Organophosphorus Poisoning

Abstract

Acute poisoning by organophosphorus (OP) compounds is a major global clinical problem, with
thousands of deaths occurring every year. Most of these pesticide poisoning and subsequent
deaths occur in developing countries following a deliberate self ingestion of the poison. Metacid
(Methyl parathion) and Nuvan (Dichlorovos) are commonly ingested OP pesticides; Dimethoate,
Profenofos, and Chlorpyrifos are other less frequently ingested compounds in Nepal. The toxicity
of these OP pesticides is due to the irreversible inhibition of acetylcholinesterase (AChE) enzyme
leading to accumulation of acetylcholine and subsequent over-activation of cholinergic receptors
in various parts of the body. Acutely, these patients present with cholinergic crisis; intermediate
syndrome and delayed polyneuropathy are other sequel of this form of poisoning. The diagnosis
depends on the history of exposure to these pesticides, characteristic manifestations of toxicity
and improvements of the signs and symptoms after administration of atropine. The supportive
treatment of OP poisoning includes the same basic principles of management of any acutely
poisoned patient i.e., rapid initial management of airways, breathing, and circulation. Gastric
lavage and activated charcoal are routinely used decontamination procedures, but their value
has not been conclusively proven in this poisoning. Atropine is the mainstay of therapy, and
can reverse the life threatening features of this acute poisoning. However, there are no clear
cut guidelines on the dose and duration of atropine therapy in OP poisoning. Cholinesterase
reactivators, by regenerating AChE, can reverse both the nicotinic and muscarinic effects;
however, this benefit has not been translated well in clinical trials. All these facts highlight that
there are many unanswered questions and controversies in the management of OP poisoning
and there is an urgent need for research on this aspect of this common and deadly poisoning.

Key Words: poisoning, organophosphorus insecticides, decontamination, antidotes

Full text

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251
ABSTRACT
Acute poisoning by organophosphorus (OP) compounds is a major global clinical problem, with
thousands of deaths occurring every year. Most of these pesticide poisoning and subsequent
deaths occur in developing countries following a deliberate self ingestion of the poison. Metacid
(Methyl parathion) and Nuvan (Dichlorovos) are commonly ingested OP pesticides; Dimethoate,
Profenofos, and Chlorpyrifos are other less frequently ingested compounds in Nepal. The toxicity
of these OP pesticides is due to the irreversible inhibition of acetylcholinesterase (AChE) enzyme
leading to accumulation of acetylcholine and subsequent over-activation of cholinergic receptors
in various parts of the body. Acutely, these patients present with cholinergic crisis; intermediate
syndrome and delayed polyneuropathy are other sequel of this form of poisoning. The diagnosis
depends on the history of exposure to these pesticides, characteristic manifestations of toxicity
and improvements of the signs and symptoms after administration of atropine. The supportive
treatment of OP poisoning includes the same basic principles of management of any acutely
poisoned patient i.e., rapid initial management of airways, breathing, and circulation. Gastric
lavage and activated charcoal are routinely used decontamination procedures, but their value
has not been conclusively proven in this poisoning. Atropine is the mainstay of therapy, and
can reverse the life threatening features of this acute poisoning. However, there are no clear
cut guidelines on the dose and duration of atropine therapy in OP poisoning. Cholinesterase
reactivators, by regenerating AChE, can reverse both the nicotinic and muscarinic effects;
however, this benet has not been translated well in clinical trials. All these facts highlight that
there are many unanswered questions and controversies in the management of OP poisoning
and there is an urgent need for research on this aspect of this common and deadly poisoning.
Key Words: poisoning, organophosphorus insecticides, decontamination, antidotes
Organophosphorus Poisoning
Paudyal BP
1
1
Department of Medicine, Patan Hospital, Lalitpur
Correspondence:
Dr. Buddhi P Paudyal
Department of Medicine
Patan Hospital, Lalitpur.
Email: buddhipaudyal@yahoo.com
REVIEW ARTICLE J Nepal Med Assoc 2008;47(172):251-8
INTRODUCTION
Organophosphorus (OP) compounds are used as
pesticides, herbicides, and chemical warfare agents
in the form of nerve gases.
1
Acute poisoning by
these agents is a major global clinical problem, with
thousands of deaths occurring every year.
2
Most of the
OP pesticide poisoning and subsequent deaths occur
in developing countries following a deliberate self
ingestion particularly in young, productive age group,
as highly toxic pesticides are readily available at the
moments of stress.
3
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Poisoning has been a common cause of medical
admissions and deaths in Nepalese hospitals.
4-11
Thirty-
one percent of all suicidal deaths in the country in 1999-
2000 were due to poisoning.
12
Hospital- based studies
from ve major hospitals across the country in 1999-
2000 showed OP compounds were the most common
form of poisoning comprising 52% of total cases.
13
Various isolated hospital-based studies also clearly
demonstrate that OP compounds occupy the greatest
burden of poisoning related morbidity and mortality in
Nepal.
4
COMPOUNDS
Organophosphorus compounds were rst developed by
Schrader shortly before and during the Second World
War. They were rst used as an agricultural insecticide
and later as potential chemical warfare agents.
14
These
compounds are normally esters, thiol esters, or acid
anhydride derivatives of phosphorus containing acids.
Of the more than 100 OP pesticides used worldwide,
the majority are either dimethyl phosphoryl or diethyl
phosphoryl compounds.
15
Nerve gas compounds like
tabun, sarin, and soman are highly potent synthetic
toxic agents of this group. Commonly available dimethyl
and diethyl OP compounds are listed in Table 1. Table
2 presents the commonly available OP pesticides with
their brand names in Nepalese market.
Table 1. Common dimethyl and diethyl phosphoryl
compounds
17
Dimethyl Ops Diethyl OPs
Parathion Methyl parathion
Diazinon Dichlorovos
Chlorpyrifos Dimethoate
Dichlorfenthion Malathion
Coumaphos Fenthion
Table 2. Common OP pesticides with their brands
available in Nepal
OP pesticide Brands available
Methyl parathion Metacid, Parahit, Paradol
Dichlorovos Nuvan, DDVP, Nudan, Suchlor
Dimethoate Rogor, Roger, Rogohit
Chlorpyrifos Durmet, Dhanuban, Radar
Fenthion Dalf, Baytex
Profenofos Current
Quinalphos Krush
Monocrotophos Phoskill
Hospital-based data from across the country show
that Methyl-parathion, Dichlorovos, Dimethoate,
Chlorpyrifos and Malathion are the common OPs related
with human poisoning. ‘Metacid’, a popular brand for
Methyl parathion is the most frequently ingested and
probably the most toxic organophosphate used for
poisoning in Nepal. Dichlorovos, or ‘Nuvan’ as it is
commonly known, is moderately volatile solution; its
use has been on rise for self harm in recent years.
4
Dimethoate has a lethal dose of 10-12 gm and there
are concerns that it causes specic cardiac toxicities in
addition to cholinergic syndrome. Malathion is relatively
less-toxic and is used for the treatment of pediculosis
and scabies in humans; and has a lethal dose is 1 gm/kg
in mammals.
16
MECHANISM OF TOXICITY
The toxic mechanism of OP compounds is based on
the irreversible inhibition of acetylcholinesterase due
to phosphorylation of the active site of the enzyme.
This leads to accumulation of acetylcholine and
subsequent over-activation of cholinergic receptors
at the neuromuscular junctions and in the autonomic
and central nervous systems. The rate and degree of
AChE inhibition differs according to the structure of
the OP compounds and the nature of their metabolite.
In general, pure thion compounds are not signicant
inhibitors in their original form and need metabolic
activation (oxidation) in vivo to oxon form. For example,
parathion has to be metabolized to paraxon in the body
so as to actively inhibit AChE.
17
The toxic mechanism
of OP pesticides differs from that of carbamates which
inhibit the same enzyme reversibly and are sometimes
useful as medicines (neostigmine, pyridostigmine) as
well as insecticides (carbaryl).
18
After the initial inhibition and formation of AChE-
OP complex two further reactions are possible: (1)
Spontaneous reactivation of the enzyme may occur at
a slow pace, much slower than the enzyme inhibition
and requiring hours to days to occur. The rate of this
regenerative process solely depends on the type of OP
compound: spontaneous reactivation half life of 0.7
hours for dimethyl and 31 hours for diethyl compounds.
In general, AChE-dimethyl OP complex spontaneously
reactivate in less than one day whereas AChE-diethyl
OP complex may take several days and reinhibition of
the newly activated enzyme can occur signicantly in
such situation. The spontaneous reactivation can be
hastened by adding nucleophilic reagents like oximes,
liberating more active enzymes. These agents thereby
act as an antidote in OP poisoning.
19
(2) With time, the enzyme-OP complex loses one alkyl
group making it no longer responsive to reactivating
agents. This progressive time dependent process
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is known as ageing. The rate of ageing depends on
various factors like pH, temperature, and type of OP
compound; dimethyl OPs have ageing half life of 3.7
hours whereas it is 33 hours for diethyl OPs.
20,21
The
slower the spontaneous reactivation, the greater the
quantity of inactive AChE available for ageing. Oximes,
by catalyzing the regeneration of active AChE from
enzyme-OP complex, reduce the quantity of inactive
AChE available for ageing. Since ageing occurs more
rapidly with dimethyl OPs, oximes are hypothetically
useful before 12 hours in such poisoning.
19
However,
in diethyl OP intoxication they may be useful for many
days.
Clinical manifestations
Acute Cholinergic Crisis
The clinical features of acute OP poisoning reect the
degree of accumulation of acetylcholine (ACh) causing
excessive stimulation of cholinergic receptors at
various organs (acute cholinergic crisis). Acetylcholine
is the principle neurotransmitter in various synapses
in the human body: parasympathetic nervous system,
autonomic ganglia, neuromuscular junction and central
nervous system. Owing to the widespread distribution
of cholinergic neurons in central and peripheral nervous
can be hastened by adding nucleophilic reagents like oximes, liberating more active
enzymes. These agents thereby act as an antidote in OP poisoning.
19
(2) With time, the enzyme-OP complex loses one alkyl group making it no longer
responsive to reactivating agents. This progressive time dependent process is known as
ageing. The rate of ageing depends on various factors like pH, temperature, and type of
OP compound; dimethyl OPs have ageing half life of 3.7 hours whereas it is 33 hours for
diethyl OPs.
20,21
The slower the spontaneous reactivation, the greater the quantity of
inactive AChE available for ageing. Oximes, by catalyzing the regeneration of active
AChE from enzyme-OP complex, reduce the quantity of inactive AChE available for
ageing. Since ageing occurs more rapidly with dimethyl OPs, oximes are hypothetically
useful before 12 hours in such poisoning.
19
However, in diethyl OP intoxication they may
be useful for many days.
Reactivation
Inactive OP (‘thion’)
(in liver)
C
y
tochrome P450
AChE
(Regenerated
enz
y
me)
Spontaneous
Induced
(by oxime)
Cholinergic
s
igns and
s
ymptoms
AChE – OP
com
p
lex
Ageing
Aged AChE – OP
c
omplex
(No reactivation
possible)
A
ctive OP (‘oxon’)
+AChE
Figure 1. Diagrammatic representation of the possible reactivation & ageing
reactions of AChE after inhibition by OP compounds
Figure 1. Diagrammatic representation of the possible reactivation & ageing reactions of AChE after inhibition by
OP compounds
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systems, the signs and symptoms involve various organ
systems. Depending on the severity of the exposure,
the spectrum of the clinical presentation varies: the
signs and symptoms may be mild, moderate or severe.
On the basis of the receptor stimulation, the acute
manifestations can be broadly divided into muscarinic,
nicotinic, and central nervous system (CNS) effects. The
important practical signicance of this classication is
that atropine only blocks muscarinic effects whereas
oximes reverse both the nicotinic and muscarinic effects
by reactivating AChE at both receptor sites because of
their ability to reactivate inhibited AChE regardless of
receptor type.
Excess ACh in muscarinic receptors lead to increased
bronchial secretions, excessive sweating, salivation,
lacrimation, miosis, bronchospasm, abdominal cramps,
vomiting, involuntary passage of stool and urine. Cardiac
manifestations comprise bradycardia, hypotension and
QT prolongation with development of various types
of arrythmias.
22
Various mnemonics have been used
to describe the muscarinic signs of OP poisoning:
DUMBELS (diarrhoea, urination, miosis, bronchospasm,
emesis, lacrimation, and salivation) and SLUDGE
(salivation, lacrimation, urine incontinence, diarrhoea,
gastrointestinal cramps and emesis) are commonly used
ones. Stimulation of the nicotinic receptors at muscle
end plate results in twitching, fasciculation, muscle
weakness and accid paralysis; whereas stimulation
of sympathetic ganglia leads to hypertension and
tachycardia. Heart rate and blood pressure can be
potentially misleading ndings as increase or decrease
Table 3. Summary of clinical features and antidotes in Acute Cholinergic Crisis
Muscarinic features Nicotinic features CNS
Parasympathetic
(Muscarinic receptor)
NMJ (NM receptor)
Symp Ganglia
(NN receptor)
Muscarinic +?NN
receptor
Receptor Locations Respiratory tract
Gastrointestinal tract
Cardiovascular system
Exocrine glands
Urinary bladder
Neuromuscular
junction (NMJ) of
striated muscles
Paravertebral
sympathetic
ganglia and
Adrenal medulla
Various parts of the
brain
Dangerous effects Bronchospasm,
Pulmonary oedema
Diarrhoea, Vomiting,
Abdominal cramps
Bradycardia, Hypotension,
Ventricular tachycardia
Excessive secretions
Urinary incontinence
Muscle weakness,
Paralysis,
Respiratory failure
Hypertension
Tachycardia
Restlessness
Seizures
Coma
Respiratory and
circulatory depression
Antidote Atropine
Oximes
Oximes ?Oximes ?Atropine
? Diazepam
can occur in both vital signs. CNS manifestations
include headache, dizziness, tremor, restlessness,
anxiety, confusion, convulsion and coma. Patients can
also develop pancreatitis, hypo or hyperglycaemia and
acute renal failure during this phase.
The time of death after a single acute exposure may
range from less than ve minutes to nearly 24 hours
depending upon the dose, route of administration,
agent and availability of treatment.
23
Respiratory failure
and hypotension are the main causes of death in acute
stage. Delay in discovery and transport, insufcient
respiratory management, aspiration pneumonia and
sepsis are common causes of death.
25
Prognosis in
acute poisoning may depend upon many factors like
dose and toxicity of the ingested OP (e.g., neurotoxicity
potential, half life, rate of ageing, pro-poison or poison),
and whether dimethyl or diethyl compound.
24
Intermediate syndrome
The intermediate syndrome is a distinct clinical entity
that usually occurs 24 to 96 hours after the ingestion
of an OP compound; after an initial cholinergic crisis but
before the expected onset of delayed polyneuropathy.
25
Approximately 10-40% of patients treated for acute
poisoning develop this illness.
26,27
This syndrome is
characterized by prominent weakness of neck exors,
muscles of respiration and proximal limb muscles.
Though originally seen with fenthion, dimethoate and
monocrotophos, it is also seen in other OP compounds.
The muscle weakness in intermediate syndrome may
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last up to 5-14 days and the condition regresses slowly
if respiratory support is available. Though the exact
pathogenesis of intermediate syndrome is unclear, the
proposed mechanisms include persistent inhibition of
AChE leading to functional paralysis of neuromuscular
transmission, muscle necrosis, and oxidative free radical
damage to the receptors.
28,29
DELAYED POLYNEUROPATHY
Delayed polyneuropathy is an uncommon consequence
of severe intoxication or intermittent and chronic contact
with OP pesticides as in occupational exposure.
30
It is
due to inhibition of neuropathy target esterase (NTE)
enzyme in nervous tissues by certain OP compounds.
Many locally available OPs have negligible NTE inhibitory
effect except chlorpyrifos which causes intermediate
degree of inhibition. Delayed polyneuropathy is often
unrecognized in humans and many times the clinical
features are easily overlooked. Clinical manifestations
are of distal symmetric sensory-motor polyneuropathy
(distal weakness, parasthesia, ataxia, diminished or
absent reexes). The symptoms usually begin 2-5
weeks after exposure to the chemical, and may last for
years.
17
Apart from these well-dened neural syndromes,
OP pesticides can also cause chronic neurotoxicity and
behavioural impairment in some patients.
DIAGNOSIS
The diagnosis of OP poisoning depends on the
history of exposure to OP compounds, characteristic
manifestations of toxicity and improvements of the
signs and symptoms after administration of atropine.
22
Diagnosis may be aided by insisting that the patient party
send someone home to search for a possible poison
container in the vicinity of the patient’s quarters.
Garlic-like smell is an added clinical sign especially if the
patient has ingested sulphur containing OP compound.
Analytical identication of OP compound in gastric
aspirate or its metabolites in the body uids gives the
clue that patient has been exposed to OP compound.
Usually the level of plasma (pseudo) cholinesterase
drops to less than 50% before signs and symptoms
appear. Clinical severity has been graded on the basis
of the pseudocholinesterase level (mild 20-50% enzyme
activity, moderate 10-20% enzyme activity and severe
<10% enzyme activity)
31
though many believe that
the enzyme activity does not correlate well with
clinical severity. On the other hand, true or erythrocyte
cholinesterase correlates well with clinical severity but
is not available in most centres, especially in developing
countries.
These laboratory tests are of limited value in acute
situation because treatment is usually required before
test results are available. However in doubtful cases
and especially if laboratory facilities are not available,
1 mg atropine can be given intravenously. If this does
not produce marked anticholinergic manifestations,
anticholinesterase poisoning should be strongly
suspected.
32
TREATMENT
General supportive treatment
The supportive treatment of OP poisoning follows
the basic principles of management of any acutely
poisoned patient. Rapid initial assessment of airways,
breathing, and circulation is essential. Comatose or
vomiting patients should be kept in lateral, preferably
head down position with neck extension to reduce the
risk of aspiration. Patent airway should be secured with
proper positioning, placement of Guedel’s airway or
with endotracheal intubation especially if the patient is
unconscious, tting, or vomiting. Frequent suctioning
is essential as excessive oropharyngeal and respiratory
secretions may occlude the airway. Oxygen is needed
in majority of these patients; and this can be assessed
by frequent assessment of arterial oxygen saturation.
The skin and clothes of these patients are frequently
contaminated with poison and vomiting. The clothes
should be removed and the skin vigorously washed
with soap and water. People involved in rst aid should
wear rubber gloves so as to prevent skin absorption of
the poison.
Gastric lavage may help to reduce the absorption of the
ingested poison and should be considered in patients
presenting within 1-2 hours of ingestion of poison.
The risks of gastric lavage include aspiration, hypoxia,
and laryngeal spasm, and these can be reduced with
proper management of airway.
33,34
The induction of
vomiting with soap water, ipecacuanha or other agents
may cause more harm than benet as many OPs are
dissolved in petroleum distillates and can cause severe
pneumonitis and acute respiratory distress syndrome
when aspirated.
35
Use of home remedies like ingestion
of milk may dilute the poison but risks increased
gastric emptying; and ‘pushing’ the poison into small
bowel from where it is readily absorbed with early
development of toxicity. On the contrary small amount
of lipid-rich home remedy (e.g. raw eggs) may slow
gastric emptying and delay the onset of poisoning and
respiratory failure.
36
Cathartics may further aggravate
the OP-induced diarrhea leading to dehydration and
electrolyte imbalance; therefore their use can not be
recommended in routine practice.
Activated charcoal helps to reduce the poison load
by adsorbing it; and this has been clearly shown to
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JNMA I VOL 47 I NO. 4 I ISSUE 172 I OCT-DEC, 2008
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be effective in OP poisoning in animal experiment.
37
Though its efcacy has not been conclusively proven
in humans, single to multiple dose activated charcoal is
routinely used in clinical practice. An ongoing randomized
controlled trial in Sri Lanka comparing single or multiple
dose activated charcoal versus placebo in OP poisoning
may settle this issue.
38
Figure 2. Decontamination Procedure in OP Poisoning
Specic Antidotal Treatment
Atropine: Atropine has been the cornerstone in the
management of OP poisoning for decades and will remain
so in the future. It acts competitively at the peripheral
and central muscarinic receptors and antagonizes the
parasympathetic effects of excess ACh at these sites.
It reverses life threatening features from poisoning;
delay or inadequate atropine can result in death
from central respiratory depression, bronchospasm,
excessive bronchosecretion, severe bradycardia, and
hypotension.
2
There are wide variations in recommended doses and
regimens of atropine therapy in different parts of the
world. Moreover, duration of atropine treatment and
titration of the dose is not clear. Current guidelines
recommend the use of bolus doses to attain target end-
points, followed by setting up an infusion to maintain
these end-points.
24
Target end-points for Atropine therapy
39
Heart rate >80/ min
Dilated pupils
Dry axillae
Systolic blood pressure >80 mm Hg
Clear chest with absence of wheeze
We use an initial bolus of 3-5 ampoules of atropine
(each ampoule containing 0.6 mg) with subsequent
doses doubled every 5 minutes until atropinization is
achieved.
39
When the patient achieves most of (at least
4 out of 5) the target end-points for atropine therapy
i.e., ‘fully atropinized’, an intravenous infusion is set up
to maintain the therapeutic effects of atropine. While
there are different approaches of atropine infusion, we
use 20% of initial atropinizing dose per hour for rst 48
hours and gradually taper over 5 -10 days, continuously
monitoring the adequacy of therapy.
There is a tendency to give excess atropine, which can
be dangerous. Atropine toxicity can result in agitation,
confusion, hyperthermia, and severe tachycardia
that can precipitate ischaemic events in patients
with underlying coronary artery disease.
2
So, close
observation and dose adjustment is essential to avoid
the features of both under- and over-atropinization.
Some centres use another anticholinergic agent
glycopyrrolinium bromide along with atropine in order
to limit the central stimulation produced by atropine,
because the former does not cross blood brain
barrier.
36
Oximes: Oximes work by reactivating
acetylcholinesterase that has been bound to the OP
molecule. Pralidoxime is the most frequently used
oxime worldwide; other members of the class include
obidoxime, and experimental HI 6 and HLO 7.
Oximes
can be highly effective in restoring skeletal muscle
strength and improving diaphragmatic weakness where
atropine has virtually no effect.
23
Notwithstanding this theoretical advantage, clinical
opinions of oxime therapy in OP poisoning are divided,
even in cases of massive human intoxication.
40
Outcomes following oxime therapy depend on various
factors like the type of poison ingested, the poison
load, time elapsed between OP ingestion and institution
of therapy, and the duration and dosage of the oxime
therapy. In some cases oximes may prove ineffective
for several reasons: inadequate dose leading to sub-
therapeutic blood levels, early termination of oxime
therapy, and continuous reinhibition of the reactivated
AChE from pesticide persisting in the body.
23
The
therapeutic window for oximes is limited by the time
taken for ‘ageing’ of the enzyme-OP complex, because
‘aged’ enzyme can no longer be reactivated by oximes
(see mechanism of toxicity, above).
However, others propose prolonged maintenance of
an appropriate oxime concentration irrespective of the
type of ingested OP.
41
Some advise oxime therapy for
the treatment of intermediate syndrome.
42
Various dosage regimens have been recommended
from intermittent oxime administration to continuous
infusion following a loading dose. While there is no clear
consensus on the dose and duration of oxime therapy,
recently the WHO recommended pralidoxime dose of
30 mg/kg bolus iv followed by continuous infusion of
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JNMA I VOL 47 I NO. 4 I ISSUE 172 I OCT-DEC, 2008
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8 mg/kg/hour until clinical improvement.
39
Dizziness,
headache, blurred vision, and diplopia, are common
side effects of oxime therapy. Rapid administration may
lead to tachycardia, laryngospasm, muscle spasm, and
transient neuromuscular blockade.
16
Difcult availability
and cost factor are other drawbacks for routine use of
oximes in clinical practice.
Benzodiazepines: Diazepam and other benzodiazepines
are widely used for the treatment of OP induced
seizures and restlessness and agitation consequent
to either poison itself or sequel of atropine therapy.
39
Moreover diazepam, due to its central respiratory
depressant action, is also believed to attenuate OP-
induced respiratory depression which usually follows
overstimulation of the CNS respiratory centers.
1
PREGNANCY
Pregnant patients who have ingested OP insecticides
during the second or third trimester of pregnancy have
been treated successfully with atropine and pralidoxime
and later delivered healthy newborns with no signicant
abnormalities.
43
However, foetal distress is a possible
complication of both of the poisoning as well as its
treatment.
16
Newer forms of therapies in OP poisoning
One small uncontrolled study from Iran concluded that
the infusion of sodium bicarbonate signicantly reduced
total hospital stay, total atropine requirement, and the
need for intensive care therapy; mortality rate was also
low in the treatment group.
44
Adrenergic receptor α2
agonists like clonidine inhibit the release of ACh from
cholinergic neurons and may decrease the excess ACh
at synaptic cleft. Though animal studies have shown
improved survival with clonidine in OP poisoning,
human studies are yet to be done.
45
Magnesium
sulphate,
46
fresh frozen plasma,
47
, antioxidants,
48
Organophosphorus hydrolases,
49
and galyclidine
(NMDA receptor antagonist)
50
are all potential forms
of therapies for the future.
46-50
ACKNOWLEDGEMENT
The authors would like to thank Mr. Macha Bhai Shakya
for his help during the preparation of this manuscript.
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