an oxime-
phosphonate and are active at both muscarinic and
nicotinic sites.
• Pralidoxime
• Obidoxime and
• Trimedoxime
• Clinical trials have yielded conflicting results (both
benefit and harm), so their role in routine clinical
practice is not confirmed.

81. • WHO recommends that oximes be given to all
symptomatic patients who need atropine.
• A slow loading dose of pralidoxime chloride or
obidoxime is given, then a continuous
infusion.
• Treatment with oximes must be instituted as soon as
possible (within 24–48 hr.)., preferably within 24
hours of ingestion of OPs.

82. • Aged acetylcholinesterase cannot be reactivated
by oximes.
• The half-life of ageing varies according to the
inhibiting pesticide:
– If dimethyl, the half-life is around 3 hr.
• Unresponsive to oximes after 12 hr (about 94 % aged).
– If diethyl, the half-life is around 33 hr.
• Oximes can be effective for up to 5 days after ingestion.
• Thus ageing has important clinical consequences.

83. • Pralidoxime therapy
– Recommended loading dose
• Inj. 30 mg/kg iv slowly over 30 minutes. 2 gm in 100 ml
normal saline in 70 kg patients
• Rapid administration leads to complications
– Vomiting (risking aspiration)
– Muscle or laryngospasm
– Tachycardia, and
– Diastolic hypertension
• If benefit follows, as reflected by improved muscle
power and less fasciculation and convulsions and
improved conscious level

84. • Pralidoxime therapy
• Maintenance dose
• Inj. infusion at 8-10 mg/kg/hour.
• Alternatively
– In severe poisoning, 1 gm 6 hourly
– In mild to moderate poisoning1 gm IV every 8 hours my be
given.
• Maintained for average 5-7 days or until
clinical recovery (12-24 hours post-
atropinization), whichever was longer

86. • Two hundred thirty-five patients were randomized to
receive pralidoxime (121) or saline placebo (114)
:30/121 (24.8%) receiving pralidoxime died,
compared with 18/114 (15.8%) receiving placebo
– Conclusions: Despite clear reactivation of red cell
acetylcholinesterase in diethyl organophosphorus pesticide
poisoned patients, there is no evidence that pralidoxime
improves survival or reduces need for intubation in patients
with organophosphorus insecticide poisoning.

87. Other therapies
• Current therapy works through only a few
mechanisms.
• Several new therapies have been studied but
results were inconclusive.
– Magnesium sulphate - reduce acetylcholine release
from pre-synaptic terminals
– FFP (use of butyrylcholinesterase)

88. • Magnesium sulphate therapy
• Magnesium reduces Ach release by blocking
presynaptic calcium channels in central and
peripheral nervous system.
• Continuous MgSO4 infusion, 16 g over 24 h could
be tried.
– Literatures shows its benefit on reducing the
hospitalization days and rate of mortality in acute
OP poisoning.

90. • The trial was run on 4 sequential group of 50 patients,
one control for every 4 patients.
• Results:
– No adverse reactions to magnesium were
observed.
– Six patients died in control group compared to 3 in
4 gm, 2 in 8 gm and 1 in 12 gm group. There was
no mortality in 16 gm group.
• Conclusion: Magnesium was well tolerated in this
study. Larger studies are required to examine for
efficacy.

91. • Fresh Frozen Plasma therapy
• FFP acts by neutralizing toxins released into
circulation by redistribution from adipose tissue.
• Turkish doctors have reported the use of
butyrylcholinesterase in FFP to treat poisoned
patients and recorded benefit.
• It also reduces the ICU stay with zero
mortality in OP poisoning.

92. • Daily reducing dose of FFP therapy for 3 consecutive
days (4 units 1st day, 3 units 2nd day, and 2 units 3rd
day) has beneficial effect in acute OP poisoning by
increasing serum cholinesterase enzymes in blood
with reduction in total dose of atropine consumption
per day.

93. • Antihistamines
• Potentially useful in emergency situations of
antidote shortages.
• The pharmacological benefits of first
generation antihistamines which are desirable
in OP poisoning are numerous such as:
– Centrally acting
– Exhibiting antimuscarinic and anticholinergic activities
– Crossing the blood brain
barrier
– Widely available
– commendably reduce

95. • Conclusions: The scope of using antihistamines in
OP poisoning is encouraging based on the evidences
available from few studies.
– The study suggests that some of the first
generation antihistamines like promethazine and
diphenhydramine may be effectively used as
antidote for OP poisoning depending upon the
degree of poisoning.
– From the literature review (literature search
retrieved thirteen articles), it appears that
promethazine may have greater potential as
alternative to atropine.

96. Outcome
• Factors affecting outcome in organophosphorus
pesticide self-poisoning
– OP compound related
– Patient related

97. OP compound related
• Toxicity
• Formulation
• Alkyl sub-groups
• Need for activation
• Duration of effect—
fat solubility and
half-life
Patient related
• Delayed transfer of
patient to the hospital
• Too much of OPC
consumption
• Comorbidities
• Clinical status at
presentation

98. • Mortality rate was markedly higher among those who
developed complications such as:
– Coma
– Convulsions
– Pulmonary edema e.t.c
• The fatal period is usually within 24 h in
untreated cases and within 10 days if treatment
is not successful.

99. Disposition and Follow-Up
• Minimal exposures:
– May require only decontamination and 6 to 8 hours of
observation in the ED to detect delayed effects.
– Reexposure should be avoided
– The discharge criteria: an asymptomatic patient in whom
atropine or oxime was not required for 1–2 days.
• Severe exposure:
– Admission to the intensive care unit
– If there is no post-hypoxic brain damage and if the patient
is treated early, symptomatic recovery occurs in 10 days.

100. Summery

102. Carbamate
Poisonings

103. • Carbamate insecticides are N-methyl
carbamates derived from carbamic acid
• Vary widely in their acute toxicity eg.
– Aldicarb (very toxic)
• LD50 o.9 mg kg
– Carbaryl (less toxic)
• LD50 300 mg kg
– Carbofuran
– Oxamyl
– Methomyl etc

104. Pathophysiology
• Carbamates inhibit AChE by depositing a carbamyl
group on the enzyme, which is then completely
inactivated; thus the clinical effect is exactly like OP
toxicity. Transient and reversible binding.
• Aging does not occur.
• Most carbamates undergo hydrolysis,
hydroxylation, and conjugation in the liver
and intestinal wall, with 90% excreted in
the urine within 3 to 4 days.

105. • The important differences distinguishing carbamates
from organophosphate toxicity:
• Carbamate toxicity is typically short-lived in
which spontaneous regeneration of enzymatic
activity usually occur within 24hours
• Carbamates produce little or no CNS toxicity
because of their inability to penetrate the blood-
brain-barrier & affect brain cholinesterase
activity
• Sign & symptoms may be more rapid & usually
abate within 24hrs regardless of therapy.

106. Clinical Features
• In adults:
– Symptoms are similar to the cholinergic syndrome
observed with organophosphate agents but are of
shorter duration
– Less central toxicity is seen, and seizures do not
occur
• In children:
– Acute presentation differs, with a predominance of
CNS depression and nicotinic effects.
– Carbamates can also produce the intermediate
syndrome.

107. Diagnosis
• Diagnosis is based on clinical history and findings.
• Measurement of acetylcholinesterase activity is
generally not helpful because enzymatic activity may
spontaneously return to normal 4 to 8 hours after a
carbamate exposure.

108. Treatment
• Initial treatment is the same as for organophosphorus
compounds
• Atropine:
– Administered for muscarinic symptoms
– Therapy is usually not needed for more than 6 to
12 hours.
• The use of pralidoxime in carbamate poisoning is
controversial & there is little need for pralidoxime.

109. • Pralidoxime should be considered:
– Mixed poisonings with an organophosphorus
compound and a carbamate or
– Unknown type of insecticide

110. Disposition and Follow-Up
• In mild poisonings, observation suffices, and the
patient may be discharged with follow-up.
• Moderate poisonings necessitate 24 hours of
observation that includes:-
– Evaluation for possible concomitant exposure to (and
toxicity from) inactive ingredients or vehicles such as
hydrocarbons.
• Most patients recover completely within 24 hours

111. References
• Goldfranks Toxicologic Emergencies, 10th Ed. 2015
• Tintinalli’s Emergency Medicine 9th edition © 2020
by McGraw-Hill Education
• Rosen’s Emergency Medicine Concepts and
Clinical practice. 9th edition/2018
• Poisoning and Drug Overdose 7th ed/2018
• Standard Treatment Protocol of Emergency
Health Service Package/GOVERNMENT OF
NEPAL MOH/2020

112. • Steven Bird. Organophosphate and carbamate
poisoning/ UpToDate 2021
• Michael Eddleston, Nick A Buckley, Peter Eyer, Andrew
H Dawso. Management of acute organophosphorus
pesticide poisoning/lancet 2007
• Y. J. Vishewshwara Reddy. Organophosphorus
Compound Poisoning: Hoping against Hope to
Reduce Morbidity and Mortality © 2019 APIK Journal
of Internal Medicine | Published by Wolters
Kluwer - Medknow